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Green fingernail
A 34-year-old woman came to our clinic because she was concerned about her thumbnail, which had turned green. Although her finger didn’t hurt, she was bothered by its appearance. Several months earlier, the woman had sought care at a different clinic because the same nail had become brittle and come loose from the nail bed, which was spongy. The physician advised her that she had onychomycosis and prescribed ciclopirox lacquer, but it didn’t help.
Over the next 3 weeks, she noticed a faint green hue developing at the tip of the nail, which expanded and intensified in color (FIGURE). The patient was a mother who worked at home, washed dishes by hand daily, and bathed her children. Her past medical history was significant for type 1 diabetes mellitus and Hashimoto’s thyroiditis. She had no other symptoms.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Dx: Green nail syndrome caused by Pseudomonas aeruginosa
This patient had green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail.1 GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.
Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa grows in these spaces.2 Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS,3,4 and it is typical for only one nail to be involved.5Pseudomonas is the most common bacterial infection of the nails, but is not well known because it is rarely reported and patients often don’t seek care.6
In our patient’s case, her prior onychomycosis helped to create a favorable environment for the growth of the bacteria. Onycholysis—characterized by separation of the nail plate from the nail bed—was also present in our patient, based on her description of a “spongy” nail bed and loose nail, allowing moisture and bacteria to infiltrate the space. Onycholysis is associated with hypothyroidism, which the patient also had.7 The frequent soaking of her hands during dishwashing and bathing her children helped to provide the moist environment in which Pseudomonas thrives.
As was the case in this patient, GNS is often painless, or may be accompanied by mild tenderness of the nail. Patients may seek treatment primarily for cosmetic reasons.
GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history.4 Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected.
Changes in nail color can be a sign of many conditions
Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases.8 The specific shade of discoloration helps to differentiate the underlying pathology.
Yellow nail syndrome. As the name implies, this syndrome typically causes yellow discoloration of the nail (although yellow-green is also possible). Yellow nail syndrome is believed to be due to microvascular permeability, which also accounts for its associated clinical triad: hypoalbuminemia, pleural effusion, and lymphedema. Yellow nail syndrome may be seen in patients with bronchiectasis, internal malignancies, immunodeficiency, and rheumatoid arthritis.8
Nail bed hematoma. Among the most common causes of nail discoloration, these lesions typically appear as reddish to reddish-black, depending on the age of the bleed, and will often have streaks at the distal margin of the lesion.9 Risk factors for hemorrhage include blood thinners and clotting disorders. Subungual hemorrhages that do not grow out with the nail, or that recur in the same place, may require biopsy.9
Subungual melanoma causes black-brown discoloration of the nails, and may form a longitudinal band in the nail.9 Longitudinal melanonychia is a common variant in African American individuals.10 Features that increase the likelihood of melanoma include a family history of melanoma, a sudden change in the appearance of the lesion, band width greater than 3 mm, pigment changes extending into the cuticle (known as Hutchinson’s sign), and nail plate disruption.
Dermoscopy, the technique of using surface microscopy to examine the skin, may be helpful in distinguishing nail lesions. (See a video on how to perform dermoscopy here: http://bit.ly/2pyJ3xN.)
Nonmelanocytic lesions tend to have homogeneously distributed pigment, while melanocytic lesions contain granules of pigment in cellular inclusions. Any suspicion of melanoma warrants a punch biopsy.11
Medication-induced effects. Minocycline may cause bluish nail discoloration similar to that produced by infection with P aeruginosa, but it is rare for only a single nail to be involved. In addition, pigmentation changes are often present elsewhere on the body, including the sclerae, teeth, and pinna.
Another medication known to color the nails blue is colloidal silver, which is still sold as a dietary supplement or homeopathic remedy to treat a wide range of ailments.6 (Of note: In 1999, the Food and Drug Administration issued a final rule saying that colloidal silver isn’t safe or effective for treating any disease or condition.12)
Glomus tumor. Another cause of blue nails is glomus tumors, relatively uncommon perivascular neoplasms that are typically found in the subungual region. These tumors are generally accompanied by localized tenderness, cold sensitivity, and paroxysms of excruciating pain that are disproportional to the size of the tumor.
Imaging studies may aid in the diagnosis, in addition to pathologic confirmation. Magnetic resonance imaging is the most sensitive imaging modality; if a glomus tumor is present, it most often appears as a well-circumscribed T2 hyperintense lesion.13
Exogenous pigmentation. Nails may become discolored due to exposure to various toxins or chemicals. Frequent culprits include eosin, methylene blue, henna, hair dye, and tobacco.9
Antibiotics and measures to keep the nail dry will help resolve infection
When chronic nail wetness is a contributing factor, treatment begins with measures to keep the nails dry. In addition, either topical or systemic antibiotics may be used to eradicate the infection. Topical applications with agents such as nadifloxacin have been shown to be effective in several case reports,3 but large-scale controlled trials are lacking. Fluoroquinolones are regarded as first-line systemic treatment.5 Briefly soaking the nail in a diluted sodium hypochlorite (bleach) solution also helps to suppress bacterial growth. Nail extraction may be required in refractory cases.
For our patient, we prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (one part bleach to 4 parts water) twice a day. We recommended that our patient wear gloves for household tasks that involved immersing her hands in water, and drying her finger with a hair dryer after bathing.
CORRESPONDENCE
David Gish, MD, University of Virginia Health System, 1215 Lee St. Charlottesville, VA 22908; [email protected].
1. Greene SL, Su WP, Muller SA. Pseudomonas aeruginosa infections of the skin. Am Fam Physician. 1984;29:193-200.
2. de Almeida HL Jr, Duquia RP, de Castro LA, et al. Scanning electron microscopy of the green nail. Int J Dermatol. 2010;49:962-963.
3. Hengge UR, Bardeli V. Images in clinical medicine. Green nails. N Engl J Med. 2009;360:1125.
4. Chiriac A, Brzezinski P, Foia L, et al. Chloronychia: green nail syndrome caused by Pseudomonas aeruginosa in elderly persons. Clin Interv Aging. 2015;10:265-267.
5. Müller S, Ebnöther M, Itin P. Green nail syndrome (Pseudomonas aeruginosa nail infection): Two cases successfully treated with topical nadifloxacin, an acne medication. Case Rep Dermatol. 2014;6:180-184.
6. Raam R, DeClerck B, Jhun P, et al. That’s some weird nail polish you got there! Ann Emerg Med. 2015;66:585-588.
7. Gregoriou S, Argyriou G, Larios G, et al. Nail disorders and systemic disease: what the nails tell us. J Fam Pract. 2008;57:509-514.
8. Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician. 2004;69:1417-1424.
9. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007;56:835-847.
10. Buka R, Friedman KA, Phelps RG, et al. Childhood longitudinal melanonychia: case reports and review of the literature. Mt Sinai J Med. 2001;68:331-335.
11. Tully AS, Trayes KP, Studdiford JS. Evaluation of nail abnormalities. Am Fam Physician. 2012;85:779-787.
12. US Food and Drug Administration. Over-the-counter drug products containing colloidal silver ingredients or silver salts. 1999. Available at: https://www.fda.gov/ohrms/dockets/98fr/081799a.txt. Accessed April 11, 2017.
13. Glazebrook KN, Laundre BJ, Schiefer TK, et al. Imaging features of glomus tumors. Skeletal Radiol. 2011;40:855-862.
A 34-year-old woman came to our clinic because she was concerned about her thumbnail, which had turned green. Although her finger didn’t hurt, she was bothered by its appearance. Several months earlier, the woman had sought care at a different clinic because the same nail had become brittle and come loose from the nail bed, which was spongy. The physician advised her that she had onychomycosis and prescribed ciclopirox lacquer, but it didn’t help.
Over the next 3 weeks, she noticed a faint green hue developing at the tip of the nail, which expanded and intensified in color (FIGURE). The patient was a mother who worked at home, washed dishes by hand daily, and bathed her children. Her past medical history was significant for type 1 diabetes mellitus and Hashimoto’s thyroiditis. She had no other symptoms.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Dx: Green nail syndrome caused by Pseudomonas aeruginosa
This patient had green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail.1 GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.
Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa grows in these spaces.2 Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS,3,4 and it is typical for only one nail to be involved.5Pseudomonas is the most common bacterial infection of the nails, but is not well known because it is rarely reported and patients often don’t seek care.6
In our patient’s case, her prior onychomycosis helped to create a favorable environment for the growth of the bacteria. Onycholysis—characterized by separation of the nail plate from the nail bed—was also present in our patient, based on her description of a “spongy” nail bed and loose nail, allowing moisture and bacteria to infiltrate the space. Onycholysis is associated with hypothyroidism, which the patient also had.7 The frequent soaking of her hands during dishwashing and bathing her children helped to provide the moist environment in which Pseudomonas thrives.
As was the case in this patient, GNS is often painless, or may be accompanied by mild tenderness of the nail. Patients may seek treatment primarily for cosmetic reasons.
GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history.4 Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected.
Changes in nail color can be a sign of many conditions
Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases.8 The specific shade of discoloration helps to differentiate the underlying pathology.
Yellow nail syndrome. As the name implies, this syndrome typically causes yellow discoloration of the nail (although yellow-green is also possible). Yellow nail syndrome is believed to be due to microvascular permeability, which also accounts for its associated clinical triad: hypoalbuminemia, pleural effusion, and lymphedema. Yellow nail syndrome may be seen in patients with bronchiectasis, internal malignancies, immunodeficiency, and rheumatoid arthritis.8
Nail bed hematoma. Among the most common causes of nail discoloration, these lesions typically appear as reddish to reddish-black, depending on the age of the bleed, and will often have streaks at the distal margin of the lesion.9 Risk factors for hemorrhage include blood thinners and clotting disorders. Subungual hemorrhages that do not grow out with the nail, or that recur in the same place, may require biopsy.9
Subungual melanoma causes black-brown discoloration of the nails, and may form a longitudinal band in the nail.9 Longitudinal melanonychia is a common variant in African American individuals.10 Features that increase the likelihood of melanoma include a family history of melanoma, a sudden change in the appearance of the lesion, band width greater than 3 mm, pigment changes extending into the cuticle (known as Hutchinson’s sign), and nail plate disruption.
Dermoscopy, the technique of using surface microscopy to examine the skin, may be helpful in distinguishing nail lesions. (See a video on how to perform dermoscopy here: http://bit.ly/2pyJ3xN.)
Nonmelanocytic lesions tend to have homogeneously distributed pigment, while melanocytic lesions contain granules of pigment in cellular inclusions. Any suspicion of melanoma warrants a punch biopsy.11
Medication-induced effects. Minocycline may cause bluish nail discoloration similar to that produced by infection with P aeruginosa, but it is rare for only a single nail to be involved. In addition, pigmentation changes are often present elsewhere on the body, including the sclerae, teeth, and pinna.
Another medication known to color the nails blue is colloidal silver, which is still sold as a dietary supplement or homeopathic remedy to treat a wide range of ailments.6 (Of note: In 1999, the Food and Drug Administration issued a final rule saying that colloidal silver isn’t safe or effective for treating any disease or condition.12)
Glomus tumor. Another cause of blue nails is glomus tumors, relatively uncommon perivascular neoplasms that are typically found in the subungual region. These tumors are generally accompanied by localized tenderness, cold sensitivity, and paroxysms of excruciating pain that are disproportional to the size of the tumor.
Imaging studies may aid in the diagnosis, in addition to pathologic confirmation. Magnetic resonance imaging is the most sensitive imaging modality; if a glomus tumor is present, it most often appears as a well-circumscribed T2 hyperintense lesion.13
Exogenous pigmentation. Nails may become discolored due to exposure to various toxins or chemicals. Frequent culprits include eosin, methylene blue, henna, hair dye, and tobacco.9
Antibiotics and measures to keep the nail dry will help resolve infection
When chronic nail wetness is a contributing factor, treatment begins with measures to keep the nails dry. In addition, either topical or systemic antibiotics may be used to eradicate the infection. Topical applications with agents such as nadifloxacin have been shown to be effective in several case reports,3 but large-scale controlled trials are lacking. Fluoroquinolones are regarded as first-line systemic treatment.5 Briefly soaking the nail in a diluted sodium hypochlorite (bleach) solution also helps to suppress bacterial growth. Nail extraction may be required in refractory cases.
For our patient, we prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (one part bleach to 4 parts water) twice a day. We recommended that our patient wear gloves for household tasks that involved immersing her hands in water, and drying her finger with a hair dryer after bathing.
CORRESPONDENCE
David Gish, MD, University of Virginia Health System, 1215 Lee St. Charlottesville, VA 22908; [email protected].
A 34-year-old woman came to our clinic because she was concerned about her thumbnail, which had turned green. Although her finger didn’t hurt, she was bothered by its appearance. Several months earlier, the woman had sought care at a different clinic because the same nail had become brittle and come loose from the nail bed, which was spongy. The physician advised her that she had onychomycosis and prescribed ciclopirox lacquer, but it didn’t help.
Over the next 3 weeks, she noticed a faint green hue developing at the tip of the nail, which expanded and intensified in color (FIGURE). The patient was a mother who worked at home, washed dishes by hand daily, and bathed her children. Her past medical history was significant for type 1 diabetes mellitus and Hashimoto’s thyroiditis. She had no other symptoms.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Dx: Green nail syndrome caused by Pseudomonas aeruginosa
This patient had green nail syndrome (GNS), an infection of the nail bed caused by Pseudomonas aeruginosa. These bacteria produce pyocyanin, a blue-green pigment that discolors the nail.1 GNS often occurs in patients with prior nail problems, such as onychomycosis, onycholysis, trauma, chronic paronychia, or psoriasis.
Nail disease disrupts the integumentary barrier and allows a portal of entry for bacteria. Scanning electron microscopy of patients with GNS has shown that fungal infections create tunnel-like structures in the nail keratin, and P aeruginosa grows in these spaces.2 Nails with prior nail disease that are chronically exposed to moisture are at greatest risk of developing GNS,3,4 and it is typical for only one nail to be involved.5Pseudomonas is the most common bacterial infection of the nails, but is not well known because it is rarely reported and patients often don’t seek care.6
In our patient’s case, her prior onychomycosis helped to create a favorable environment for the growth of the bacteria. Onycholysis—characterized by separation of the nail plate from the nail bed—was also present in our patient, based on her description of a “spongy” nail bed and loose nail, allowing moisture and bacteria to infiltrate the space. Onycholysis is associated with hypothyroidism, which the patient also had.7 The frequent soaking of her hands during dishwashing and bathing her children helped to provide the moist environment in which Pseudomonas thrives.
As was the case in this patient, GNS is often painless, or may be accompanied by mild tenderness of the nail. Patients may seek treatment primarily for cosmetic reasons.
GNS can be diagnosed by clinical observation and characteristic pigmentation along with an appropriate patient history.4 Culture of the nail bed may be helpful if bacterial resistance or co-infection with fungal organisms is suspected.
Changes in nail color can be a sign of many conditions
Nail discoloration, or chromonychia, can present in a variety of colors. Nail findings may represent an isolated disease or provide an important clinical clue to other systemic diseases.8 The specific shade of discoloration helps to differentiate the underlying pathology.
Yellow nail syndrome. As the name implies, this syndrome typically causes yellow discoloration of the nail (although yellow-green is also possible). Yellow nail syndrome is believed to be due to microvascular permeability, which also accounts for its associated clinical triad: hypoalbuminemia, pleural effusion, and lymphedema. Yellow nail syndrome may be seen in patients with bronchiectasis, internal malignancies, immunodeficiency, and rheumatoid arthritis.8
Nail bed hematoma. Among the most common causes of nail discoloration, these lesions typically appear as reddish to reddish-black, depending on the age of the bleed, and will often have streaks at the distal margin of the lesion.9 Risk factors for hemorrhage include blood thinners and clotting disorders. Subungual hemorrhages that do not grow out with the nail, or that recur in the same place, may require biopsy.9
Subungual melanoma causes black-brown discoloration of the nails, and may form a longitudinal band in the nail.9 Longitudinal melanonychia is a common variant in African American individuals.10 Features that increase the likelihood of melanoma include a family history of melanoma, a sudden change in the appearance of the lesion, band width greater than 3 mm, pigment changes extending into the cuticle (known as Hutchinson’s sign), and nail plate disruption.
Dermoscopy, the technique of using surface microscopy to examine the skin, may be helpful in distinguishing nail lesions. (See a video on how to perform dermoscopy here: http://bit.ly/2pyJ3xN.)
Nonmelanocytic lesions tend to have homogeneously distributed pigment, while melanocytic lesions contain granules of pigment in cellular inclusions. Any suspicion of melanoma warrants a punch biopsy.11
Medication-induced effects. Minocycline may cause bluish nail discoloration similar to that produced by infection with P aeruginosa, but it is rare for only a single nail to be involved. In addition, pigmentation changes are often present elsewhere on the body, including the sclerae, teeth, and pinna.
Another medication known to color the nails blue is colloidal silver, which is still sold as a dietary supplement or homeopathic remedy to treat a wide range of ailments.6 (Of note: In 1999, the Food and Drug Administration issued a final rule saying that colloidal silver isn’t safe or effective for treating any disease or condition.12)
Glomus tumor. Another cause of blue nails is glomus tumors, relatively uncommon perivascular neoplasms that are typically found in the subungual region. These tumors are generally accompanied by localized tenderness, cold sensitivity, and paroxysms of excruciating pain that are disproportional to the size of the tumor.
Imaging studies may aid in the diagnosis, in addition to pathologic confirmation. Magnetic resonance imaging is the most sensitive imaging modality; if a glomus tumor is present, it most often appears as a well-circumscribed T2 hyperintense lesion.13
Exogenous pigmentation. Nails may become discolored due to exposure to various toxins or chemicals. Frequent culprits include eosin, methylene blue, henna, hair dye, and tobacco.9
Antibiotics and measures to keep the nail dry will help resolve infection
When chronic nail wetness is a contributing factor, treatment begins with measures to keep the nails dry. In addition, either topical or systemic antibiotics may be used to eradicate the infection. Topical applications with agents such as nadifloxacin have been shown to be effective in several case reports,3 but large-scale controlled trials are lacking. Fluoroquinolones are regarded as first-line systemic treatment.5 Briefly soaking the nail in a diluted sodium hypochlorite (bleach) solution also helps to suppress bacterial growth. Nail extraction may be required in refractory cases.
For our patient, we prescribed ciprofloxacin 500 mg twice a day for 10 days, plus bleach soaks (one part bleach to 4 parts water) twice a day. We recommended that our patient wear gloves for household tasks that involved immersing her hands in water, and drying her finger with a hair dryer after bathing.
CORRESPONDENCE
David Gish, MD, University of Virginia Health System, 1215 Lee St. Charlottesville, VA 22908; [email protected].
1. Greene SL, Su WP, Muller SA. Pseudomonas aeruginosa infections of the skin. Am Fam Physician. 1984;29:193-200.
2. de Almeida HL Jr, Duquia RP, de Castro LA, et al. Scanning electron microscopy of the green nail. Int J Dermatol. 2010;49:962-963.
3. Hengge UR, Bardeli V. Images in clinical medicine. Green nails. N Engl J Med. 2009;360:1125.
4. Chiriac A, Brzezinski P, Foia L, et al. Chloronychia: green nail syndrome caused by Pseudomonas aeruginosa in elderly persons. Clin Interv Aging. 2015;10:265-267.
5. Müller S, Ebnöther M, Itin P. Green nail syndrome (Pseudomonas aeruginosa nail infection): Two cases successfully treated with topical nadifloxacin, an acne medication. Case Rep Dermatol. 2014;6:180-184.
6. Raam R, DeClerck B, Jhun P, et al. That’s some weird nail polish you got there! Ann Emerg Med. 2015;66:585-588.
7. Gregoriou S, Argyriou G, Larios G, et al. Nail disorders and systemic disease: what the nails tell us. J Fam Pract. 2008;57:509-514.
8. Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician. 2004;69:1417-1424.
9. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007;56:835-847.
10. Buka R, Friedman KA, Phelps RG, et al. Childhood longitudinal melanonychia: case reports and review of the literature. Mt Sinai J Med. 2001;68:331-335.
11. Tully AS, Trayes KP, Studdiford JS. Evaluation of nail abnormalities. Am Fam Physician. 2012;85:779-787.
12. US Food and Drug Administration. Over-the-counter drug products containing colloidal silver ingredients or silver salts. 1999. Available at: https://www.fda.gov/ohrms/dockets/98fr/081799a.txt. Accessed April 11, 2017.
13. Glazebrook KN, Laundre BJ, Schiefer TK, et al. Imaging features of glomus tumors. Skeletal Radiol. 2011;40:855-862.
1. Greene SL, Su WP, Muller SA. Pseudomonas aeruginosa infections of the skin. Am Fam Physician. 1984;29:193-200.
2. de Almeida HL Jr, Duquia RP, de Castro LA, et al. Scanning electron microscopy of the green nail. Int J Dermatol. 2010;49:962-963.
3. Hengge UR, Bardeli V. Images in clinical medicine. Green nails. N Engl J Med. 2009;360:1125.
4. Chiriac A, Brzezinski P, Foia L, et al. Chloronychia: green nail syndrome caused by Pseudomonas aeruginosa in elderly persons. Clin Interv Aging. 2015;10:265-267.
5. Müller S, Ebnöther M, Itin P. Green nail syndrome (Pseudomonas aeruginosa nail infection): Two cases successfully treated with topical nadifloxacin, an acne medication. Case Rep Dermatol. 2014;6:180-184.
6. Raam R, DeClerck B, Jhun P, et al. That’s some weird nail polish you got there! Ann Emerg Med. 2015;66:585-588.
7. Gregoriou S, Argyriou G, Larios G, et al. Nail disorders and systemic disease: what the nails tell us. J Fam Pract. 2008;57:509-514.
8. Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician. 2004;69:1417-1424.
9. Braun RP, Baran R, Le Gal FA, et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol. 2007;56:835-847.
10. Buka R, Friedman KA, Phelps RG, et al. Childhood longitudinal melanonychia: case reports and review of the literature. Mt Sinai J Med. 2001;68:331-335.
11. Tully AS, Trayes KP, Studdiford JS. Evaluation of nail abnormalities. Am Fam Physician. 2012;85:779-787.
12. US Food and Drug Administration. Over-the-counter drug products containing colloidal silver ingredients or silver salts. 1999. Available at: https://www.fda.gov/ohrms/dockets/98fr/081799a.txt. Accessed April 11, 2017.
13. Glazebrook KN, Laundre BJ, Schiefer TK, et al. Imaging features of glomus tumors. Skeletal Radiol. 2011;40:855-862.
Fever, petechiae, and joint pain
A 59-year-old woman presented to our emergency department with a rash, severe acute pain in her left hip and lower back, and dyspnea on exertion. She denied having a headache and her mental status was at baseline. The woman reported exposure to rats and snakes one week prior to presentation, and mentioned getting bitten by a rat multiple times on the back of both of her hands while feeding it to her son’s pet snake. The patient had a history of a left hip replacement, with a revision and bone graft 5 years earlier.
The patient had a fever of 103° F during the physical examination. She had erythematous papules and central hemorrhagic eschars at the sites of the bites (FIGURE 1). She also had nonblanching petechiae on both of her lower legs (FIGURE 2) and on the dorsal and palmar aspects of her hands.
The patient’s lab work showed mild normocytic anemia with a hemoglobin level of 11.4 g/dL (normal, 12-16 g/dL) and a platelet count of 129,000/mcL (normal, 130,000-400,000/mcL). Her white blood cell count, chemistries, brain natriuretic peptide test, and chest x-ray were normal.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Rat bite fever
Based on the patient’s symptoms, history, and lab work, we concluded that this was a case of rat bite fever. RBF is a zoonotic systemic illness caused by infection from either the gram-negative bacillus Streptobacillus moniliformis, commonly found in the United States, or the gram-negative rod Spirillum minus, commonly seen in Asia. Anyone with exposure to rats is at risk for RBF, especially pet shop employees, lab workers, and people living in areas with rat infestations.1
The rash associated with RBF can be petechial, purpuric, or maculopapular, but the presence of hemorrhagic nodules and ulcers at the site of the bite is especially indicative of the illness. The rash often involves the hands and feet, including the palms and soles.
To make the diagnosis of RBF, a careful history and a high index of suspicion are important. Fever and rigor are often the first symptoms to appear, beginning 3 to 10 days after the bite. Three to 4 days after the onset of fever, up to 75% of patients will develop a rash.2 Joint and muscle aches are also common, as is a migrating pattern of arthritis.2,3
Rule out other infections related to animal exposure
The differential diagnosis for RBF includes other animal-related infections, such as those from snake bites, leptospirosis, rabies, and pasteurellosis.
Symptoms associated with snake bite injuries appear rapidly after the bite and vary with the type of snake toxin. Hemotoxic symptoms may include intense pain, edema, petechiae, and ecchymosis from coagulopathy. Neurotoxic symptoms may include ptosis, weakness, and paresthesias. All snake bites should be treated with supportive care, and antivenin is indicated when symptoms or history indicate a bite from a venomous snake. Venomous snakes are rarely intentionally kept as pets.2
Leptospirosis is a zoonotic bacterial infection that may be spread through the urine of rats, dogs, or other mammals. Symptoms may be mild and limited to conjunctivitis, vomiting, and fever; life-threatening symptoms include hemorrhage and kidney failure. A petechial rash is not typical.4 Beta-lactam antibiotics are the treatment of choice.
Rabies is a viral infection that occurs after exposure to infected animals (most commonly raccoons, bats, skunks, and foxes). Symptoms include fever and mental status changes that can lead to death; rash is not a typical symptom. Exposed patients should receive post-exposure prophylaxis with immune globulin or a rabies vaccine.5
Pasteurellosis may also cause hemorrhagic nodules at the site of the bite or scratch, but bites are typically caused by larger animals such as dogs and livestock. Other symptoms include fever, sepsis, and osteomyelitis. Treatment includes amoxicillin-clavulanate or a fluoroquinolone-clindamycin combination.6
In cases of high suspicion, special culture tubes may be needed
Blood cultures and cerebrospinal fluid cultures are often falsely negative. Special culture tubes without polyanethol sulfonate preservative, which inhibits the growth of S moniliformis, may be required in cases of high suspicion. S moniliformis polymerase chain reaction may be available in some specialized labs.7,8
Treatment options include 7 to 10 days of antibiotic therapy with oral penicillin 500 mg 4 times daily, amoxicillin-clavulanate 875/125 mg twice daily, or oral doxycycline 100 mg every 12 hours.9
RBF may be fatal if not treated.3 Complications may include bacteremia, septicemia, meningitis, and endocarditis.
Our patient received empiric intravenous ceftriaxone 1 g every 24 hours and her fever and joint pain resolved within 48 hours. On Day 3 she was discharged home to complete a 10-day course of oral amoxicillin-clavulanate 875/125 mg. Her primary care physician reported that the rash resolved and the patient made a full recovery.
CORRESPONDENCE
Kate Rowland, MD, MS, Rush-Copley Family Medicine Residency, 2020 Ogden Ave. Suite 325, Aurora, IL 60504; [email protected].
1. Centers for Disease Control and Prevention. Rat-bite fever (RBF). Centers for Disease Control and Prevention Web site. Available at: http://www.cdc.gov/rat-bite-fever/index.html. Accessed December 1, 2015.
2. Elliott SP. Rat bite fever and Streptobacillus moniliformis. Clin Microbiol Rev. 2007;20:13-22.
3. Juckett G, Hancox JG. Venomous snakebites in the United States: management review and update. Am Fam Physician. 2002;65:1367-1374.
4. Rabinowitz PM, Gordon Z, Odofin L. Pet-related infections. Am Fam Physician. 2007;76:1314-1322.
5. Fishbein DB, Robinson LE. Rabies. N Engl J Med. 1993;329:1632-1638.
6. Wilson BA, Ho M. Pasteurella multocida: from zoonosis to cellular microbiology. Clin Microbiol Rev. 2013;26:631-655.
7. Eng J. Effect of sodium polyanethol sulfonate in blood cultures. J Clin Microbiol. 1975;1:119-123.
8. Nakagomi D, Deguchi N, Yagasaki A, et al. Rat-bite fever identified by polymerase chain reaction detection of Streptobacillus moniliformis DNA. J Dermatol. 2008;35:667-670.
9. Bush LM, Perez MT. Rat-bite fever. In: The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2011.
A 59-year-old woman presented to our emergency department with a rash, severe acute pain in her left hip and lower back, and dyspnea on exertion. She denied having a headache and her mental status was at baseline. The woman reported exposure to rats and snakes one week prior to presentation, and mentioned getting bitten by a rat multiple times on the back of both of her hands while feeding it to her son’s pet snake. The patient had a history of a left hip replacement, with a revision and bone graft 5 years earlier.
The patient had a fever of 103° F during the physical examination. She had erythematous papules and central hemorrhagic eschars at the sites of the bites (FIGURE 1). She also had nonblanching petechiae on both of her lower legs (FIGURE 2) and on the dorsal and palmar aspects of her hands.
The patient’s lab work showed mild normocytic anemia with a hemoglobin level of 11.4 g/dL (normal, 12-16 g/dL) and a platelet count of 129,000/mcL (normal, 130,000-400,000/mcL). Her white blood cell count, chemistries, brain natriuretic peptide test, and chest x-ray were normal.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Rat bite fever
Based on the patient’s symptoms, history, and lab work, we concluded that this was a case of rat bite fever. RBF is a zoonotic systemic illness caused by infection from either the gram-negative bacillus Streptobacillus moniliformis, commonly found in the United States, or the gram-negative rod Spirillum minus, commonly seen in Asia. Anyone with exposure to rats is at risk for RBF, especially pet shop employees, lab workers, and people living in areas with rat infestations.1
The rash associated with RBF can be petechial, purpuric, or maculopapular, but the presence of hemorrhagic nodules and ulcers at the site of the bite is especially indicative of the illness. The rash often involves the hands and feet, including the palms and soles.
To make the diagnosis of RBF, a careful history and a high index of suspicion are important. Fever and rigor are often the first symptoms to appear, beginning 3 to 10 days after the bite. Three to 4 days after the onset of fever, up to 75% of patients will develop a rash.2 Joint and muscle aches are also common, as is a migrating pattern of arthritis.2,3
Rule out other infections related to animal exposure
The differential diagnosis for RBF includes other animal-related infections, such as those from snake bites, leptospirosis, rabies, and pasteurellosis.
Symptoms associated with snake bite injuries appear rapidly after the bite and vary with the type of snake toxin. Hemotoxic symptoms may include intense pain, edema, petechiae, and ecchymosis from coagulopathy. Neurotoxic symptoms may include ptosis, weakness, and paresthesias. All snake bites should be treated with supportive care, and antivenin is indicated when symptoms or history indicate a bite from a venomous snake. Venomous snakes are rarely intentionally kept as pets.2
Leptospirosis is a zoonotic bacterial infection that may be spread through the urine of rats, dogs, or other mammals. Symptoms may be mild and limited to conjunctivitis, vomiting, and fever; life-threatening symptoms include hemorrhage and kidney failure. A petechial rash is not typical.4 Beta-lactam antibiotics are the treatment of choice.
Rabies is a viral infection that occurs after exposure to infected animals (most commonly raccoons, bats, skunks, and foxes). Symptoms include fever and mental status changes that can lead to death; rash is not a typical symptom. Exposed patients should receive post-exposure prophylaxis with immune globulin or a rabies vaccine.5
Pasteurellosis may also cause hemorrhagic nodules at the site of the bite or scratch, but bites are typically caused by larger animals such as dogs and livestock. Other symptoms include fever, sepsis, and osteomyelitis. Treatment includes amoxicillin-clavulanate or a fluoroquinolone-clindamycin combination.6
In cases of high suspicion, special culture tubes may be needed
Blood cultures and cerebrospinal fluid cultures are often falsely negative. Special culture tubes without polyanethol sulfonate preservative, which inhibits the growth of S moniliformis, may be required in cases of high suspicion. S moniliformis polymerase chain reaction may be available in some specialized labs.7,8
Treatment options include 7 to 10 days of antibiotic therapy with oral penicillin 500 mg 4 times daily, amoxicillin-clavulanate 875/125 mg twice daily, or oral doxycycline 100 mg every 12 hours.9
RBF may be fatal if not treated.3 Complications may include bacteremia, septicemia, meningitis, and endocarditis.
Our patient received empiric intravenous ceftriaxone 1 g every 24 hours and her fever and joint pain resolved within 48 hours. On Day 3 she was discharged home to complete a 10-day course of oral amoxicillin-clavulanate 875/125 mg. Her primary care physician reported that the rash resolved and the patient made a full recovery.
CORRESPONDENCE
Kate Rowland, MD, MS, Rush-Copley Family Medicine Residency, 2020 Ogden Ave. Suite 325, Aurora, IL 60504; [email protected].
A 59-year-old woman presented to our emergency department with a rash, severe acute pain in her left hip and lower back, and dyspnea on exertion. She denied having a headache and her mental status was at baseline. The woman reported exposure to rats and snakes one week prior to presentation, and mentioned getting bitten by a rat multiple times on the back of both of her hands while feeding it to her son’s pet snake. The patient had a history of a left hip replacement, with a revision and bone graft 5 years earlier.
The patient had a fever of 103° F during the physical examination. She had erythematous papules and central hemorrhagic eschars at the sites of the bites (FIGURE 1). She also had nonblanching petechiae on both of her lower legs (FIGURE 2) and on the dorsal and palmar aspects of her hands.
The patient’s lab work showed mild normocytic anemia with a hemoglobin level of 11.4 g/dL (normal, 12-16 g/dL) and a platelet count of 129,000/mcL (normal, 130,000-400,000/mcL). Her white blood cell count, chemistries, brain natriuretic peptide test, and chest x-ray were normal.
WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?
Diagnosis: Rat bite fever
Based on the patient’s symptoms, history, and lab work, we concluded that this was a case of rat bite fever. RBF is a zoonotic systemic illness caused by infection from either the gram-negative bacillus Streptobacillus moniliformis, commonly found in the United States, or the gram-negative rod Spirillum minus, commonly seen in Asia. Anyone with exposure to rats is at risk for RBF, especially pet shop employees, lab workers, and people living in areas with rat infestations.1
The rash associated with RBF can be petechial, purpuric, or maculopapular, but the presence of hemorrhagic nodules and ulcers at the site of the bite is especially indicative of the illness. The rash often involves the hands and feet, including the palms and soles.
To make the diagnosis of RBF, a careful history and a high index of suspicion are important. Fever and rigor are often the first symptoms to appear, beginning 3 to 10 days after the bite. Three to 4 days after the onset of fever, up to 75% of patients will develop a rash.2 Joint and muscle aches are also common, as is a migrating pattern of arthritis.2,3
Rule out other infections related to animal exposure
The differential diagnosis for RBF includes other animal-related infections, such as those from snake bites, leptospirosis, rabies, and pasteurellosis.
Symptoms associated with snake bite injuries appear rapidly after the bite and vary with the type of snake toxin. Hemotoxic symptoms may include intense pain, edema, petechiae, and ecchymosis from coagulopathy. Neurotoxic symptoms may include ptosis, weakness, and paresthesias. All snake bites should be treated with supportive care, and antivenin is indicated when symptoms or history indicate a bite from a venomous snake. Venomous snakes are rarely intentionally kept as pets.2
Leptospirosis is a zoonotic bacterial infection that may be spread through the urine of rats, dogs, or other mammals. Symptoms may be mild and limited to conjunctivitis, vomiting, and fever; life-threatening symptoms include hemorrhage and kidney failure. A petechial rash is not typical.4 Beta-lactam antibiotics are the treatment of choice.
Rabies is a viral infection that occurs after exposure to infected animals (most commonly raccoons, bats, skunks, and foxes). Symptoms include fever and mental status changes that can lead to death; rash is not a typical symptom. Exposed patients should receive post-exposure prophylaxis with immune globulin or a rabies vaccine.5
Pasteurellosis may also cause hemorrhagic nodules at the site of the bite or scratch, but bites are typically caused by larger animals such as dogs and livestock. Other symptoms include fever, sepsis, and osteomyelitis. Treatment includes amoxicillin-clavulanate or a fluoroquinolone-clindamycin combination.6
In cases of high suspicion, special culture tubes may be needed
Blood cultures and cerebrospinal fluid cultures are often falsely negative. Special culture tubes without polyanethol sulfonate preservative, which inhibits the growth of S moniliformis, may be required in cases of high suspicion. S moniliformis polymerase chain reaction may be available in some specialized labs.7,8
Treatment options include 7 to 10 days of antibiotic therapy with oral penicillin 500 mg 4 times daily, amoxicillin-clavulanate 875/125 mg twice daily, or oral doxycycline 100 mg every 12 hours.9
RBF may be fatal if not treated.3 Complications may include bacteremia, septicemia, meningitis, and endocarditis.
Our patient received empiric intravenous ceftriaxone 1 g every 24 hours and her fever and joint pain resolved within 48 hours. On Day 3 she was discharged home to complete a 10-day course of oral amoxicillin-clavulanate 875/125 mg. Her primary care physician reported that the rash resolved and the patient made a full recovery.
CORRESPONDENCE
Kate Rowland, MD, MS, Rush-Copley Family Medicine Residency, 2020 Ogden Ave. Suite 325, Aurora, IL 60504; [email protected].
1. Centers for Disease Control and Prevention. Rat-bite fever (RBF). Centers for Disease Control and Prevention Web site. Available at: http://www.cdc.gov/rat-bite-fever/index.html. Accessed December 1, 2015.
2. Elliott SP. Rat bite fever and Streptobacillus moniliformis. Clin Microbiol Rev. 2007;20:13-22.
3. Juckett G, Hancox JG. Venomous snakebites in the United States: management review and update. Am Fam Physician. 2002;65:1367-1374.
4. Rabinowitz PM, Gordon Z, Odofin L. Pet-related infections. Am Fam Physician. 2007;76:1314-1322.
5. Fishbein DB, Robinson LE. Rabies. N Engl J Med. 1993;329:1632-1638.
6. Wilson BA, Ho M. Pasteurella multocida: from zoonosis to cellular microbiology. Clin Microbiol Rev. 2013;26:631-655.
7. Eng J. Effect of sodium polyanethol sulfonate in blood cultures. J Clin Microbiol. 1975;1:119-123.
8. Nakagomi D, Deguchi N, Yagasaki A, et al. Rat-bite fever identified by polymerase chain reaction detection of Streptobacillus moniliformis DNA. J Dermatol. 2008;35:667-670.
9. Bush LM, Perez MT. Rat-bite fever. In: The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2011.
1. Centers for Disease Control and Prevention. Rat-bite fever (RBF). Centers for Disease Control and Prevention Web site. Available at: http://www.cdc.gov/rat-bite-fever/index.html. Accessed December 1, 2015.
2. Elliott SP. Rat bite fever and Streptobacillus moniliformis. Clin Microbiol Rev. 2007;20:13-22.
3. Juckett G, Hancox JG. Venomous snakebites in the United States: management review and update. Am Fam Physician. 2002;65:1367-1374.
4. Rabinowitz PM, Gordon Z, Odofin L. Pet-related infections. Am Fam Physician. 2007;76:1314-1322.
5. Fishbein DB, Robinson LE. Rabies. N Engl J Med. 1993;329:1632-1638.
6. Wilson BA, Ho M. Pasteurella multocida: from zoonosis to cellular microbiology. Clin Microbiol Rev. 2013;26:631-655.
7. Eng J. Effect of sodium polyanethol sulfonate in blood cultures. J Clin Microbiol. 1975;1:119-123.
8. Nakagomi D, Deguchi N, Yagasaki A, et al. Rat-bite fever identified by polymerase chain reaction detection of Streptobacillus moniliformis DNA. J Dermatol. 2008;35:667-670.
9. Bush LM, Perez MT. Rat-bite fever. In: The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2011.
Severe headache • neck pain • intermittent cough • Dx?
THE CASE
A 32-year-old Chinese woman sought care from our family medicine clinic because she had a headache, neck pain, and an intermittent cough that had produced white sputum for 7 days. She described the headache as severe and pressure-like, and said that it had progressively worsened over the previous 3 weeks, coinciding with her first trip outside of China to the United States. The patient indicated that she also had occasional vomiting, dizziness, a low-grade fever, chills, night sweats, and increasing fatigue.
Prior to this visit, the patient had gone to the emergency department (ED) twice in one week, but was told that she had a migraine headache and a viral syndrome and was sent home. She was also told to make a follow-up appointment at our family medicine outpatient clinic.
Besides the symptoms that brought her to our clinic, the only other notable element of the patient’s history was a “neck mass” resection in China 8 years earlier. (The diagnosis of the neck mass was unknown.)
Concerned about her presenting signs and symptoms, we sent the patient to the ED, where she was admitted for further evaluation and treatment of possible meningitis. In the ED, she had a temperature of 101.5° F; her other vital signs were normal. A physical exam revealed mild neck stiffness.
THE DIAGNOSIS
A chest computed tomography (CT) scan demonstrated extensive confluent nodular infiltrates in the lung apices bilaterally with the largest confluent nodule measuring 6 cm (FIGURE 1). A chest x-ray demonstrated extensive bilateral pulmonary interstitial infiltrates that were most pronounced in the upper lung fields (FIGURE 2).
Lumbar puncture results revealed lymphocytic pleocytosis with elevated protein and low glucose levels (TABLE). Based on these results, the family medicine team suspected that our patient had tuberculous meningitis (TBM).
The team consulted with Infectious Diseases for management of TBM, and they placed our patient in a negative pressure room on airborne isolation. In addition, she was started on rifampin 450 mg/d, pyrazinamide 1000 mg/d, ethambutol 800 mg/d, and isoniazid (INH) 800 mg/d, as well as pyridoxine and intravenous dexamethasone.
DISCUSSION
TBM accounts for approximately 1% of all cases of TB and 5% of extrapulmonary diseases in immunocompetent individuals.1 In 2015, there were approximately 10.4 million cases of TB worldwide, and 6 countries accounted for 60% of the global total: India, Indonesia, China, Nigeria, Pakistan, and South Africa.2 TBM is typically a subacute disease with symptoms that can persist for weeks before diagnosis.3 An early diagnosis is critical, as the mortality rate remains relatively high (as high as nearly 70% in underdeveloped and developed countries) despite effective treatment regimens.3 (For updated recommendations on TB screening, see this month’s Practice Alert.)
Most health care facilities use AFB smears to determine when patients with suspected TB should be isolated. However, AFB smears are positive in only 60% of TB cases.4 One study indicated that nucleic acid amplification by PCR can improve sensitivity from 60% to 87% and specificity from 98% to 100%.5
The presentation of TBM varies by phase of disease:
- The prodromal phase typically lasts for 2 to 3 weeks. It is characterized by an insidious onset of malaise, headache, low-grade fever, irritability, and personality changes.
- The meningitis phase is characterized by pronounced neurologic features such as meningismus, protracted headache, confusion, myelopathy, and sensory deficits, as well as vomiting, lethargy, and urinary retention.
- During the paralytic phase, patients experience profound confusion, followed by stupor, coma, seizures, progressive paraplegia, and often, hemiparesis.1,3,6
Treatment should be given for a total of 9 to 12 months
Initiate treatment for TB based on a strong clinical suspicion for the disease. Treatment of TBM consists of an intensive phase with 4 anti-TB drugs for 2 months (typically INH 800 mg/d, rifampin 450 mg/d, pyrazinamide 1000 mg/d, and ethambutol 800 mg/d) and a continuation phase with 2 drugs (INH and rifampin) for 7 to 10 additional months, resulting in a total treatment duration of 9 to 12 months.
Our patient was discharged from the hospital after 2 weeks on an anti-TB medication regimen of INH, rifampin, and pyrazinamide, along with pyridoxine and a tapering dose of dexamethasone. After the initial 2 months of intensive phase therapy, she was switched to INH 300 mg/d and rifampin 450 mg/d for the continuation phase. The patient followed up at our family medicine outpatient clinic with slow improvement of her muscle weakness before returning to China once she was placed on the continuation phase drugs.
THE TAKEAWAY
Suspect TB in high-risk patients traveling from endemic areas. Our patient, a Chinese woman visiting Brooklyn, New York, should’ve been considered high risk for TB even without her travel history from China because Brooklyn has a high rate of TB, as well. (In 2015, Sunset Park, Brooklyn had 18.2 cases of TB per 100,000 people, which was more than double the citywide rate.7)
TBM is a subacute disease with an often subtle presentation. Once you suspect TBM, isolate the patient, obtain appropriate cultures and smears, and start anti-TB drugs and adjunctive corticosteroids immediately, while the results of studies for AFB are still pending. Prompt diagnosis and treatment can save a patient’s life.
1. Garcia-Monco JC. Central nervous system tuberculosis. Neurol Clin. 1999;17:737-759.
2. World Health Organization. Global tuberculosis report, 2016. Available at: http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1. Accessed March 29, 2017.
3. Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat. 2011;2011:798764.
4. Siddiqui AH, Perl TM, Conlon M, et al. Preventing nosocomial transmission of pulmonary tuberculosis: when may isolation be discontinued for patients with suspected tuberculosis? Infect Control Hosp Epidemiol. 2002;23:141-144.
5. Tang YW, Meng S, Li H, et al. PCR enhances acid-fast bacillus stain-based rapid detection of Mycobacterium tuberculosis. J Clin Microbiol. 2004;42:1849-1850.
6. Long R, Gardam M. Tumour necrosis factor-alpha inhibitors and the reactivation of latent tuberculosis infection. CMAJ. 2003;168:1153-1156.
7. New York City Department of Health and Mental Hygiene. Tuberculosis in New York City, 2015. New York City Bureau of Tuberculosis Control Annual Summary. Available at: http://www1.nyc.gov/assets/doh/downloads/pdf/tb/tb2015.pdf. Accessed April 7, 2017.
THE CASE
A 32-year-old Chinese woman sought care from our family medicine clinic because she had a headache, neck pain, and an intermittent cough that had produced white sputum for 7 days. She described the headache as severe and pressure-like, and said that it had progressively worsened over the previous 3 weeks, coinciding with her first trip outside of China to the United States. The patient indicated that she also had occasional vomiting, dizziness, a low-grade fever, chills, night sweats, and increasing fatigue.
Prior to this visit, the patient had gone to the emergency department (ED) twice in one week, but was told that she had a migraine headache and a viral syndrome and was sent home. She was also told to make a follow-up appointment at our family medicine outpatient clinic.
Besides the symptoms that brought her to our clinic, the only other notable element of the patient’s history was a “neck mass” resection in China 8 years earlier. (The diagnosis of the neck mass was unknown.)
Concerned about her presenting signs and symptoms, we sent the patient to the ED, where she was admitted for further evaluation and treatment of possible meningitis. In the ED, she had a temperature of 101.5° F; her other vital signs were normal. A physical exam revealed mild neck stiffness.
THE DIAGNOSIS
A chest computed tomography (CT) scan demonstrated extensive confluent nodular infiltrates in the lung apices bilaterally with the largest confluent nodule measuring 6 cm (FIGURE 1). A chest x-ray demonstrated extensive bilateral pulmonary interstitial infiltrates that were most pronounced in the upper lung fields (FIGURE 2).
Lumbar puncture results revealed lymphocytic pleocytosis with elevated protein and low glucose levels (TABLE). Based on these results, the family medicine team suspected that our patient had tuberculous meningitis (TBM).
The team consulted with Infectious Diseases for management of TBM, and they placed our patient in a negative pressure room on airborne isolation. In addition, she was started on rifampin 450 mg/d, pyrazinamide 1000 mg/d, ethambutol 800 mg/d, and isoniazid (INH) 800 mg/d, as well as pyridoxine and intravenous dexamethasone.
DISCUSSION
TBM accounts for approximately 1% of all cases of TB and 5% of extrapulmonary diseases in immunocompetent individuals.1 In 2015, there were approximately 10.4 million cases of TB worldwide, and 6 countries accounted for 60% of the global total: India, Indonesia, China, Nigeria, Pakistan, and South Africa.2 TBM is typically a subacute disease with symptoms that can persist for weeks before diagnosis.3 An early diagnosis is critical, as the mortality rate remains relatively high (as high as nearly 70% in underdeveloped and developed countries) despite effective treatment regimens.3 (For updated recommendations on TB screening, see this month’s Practice Alert.)
Most health care facilities use AFB smears to determine when patients with suspected TB should be isolated. However, AFB smears are positive in only 60% of TB cases.4 One study indicated that nucleic acid amplification by PCR can improve sensitivity from 60% to 87% and specificity from 98% to 100%.5
The presentation of TBM varies by phase of disease:
- The prodromal phase typically lasts for 2 to 3 weeks. It is characterized by an insidious onset of malaise, headache, low-grade fever, irritability, and personality changes.
- The meningitis phase is characterized by pronounced neurologic features such as meningismus, protracted headache, confusion, myelopathy, and sensory deficits, as well as vomiting, lethargy, and urinary retention.
- During the paralytic phase, patients experience profound confusion, followed by stupor, coma, seizures, progressive paraplegia, and often, hemiparesis.1,3,6
Treatment should be given for a total of 9 to 12 months
Initiate treatment for TB based on a strong clinical suspicion for the disease. Treatment of TBM consists of an intensive phase with 4 anti-TB drugs for 2 months (typically INH 800 mg/d, rifampin 450 mg/d, pyrazinamide 1000 mg/d, and ethambutol 800 mg/d) and a continuation phase with 2 drugs (INH and rifampin) for 7 to 10 additional months, resulting in a total treatment duration of 9 to 12 months.
Our patient was discharged from the hospital after 2 weeks on an anti-TB medication regimen of INH, rifampin, and pyrazinamide, along with pyridoxine and a tapering dose of dexamethasone. After the initial 2 months of intensive phase therapy, she was switched to INH 300 mg/d and rifampin 450 mg/d for the continuation phase. The patient followed up at our family medicine outpatient clinic with slow improvement of her muscle weakness before returning to China once she was placed on the continuation phase drugs.
THE TAKEAWAY
Suspect TB in high-risk patients traveling from endemic areas. Our patient, a Chinese woman visiting Brooklyn, New York, should’ve been considered high risk for TB even without her travel history from China because Brooklyn has a high rate of TB, as well. (In 2015, Sunset Park, Brooklyn had 18.2 cases of TB per 100,000 people, which was more than double the citywide rate.7)
TBM is a subacute disease with an often subtle presentation. Once you suspect TBM, isolate the patient, obtain appropriate cultures and smears, and start anti-TB drugs and adjunctive corticosteroids immediately, while the results of studies for AFB are still pending. Prompt diagnosis and treatment can save a patient’s life.
THE CASE
A 32-year-old Chinese woman sought care from our family medicine clinic because she had a headache, neck pain, and an intermittent cough that had produced white sputum for 7 days. She described the headache as severe and pressure-like, and said that it had progressively worsened over the previous 3 weeks, coinciding with her first trip outside of China to the United States. The patient indicated that she also had occasional vomiting, dizziness, a low-grade fever, chills, night sweats, and increasing fatigue.
Prior to this visit, the patient had gone to the emergency department (ED) twice in one week, but was told that she had a migraine headache and a viral syndrome and was sent home. She was also told to make a follow-up appointment at our family medicine outpatient clinic.
Besides the symptoms that brought her to our clinic, the only other notable element of the patient’s history was a “neck mass” resection in China 8 years earlier. (The diagnosis of the neck mass was unknown.)
Concerned about her presenting signs and symptoms, we sent the patient to the ED, where she was admitted for further evaluation and treatment of possible meningitis. In the ED, she had a temperature of 101.5° F; her other vital signs were normal. A physical exam revealed mild neck stiffness.
THE DIAGNOSIS
A chest computed tomography (CT) scan demonstrated extensive confluent nodular infiltrates in the lung apices bilaterally with the largest confluent nodule measuring 6 cm (FIGURE 1). A chest x-ray demonstrated extensive bilateral pulmonary interstitial infiltrates that were most pronounced in the upper lung fields (FIGURE 2).
Lumbar puncture results revealed lymphocytic pleocytosis with elevated protein and low glucose levels (TABLE). Based on these results, the family medicine team suspected that our patient had tuberculous meningitis (TBM).
The team consulted with Infectious Diseases for management of TBM, and they placed our patient in a negative pressure room on airborne isolation. In addition, she was started on rifampin 450 mg/d, pyrazinamide 1000 mg/d, ethambutol 800 mg/d, and isoniazid (INH) 800 mg/d, as well as pyridoxine and intravenous dexamethasone.
DISCUSSION
TBM accounts for approximately 1% of all cases of TB and 5% of extrapulmonary diseases in immunocompetent individuals.1 In 2015, there were approximately 10.4 million cases of TB worldwide, and 6 countries accounted for 60% of the global total: India, Indonesia, China, Nigeria, Pakistan, and South Africa.2 TBM is typically a subacute disease with symptoms that can persist for weeks before diagnosis.3 An early diagnosis is critical, as the mortality rate remains relatively high (as high as nearly 70% in underdeveloped and developed countries) despite effective treatment regimens.3 (For updated recommendations on TB screening, see this month’s Practice Alert.)
Most health care facilities use AFB smears to determine when patients with suspected TB should be isolated. However, AFB smears are positive in only 60% of TB cases.4 One study indicated that nucleic acid amplification by PCR can improve sensitivity from 60% to 87% and specificity from 98% to 100%.5
The presentation of TBM varies by phase of disease:
- The prodromal phase typically lasts for 2 to 3 weeks. It is characterized by an insidious onset of malaise, headache, low-grade fever, irritability, and personality changes.
- The meningitis phase is characterized by pronounced neurologic features such as meningismus, protracted headache, confusion, myelopathy, and sensory deficits, as well as vomiting, lethargy, and urinary retention.
- During the paralytic phase, patients experience profound confusion, followed by stupor, coma, seizures, progressive paraplegia, and often, hemiparesis.1,3,6
Treatment should be given for a total of 9 to 12 months
Initiate treatment for TB based on a strong clinical suspicion for the disease. Treatment of TBM consists of an intensive phase with 4 anti-TB drugs for 2 months (typically INH 800 mg/d, rifampin 450 mg/d, pyrazinamide 1000 mg/d, and ethambutol 800 mg/d) and a continuation phase with 2 drugs (INH and rifampin) for 7 to 10 additional months, resulting in a total treatment duration of 9 to 12 months.
Our patient was discharged from the hospital after 2 weeks on an anti-TB medication regimen of INH, rifampin, and pyrazinamide, along with pyridoxine and a tapering dose of dexamethasone. After the initial 2 months of intensive phase therapy, she was switched to INH 300 mg/d and rifampin 450 mg/d for the continuation phase. The patient followed up at our family medicine outpatient clinic with slow improvement of her muscle weakness before returning to China once she was placed on the continuation phase drugs.
THE TAKEAWAY
Suspect TB in high-risk patients traveling from endemic areas. Our patient, a Chinese woman visiting Brooklyn, New York, should’ve been considered high risk for TB even without her travel history from China because Brooklyn has a high rate of TB, as well. (In 2015, Sunset Park, Brooklyn had 18.2 cases of TB per 100,000 people, which was more than double the citywide rate.7)
TBM is a subacute disease with an often subtle presentation. Once you suspect TBM, isolate the patient, obtain appropriate cultures and smears, and start anti-TB drugs and adjunctive corticosteroids immediately, while the results of studies for AFB are still pending. Prompt diagnosis and treatment can save a patient’s life.
1. Garcia-Monco JC. Central nervous system tuberculosis. Neurol Clin. 1999;17:737-759.
2. World Health Organization. Global tuberculosis report, 2016. Available at: http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1. Accessed March 29, 2017.
3. Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat. 2011;2011:798764.
4. Siddiqui AH, Perl TM, Conlon M, et al. Preventing nosocomial transmission of pulmonary tuberculosis: when may isolation be discontinued for patients with suspected tuberculosis? Infect Control Hosp Epidemiol. 2002;23:141-144.
5. Tang YW, Meng S, Li H, et al. PCR enhances acid-fast bacillus stain-based rapid detection of Mycobacterium tuberculosis. J Clin Microbiol. 2004;42:1849-1850.
6. Long R, Gardam M. Tumour necrosis factor-alpha inhibitors and the reactivation of latent tuberculosis infection. CMAJ. 2003;168:1153-1156.
7. New York City Department of Health and Mental Hygiene. Tuberculosis in New York City, 2015. New York City Bureau of Tuberculosis Control Annual Summary. Available at: http://www1.nyc.gov/assets/doh/downloads/pdf/tb/tb2015.pdf. Accessed April 7, 2017.
1. Garcia-Monco JC. Central nervous system tuberculosis. Neurol Clin. 1999;17:737-759.
2. World Health Organization. Global tuberculosis report, 2016. Available at: http://apps.who.int/iris/bitstream/10665/250441/1/9789241565394-eng.pdf?ua=1. Accessed March 29, 2017.
3. Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat. 2011;2011:798764.
4. Siddiqui AH, Perl TM, Conlon M, et al. Preventing nosocomial transmission of pulmonary tuberculosis: when may isolation be discontinued for patients with suspected tuberculosis? Infect Control Hosp Epidemiol. 2002;23:141-144.
5. Tang YW, Meng S, Li H, et al. PCR enhances acid-fast bacillus stain-based rapid detection of Mycobacterium tuberculosis. J Clin Microbiol. 2004;42:1849-1850.
6. Long R, Gardam M. Tumour necrosis factor-alpha inhibitors and the reactivation of latent tuberculosis infection. CMAJ. 2003;168:1153-1156.
7. New York City Department of Health and Mental Hygiene. Tuberculosis in New York City, 2015. New York City Bureau of Tuberculosis Control Annual Summary. Available at: http://www1.nyc.gov/assets/doh/downloads/pdf/tb/tb2015.pdf. Accessed April 7, 2017.
USPSTF recommendations: A 2017 roundup
Since the last Practice Alert update on the United States Preventive Services Task Force in May of 2016,1 the Task Force has released 19 recommendations on 13 topics that include: the use of aspirin and statins for the prevention of cardiovascular disease (CVD); support for breastfeeding; use of folic acid during pregnancy; and screening for syphilis, latent tuberculosis (TB), herpes, chronic obstructive pulmonary disease (COPD), colorectal cancer (CRC), obstructive sleep apnea (OSA), celiac disease, and skin cancer. The Task Force also released a draft recommendation regarding prostate cancer screening in asymptomatic men (see “A change for prostate cancer screening?”) and addressed screening pelvic examinations in asymptomatic women, the subject of this month’s audiocast. (To listen, go to: http://bit.ly/2nIVoD5.)
Recommendations to implement
Recommendations from the past year that family physicians should put into practice are detailed below and in TABLE 1.2-8
CRC: Screen all individuals ages 50 to 75, but 76 to 85 selectively. The Task Force reaffirmed its 2008 finding that screening for CRC in adults ages 50 to 75 years is substantially beneficial.2 In contrast to the previous recommendation, however, the new one does not state which screening tests are preferred. The tests considered were 3 stool tests (fecal immunochemical test [FIT], FIT-tumor DNA testing [FIT-DNA], and guaiac-based fecal occult blood test [gFOBT]), as well as 3 direct visualization tests (colonoscopy, sigmoidoscopy, and CT colonoscopy). The Task Force assessed various testing frequencies of each test and some test combinations. While the Task Force does not recommend any one screening strategy, there are still significant unknowns about FIT-DNA and CT colonoscopy. The American Academy of Family Physicians does not recommend using these 2 tests for screening purposes at this time.9
CRC screening for adults ages 76 to 85 was given a “C” recommendation, which means the value of the service to the population overall is small, but that certain individuals may benefit from it. The Task Force advises selectively offering a “C” service to individuals based on professional judgment and patient preferences. Regarding CRC screening in individuals 76 years or older, the ones most likely to benefit are those who have never been screened and those without significant comorbidities that could limit life expectancy. All “C” recommendations from the past year are listed in TABLE 2.2-4
CVD prevention: When aspirin or a statin is indicated. The Task Force released 2 recommendations for the prevention of CVD this past year. One pertained to the use of low-dose aspirin3 (which also helps to prevent CRC), and the other addressed the use of low- to moderate-dose statins.4 Each recommendation is fairly complicated and nuanced in terms of age and risk for CVD. A decision to use low-dose aspirin must also consider the risk of bleeding.
To calculate a patient’s risk for CVD, the Task Force recommends using the risk calculator developed by the American College of Cardiology and the American Heart Association (http://www.cvriskcalculator.com/).
Adults for whom low-dose aspirin and low- to moderate-dose statins are recommended are described in TABLE 1.2-8 Patients for whom individual decision making is advised, rather than a generalized recommendation, are reviewed in TABLE 2.2-4 There is insufficient evidence to make a recommendation for the use of aspirin before age 50 or at age 70 and older,3 and for the use of statins in adults age 76 and older who do not have a history of CVD4 (TABLE 33,4,10-14). The use of low-dose aspirin and low-to-moderate dose statins have been the subject of JFP audiocasts in May 2016 and January 2017. (See http://bit.ly/2oiun8d and http://bit.ly/2oqkohR.)
2 pregnancy-related recommendations. To prevent neural tube defects in newborns, the Task Force now recommends daily folic acid, 0.4 to 0.8 mg (400 to 800 mcg), for all women who are planning on or are capable of becoming pregnant.5 This is an update of a 2009 recommendation that was worded slightly differently, recommending the supplement for all women of childbearing age.
A new recommendation on breastfeeding recognizes its benefits for both mother and baby and finds that interventions to encourage breastfeeding increase the prevalence of this practice and its duration.6 Interventions—provided to individuals or groups by professionals or peers or through formal education—include promoting the benefits of breastfeeding, giving practical advice and direct support on how to breastfeed, and offering psychological support.
Latent TB: Advantages of newer testing method. The recommendation on screening for latent tuberculosis (TB) is an update from the one made in 1996.7 At that time, screening for latent infection was performed using a tuberculin skin test (TST). Now a TST or interferon-gamma release assay (IGRA) can be used. Testing with IGRA may be the best option for those who have received a bacille Calmette–Guérin vaccination (because it can cause a false-positive TST) or for those who are not likely to return to have their TST read.
Those at high risk for latent TB include people who were born or have resided in countries with a high TB prevalence, those who have lived in a correctional institution or homeless shelter, and anyone in a high-risk group based on local epidemiology of the disease. (Read more on TB in this month’s Case Report.) Others at high risk are those who are immune suppressed because of infection or medications, and those who work in health care or correctional facilities. Screening of these groups is usually conducted as part of occupational health or is considered part of routine health care.
Syphilis: Screen high-risk individuals in 2 steps. The recommendation on syphilis screening basically reaffirms the one from 2004.8 Those at high risk for syphilis include men who have sex with men (who now account for 90% of new cases), those who are HIV positive, and those who engage in commercial sex work. Other racial and demographic groups can be at high risk depending on the local epidemiology of the disease. In a separate recommendation, the Task Force advises screening all pregnant women for syphilis.
Screening for syphilis infection involves 2 steps: first, a nontreponemal test (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] test); second, a confirmatory treponemal antibody detection test (fluorescent treponemal antibody absorption [FTA-ABS] or Treponema pallidum particle agglutination [TPPA] test). Treatment for syphilis remains benzathine penicillin with the number of injections depending on the stage of infection. The Centers for Disease Control and Prevention is the best source for current recommendations for treatment of all sexually transmitted infections.15
Screening tests to avoid
TABLE 416,17 lists screening tests the Task Force recommends against. While chronic obstructive pulmonary disease afflicts 14% of US adults ages 40 to 79 years and is the third leading cause of death in the country, the Task Force found that early detection in asymptomatic adults does not affect the course of the illness and is of no benefit.16
Genital herpes, also prevalent, infects an estimated one out of 6 individuals, ages 14 to 49. It causes little mortality, except in neonates, but those infected can have recurrent flares and suffer psychological harms from stigmatization. Most genital herpes is caused by herpes simplex virus-2, and there is a serological test to detect it. However, the Task Force recommends against using the test to screen asymptomatic adults and adolescents, including those who are pregnant. This recommendation is based on the test’s high false-positive rate, which can cause emotional harm, and on the lack of evidence that detection through screening improves outcomes.17
The evidence is lacking for these practices
The Task Force is one of only a few organizations that will not make a recommendation if evidence is lacking on benefits and harms. In addition to the ‘I’ statements regarding CVD and CRC mentioned earlier, the Task Force found insufficient evidence to recommend screening for lipid disorders in individuals ages 20 years or younger,10 performing a visual skin exam as a screening tool for skin cancer,11 screening for celiac disease,12 performing a periodic pelvic examination in asymptomatic women,13 and screening for obstructive sleep apnea using screening questionnaires14 (TABLE 33,4,10-14).
SIDEBAR
A change for prostate cancer screening?The USPSTF recently issued new draft recommendations regarding prostate cancer screening in asymptomatic men (available at: https://screeningforprostatecancer.org/).
The draft now divides men into 2 age groups, stating that the decision to screen for prostate cancer using a prostate specific antigen (PSA) test should be individualized for men ages 55 to 69 years (a C recommendation, meaning that there is at least moderate certainty that the net benefit is small), and that men ages 70 and older (lowered from age 75 in the previous 2012 recommendation1) should not be screened (a D recommendation, meaning that there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits).
The USPSTF believes that clinicians should explain to men ages 55 to 69 years that screening offers a small potential benefit of reducing the chance of dying from prostate cancer, but also comes with potential harms, including false-positive results requiring additional testing/procedures, overdiagnosis and overtreatment, and treatment complications such as incontinence and impotence. In this way, each man has the chance to incorporate his values and preferences into the decision.
For men ages 70 and older, the potential benefits simply do not outweigh the potential harms, according to the USPSTF.
1. USPSTF. Final recommendation statement. Prostate cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening#Pod1. Accessed April 11, 2017.
1. Campos-Outcalt D. Eight USPSTF recommendations FPs need to know about. J Fam Pract. 2016;65:338-341.
2. USPSTF. Colorectal cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/colorectal-cancer-screening2. Accessed March 22, 2017.
3. USPSTF. Aspirin use to prevent cardiovascular disease and colorectal cancer: preventive medications. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer. Accessed March 22, 2017.
4. USPSTF. Statin use for the prevention of cardiovascular disease in adults: preventive medication. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/statin-use-in-adults-preventive-medication1. Accessed March 22, 2017.
5. USPSTF. Folic acid for the prevention of neural tube defects: preventive medication. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/folic-acid-for-the-prevention-of-neural-tube-defects-preventive-medication. Accessed March 22, 2017.
6. USPSTF. Breastfeeding: primary care interventions. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breastfeeding-primary-care-interventions. Accessed March 22, 2017.
7. USPSTF. Latent tuberculosis infection: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/latent-tuberculosis-infection-screening. Accessed March 22, 2017.
8. USPSTF. Syphilis infection in nonpregnant adults and adolescents: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents. Accessed March 22, 2017.
9. AAFP. Colorectal cancer screening, adults. Available at: http://www.aafp.org/patient-care/clinical-recommendations/all/colorectal-cancer.html. Accessed March 22, 2017.
10. USPSTF. Lipid disorders in children and adolescents: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lipid-disorders-in-children-screening1. Accessed March 22, 2017.
11. USPSTF. Skin cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/skin-cancer-screening2. Accessed March 22, 2017.
12. USPSTF. Celiac disease: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/celiac-disease-screening. Accessed March 22, 2017.
13. USPSTF. Gynecological conditions: periodic screening with the pelvic examination. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/gynecological-conditions-screening-with-the-pelvic-examination. Accessed March 22, 2017.
14. USPSTF. Obstructive sleep apnea in adults: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/obstructive-sleep-apnea-in-adults-screening. Accessed March 22, 2017.
15. CDC. 2015 sexually transmitted diseases treatment guidelines. Available at: https://www.cdc.gov/std/tg2015/default.htm. Accessed March 22, 2017.
16. USPSTF. Chronic obstructive pulmonary disease: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/chronic-obstructive-pulmonary-disease-screening. Accessed March 22, 2017.
17. USPSTF. Genital herpes infection: serologic screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/genital-herpes-screening1. Accessed March 22, 2017.
Since the last Practice Alert update on the United States Preventive Services Task Force in May of 2016,1 the Task Force has released 19 recommendations on 13 topics that include: the use of aspirin and statins for the prevention of cardiovascular disease (CVD); support for breastfeeding; use of folic acid during pregnancy; and screening for syphilis, latent tuberculosis (TB), herpes, chronic obstructive pulmonary disease (COPD), colorectal cancer (CRC), obstructive sleep apnea (OSA), celiac disease, and skin cancer. The Task Force also released a draft recommendation regarding prostate cancer screening in asymptomatic men (see “A change for prostate cancer screening?”) and addressed screening pelvic examinations in asymptomatic women, the subject of this month’s audiocast. (To listen, go to: http://bit.ly/2nIVoD5.)
Recommendations to implement
Recommendations from the past year that family physicians should put into practice are detailed below and in TABLE 1.2-8
CRC: Screen all individuals ages 50 to 75, but 76 to 85 selectively. The Task Force reaffirmed its 2008 finding that screening for CRC in adults ages 50 to 75 years is substantially beneficial.2 In contrast to the previous recommendation, however, the new one does not state which screening tests are preferred. The tests considered were 3 stool tests (fecal immunochemical test [FIT], FIT-tumor DNA testing [FIT-DNA], and guaiac-based fecal occult blood test [gFOBT]), as well as 3 direct visualization tests (colonoscopy, sigmoidoscopy, and CT colonoscopy). The Task Force assessed various testing frequencies of each test and some test combinations. While the Task Force does not recommend any one screening strategy, there are still significant unknowns about FIT-DNA and CT colonoscopy. The American Academy of Family Physicians does not recommend using these 2 tests for screening purposes at this time.9
CRC screening for adults ages 76 to 85 was given a “C” recommendation, which means the value of the service to the population overall is small, but that certain individuals may benefit from it. The Task Force advises selectively offering a “C” service to individuals based on professional judgment and patient preferences. Regarding CRC screening in individuals 76 years or older, the ones most likely to benefit are those who have never been screened and those without significant comorbidities that could limit life expectancy. All “C” recommendations from the past year are listed in TABLE 2.2-4
CVD prevention: When aspirin or a statin is indicated. The Task Force released 2 recommendations for the prevention of CVD this past year. One pertained to the use of low-dose aspirin3 (which also helps to prevent CRC), and the other addressed the use of low- to moderate-dose statins.4 Each recommendation is fairly complicated and nuanced in terms of age and risk for CVD. A decision to use low-dose aspirin must also consider the risk of bleeding.
To calculate a patient’s risk for CVD, the Task Force recommends using the risk calculator developed by the American College of Cardiology and the American Heart Association (http://www.cvriskcalculator.com/).
Adults for whom low-dose aspirin and low- to moderate-dose statins are recommended are described in TABLE 1.2-8 Patients for whom individual decision making is advised, rather than a generalized recommendation, are reviewed in TABLE 2.2-4 There is insufficient evidence to make a recommendation for the use of aspirin before age 50 or at age 70 and older,3 and for the use of statins in adults age 76 and older who do not have a history of CVD4 (TABLE 33,4,10-14). The use of low-dose aspirin and low-to-moderate dose statins have been the subject of JFP audiocasts in May 2016 and January 2017. (See http://bit.ly/2oiun8d and http://bit.ly/2oqkohR.)
2 pregnancy-related recommendations. To prevent neural tube defects in newborns, the Task Force now recommends daily folic acid, 0.4 to 0.8 mg (400 to 800 mcg), for all women who are planning on or are capable of becoming pregnant.5 This is an update of a 2009 recommendation that was worded slightly differently, recommending the supplement for all women of childbearing age.
A new recommendation on breastfeeding recognizes its benefits for both mother and baby and finds that interventions to encourage breastfeeding increase the prevalence of this practice and its duration.6 Interventions—provided to individuals or groups by professionals or peers or through formal education—include promoting the benefits of breastfeeding, giving practical advice and direct support on how to breastfeed, and offering psychological support.
Latent TB: Advantages of newer testing method. The recommendation on screening for latent tuberculosis (TB) is an update from the one made in 1996.7 At that time, screening for latent infection was performed using a tuberculin skin test (TST). Now a TST or interferon-gamma release assay (IGRA) can be used. Testing with IGRA may be the best option for those who have received a bacille Calmette–Guérin vaccination (because it can cause a false-positive TST) or for those who are not likely to return to have their TST read.
Those at high risk for latent TB include people who were born or have resided in countries with a high TB prevalence, those who have lived in a correctional institution or homeless shelter, and anyone in a high-risk group based on local epidemiology of the disease. (Read more on TB in this month’s Case Report.) Others at high risk are those who are immune suppressed because of infection or medications, and those who work in health care or correctional facilities. Screening of these groups is usually conducted as part of occupational health or is considered part of routine health care.
Syphilis: Screen high-risk individuals in 2 steps. The recommendation on syphilis screening basically reaffirms the one from 2004.8 Those at high risk for syphilis include men who have sex with men (who now account for 90% of new cases), those who are HIV positive, and those who engage in commercial sex work. Other racial and demographic groups can be at high risk depending on the local epidemiology of the disease. In a separate recommendation, the Task Force advises screening all pregnant women for syphilis.
Screening for syphilis infection involves 2 steps: first, a nontreponemal test (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] test); second, a confirmatory treponemal antibody detection test (fluorescent treponemal antibody absorption [FTA-ABS] or Treponema pallidum particle agglutination [TPPA] test). Treatment for syphilis remains benzathine penicillin with the number of injections depending on the stage of infection. The Centers for Disease Control and Prevention is the best source for current recommendations for treatment of all sexually transmitted infections.15
Screening tests to avoid
TABLE 416,17 lists screening tests the Task Force recommends against. While chronic obstructive pulmonary disease afflicts 14% of US adults ages 40 to 79 years and is the third leading cause of death in the country, the Task Force found that early detection in asymptomatic adults does not affect the course of the illness and is of no benefit.16
Genital herpes, also prevalent, infects an estimated one out of 6 individuals, ages 14 to 49. It causes little mortality, except in neonates, but those infected can have recurrent flares and suffer psychological harms from stigmatization. Most genital herpes is caused by herpes simplex virus-2, and there is a serological test to detect it. However, the Task Force recommends against using the test to screen asymptomatic adults and adolescents, including those who are pregnant. This recommendation is based on the test’s high false-positive rate, which can cause emotional harm, and on the lack of evidence that detection through screening improves outcomes.17
The evidence is lacking for these practices
The Task Force is one of only a few organizations that will not make a recommendation if evidence is lacking on benefits and harms. In addition to the ‘I’ statements regarding CVD and CRC mentioned earlier, the Task Force found insufficient evidence to recommend screening for lipid disorders in individuals ages 20 years or younger,10 performing a visual skin exam as a screening tool for skin cancer,11 screening for celiac disease,12 performing a periodic pelvic examination in asymptomatic women,13 and screening for obstructive sleep apnea using screening questionnaires14 (TABLE 33,4,10-14).
SIDEBAR
A change for prostate cancer screening?The USPSTF recently issued new draft recommendations regarding prostate cancer screening in asymptomatic men (available at: https://screeningforprostatecancer.org/).
The draft now divides men into 2 age groups, stating that the decision to screen for prostate cancer using a prostate specific antigen (PSA) test should be individualized for men ages 55 to 69 years (a C recommendation, meaning that there is at least moderate certainty that the net benefit is small), and that men ages 70 and older (lowered from age 75 in the previous 2012 recommendation1) should not be screened (a D recommendation, meaning that there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits).
The USPSTF believes that clinicians should explain to men ages 55 to 69 years that screening offers a small potential benefit of reducing the chance of dying from prostate cancer, but also comes with potential harms, including false-positive results requiring additional testing/procedures, overdiagnosis and overtreatment, and treatment complications such as incontinence and impotence. In this way, each man has the chance to incorporate his values and preferences into the decision.
For men ages 70 and older, the potential benefits simply do not outweigh the potential harms, according to the USPSTF.
1. USPSTF. Final recommendation statement. Prostate cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening#Pod1. Accessed April 11, 2017.
Since the last Practice Alert update on the United States Preventive Services Task Force in May of 2016,1 the Task Force has released 19 recommendations on 13 topics that include: the use of aspirin and statins for the prevention of cardiovascular disease (CVD); support for breastfeeding; use of folic acid during pregnancy; and screening for syphilis, latent tuberculosis (TB), herpes, chronic obstructive pulmonary disease (COPD), colorectal cancer (CRC), obstructive sleep apnea (OSA), celiac disease, and skin cancer. The Task Force also released a draft recommendation regarding prostate cancer screening in asymptomatic men (see “A change for prostate cancer screening?”) and addressed screening pelvic examinations in asymptomatic women, the subject of this month’s audiocast. (To listen, go to: http://bit.ly/2nIVoD5.)
Recommendations to implement
Recommendations from the past year that family physicians should put into practice are detailed below and in TABLE 1.2-8
CRC: Screen all individuals ages 50 to 75, but 76 to 85 selectively. The Task Force reaffirmed its 2008 finding that screening for CRC in adults ages 50 to 75 years is substantially beneficial.2 In contrast to the previous recommendation, however, the new one does not state which screening tests are preferred. The tests considered were 3 stool tests (fecal immunochemical test [FIT], FIT-tumor DNA testing [FIT-DNA], and guaiac-based fecal occult blood test [gFOBT]), as well as 3 direct visualization tests (colonoscopy, sigmoidoscopy, and CT colonoscopy). The Task Force assessed various testing frequencies of each test and some test combinations. While the Task Force does not recommend any one screening strategy, there are still significant unknowns about FIT-DNA and CT colonoscopy. The American Academy of Family Physicians does not recommend using these 2 tests for screening purposes at this time.9
CRC screening for adults ages 76 to 85 was given a “C” recommendation, which means the value of the service to the population overall is small, but that certain individuals may benefit from it. The Task Force advises selectively offering a “C” service to individuals based on professional judgment and patient preferences. Regarding CRC screening in individuals 76 years or older, the ones most likely to benefit are those who have never been screened and those without significant comorbidities that could limit life expectancy. All “C” recommendations from the past year are listed in TABLE 2.2-4
CVD prevention: When aspirin or a statin is indicated. The Task Force released 2 recommendations for the prevention of CVD this past year. One pertained to the use of low-dose aspirin3 (which also helps to prevent CRC), and the other addressed the use of low- to moderate-dose statins.4 Each recommendation is fairly complicated and nuanced in terms of age and risk for CVD. A decision to use low-dose aspirin must also consider the risk of bleeding.
To calculate a patient’s risk for CVD, the Task Force recommends using the risk calculator developed by the American College of Cardiology and the American Heart Association (http://www.cvriskcalculator.com/).
Adults for whom low-dose aspirin and low- to moderate-dose statins are recommended are described in TABLE 1.2-8 Patients for whom individual decision making is advised, rather than a generalized recommendation, are reviewed in TABLE 2.2-4 There is insufficient evidence to make a recommendation for the use of aspirin before age 50 or at age 70 and older,3 and for the use of statins in adults age 76 and older who do not have a history of CVD4 (TABLE 33,4,10-14). The use of low-dose aspirin and low-to-moderate dose statins have been the subject of JFP audiocasts in May 2016 and January 2017. (See http://bit.ly/2oiun8d and http://bit.ly/2oqkohR.)
2 pregnancy-related recommendations. To prevent neural tube defects in newborns, the Task Force now recommends daily folic acid, 0.4 to 0.8 mg (400 to 800 mcg), for all women who are planning on or are capable of becoming pregnant.5 This is an update of a 2009 recommendation that was worded slightly differently, recommending the supplement for all women of childbearing age.
A new recommendation on breastfeeding recognizes its benefits for both mother and baby and finds that interventions to encourage breastfeeding increase the prevalence of this practice and its duration.6 Interventions—provided to individuals or groups by professionals or peers or through formal education—include promoting the benefits of breastfeeding, giving practical advice and direct support on how to breastfeed, and offering psychological support.
Latent TB: Advantages of newer testing method. The recommendation on screening for latent tuberculosis (TB) is an update from the one made in 1996.7 At that time, screening for latent infection was performed using a tuberculin skin test (TST). Now a TST or interferon-gamma release assay (IGRA) can be used. Testing with IGRA may be the best option for those who have received a bacille Calmette–Guérin vaccination (because it can cause a false-positive TST) or for those who are not likely to return to have their TST read.
Those at high risk for latent TB include people who were born or have resided in countries with a high TB prevalence, those who have lived in a correctional institution or homeless shelter, and anyone in a high-risk group based on local epidemiology of the disease. (Read more on TB in this month’s Case Report.) Others at high risk are those who are immune suppressed because of infection or medications, and those who work in health care or correctional facilities. Screening of these groups is usually conducted as part of occupational health or is considered part of routine health care.
Syphilis: Screen high-risk individuals in 2 steps. The recommendation on syphilis screening basically reaffirms the one from 2004.8 Those at high risk for syphilis include men who have sex with men (who now account for 90% of new cases), those who are HIV positive, and those who engage in commercial sex work. Other racial and demographic groups can be at high risk depending on the local epidemiology of the disease. In a separate recommendation, the Task Force advises screening all pregnant women for syphilis.
Screening for syphilis infection involves 2 steps: first, a nontreponemal test (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] test); second, a confirmatory treponemal antibody detection test (fluorescent treponemal antibody absorption [FTA-ABS] or Treponema pallidum particle agglutination [TPPA] test). Treatment for syphilis remains benzathine penicillin with the number of injections depending on the stage of infection. The Centers for Disease Control and Prevention is the best source for current recommendations for treatment of all sexually transmitted infections.15
Screening tests to avoid
TABLE 416,17 lists screening tests the Task Force recommends against. While chronic obstructive pulmonary disease afflicts 14% of US adults ages 40 to 79 years and is the third leading cause of death in the country, the Task Force found that early detection in asymptomatic adults does not affect the course of the illness and is of no benefit.16
Genital herpes, also prevalent, infects an estimated one out of 6 individuals, ages 14 to 49. It causes little mortality, except in neonates, but those infected can have recurrent flares and suffer psychological harms from stigmatization. Most genital herpes is caused by herpes simplex virus-2, and there is a serological test to detect it. However, the Task Force recommends against using the test to screen asymptomatic adults and adolescents, including those who are pregnant. This recommendation is based on the test’s high false-positive rate, which can cause emotional harm, and on the lack of evidence that detection through screening improves outcomes.17
The evidence is lacking for these practices
The Task Force is one of only a few organizations that will not make a recommendation if evidence is lacking on benefits and harms. In addition to the ‘I’ statements regarding CVD and CRC mentioned earlier, the Task Force found insufficient evidence to recommend screening for lipid disorders in individuals ages 20 years or younger,10 performing a visual skin exam as a screening tool for skin cancer,11 screening for celiac disease,12 performing a periodic pelvic examination in asymptomatic women,13 and screening for obstructive sleep apnea using screening questionnaires14 (TABLE 33,4,10-14).
SIDEBAR
A change for prostate cancer screening?The USPSTF recently issued new draft recommendations regarding prostate cancer screening in asymptomatic men (available at: https://screeningforprostatecancer.org/).
The draft now divides men into 2 age groups, stating that the decision to screen for prostate cancer using a prostate specific antigen (PSA) test should be individualized for men ages 55 to 69 years (a C recommendation, meaning that there is at least moderate certainty that the net benefit is small), and that men ages 70 and older (lowered from age 75 in the previous 2012 recommendation1) should not be screened (a D recommendation, meaning that there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits).
The USPSTF believes that clinicians should explain to men ages 55 to 69 years that screening offers a small potential benefit of reducing the chance of dying from prostate cancer, but also comes with potential harms, including false-positive results requiring additional testing/procedures, overdiagnosis and overtreatment, and treatment complications such as incontinence and impotence. In this way, each man has the chance to incorporate his values and preferences into the decision.
For men ages 70 and older, the potential benefits simply do not outweigh the potential harms, according to the USPSTF.
1. USPSTF. Final recommendation statement. Prostate cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening#Pod1. Accessed April 11, 2017.
1. Campos-Outcalt D. Eight USPSTF recommendations FPs need to know about. J Fam Pract. 2016;65:338-341.
2. USPSTF. Colorectal cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/colorectal-cancer-screening2. Accessed March 22, 2017.
3. USPSTF. Aspirin use to prevent cardiovascular disease and colorectal cancer: preventive medications. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer. Accessed March 22, 2017.
4. USPSTF. Statin use for the prevention of cardiovascular disease in adults: preventive medication. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/statin-use-in-adults-preventive-medication1. Accessed March 22, 2017.
5. USPSTF. Folic acid for the prevention of neural tube defects: preventive medication. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/folic-acid-for-the-prevention-of-neural-tube-defects-preventive-medication. Accessed March 22, 2017.
6. USPSTF. Breastfeeding: primary care interventions. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breastfeeding-primary-care-interventions. Accessed March 22, 2017.
7. USPSTF. Latent tuberculosis infection: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/latent-tuberculosis-infection-screening. Accessed March 22, 2017.
8. USPSTF. Syphilis infection in nonpregnant adults and adolescents: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents. Accessed March 22, 2017.
9. AAFP. Colorectal cancer screening, adults. Available at: http://www.aafp.org/patient-care/clinical-recommendations/all/colorectal-cancer.html. Accessed March 22, 2017.
10. USPSTF. Lipid disorders in children and adolescents: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lipid-disorders-in-children-screening1. Accessed March 22, 2017.
11. USPSTF. Skin cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/skin-cancer-screening2. Accessed March 22, 2017.
12. USPSTF. Celiac disease: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/celiac-disease-screening. Accessed March 22, 2017.
13. USPSTF. Gynecological conditions: periodic screening with the pelvic examination. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/gynecological-conditions-screening-with-the-pelvic-examination. Accessed March 22, 2017.
14. USPSTF. Obstructive sleep apnea in adults: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/obstructive-sleep-apnea-in-adults-screening. Accessed March 22, 2017.
15. CDC. 2015 sexually transmitted diseases treatment guidelines. Available at: https://www.cdc.gov/std/tg2015/default.htm. Accessed March 22, 2017.
16. USPSTF. Chronic obstructive pulmonary disease: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/chronic-obstructive-pulmonary-disease-screening. Accessed March 22, 2017.
17. USPSTF. Genital herpes infection: serologic screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/genital-herpes-screening1. Accessed March 22, 2017.
1. Campos-Outcalt D. Eight USPSTF recommendations FPs need to know about. J Fam Pract. 2016;65:338-341.
2. USPSTF. Colorectal cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/colorectal-cancer-screening2. Accessed March 22, 2017.
3. USPSTF. Aspirin use to prevent cardiovascular disease and colorectal cancer: preventive medications. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/aspirin-to-prevent-cardiovascular-disease-and-cancer. Accessed March 22, 2017.
4. USPSTF. Statin use for the prevention of cardiovascular disease in adults: preventive medication. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/statin-use-in-adults-preventive-medication1. Accessed March 22, 2017.
5. USPSTF. Folic acid for the prevention of neural tube defects: preventive medication. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/folic-acid-for-the-prevention-of-neural-tube-defects-preventive-medication. Accessed March 22, 2017.
6. USPSTF. Breastfeeding: primary care interventions. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/breastfeeding-primary-care-interventions. Accessed March 22, 2017.
7. USPSTF. Latent tuberculosis infection: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/latent-tuberculosis-infection-screening. Accessed March 22, 2017.
8. USPSTF. Syphilis infection in nonpregnant adults and adolescents: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents. Accessed March 22, 2017.
9. AAFP. Colorectal cancer screening, adults. Available at: http://www.aafp.org/patient-care/clinical-recommendations/all/colorectal-cancer.html. Accessed March 22, 2017.
10. USPSTF. Lipid disorders in children and adolescents: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lipid-disorders-in-children-screening1. Accessed March 22, 2017.
11. USPSTF. Skin cancer: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/skin-cancer-screening2. Accessed March 22, 2017.
12. USPSTF. Celiac disease: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/celiac-disease-screening. Accessed March 22, 2017.
13. USPSTF. Gynecological conditions: periodic screening with the pelvic examination. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/gynecological-conditions-screening-with-the-pelvic-examination. Accessed March 22, 2017.
14. USPSTF. Obstructive sleep apnea in adults: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/obstructive-sleep-apnea-in-adults-screening. Accessed March 22, 2017.
15. CDC. 2015 sexually transmitted diseases treatment guidelines. Available at: https://www.cdc.gov/std/tg2015/default.htm. Accessed March 22, 2017.
16. USPSTF. Chronic obstructive pulmonary disease: screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/chronic-obstructive-pulmonary-disease-screening. Accessed March 22, 2017.
17. USPSTF. Genital herpes infection: serologic screening. Available at: https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/genital-herpes-screening1. Accessed March 22, 2017.
Management of bow legs in children: A primary care protocol
ABSTRACT
Objective To reduce unnecessary orthopedic referrals by developing a protocol for managing physiologic bow legs in the primary care environment through the use of a noninvasive technique that simultaneously tracks normal varus progression and screens for potential pathologic bowing requiring an orthopedic referral.
Methods Retrospective study of 155 patients with physiologic genu varum and 10 with infantile Blount’s disease. We used fingerbreadth measurements to document progression or resolution of bow legs. Final diagnoses were made by one orthopedic surgeon using clinical and radiographic evidence. We divided genu varum patients into 3 groups: patients presenting with bow legs before 18 months of age (MOA), patients presenting between 18 and 23 MOA, and patients presenting at 24 MOA or older for analyses relevant to the development of the follow-up protocol.
Results Physiologic genu varum patients walked earlier than average infants (10 months vs 12-15 months; P<.001). Physiologic genu varum patients presenting before 18 MOA demonstrated initial signs of correction between 18 and 24 MOA and resolution by 30 MOA. Physiologic genu varum patients presenting between 18 and 23 MOA demonstrated initial signs of correction between 24 MOA and 30 MOA and resolution by 36 MOA.
Conclusion Primary care physicians can manage most children presenting with bow legs. Management focuses on following the progression or resolution of varus with regular follow-up. For patients presenting with bow legs, we recommend a follow-up protocol using mainly well-child checkups and a simple clinical assessment to monitor varus progression and screen for pathologic bowing.
Bow legs in young children can be a concern for parents.1,2 By far, the most common reason for bow legs is physiologic genu varum,3-5 a nonprogressive stage of normal development in young children that generally resolves spontaneously without treatment.1,6-11 Normally developing children undergo a varus phase between birth and 18 to 24 months of age (MOA), at which time there is usually a transition in alignment from varus to straight to valgus (knock knees), which will correct to straight or mild valgus throughout adolescence.1,6,7,9,10,12-17
The most common form of pathologic bow legs is Blount’s disease, also known as tibia vara, which must be differentiated from physiologic genu varum.8-10,15,18-24 The progressive varus deformity of Blount’s disease usually requires orthopedic intervention.1,10,23-26 Early diagnosis may spare patients complex interventions, improve prognosis, and limit complications that include gait abnormalities,4,8,10,27 knee joint instability,4,24,27 osteoarthritis,9,20,27 meniscal tears,27 and degenerative joint disease.19,20,27
Although variables such as walking age, race, weight, and gender have been suggested as risk factors for Blount’s disease, they have not been useful in differentiating between Blount’s pathology and physiologic genu varum.1,4,5,7,10,20,28 In the primary care setting, distinguishing physiologic from pathologic forms of bow legs is possible with a thorough history and physical exam and with radiographs, as warranted.1,2,15 More than 40% of genu varum/genu valgum cases referred for orthopedic consultation turn out to be the physiologic form,2 suggesting a need for guidelines in the primary care setting to help direct referral and follow-up. The purpose of this study was to provide recommendations to family physicians for evaluating and managing children with bow legs.
Materials and methods
This study, approved by the Internal Review Board of Akron Children’s Hospital, is a retrospective review of children seen by a single pediatric orthopedic surgeon (DSW) from 1970 to 2012. Four-hundred twenty-four children were received for evaluation of bow legs. Excluded from our final analysis were 220 subjects seen only once for this specific referral and 39 subjects diagnosed with a condition other than genu varum or Blount’s disease (ie, rickets, skeletal dysplasia, sequelae of trauma, or infection). Ten subjects with Blount’s disease and 155 subjects with physiologic genu varum were included in the final data analysis.
In addition to noting the age at which a patient walked independently, at each visit we documented age and the fingerbreadth (varus) distance between the medial femoral condyles with the child’s ankles held together. Parents reported age of independent walking for just 3 children with Blount’s disease and for 134 children with physiologic genu varum. Study variables for the genu varum data analysis were age of walking, age at presentation, age at varus correction, age at varus resolution, time between presentation and varus correction, and time between presentation and varus resolution. Varus correction is defined as any decrease in varus angulation since presentation. Varus resolution is defined as varus correction to less than or equal to half of the varus angulation at presentation. For inclusion in the age-at-resolution analysis, a child must have been evaluated at regular follow-up visits (all rechecks within 8 months).
To measure varus distance, we used the fingerbreadth method described by Weiner in a study of 600 cases (FIGURE).6 This simple technique, which requires no special equipment, accurately detected differences in varus angulation and tracked the normal pattern of lower limb angular development. The patient should be supine on the examination table with legs extended. With one hand, the examiner holds the child’s ankles together, ensuring the medial malleoli are in contact. With the other hand, the examiner measures the fingerbreadth distance between the medial femoral condyles. Alternatively, a ruler may be used to measure the distance. This latter method may be especially useful in practices where the patient is likely to see more than one provider for well child care.
We divided the genu varum subject group into 3 subgroups by age at presentation: 103 subjects were younger than 18 months; 47 were 18 to 23 months; and 5 were 24 months or older. We used the data analysis toolkit in Microsoft Excel 2013 to perform a statistical analysis of study variables. We assumed the genu varum population is a normally distributed population. We used a 95% confidence level (α=0.05) for all calculations of confidence intervals (CIs), student t-tests, and tolerance intervals. Based on the data analysis results, we developed a series of follow-up and referral guidelines for practitioners.
Results
The mean walking age for those diagnosed with physiologic genu varum was 10 months (95% CI, 9.8-10.4), which is significantly younger than the 12 months of age (at the earliest) typical of toddlers in general (P<.001). There was no significant difference between the walking age of male and female children diagnosed with genu varum (P=.37).
Of the children presenting with the primary complaint of bow legs, 6% subsequently developed Blount’s disease. These patients presented at a mean age of 20.9 months and were diagnosed at a mean age of 23.9 months. Following the Blount’s disease diagnosis, we initiated therapy in all cases (3 surgical, 7 bracing).
Physiologic genu varum patients presented at a mean age of 16.4 months, with only 3.23% presenting at older than 23 months. On average, physiologic genu varum patients presenting before 24 months of age showed measurable varus correction 5 months after presentation and achieved varus resolution 7.3 months after presentation (TABLE 1). Assuming the patient population is normally distributed, we can be 95% confident that 95% of physiologic genu varum patients presenting before 18 months of age will show measurable varus correction by 24 months and will resolve without intervention by 30 months (TABLE 2). Patients presenting between 18 and 23 months of age should show measurable varus correction by 30 months and resolution by 36 months (TABLE 3).
Discussion
Primary care physicians have the ability to differentiate physiologic genu varum from pathologic forms of bow legs with a thorough history, physical exam, and radiographic examination, if necessary1,2,13 (TABLE 41,7,8,10,12,14,18-20,22,24,27). Several approaches to differentiating Blount’s disease and physiologic genu varum have been described in the literature.1,4,7,8,10,14,22,23
The average age at which children begin to walk independently is between 13 and 15 months.5,18,29-31 Recently, it has been suggested that the range be expanded to include 12 months of age.30 The association between early walking (at 10-11 months)12,20,22 and Blount’s disease is generally accepted in the orthopedic literature.1,4,7,10,19-22 However, some authors have suggested early walking also contributes to genu varum.1,5,8,10,18,28 The mean age of independent walking for children with physiologic genu varum suggested in the literature (10 months) was confirmed in our study and found to be significantly younger than the average for toddlers generally.1,22 Early walking is clearly associated with both physiologic genu varum and Blount’s disease, but no direct causation has been identified in either case. An alternative means of differentiating these entities is needed.
Radiographic examination of the knee is essential to the diagnosis of Blount’s disease as well as other, less common causes of pathologic bow legs (skeletal dysplasia, rickets, traumatic growth plate insults, infections, neoplasms).1,8,14,19 The common radiologic classification of staging for Blount’s disease is the Langenskiöld staging system, which involves identification of characteristic radiographic changes at the tibial physis.5,8,14,15,18,22,24
Sequential measurement of genu varum is most useful in differentiating between physiologic and pathologic processes. Physiologic genu varum, an exaggeration of the normal developmental pattern, characteristically resolves and evolves into physiologic genu valgum by 3 years of age.1,6-11 The pathophysiology of Blount’s disease is believed to be related to biomechanical overloading of the posteromedial proximal tibia during gait with the knee in a varus orientation. Excess loading on the proximal medial physis contributes to varus progression.4,10,14,20,25,27 Patients with Blount’s disease progress with varus and concomitant internal tibial torsion associated with growth plate irregularities and eventually exhibit premature closure.1,10,14,18,20,23,24,26 In the months prior to Blount’s disease diagnosis, increasing varus has been reported.4,7,10,19 Varus progression that differs from the expected pattern indicates possible pathologic bow legs and should prompt radiologic evaluation and, often, an orthopedic referral.3,4,7-9,12,13,21
In our study, only 3% of children with physiologic genu varum presented at 24 months of age or older, compared with 20% of Blount’s disease patients. We recommend considering orthopedic referral for any patient presenting with bow legs at 24 months of age or older. Additionally, consider orthopedic referral for any patient whose varus has not begun to correct within 8 months or has not resolved within 14 months of presentation, as more than 95% of patients with physiologic genu varum are expected to meet these milestones (TABLE 1). And do not hesitate to refer patients at any stage of follow-up if you suspect pathology or if parents are anxious.
If no sign of pathology is immediately identified, we recommend the following course of action:
- Record a reference fingerbreadth or ruler measurement at the initial presentation.
- Re-examine the knee varus at the next regular well-child visit (TABLE 5).
Re-examining the patient prior to the next well-child visit is unnecessary, as some degree of bowing is typical until age 18 to 24 months.1,6,7,9,12,13,17 Recommend orthopedic referral for any patient with varus that has progressed since initial presentation. Without signs of pathology, repeat varus assessment at the next well-child visit. This schedule minimizes the need for additional physician appointments by integrating follow-up into the typical well-child visits at 18, 24, 30, and 36 months of age.32 The 6-month follow-up interval was a feature of our study and is recommended in the related literature.12
- Consider orthopedic referral for patients whose varus has not corrected by the second follow-up appointment, as more than 95% of patients should have measurable varus correction at this visit. Most patients will have exhibited varus resolution by this time and will not require additional follow-up. For patients with observable correction who do not yet meet the criteria for resolution, we recommend a third, final follow-up appointment in another 6 months.
- Refer any patient whose varus has not resolved by the third follow-up appointment, as more than 95% of genu varum cases should have resolved by this time. This finding is echoed in the literature; any varus beyond 36 months of age is considered abnormal and suggestive of pathology.5,7,8,13,14 If evidence of Blount’s or skeletal dysplasia is identified, orthopedic management will likely consist of bracing (orthotics) or surgical management.
CORRESPONDENCE
Dennis S. Weiner, MD, Department of Orthopedic Surgery, Akron Children’s Hospital, 300 Locust Street, Suite 250, Akron, OH, 44302; [email protected].
ACKNOWLEDGEMENTS
The authors thank Meadow Newton, BS, assistant research coordinator, Akron Children’s Hospital, for her editing and technical assistance and Richard Steiner, PhD, The University of Akron, for his statistical review.
1. Weiner DS. Pediatric orthopedics for primary care physicians. 2nd ed. Jones K, ed. Cambridge, United Kingdom: Cambridge University Press; 2004.
2. Carli A, Saran N, Kruijt J, et al. Physiological referrals for paediatric musculoskeletal complaints: a costly problem that needs to be addressed. Paediatr Child Health. 2012;17:e93-e97.
3. Fabry G. Clinical practice. Static, axial, and rotational deformities of the lower extremities in children. Eur J Pediatr. 2010;169:529-534.
4. Davids JR, Blackhurst DW, Allen Jr BL. Clinical evaluation of bowed legs in children. J Pediatr Orthop B. 2000;9:278-284.
5. Bateson EM. The relationship between Blount’s disease and bow legs. Br J Radiol. 1968;41:107-114.
6. Weiner DS. The natural history of “bow legs” and “knock knees” in childhood. Orthopedics. 1981;4:156-160.
7. Greene WB. Genu varum and genu valgum in children: differential diagnosis and guidelines for evaluation. Compr Ther. 1996;22:22-29.
8. Do TT. Clinical and radiographic evaluation of bowlegs. Curr Opin Pediatr. 2001;13:42-46.
9. Bleck EE. Developmental orthopaedics. III: Toddlers. Dev Med Child Neurol. 1982;24:533-555.
10. Brooks WC, Gross RH. Genu Varum in Children: Diagnosis and Treatment. J Am Acad Orthop Surg. 1995;3:326-335.
11. Greenberg LA, Swartz AA. Genu varum and genu valgum. Another look. Am J Dis Child. 1971;121:219-221.
12. Scherl SA. Common lower extremity problems in children. Pediatr Rev. 2004;25:52-62.
13. Wall EJ. Practical primary pediatric orthopedics. Nurs Clin North Am. 2000;35:95-113.
14. Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003;23:871-880.
15. McCarthy JJ, Betz RR, Kim A, et al. Early radiographic differentiation of infantile tibia vara from physiologic bowing using the femoral-tibial ratio. J Pediatr Orthop. 2001;21:545-548.
16. Salenius P, Vankka E. The development of the tibiofemoral angle in children. J Bone Joint Surg Am. 1975;57:259-261.
17. Engel GM, Staheli LT. The natural history of torsion and other factors influencing gait in childhood. A study of the angle of gait, tibial torsion, knee angle, hip rotation, and development of the arch in normal children. Clin Orthop Relat Res. 1974;99:12-17.
18. Golding J, Bateson E, McNeil-Smith G. Infantile tibia vara. In: The Growth Plate and Its Disorders. Rang M, ed. Baltimore, MD: Williams and Wilkins; 1969:109-119.
19. Greene WB. Infantile tibia vara. J Bone Joint Surg Am. 1993;75:130-143.
20. Golding J, McNeil-Smith JDG. Observations on the etiology of tibia vara. J Bone Joint Surg Br. 1963;45-B:320-325.
21. Eggert P, Viemann M. Physiological bowlegs or infantile Blount’s disease. Some new aspects on an old problem. Pediatr Radiol. 1996;26:349-352.
22. Levine AM, Drennan JC. Physiological bowing and tibia vara. The metaphyseal-diaphyseal angle in the measurement of bowleg deformities. J Bone Joint Surg Am. 1982;64:1158-1163.
23. Kessel L. Annotations on the etiology and treatment of tibia vara. J Bone Joint Surg Br. 1970;52:93-99.
24. Blount WP. Tibia vara: osteochondrosis deformans tibiae. J Bone Joint Surg Am. 1937;19:1-29.
25. Davids JR, Blackhurst DW, Allen BL Jr. Radiographic evaluation of bowed legs in children. J Pediatr Orthop. 2001;21:257-263.
26. Cook SD, Lavernia CJ, Burke SW, et al. A biomechanical analysis of the etiology of tibia vara. J Pediatr Orthop. 1983;3:449-454.
27. Birch JG. Blount disease. J Am Acad Orthop Surg. 2013;21:408-418.
28. Bateson EM. Non-rachitic bow leg and knock-knee deformities in young Jamaican children. Br J Radiol. 1966;39:92-101.
29. Grantham-McGregor SM, Back EH. Gross motor development in Jamaican infants. Dev Med Child Neurol. 1971;13:79-87.
30. Størvold GV, Aarethun K, Bratberg GH. Age for onset of walking and prewalking strategies. Early Hum Dev. 2013;89:655-659.
31. Garrett M, McElroy AM, Staines A. Locomotor milestones and babywalkers: cross sectional study. BMJ. 2002;324:1494.
32. Simon GR, Baker C, Barden GA 3rd, et al; Committee on Practice and Ambulatory Medicine, Curry ES, Dunca PM, Hagan JF Jr, et al; Bright Futures Periodicity Schedule Workgroup. 2014 recommendations for pediatric preventive health care. Pediatrics. 2014;133:568-570.
ABSTRACT
Objective To reduce unnecessary orthopedic referrals by developing a protocol for managing physiologic bow legs in the primary care environment through the use of a noninvasive technique that simultaneously tracks normal varus progression and screens for potential pathologic bowing requiring an orthopedic referral.
Methods Retrospective study of 155 patients with physiologic genu varum and 10 with infantile Blount’s disease. We used fingerbreadth measurements to document progression or resolution of bow legs. Final diagnoses were made by one orthopedic surgeon using clinical and radiographic evidence. We divided genu varum patients into 3 groups: patients presenting with bow legs before 18 months of age (MOA), patients presenting between 18 and 23 MOA, and patients presenting at 24 MOA or older for analyses relevant to the development of the follow-up protocol.
Results Physiologic genu varum patients walked earlier than average infants (10 months vs 12-15 months; P<.001). Physiologic genu varum patients presenting before 18 MOA demonstrated initial signs of correction between 18 and 24 MOA and resolution by 30 MOA. Physiologic genu varum patients presenting between 18 and 23 MOA demonstrated initial signs of correction between 24 MOA and 30 MOA and resolution by 36 MOA.
Conclusion Primary care physicians can manage most children presenting with bow legs. Management focuses on following the progression or resolution of varus with regular follow-up. For patients presenting with bow legs, we recommend a follow-up protocol using mainly well-child checkups and a simple clinical assessment to monitor varus progression and screen for pathologic bowing.
Bow legs in young children can be a concern for parents.1,2 By far, the most common reason for bow legs is physiologic genu varum,3-5 a nonprogressive stage of normal development in young children that generally resolves spontaneously without treatment.1,6-11 Normally developing children undergo a varus phase between birth and 18 to 24 months of age (MOA), at which time there is usually a transition in alignment from varus to straight to valgus (knock knees), which will correct to straight or mild valgus throughout adolescence.1,6,7,9,10,12-17
The most common form of pathologic bow legs is Blount’s disease, also known as tibia vara, which must be differentiated from physiologic genu varum.8-10,15,18-24 The progressive varus deformity of Blount’s disease usually requires orthopedic intervention.1,10,23-26 Early diagnosis may spare patients complex interventions, improve prognosis, and limit complications that include gait abnormalities,4,8,10,27 knee joint instability,4,24,27 osteoarthritis,9,20,27 meniscal tears,27 and degenerative joint disease.19,20,27
Although variables such as walking age, race, weight, and gender have been suggested as risk factors for Blount’s disease, they have not been useful in differentiating between Blount’s pathology and physiologic genu varum.1,4,5,7,10,20,28 In the primary care setting, distinguishing physiologic from pathologic forms of bow legs is possible with a thorough history and physical exam and with radiographs, as warranted.1,2,15 More than 40% of genu varum/genu valgum cases referred for orthopedic consultation turn out to be the physiologic form,2 suggesting a need for guidelines in the primary care setting to help direct referral and follow-up. The purpose of this study was to provide recommendations to family physicians for evaluating and managing children with bow legs.
Materials and methods
This study, approved by the Internal Review Board of Akron Children’s Hospital, is a retrospective review of children seen by a single pediatric orthopedic surgeon (DSW) from 1970 to 2012. Four-hundred twenty-four children were received for evaluation of bow legs. Excluded from our final analysis were 220 subjects seen only once for this specific referral and 39 subjects diagnosed with a condition other than genu varum or Blount’s disease (ie, rickets, skeletal dysplasia, sequelae of trauma, or infection). Ten subjects with Blount’s disease and 155 subjects with physiologic genu varum were included in the final data analysis.
In addition to noting the age at which a patient walked independently, at each visit we documented age and the fingerbreadth (varus) distance between the medial femoral condyles with the child’s ankles held together. Parents reported age of independent walking for just 3 children with Blount’s disease and for 134 children with physiologic genu varum. Study variables for the genu varum data analysis were age of walking, age at presentation, age at varus correction, age at varus resolution, time between presentation and varus correction, and time between presentation and varus resolution. Varus correction is defined as any decrease in varus angulation since presentation. Varus resolution is defined as varus correction to less than or equal to half of the varus angulation at presentation. For inclusion in the age-at-resolution analysis, a child must have been evaluated at regular follow-up visits (all rechecks within 8 months).
To measure varus distance, we used the fingerbreadth method described by Weiner in a study of 600 cases (FIGURE).6 This simple technique, which requires no special equipment, accurately detected differences in varus angulation and tracked the normal pattern of lower limb angular development. The patient should be supine on the examination table with legs extended. With one hand, the examiner holds the child’s ankles together, ensuring the medial malleoli are in contact. With the other hand, the examiner measures the fingerbreadth distance between the medial femoral condyles. Alternatively, a ruler may be used to measure the distance. This latter method may be especially useful in practices where the patient is likely to see more than one provider for well child care.
We divided the genu varum subject group into 3 subgroups by age at presentation: 103 subjects were younger than 18 months; 47 were 18 to 23 months; and 5 were 24 months or older. We used the data analysis toolkit in Microsoft Excel 2013 to perform a statistical analysis of study variables. We assumed the genu varum population is a normally distributed population. We used a 95% confidence level (α=0.05) for all calculations of confidence intervals (CIs), student t-tests, and tolerance intervals. Based on the data analysis results, we developed a series of follow-up and referral guidelines for practitioners.
Results
The mean walking age for those diagnosed with physiologic genu varum was 10 months (95% CI, 9.8-10.4), which is significantly younger than the 12 months of age (at the earliest) typical of toddlers in general (P<.001). There was no significant difference between the walking age of male and female children diagnosed with genu varum (P=.37).
Of the children presenting with the primary complaint of bow legs, 6% subsequently developed Blount’s disease. These patients presented at a mean age of 20.9 months and were diagnosed at a mean age of 23.9 months. Following the Blount’s disease diagnosis, we initiated therapy in all cases (3 surgical, 7 bracing).
Physiologic genu varum patients presented at a mean age of 16.4 months, with only 3.23% presenting at older than 23 months. On average, physiologic genu varum patients presenting before 24 months of age showed measurable varus correction 5 months after presentation and achieved varus resolution 7.3 months after presentation (TABLE 1). Assuming the patient population is normally distributed, we can be 95% confident that 95% of physiologic genu varum patients presenting before 18 months of age will show measurable varus correction by 24 months and will resolve without intervention by 30 months (TABLE 2). Patients presenting between 18 and 23 months of age should show measurable varus correction by 30 months and resolution by 36 months (TABLE 3).
Discussion
Primary care physicians have the ability to differentiate physiologic genu varum from pathologic forms of bow legs with a thorough history, physical exam, and radiographic examination, if necessary1,2,13 (TABLE 41,7,8,10,12,14,18-20,22,24,27). Several approaches to differentiating Blount’s disease and physiologic genu varum have been described in the literature.1,4,7,8,10,14,22,23
The average age at which children begin to walk independently is between 13 and 15 months.5,18,29-31 Recently, it has been suggested that the range be expanded to include 12 months of age.30 The association between early walking (at 10-11 months)12,20,22 and Blount’s disease is generally accepted in the orthopedic literature.1,4,7,10,19-22 However, some authors have suggested early walking also contributes to genu varum.1,5,8,10,18,28 The mean age of independent walking for children with physiologic genu varum suggested in the literature (10 months) was confirmed in our study and found to be significantly younger than the average for toddlers generally.1,22 Early walking is clearly associated with both physiologic genu varum and Blount’s disease, but no direct causation has been identified in either case. An alternative means of differentiating these entities is needed.
Radiographic examination of the knee is essential to the diagnosis of Blount’s disease as well as other, less common causes of pathologic bow legs (skeletal dysplasia, rickets, traumatic growth plate insults, infections, neoplasms).1,8,14,19 The common radiologic classification of staging for Blount’s disease is the Langenskiöld staging system, which involves identification of characteristic radiographic changes at the tibial physis.5,8,14,15,18,22,24
Sequential measurement of genu varum is most useful in differentiating between physiologic and pathologic processes. Physiologic genu varum, an exaggeration of the normal developmental pattern, characteristically resolves and evolves into physiologic genu valgum by 3 years of age.1,6-11 The pathophysiology of Blount’s disease is believed to be related to biomechanical overloading of the posteromedial proximal tibia during gait with the knee in a varus orientation. Excess loading on the proximal medial physis contributes to varus progression.4,10,14,20,25,27 Patients with Blount’s disease progress with varus and concomitant internal tibial torsion associated with growth plate irregularities and eventually exhibit premature closure.1,10,14,18,20,23,24,26 In the months prior to Blount’s disease diagnosis, increasing varus has been reported.4,7,10,19 Varus progression that differs from the expected pattern indicates possible pathologic bow legs and should prompt radiologic evaluation and, often, an orthopedic referral.3,4,7-9,12,13,21
In our study, only 3% of children with physiologic genu varum presented at 24 months of age or older, compared with 20% of Blount’s disease patients. We recommend considering orthopedic referral for any patient presenting with bow legs at 24 months of age or older. Additionally, consider orthopedic referral for any patient whose varus has not begun to correct within 8 months or has not resolved within 14 months of presentation, as more than 95% of patients with physiologic genu varum are expected to meet these milestones (TABLE 1). And do not hesitate to refer patients at any stage of follow-up if you suspect pathology or if parents are anxious.
If no sign of pathology is immediately identified, we recommend the following course of action:
- Record a reference fingerbreadth or ruler measurement at the initial presentation.
- Re-examine the knee varus at the next regular well-child visit (TABLE 5).
Re-examining the patient prior to the next well-child visit is unnecessary, as some degree of bowing is typical until age 18 to 24 months.1,6,7,9,12,13,17 Recommend orthopedic referral for any patient with varus that has progressed since initial presentation. Without signs of pathology, repeat varus assessment at the next well-child visit. This schedule minimizes the need for additional physician appointments by integrating follow-up into the typical well-child visits at 18, 24, 30, and 36 months of age.32 The 6-month follow-up interval was a feature of our study and is recommended in the related literature.12
- Consider orthopedic referral for patients whose varus has not corrected by the second follow-up appointment, as more than 95% of patients should have measurable varus correction at this visit. Most patients will have exhibited varus resolution by this time and will not require additional follow-up. For patients with observable correction who do not yet meet the criteria for resolution, we recommend a third, final follow-up appointment in another 6 months.
- Refer any patient whose varus has not resolved by the third follow-up appointment, as more than 95% of genu varum cases should have resolved by this time. This finding is echoed in the literature; any varus beyond 36 months of age is considered abnormal and suggestive of pathology.5,7,8,13,14 If evidence of Blount’s or skeletal dysplasia is identified, orthopedic management will likely consist of bracing (orthotics) or surgical management.
CORRESPONDENCE
Dennis S. Weiner, MD, Department of Orthopedic Surgery, Akron Children’s Hospital, 300 Locust Street, Suite 250, Akron, OH, 44302; [email protected].
ACKNOWLEDGEMENTS
The authors thank Meadow Newton, BS, assistant research coordinator, Akron Children’s Hospital, for her editing and technical assistance and Richard Steiner, PhD, The University of Akron, for his statistical review.
ABSTRACT
Objective To reduce unnecessary orthopedic referrals by developing a protocol for managing physiologic bow legs in the primary care environment through the use of a noninvasive technique that simultaneously tracks normal varus progression and screens for potential pathologic bowing requiring an orthopedic referral.
Methods Retrospective study of 155 patients with physiologic genu varum and 10 with infantile Blount’s disease. We used fingerbreadth measurements to document progression or resolution of bow legs. Final diagnoses were made by one orthopedic surgeon using clinical and radiographic evidence. We divided genu varum patients into 3 groups: patients presenting with bow legs before 18 months of age (MOA), patients presenting between 18 and 23 MOA, and patients presenting at 24 MOA or older for analyses relevant to the development of the follow-up protocol.
Results Physiologic genu varum patients walked earlier than average infants (10 months vs 12-15 months; P<.001). Physiologic genu varum patients presenting before 18 MOA demonstrated initial signs of correction between 18 and 24 MOA and resolution by 30 MOA. Physiologic genu varum patients presenting between 18 and 23 MOA demonstrated initial signs of correction between 24 MOA and 30 MOA and resolution by 36 MOA.
Conclusion Primary care physicians can manage most children presenting with bow legs. Management focuses on following the progression or resolution of varus with regular follow-up. For patients presenting with bow legs, we recommend a follow-up protocol using mainly well-child checkups and a simple clinical assessment to monitor varus progression and screen for pathologic bowing.
Bow legs in young children can be a concern for parents.1,2 By far, the most common reason for bow legs is physiologic genu varum,3-5 a nonprogressive stage of normal development in young children that generally resolves spontaneously without treatment.1,6-11 Normally developing children undergo a varus phase between birth and 18 to 24 months of age (MOA), at which time there is usually a transition in alignment from varus to straight to valgus (knock knees), which will correct to straight or mild valgus throughout adolescence.1,6,7,9,10,12-17
The most common form of pathologic bow legs is Blount’s disease, also known as tibia vara, which must be differentiated from physiologic genu varum.8-10,15,18-24 The progressive varus deformity of Blount’s disease usually requires orthopedic intervention.1,10,23-26 Early diagnosis may spare patients complex interventions, improve prognosis, and limit complications that include gait abnormalities,4,8,10,27 knee joint instability,4,24,27 osteoarthritis,9,20,27 meniscal tears,27 and degenerative joint disease.19,20,27
Although variables such as walking age, race, weight, and gender have been suggested as risk factors for Blount’s disease, they have not been useful in differentiating between Blount’s pathology and physiologic genu varum.1,4,5,7,10,20,28 In the primary care setting, distinguishing physiologic from pathologic forms of bow legs is possible with a thorough history and physical exam and with radiographs, as warranted.1,2,15 More than 40% of genu varum/genu valgum cases referred for orthopedic consultation turn out to be the physiologic form,2 suggesting a need for guidelines in the primary care setting to help direct referral and follow-up. The purpose of this study was to provide recommendations to family physicians for evaluating and managing children with bow legs.
Materials and methods
This study, approved by the Internal Review Board of Akron Children’s Hospital, is a retrospective review of children seen by a single pediatric orthopedic surgeon (DSW) from 1970 to 2012. Four-hundred twenty-four children were received for evaluation of bow legs. Excluded from our final analysis were 220 subjects seen only once for this specific referral and 39 subjects diagnosed with a condition other than genu varum or Blount’s disease (ie, rickets, skeletal dysplasia, sequelae of trauma, or infection). Ten subjects with Blount’s disease and 155 subjects with physiologic genu varum were included in the final data analysis.
In addition to noting the age at which a patient walked independently, at each visit we documented age and the fingerbreadth (varus) distance between the medial femoral condyles with the child’s ankles held together. Parents reported age of independent walking for just 3 children with Blount’s disease and for 134 children with physiologic genu varum. Study variables for the genu varum data analysis were age of walking, age at presentation, age at varus correction, age at varus resolution, time between presentation and varus correction, and time between presentation and varus resolution. Varus correction is defined as any decrease in varus angulation since presentation. Varus resolution is defined as varus correction to less than or equal to half of the varus angulation at presentation. For inclusion in the age-at-resolution analysis, a child must have been evaluated at regular follow-up visits (all rechecks within 8 months).
To measure varus distance, we used the fingerbreadth method described by Weiner in a study of 600 cases (FIGURE).6 This simple technique, which requires no special equipment, accurately detected differences in varus angulation and tracked the normal pattern of lower limb angular development. The patient should be supine on the examination table with legs extended. With one hand, the examiner holds the child’s ankles together, ensuring the medial malleoli are in contact. With the other hand, the examiner measures the fingerbreadth distance between the medial femoral condyles. Alternatively, a ruler may be used to measure the distance. This latter method may be especially useful in practices where the patient is likely to see more than one provider for well child care.
We divided the genu varum subject group into 3 subgroups by age at presentation: 103 subjects were younger than 18 months; 47 were 18 to 23 months; and 5 were 24 months or older. We used the data analysis toolkit in Microsoft Excel 2013 to perform a statistical analysis of study variables. We assumed the genu varum population is a normally distributed population. We used a 95% confidence level (α=0.05) for all calculations of confidence intervals (CIs), student t-tests, and tolerance intervals. Based on the data analysis results, we developed a series of follow-up and referral guidelines for practitioners.
Results
The mean walking age for those diagnosed with physiologic genu varum was 10 months (95% CI, 9.8-10.4), which is significantly younger than the 12 months of age (at the earliest) typical of toddlers in general (P<.001). There was no significant difference between the walking age of male and female children diagnosed with genu varum (P=.37).
Of the children presenting with the primary complaint of bow legs, 6% subsequently developed Blount’s disease. These patients presented at a mean age of 20.9 months and were diagnosed at a mean age of 23.9 months. Following the Blount’s disease diagnosis, we initiated therapy in all cases (3 surgical, 7 bracing).
Physiologic genu varum patients presented at a mean age of 16.4 months, with only 3.23% presenting at older than 23 months. On average, physiologic genu varum patients presenting before 24 months of age showed measurable varus correction 5 months after presentation and achieved varus resolution 7.3 months after presentation (TABLE 1). Assuming the patient population is normally distributed, we can be 95% confident that 95% of physiologic genu varum patients presenting before 18 months of age will show measurable varus correction by 24 months and will resolve without intervention by 30 months (TABLE 2). Patients presenting between 18 and 23 months of age should show measurable varus correction by 30 months and resolution by 36 months (TABLE 3).
Discussion
Primary care physicians have the ability to differentiate physiologic genu varum from pathologic forms of bow legs with a thorough history, physical exam, and radiographic examination, if necessary1,2,13 (TABLE 41,7,8,10,12,14,18-20,22,24,27). Several approaches to differentiating Blount’s disease and physiologic genu varum have been described in the literature.1,4,7,8,10,14,22,23
The average age at which children begin to walk independently is between 13 and 15 months.5,18,29-31 Recently, it has been suggested that the range be expanded to include 12 months of age.30 The association between early walking (at 10-11 months)12,20,22 and Blount’s disease is generally accepted in the orthopedic literature.1,4,7,10,19-22 However, some authors have suggested early walking also contributes to genu varum.1,5,8,10,18,28 The mean age of independent walking for children with physiologic genu varum suggested in the literature (10 months) was confirmed in our study and found to be significantly younger than the average for toddlers generally.1,22 Early walking is clearly associated with both physiologic genu varum and Blount’s disease, but no direct causation has been identified in either case. An alternative means of differentiating these entities is needed.
Radiographic examination of the knee is essential to the diagnosis of Blount’s disease as well as other, less common causes of pathologic bow legs (skeletal dysplasia, rickets, traumatic growth plate insults, infections, neoplasms).1,8,14,19 The common radiologic classification of staging for Blount’s disease is the Langenskiöld staging system, which involves identification of characteristic radiographic changes at the tibial physis.5,8,14,15,18,22,24
Sequential measurement of genu varum is most useful in differentiating between physiologic and pathologic processes. Physiologic genu varum, an exaggeration of the normal developmental pattern, characteristically resolves and evolves into physiologic genu valgum by 3 years of age.1,6-11 The pathophysiology of Blount’s disease is believed to be related to biomechanical overloading of the posteromedial proximal tibia during gait with the knee in a varus orientation. Excess loading on the proximal medial physis contributes to varus progression.4,10,14,20,25,27 Patients with Blount’s disease progress with varus and concomitant internal tibial torsion associated with growth plate irregularities and eventually exhibit premature closure.1,10,14,18,20,23,24,26 In the months prior to Blount’s disease diagnosis, increasing varus has been reported.4,7,10,19 Varus progression that differs from the expected pattern indicates possible pathologic bow legs and should prompt radiologic evaluation and, often, an orthopedic referral.3,4,7-9,12,13,21
In our study, only 3% of children with physiologic genu varum presented at 24 months of age or older, compared with 20% of Blount’s disease patients. We recommend considering orthopedic referral for any patient presenting with bow legs at 24 months of age or older. Additionally, consider orthopedic referral for any patient whose varus has not begun to correct within 8 months or has not resolved within 14 months of presentation, as more than 95% of patients with physiologic genu varum are expected to meet these milestones (TABLE 1). And do not hesitate to refer patients at any stage of follow-up if you suspect pathology or if parents are anxious.
If no sign of pathology is immediately identified, we recommend the following course of action:
- Record a reference fingerbreadth or ruler measurement at the initial presentation.
- Re-examine the knee varus at the next regular well-child visit (TABLE 5).
Re-examining the patient prior to the next well-child visit is unnecessary, as some degree of bowing is typical until age 18 to 24 months.1,6,7,9,12,13,17 Recommend orthopedic referral for any patient with varus that has progressed since initial presentation. Without signs of pathology, repeat varus assessment at the next well-child visit. This schedule minimizes the need for additional physician appointments by integrating follow-up into the typical well-child visits at 18, 24, 30, and 36 months of age.32 The 6-month follow-up interval was a feature of our study and is recommended in the related literature.12
- Consider orthopedic referral for patients whose varus has not corrected by the second follow-up appointment, as more than 95% of patients should have measurable varus correction at this visit. Most patients will have exhibited varus resolution by this time and will not require additional follow-up. For patients with observable correction who do not yet meet the criteria for resolution, we recommend a third, final follow-up appointment in another 6 months.
- Refer any patient whose varus has not resolved by the third follow-up appointment, as more than 95% of genu varum cases should have resolved by this time. This finding is echoed in the literature; any varus beyond 36 months of age is considered abnormal and suggestive of pathology.5,7,8,13,14 If evidence of Blount’s or skeletal dysplasia is identified, orthopedic management will likely consist of bracing (orthotics) or surgical management.
CORRESPONDENCE
Dennis S. Weiner, MD, Department of Orthopedic Surgery, Akron Children’s Hospital, 300 Locust Street, Suite 250, Akron, OH, 44302; [email protected].
ACKNOWLEDGEMENTS
The authors thank Meadow Newton, BS, assistant research coordinator, Akron Children’s Hospital, for her editing and technical assistance and Richard Steiner, PhD, The University of Akron, for his statistical review.
1. Weiner DS. Pediatric orthopedics for primary care physicians. 2nd ed. Jones K, ed. Cambridge, United Kingdom: Cambridge University Press; 2004.
2. Carli A, Saran N, Kruijt J, et al. Physiological referrals for paediatric musculoskeletal complaints: a costly problem that needs to be addressed. Paediatr Child Health. 2012;17:e93-e97.
3. Fabry G. Clinical practice. Static, axial, and rotational deformities of the lower extremities in children. Eur J Pediatr. 2010;169:529-534.
4. Davids JR, Blackhurst DW, Allen Jr BL. Clinical evaluation of bowed legs in children. J Pediatr Orthop B. 2000;9:278-284.
5. Bateson EM. The relationship between Blount’s disease and bow legs. Br J Radiol. 1968;41:107-114.
6. Weiner DS. The natural history of “bow legs” and “knock knees” in childhood. Orthopedics. 1981;4:156-160.
7. Greene WB. Genu varum and genu valgum in children: differential diagnosis and guidelines for evaluation. Compr Ther. 1996;22:22-29.
8. Do TT. Clinical and radiographic evaluation of bowlegs. Curr Opin Pediatr. 2001;13:42-46.
9. Bleck EE. Developmental orthopaedics. III: Toddlers. Dev Med Child Neurol. 1982;24:533-555.
10. Brooks WC, Gross RH. Genu Varum in Children: Diagnosis and Treatment. J Am Acad Orthop Surg. 1995;3:326-335.
11. Greenberg LA, Swartz AA. Genu varum and genu valgum. Another look. Am J Dis Child. 1971;121:219-221.
12. Scherl SA. Common lower extremity problems in children. Pediatr Rev. 2004;25:52-62.
13. Wall EJ. Practical primary pediatric orthopedics. Nurs Clin North Am. 2000;35:95-113.
14. Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003;23:871-880.
15. McCarthy JJ, Betz RR, Kim A, et al. Early radiographic differentiation of infantile tibia vara from physiologic bowing using the femoral-tibial ratio. J Pediatr Orthop. 2001;21:545-548.
16. Salenius P, Vankka E. The development of the tibiofemoral angle in children. J Bone Joint Surg Am. 1975;57:259-261.
17. Engel GM, Staheli LT. The natural history of torsion and other factors influencing gait in childhood. A study of the angle of gait, tibial torsion, knee angle, hip rotation, and development of the arch in normal children. Clin Orthop Relat Res. 1974;99:12-17.
18. Golding J, Bateson E, McNeil-Smith G. Infantile tibia vara. In: The Growth Plate and Its Disorders. Rang M, ed. Baltimore, MD: Williams and Wilkins; 1969:109-119.
19. Greene WB. Infantile tibia vara. J Bone Joint Surg Am. 1993;75:130-143.
20. Golding J, McNeil-Smith JDG. Observations on the etiology of tibia vara. J Bone Joint Surg Br. 1963;45-B:320-325.
21. Eggert P, Viemann M. Physiological bowlegs or infantile Blount’s disease. Some new aspects on an old problem. Pediatr Radiol. 1996;26:349-352.
22. Levine AM, Drennan JC. Physiological bowing and tibia vara. The metaphyseal-diaphyseal angle in the measurement of bowleg deformities. J Bone Joint Surg Am. 1982;64:1158-1163.
23. Kessel L. Annotations on the etiology and treatment of tibia vara. J Bone Joint Surg Br. 1970;52:93-99.
24. Blount WP. Tibia vara: osteochondrosis deformans tibiae. J Bone Joint Surg Am. 1937;19:1-29.
25. Davids JR, Blackhurst DW, Allen BL Jr. Radiographic evaluation of bowed legs in children. J Pediatr Orthop. 2001;21:257-263.
26. Cook SD, Lavernia CJ, Burke SW, et al. A biomechanical analysis of the etiology of tibia vara. J Pediatr Orthop. 1983;3:449-454.
27. Birch JG. Blount disease. J Am Acad Orthop Surg. 2013;21:408-418.
28. Bateson EM. Non-rachitic bow leg and knock-knee deformities in young Jamaican children. Br J Radiol. 1966;39:92-101.
29. Grantham-McGregor SM, Back EH. Gross motor development in Jamaican infants. Dev Med Child Neurol. 1971;13:79-87.
30. Størvold GV, Aarethun K, Bratberg GH. Age for onset of walking and prewalking strategies. Early Hum Dev. 2013;89:655-659.
31. Garrett M, McElroy AM, Staines A. Locomotor milestones and babywalkers: cross sectional study. BMJ. 2002;324:1494.
32. Simon GR, Baker C, Barden GA 3rd, et al; Committee on Practice and Ambulatory Medicine, Curry ES, Dunca PM, Hagan JF Jr, et al; Bright Futures Periodicity Schedule Workgroup. 2014 recommendations for pediatric preventive health care. Pediatrics. 2014;133:568-570.
1. Weiner DS. Pediatric orthopedics for primary care physicians. 2nd ed. Jones K, ed. Cambridge, United Kingdom: Cambridge University Press; 2004.
2. Carli A, Saran N, Kruijt J, et al. Physiological referrals for paediatric musculoskeletal complaints: a costly problem that needs to be addressed. Paediatr Child Health. 2012;17:e93-e97.
3. Fabry G. Clinical practice. Static, axial, and rotational deformities of the lower extremities in children. Eur J Pediatr. 2010;169:529-534.
4. Davids JR, Blackhurst DW, Allen Jr BL. Clinical evaluation of bowed legs in children. J Pediatr Orthop B. 2000;9:278-284.
5. Bateson EM. The relationship between Blount’s disease and bow legs. Br J Radiol. 1968;41:107-114.
6. Weiner DS. The natural history of “bow legs” and “knock knees” in childhood. Orthopedics. 1981;4:156-160.
7. Greene WB. Genu varum and genu valgum in children: differential diagnosis and guidelines for evaluation. Compr Ther. 1996;22:22-29.
8. Do TT. Clinical and radiographic evaluation of bowlegs. Curr Opin Pediatr. 2001;13:42-46.
9. Bleck EE. Developmental orthopaedics. III: Toddlers. Dev Med Child Neurol. 1982;24:533-555.
10. Brooks WC, Gross RH. Genu Varum in Children: Diagnosis and Treatment. J Am Acad Orthop Surg. 1995;3:326-335.
11. Greenberg LA, Swartz AA. Genu varum and genu valgum. Another look. Am J Dis Child. 1971;121:219-221.
12. Scherl SA. Common lower extremity problems in children. Pediatr Rev. 2004;25:52-62.
13. Wall EJ. Practical primary pediatric orthopedics. Nurs Clin North Am. 2000;35:95-113.
14. Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003;23:871-880.
15. McCarthy JJ, Betz RR, Kim A, et al. Early radiographic differentiation of infantile tibia vara from physiologic bowing using the femoral-tibial ratio. J Pediatr Orthop. 2001;21:545-548.
16. Salenius P, Vankka E. The development of the tibiofemoral angle in children. J Bone Joint Surg Am. 1975;57:259-261.
17. Engel GM, Staheli LT. The natural history of torsion and other factors influencing gait in childhood. A study of the angle of gait, tibial torsion, knee angle, hip rotation, and development of the arch in normal children. Clin Orthop Relat Res. 1974;99:12-17.
18. Golding J, Bateson E, McNeil-Smith G. Infantile tibia vara. In: The Growth Plate and Its Disorders. Rang M, ed. Baltimore, MD: Williams and Wilkins; 1969:109-119.
19. Greene WB. Infantile tibia vara. J Bone Joint Surg Am. 1993;75:130-143.
20. Golding J, McNeil-Smith JDG. Observations on the etiology of tibia vara. J Bone Joint Surg Br. 1963;45-B:320-325.
21. Eggert P, Viemann M. Physiological bowlegs or infantile Blount’s disease. Some new aspects on an old problem. Pediatr Radiol. 1996;26:349-352.
22. Levine AM, Drennan JC. Physiological bowing and tibia vara. The metaphyseal-diaphyseal angle in the measurement of bowleg deformities. J Bone Joint Surg Am. 1982;64:1158-1163.
23. Kessel L. Annotations on the etiology and treatment of tibia vara. J Bone Joint Surg Br. 1970;52:93-99.
24. Blount WP. Tibia vara: osteochondrosis deformans tibiae. J Bone Joint Surg Am. 1937;19:1-29.
25. Davids JR, Blackhurst DW, Allen BL Jr. Radiographic evaluation of bowed legs in children. J Pediatr Orthop. 2001;21:257-263.
26. Cook SD, Lavernia CJ, Burke SW, et al. A biomechanical analysis of the etiology of tibia vara. J Pediatr Orthop. 1983;3:449-454.
27. Birch JG. Blount disease. J Am Acad Orthop Surg. 2013;21:408-418.
28. Bateson EM. Non-rachitic bow leg and knock-knee deformities in young Jamaican children. Br J Radiol. 1966;39:92-101.
29. Grantham-McGregor SM, Back EH. Gross motor development in Jamaican infants. Dev Med Child Neurol. 1971;13:79-87.
30. Størvold GV, Aarethun K, Bratberg GH. Age for onset of walking and prewalking strategies. Early Hum Dev. 2013;89:655-659.
31. Garrett M, McElroy AM, Staines A. Locomotor milestones and babywalkers: cross sectional study. BMJ. 2002;324:1494.
32. Simon GR, Baker C, Barden GA 3rd, et al; Committee on Practice and Ambulatory Medicine, Curry ES, Dunca PM, Hagan JF Jr, et al; Bright Futures Periodicity Schedule Workgroup. 2014 recommendations for pediatric preventive health care. Pediatrics. 2014;133:568-570.
Assessment steps and treatment tips for ankle arthritis
CASE › A 57-year-old man had been experiencing intermittent pain in his left ankle for the past 2.5 years. About 6 weeks before coming to our clinic, his symptoms became significantly worse after playing a pickup game of basketball. At the clinic visit, he reported no other recent injury or trauma to the leg. However, 15 years earlier he had fractured his left ankle and was treated conservatively with a short period in a cast followed by a course of physical therapy. After completing the physical therapy, he noted significant improvement, although he continued to have minor episodes of pain. He felt no instability or mechanical locking but did note a decreased ability to move the ankle. And it felt much stiffer than his right ankle.
Examination of his left ankle revealed tenderness over the anterior aspect at the tibiotalar joint. He also exhibited decreased dorsiflexion and was unable to perform a toe raise. There was no tenderness over the major ligaments, and results of anterior drawer and talar tilt tests were normal. X-rays revealed tibiotalar joint arthritis (FIGURE).
How would you proceed if this were your patient?
Arthritis of the tibiotalar joint, which has an estimated prevalence of approximately 1%, occurs much less frequently than arthritis of the knee or hip joints.1 This low prevalence is primarily due to the ankle joint’s unique biomechanics and the features of the cartilage within the joint, including its thickness.2
Specifically, the hip and knee joints have greater degrees of freedom than the tibiotalar articulation, which is significantly constrained. The bony congruity between the talus, tibia, and fibula provides inherent stability to the ankle joint, thus protecting against primary osteoarthritis (OA).
Additionally, the large number of ligamentous structures and overall strength of the ligaments provide significant supplemental stability to the ankle joint articulation. Articular cartilage within the ankle joint is thicker than that of the knee and hip (1-1.7 mm). This cartilage also tends to retain its tensile strength with age, unlike cartilage in the hip; the ankle is therefore more resistant to age-related degeneration.3
Metabolic factors also protect against arthritis. Chondrocytes in the ankle are less responsive to inflammatory mediators, including interleukin-1 (IL-1), and therefore produce fewer matrix metalloproteinases.1,2,4 There are also fewer IL-1 receptors on ankle chondrocytes.
The role of trauma in ankle OA. Given the ankle joint’s inherent stability, the most common cause of ankle OA is trauma,4 mainly ankle fracture and, less commonly, ligamentous injury.5,6 Other rarer causes of ankle arthritis include primary OA, crystalline arthropathy, inflammatory disease, septic arthritis, neuroarthropathy, hemochromatosis, and ochronosis.
The ankle’s characteristics that protect it against primary OA may facilitate the pathogenesis of post-traumatic OA through 2 main mechanisms. First, direct trauma to the chondral surfaces can hasten the onset of progressive degeneration. Second, articular incongruity from a fracture can lead to insidious deterioration. The stiffer cartilage layer may be less adaptable to malalignment, and incongruity may cause secondary instability and chronic overloading. Ultimately, the joint breaks down with associated cartilage wear.6,7
The importance of the normal ankle’s congruity and stability became clear in the landmark study by Ramsey and colleagues,8 showing that the contact area between the talus and the tibia decreases as talar displacement increases laterally. This innate stability explains why the contact area of the ankle joint can bear loads similar to those of the hip and knee, yet does not experience primary OA nearly as often.
A stepwise diagnostic appraisal
Ask these questions. Since most ankle pain results from trauma, ask about any recent or remote injury to the affected ankle. Knowing the type of injury that occurred and the exact treatment, if received, may shed light on the relationship between the injury and current symptoms. Acute traumatic events can cause fractures or injury to various soft-tissue structures traversing the ankle joint. Ankle ligament sprains or tendon strains may result after abnormal rotation of the foot. Alternatively, chronic overuse injuries may lead to tendinopathy in any of the tendons that control motion throughout the foot and ankle or degenerative changes within the tibiotalar joint. Knowing the exact location of pain may also help identify the pathology (TABLE 1).
The patient in our case had not suffered a recent injury, so it was important to learn as much as possible about his prior fracture. Was the injury treated conservatively or surgically? If management was conservative, the type and duration of treatment could offer clues to the mechanism underlying symptoms. If a patient has undergone surgery, knowledge of the exact procedure could suggest specific problems. For example, surgical fixation would likely indicate there was ankle instability, thus altering the normal biomechanics in the injured tibiotalar joint.
Other key questions to ask. Most patients with ankle pain also complain of limitations in their usual activities. Ask about the duration and type of pain and other symptoms. Also ask about the position of the foot and ankle when the pain is at its greatest, which will provide insight into likely areas of pathology. For example, if pain arises when the patient navigates uneven ground, subtalar pathology is highly likely. If the patient complains of pain while walking down stairs, suspect injury to the posterior (plantar flexed) ankle; pain while walking up stairs more likely indicates anterior (dorsiflexed) pathology.
Finally, ask about nonorthopedic medical problems and all medications being taken. Systemic conditions, too, can lead to ankle pain—eg, inflammatory arthropathies, infections, and crystalline arthropathy.
Physical examination. Observe the patient’s gait to assess any functional or range-of-motion limitations or abnormal loading throughout the foot and ankle.9 With the patient standing, evaluate any malalignment from the foot through the knees and to the hips. Evaluate the skin for any lesions, wounds, or evidence of trauma or surgery. Next, with the patient seated, examine carefully for neuropathy or vascular abnormalities. Evaluate the ankle’s range of motion and assess for any mechanical locking, clicking, or crepitus. Palpate all bony and ligamentous landmarks to reveal areas of tenderness or swelling. Perform anterior drawer and varus tilt tests to determine overall ligamentous stability of the ankle, and compare your findings with test results of the opposite, uninjured ankle.
Diagnostic imaging. Order weight-bearing radiographs of the foot and ankle. Including the foot allows you to identify additional potential concerns such as malalignment, deformity, or adjacent joint arthritis. Look particularly for joint space narrowing, malalignment, post-traumatic changes, or implanted hardware. Advanced imaging studies—computerized tomography, magnetic resonance imaging, bone scan—are reserved for cases that necessitate ruling out alternative diagnoses, or for preoperative evaluation by an orthopedic surgeon.
Management: Make use of multiple modalities
Conservative management options for ankle OA are limited, and high-quality evidence of efficacy is lacking. Surgical alternatives, however, are invasive and yield modest outcomes. Therefore, unless specific indications for surgery are present, exhaust conservative options (TABLE 2) before considering referral.
Weight loss is important for those who are overweight—as with knee OA management—to decrease the reactive forces within the ankle joint and to decrease pain. Weight loss will also enhance the outcomes of other treatment modalities and improve overall health.10,11
Activity modification is usually required, even though this may make weight loss more difficult. Avoiding vigorous activities, restricting work-related movements that place high-impact stress on the ankle, and decreasing overall walking time often reduce the severity of symptoms and improve functioning in other activities. Use of assistive-devices, such as a cane, can decrease the weight-bearing load on the affected joint.10,11
Physical therapy has not been shown to alleviate pain in ankle arthritis, although stretching, joint mobilization, and gait training may help prevent further progression of arthritis and improve function.11 The strength of dorsiflexion and plantar-flexion muscles is often decreased in individuals with ankle arthritis. Strengthening exercises may be indicated in individuals exhibiting deficits.
Prescriptive conservative management. Begin with a combination, as needed, of anti-inflammatory medications, orthotic devices, and footwear modifications.
Nonsteroidal anti-inflammatory agents are generally safe, but long-term use requires monitoring. Intra-articular steroid injections have some supporting evidence of effectiveness, but any benefit is short-lived.12 Glucosamine and chondroitin, although unlikely to cause harm, are not supported by the evidence for use in ankle arthritis. Intra-articular viscosupplementation is controversial, and evidence is limited regarding its efficacy.1
Adding a rocker-bottom sole and a solid ankle cushion heel to a shoe helps decrease heel strike impact in individuals with decreased ankle motion, and they aid in the transition from the heel strike to the push-off during level walking.11 If the arthritic joint is unstable, a lace-up ankle support may help with proprioception and stability. A polypropylene ankle-foot orthosis, custom leather ankle corset, or a double-upright brace with a patellar-tendon-bearing support are options to restrict ankle motion and decrease weight-bearing forces.10,11
Immobilization is not recommended except for short-term use during an arthritic flare. Limiting ankle motion reduces pain, but the downside tradeoff is acquired stiffness and weakness that accompanies prolonged periods of immobilization. A controlled ankle motion walking boot or walking plaster cast are both reasonable options for the short term.
Consider surgical referral for specific indications such as osteophytes, loose bodies, and chondral defects, which may be treated with arthroscopy. Patients with large areas of exposed chondral bone or rapid onset of degeneration have poorer outcomes with conservative management and should also be referred to a surgeon earlier. Otherwise, consider surgical referral only after a full trial of conservative management.11
Surgical options vary in scope and effectiveness and include osteotomy, arthrodesis, and arthroplasty. Osteotomies can be performed in early OA to correct bony alignment deformities. Arthrodesis in neutral dorsiflexion with roughly 5 degrees of external rotation is reserved for end-stage ankle OA to allow for near normal gait and pain relief. Total ankle arthroplasty is an emerging option for severe ankle OA, resulting in improved pain relief, gait, and patient satisfaction, but potentially has a higher reoperation rate when compared with arthrodesis.1,2
CASE › We prescribed short-term immobilization with a controlled ankle motion boot and administered an intra-articular corticosteroid injection. At the patient’s follow-up visit 6 weeks later, he reported only moderate improvement in pain. We then advised physical therapy at a specialty ankle rehabilitation program to focus on mobilization, strengthening, and gait training. Nearly one year after his initial visit to our clinic, he is doing well. He understands, however, that the nature of his ankle arthrosis may necessitate surgical intervention in the future.
CORRESPONDENCE
Adam Bitterman, DO, Department of Orthopedic Surgery, Hofstra Northwell School of Medicine at Huntington Hospital, 155 East Main Street, Huntington, NY 11743; [email protected].
1. Valderrabano V, Horisberger M, Russell I, et al. Etiology of ankle osteoarthritis. Clin Orthop Relat Res. 2009;467:1800-1806.
2. Huch K, Kuettner KE, Dieppe P. Osteoarthritis in ankle and knee joints. Semin Arthritis Rheum. 1997;26:667-674.
3. Kempson GE. Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint. Biochim Biophys Acta. 1991;1075:223-230.
4. Saltzman CL, Salamon ML, Blanchard GM, et al. Epidemiology of ankle arthritis: Report of a consecutive series of 639 patients from a tertiary orthopaedic center. Iowa Orthop J. 2005;25:44-46.
5. Brown T, Johnston R, Saltzman C, et al. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20:739-744.
6. Barg A, Pagenstert G, Hügle T, et al. Ankle osteoarthritis etiology, diagnostics and classification. Foot Ankle Clin. 2013;18:411-426.
7. Schenker M, Mauck R, Ahn J, et al. Pathogenesis and prevention of posttraumatic osteoarthritis after intra-articular fracture. J Am Acad Orthop Surg. 2014;22:20-28.
8. Ramsey PL, Hamilton W. Changes in tibiotalar area of contact caused by lateral talar shift. J Bone Joint Surg Am. 1976;58:356-357.
9. Hayes BJ, Gonzalez T, Smith JT, et al. Ankle arthritis: you can’t always replace it. J Am Acad Orthop Surg. 2016;24:e29-e38.
10. Thomas R, Daniels T. Current concepts review ankle arthritis. J Bone Joint Surg Am. 2003;85A:923-936.
11. Martin RL, Stewart GW, Conti SF. Posttraumatic ankle arthritis: an update on conservative and surgical management. J Orthop Sports Phys Ther. 2007:37:253-259.
12. Pekarek B, Osher L, Buck S, et al. Intra-articular corticosteroid injections: a critical literature review with up-to-date findings. Foot. 2011;21:66-70.
13. Abate M, Schiavone C, Salini V. Hyaluronic acid in ankle arthritis: why evidence of efficacy is still lacking? Clin Exp Rheumatol. 2012;30:277-281.
14. Witteveen AG, Hofstad CJ, Kerkhoffs GM. Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle. Cochrane Database Syst Rev. 2015;(10):CD010643.
15. Rao S, Ellis SJ, Deland JT, et al. Nonmedicinal therapy in the management of ankle arthritis. Curr Opin Rheumatol. 2010;22:223-228.
CASE › A 57-year-old man had been experiencing intermittent pain in his left ankle for the past 2.5 years. About 6 weeks before coming to our clinic, his symptoms became significantly worse after playing a pickup game of basketball. At the clinic visit, he reported no other recent injury or trauma to the leg. However, 15 years earlier he had fractured his left ankle and was treated conservatively with a short period in a cast followed by a course of physical therapy. After completing the physical therapy, he noted significant improvement, although he continued to have minor episodes of pain. He felt no instability or mechanical locking but did note a decreased ability to move the ankle. And it felt much stiffer than his right ankle.
Examination of his left ankle revealed tenderness over the anterior aspect at the tibiotalar joint. He also exhibited decreased dorsiflexion and was unable to perform a toe raise. There was no tenderness over the major ligaments, and results of anterior drawer and talar tilt tests were normal. X-rays revealed tibiotalar joint arthritis (FIGURE).
How would you proceed if this were your patient?
Arthritis of the tibiotalar joint, which has an estimated prevalence of approximately 1%, occurs much less frequently than arthritis of the knee or hip joints.1 This low prevalence is primarily due to the ankle joint’s unique biomechanics and the features of the cartilage within the joint, including its thickness.2
Specifically, the hip and knee joints have greater degrees of freedom than the tibiotalar articulation, which is significantly constrained. The bony congruity between the talus, tibia, and fibula provides inherent stability to the ankle joint, thus protecting against primary osteoarthritis (OA).
Additionally, the large number of ligamentous structures and overall strength of the ligaments provide significant supplemental stability to the ankle joint articulation. Articular cartilage within the ankle joint is thicker than that of the knee and hip (1-1.7 mm). This cartilage also tends to retain its tensile strength with age, unlike cartilage in the hip; the ankle is therefore more resistant to age-related degeneration.3
Metabolic factors also protect against arthritis. Chondrocytes in the ankle are less responsive to inflammatory mediators, including interleukin-1 (IL-1), and therefore produce fewer matrix metalloproteinases.1,2,4 There are also fewer IL-1 receptors on ankle chondrocytes.
The role of trauma in ankle OA. Given the ankle joint’s inherent stability, the most common cause of ankle OA is trauma,4 mainly ankle fracture and, less commonly, ligamentous injury.5,6 Other rarer causes of ankle arthritis include primary OA, crystalline arthropathy, inflammatory disease, septic arthritis, neuroarthropathy, hemochromatosis, and ochronosis.
The ankle’s characteristics that protect it against primary OA may facilitate the pathogenesis of post-traumatic OA through 2 main mechanisms. First, direct trauma to the chondral surfaces can hasten the onset of progressive degeneration. Second, articular incongruity from a fracture can lead to insidious deterioration. The stiffer cartilage layer may be less adaptable to malalignment, and incongruity may cause secondary instability and chronic overloading. Ultimately, the joint breaks down with associated cartilage wear.6,7
The importance of the normal ankle’s congruity and stability became clear in the landmark study by Ramsey and colleagues,8 showing that the contact area between the talus and the tibia decreases as talar displacement increases laterally. This innate stability explains why the contact area of the ankle joint can bear loads similar to those of the hip and knee, yet does not experience primary OA nearly as often.
A stepwise diagnostic appraisal
Ask these questions. Since most ankle pain results from trauma, ask about any recent or remote injury to the affected ankle. Knowing the type of injury that occurred and the exact treatment, if received, may shed light on the relationship between the injury and current symptoms. Acute traumatic events can cause fractures or injury to various soft-tissue structures traversing the ankle joint. Ankle ligament sprains or tendon strains may result after abnormal rotation of the foot. Alternatively, chronic overuse injuries may lead to tendinopathy in any of the tendons that control motion throughout the foot and ankle or degenerative changes within the tibiotalar joint. Knowing the exact location of pain may also help identify the pathology (TABLE 1).
The patient in our case had not suffered a recent injury, so it was important to learn as much as possible about his prior fracture. Was the injury treated conservatively or surgically? If management was conservative, the type and duration of treatment could offer clues to the mechanism underlying symptoms. If a patient has undergone surgery, knowledge of the exact procedure could suggest specific problems. For example, surgical fixation would likely indicate there was ankle instability, thus altering the normal biomechanics in the injured tibiotalar joint.
Other key questions to ask. Most patients with ankle pain also complain of limitations in their usual activities. Ask about the duration and type of pain and other symptoms. Also ask about the position of the foot and ankle when the pain is at its greatest, which will provide insight into likely areas of pathology. For example, if pain arises when the patient navigates uneven ground, subtalar pathology is highly likely. If the patient complains of pain while walking down stairs, suspect injury to the posterior (plantar flexed) ankle; pain while walking up stairs more likely indicates anterior (dorsiflexed) pathology.
Finally, ask about nonorthopedic medical problems and all medications being taken. Systemic conditions, too, can lead to ankle pain—eg, inflammatory arthropathies, infections, and crystalline arthropathy.
Physical examination. Observe the patient’s gait to assess any functional or range-of-motion limitations or abnormal loading throughout the foot and ankle.9 With the patient standing, evaluate any malalignment from the foot through the knees and to the hips. Evaluate the skin for any lesions, wounds, or evidence of trauma or surgery. Next, with the patient seated, examine carefully for neuropathy or vascular abnormalities. Evaluate the ankle’s range of motion and assess for any mechanical locking, clicking, or crepitus. Palpate all bony and ligamentous landmarks to reveal areas of tenderness or swelling. Perform anterior drawer and varus tilt tests to determine overall ligamentous stability of the ankle, and compare your findings with test results of the opposite, uninjured ankle.
Diagnostic imaging. Order weight-bearing radiographs of the foot and ankle. Including the foot allows you to identify additional potential concerns such as malalignment, deformity, or adjacent joint arthritis. Look particularly for joint space narrowing, malalignment, post-traumatic changes, or implanted hardware. Advanced imaging studies—computerized tomography, magnetic resonance imaging, bone scan—are reserved for cases that necessitate ruling out alternative diagnoses, or for preoperative evaluation by an orthopedic surgeon.
Management: Make use of multiple modalities
Conservative management options for ankle OA are limited, and high-quality evidence of efficacy is lacking. Surgical alternatives, however, are invasive and yield modest outcomes. Therefore, unless specific indications for surgery are present, exhaust conservative options (TABLE 2) before considering referral.
Weight loss is important for those who are overweight—as with knee OA management—to decrease the reactive forces within the ankle joint and to decrease pain. Weight loss will also enhance the outcomes of other treatment modalities and improve overall health.10,11
Activity modification is usually required, even though this may make weight loss more difficult. Avoiding vigorous activities, restricting work-related movements that place high-impact stress on the ankle, and decreasing overall walking time often reduce the severity of symptoms and improve functioning in other activities. Use of assistive-devices, such as a cane, can decrease the weight-bearing load on the affected joint.10,11
Physical therapy has not been shown to alleviate pain in ankle arthritis, although stretching, joint mobilization, and gait training may help prevent further progression of arthritis and improve function.11 The strength of dorsiflexion and plantar-flexion muscles is often decreased in individuals with ankle arthritis. Strengthening exercises may be indicated in individuals exhibiting deficits.
Prescriptive conservative management. Begin with a combination, as needed, of anti-inflammatory medications, orthotic devices, and footwear modifications.
Nonsteroidal anti-inflammatory agents are generally safe, but long-term use requires monitoring. Intra-articular steroid injections have some supporting evidence of effectiveness, but any benefit is short-lived.12 Glucosamine and chondroitin, although unlikely to cause harm, are not supported by the evidence for use in ankle arthritis. Intra-articular viscosupplementation is controversial, and evidence is limited regarding its efficacy.1
Adding a rocker-bottom sole and a solid ankle cushion heel to a shoe helps decrease heel strike impact in individuals with decreased ankle motion, and they aid in the transition from the heel strike to the push-off during level walking.11 If the arthritic joint is unstable, a lace-up ankle support may help with proprioception and stability. A polypropylene ankle-foot orthosis, custom leather ankle corset, or a double-upright brace with a patellar-tendon-bearing support are options to restrict ankle motion and decrease weight-bearing forces.10,11
Immobilization is not recommended except for short-term use during an arthritic flare. Limiting ankle motion reduces pain, but the downside tradeoff is acquired stiffness and weakness that accompanies prolonged periods of immobilization. A controlled ankle motion walking boot or walking plaster cast are both reasonable options for the short term.
Consider surgical referral for specific indications such as osteophytes, loose bodies, and chondral defects, which may be treated with arthroscopy. Patients with large areas of exposed chondral bone or rapid onset of degeneration have poorer outcomes with conservative management and should also be referred to a surgeon earlier. Otherwise, consider surgical referral only after a full trial of conservative management.11
Surgical options vary in scope and effectiveness and include osteotomy, arthrodesis, and arthroplasty. Osteotomies can be performed in early OA to correct bony alignment deformities. Arthrodesis in neutral dorsiflexion with roughly 5 degrees of external rotation is reserved for end-stage ankle OA to allow for near normal gait and pain relief. Total ankle arthroplasty is an emerging option for severe ankle OA, resulting in improved pain relief, gait, and patient satisfaction, but potentially has a higher reoperation rate when compared with arthrodesis.1,2
CASE › We prescribed short-term immobilization with a controlled ankle motion boot and administered an intra-articular corticosteroid injection. At the patient’s follow-up visit 6 weeks later, he reported only moderate improvement in pain. We then advised physical therapy at a specialty ankle rehabilitation program to focus on mobilization, strengthening, and gait training. Nearly one year after his initial visit to our clinic, he is doing well. He understands, however, that the nature of his ankle arthrosis may necessitate surgical intervention in the future.
CORRESPONDENCE
Adam Bitterman, DO, Department of Orthopedic Surgery, Hofstra Northwell School of Medicine at Huntington Hospital, 155 East Main Street, Huntington, NY 11743; [email protected].
CASE › A 57-year-old man had been experiencing intermittent pain in his left ankle for the past 2.5 years. About 6 weeks before coming to our clinic, his symptoms became significantly worse after playing a pickup game of basketball. At the clinic visit, he reported no other recent injury or trauma to the leg. However, 15 years earlier he had fractured his left ankle and was treated conservatively with a short period in a cast followed by a course of physical therapy. After completing the physical therapy, he noted significant improvement, although he continued to have minor episodes of pain. He felt no instability or mechanical locking but did note a decreased ability to move the ankle. And it felt much stiffer than his right ankle.
Examination of his left ankle revealed tenderness over the anterior aspect at the tibiotalar joint. He also exhibited decreased dorsiflexion and was unable to perform a toe raise. There was no tenderness over the major ligaments, and results of anterior drawer and talar tilt tests were normal. X-rays revealed tibiotalar joint arthritis (FIGURE).
How would you proceed if this were your patient?
Arthritis of the tibiotalar joint, which has an estimated prevalence of approximately 1%, occurs much less frequently than arthritis of the knee or hip joints.1 This low prevalence is primarily due to the ankle joint’s unique biomechanics and the features of the cartilage within the joint, including its thickness.2
Specifically, the hip and knee joints have greater degrees of freedom than the tibiotalar articulation, which is significantly constrained. The bony congruity between the talus, tibia, and fibula provides inherent stability to the ankle joint, thus protecting against primary osteoarthritis (OA).
Additionally, the large number of ligamentous structures and overall strength of the ligaments provide significant supplemental stability to the ankle joint articulation. Articular cartilage within the ankle joint is thicker than that of the knee and hip (1-1.7 mm). This cartilage also tends to retain its tensile strength with age, unlike cartilage in the hip; the ankle is therefore more resistant to age-related degeneration.3
Metabolic factors also protect against arthritis. Chondrocytes in the ankle are less responsive to inflammatory mediators, including interleukin-1 (IL-1), and therefore produce fewer matrix metalloproteinases.1,2,4 There are also fewer IL-1 receptors on ankle chondrocytes.
The role of trauma in ankle OA. Given the ankle joint’s inherent stability, the most common cause of ankle OA is trauma,4 mainly ankle fracture and, less commonly, ligamentous injury.5,6 Other rarer causes of ankle arthritis include primary OA, crystalline arthropathy, inflammatory disease, septic arthritis, neuroarthropathy, hemochromatosis, and ochronosis.
The ankle’s characteristics that protect it against primary OA may facilitate the pathogenesis of post-traumatic OA through 2 main mechanisms. First, direct trauma to the chondral surfaces can hasten the onset of progressive degeneration. Second, articular incongruity from a fracture can lead to insidious deterioration. The stiffer cartilage layer may be less adaptable to malalignment, and incongruity may cause secondary instability and chronic overloading. Ultimately, the joint breaks down with associated cartilage wear.6,7
The importance of the normal ankle’s congruity and stability became clear in the landmark study by Ramsey and colleagues,8 showing that the contact area between the talus and the tibia decreases as talar displacement increases laterally. This innate stability explains why the contact area of the ankle joint can bear loads similar to those of the hip and knee, yet does not experience primary OA nearly as often.
A stepwise diagnostic appraisal
Ask these questions. Since most ankle pain results from trauma, ask about any recent or remote injury to the affected ankle. Knowing the type of injury that occurred and the exact treatment, if received, may shed light on the relationship between the injury and current symptoms. Acute traumatic events can cause fractures or injury to various soft-tissue structures traversing the ankle joint. Ankle ligament sprains or tendon strains may result after abnormal rotation of the foot. Alternatively, chronic overuse injuries may lead to tendinopathy in any of the tendons that control motion throughout the foot and ankle or degenerative changes within the tibiotalar joint. Knowing the exact location of pain may also help identify the pathology (TABLE 1).
The patient in our case had not suffered a recent injury, so it was important to learn as much as possible about his prior fracture. Was the injury treated conservatively or surgically? If management was conservative, the type and duration of treatment could offer clues to the mechanism underlying symptoms. If a patient has undergone surgery, knowledge of the exact procedure could suggest specific problems. For example, surgical fixation would likely indicate there was ankle instability, thus altering the normal biomechanics in the injured tibiotalar joint.
Other key questions to ask. Most patients with ankle pain also complain of limitations in their usual activities. Ask about the duration and type of pain and other symptoms. Also ask about the position of the foot and ankle when the pain is at its greatest, which will provide insight into likely areas of pathology. For example, if pain arises when the patient navigates uneven ground, subtalar pathology is highly likely. If the patient complains of pain while walking down stairs, suspect injury to the posterior (plantar flexed) ankle; pain while walking up stairs more likely indicates anterior (dorsiflexed) pathology.
Finally, ask about nonorthopedic medical problems and all medications being taken. Systemic conditions, too, can lead to ankle pain—eg, inflammatory arthropathies, infections, and crystalline arthropathy.
Physical examination. Observe the patient’s gait to assess any functional or range-of-motion limitations or abnormal loading throughout the foot and ankle.9 With the patient standing, evaluate any malalignment from the foot through the knees and to the hips. Evaluate the skin for any lesions, wounds, or evidence of trauma or surgery. Next, with the patient seated, examine carefully for neuropathy or vascular abnormalities. Evaluate the ankle’s range of motion and assess for any mechanical locking, clicking, or crepitus. Palpate all bony and ligamentous landmarks to reveal areas of tenderness or swelling. Perform anterior drawer and varus tilt tests to determine overall ligamentous stability of the ankle, and compare your findings with test results of the opposite, uninjured ankle.
Diagnostic imaging. Order weight-bearing radiographs of the foot and ankle. Including the foot allows you to identify additional potential concerns such as malalignment, deformity, or adjacent joint arthritis. Look particularly for joint space narrowing, malalignment, post-traumatic changes, or implanted hardware. Advanced imaging studies—computerized tomography, magnetic resonance imaging, bone scan—are reserved for cases that necessitate ruling out alternative diagnoses, or for preoperative evaluation by an orthopedic surgeon.
Management: Make use of multiple modalities
Conservative management options for ankle OA are limited, and high-quality evidence of efficacy is lacking. Surgical alternatives, however, are invasive and yield modest outcomes. Therefore, unless specific indications for surgery are present, exhaust conservative options (TABLE 2) before considering referral.
Weight loss is important for those who are overweight—as with knee OA management—to decrease the reactive forces within the ankle joint and to decrease pain. Weight loss will also enhance the outcomes of other treatment modalities and improve overall health.10,11
Activity modification is usually required, even though this may make weight loss more difficult. Avoiding vigorous activities, restricting work-related movements that place high-impact stress on the ankle, and decreasing overall walking time often reduce the severity of symptoms and improve functioning in other activities. Use of assistive-devices, such as a cane, can decrease the weight-bearing load on the affected joint.10,11
Physical therapy has not been shown to alleviate pain in ankle arthritis, although stretching, joint mobilization, and gait training may help prevent further progression of arthritis and improve function.11 The strength of dorsiflexion and plantar-flexion muscles is often decreased in individuals with ankle arthritis. Strengthening exercises may be indicated in individuals exhibiting deficits.
Prescriptive conservative management. Begin with a combination, as needed, of anti-inflammatory medications, orthotic devices, and footwear modifications.
Nonsteroidal anti-inflammatory agents are generally safe, but long-term use requires monitoring. Intra-articular steroid injections have some supporting evidence of effectiveness, but any benefit is short-lived.12 Glucosamine and chondroitin, although unlikely to cause harm, are not supported by the evidence for use in ankle arthritis. Intra-articular viscosupplementation is controversial, and evidence is limited regarding its efficacy.1
Adding a rocker-bottom sole and a solid ankle cushion heel to a shoe helps decrease heel strike impact in individuals with decreased ankle motion, and they aid in the transition from the heel strike to the push-off during level walking.11 If the arthritic joint is unstable, a lace-up ankle support may help with proprioception and stability. A polypropylene ankle-foot orthosis, custom leather ankle corset, or a double-upright brace with a patellar-tendon-bearing support are options to restrict ankle motion and decrease weight-bearing forces.10,11
Immobilization is not recommended except for short-term use during an arthritic flare. Limiting ankle motion reduces pain, but the downside tradeoff is acquired stiffness and weakness that accompanies prolonged periods of immobilization. A controlled ankle motion walking boot or walking plaster cast are both reasonable options for the short term.
Consider surgical referral for specific indications such as osteophytes, loose bodies, and chondral defects, which may be treated with arthroscopy. Patients with large areas of exposed chondral bone or rapid onset of degeneration have poorer outcomes with conservative management and should also be referred to a surgeon earlier. Otherwise, consider surgical referral only after a full trial of conservative management.11
Surgical options vary in scope and effectiveness and include osteotomy, arthrodesis, and arthroplasty. Osteotomies can be performed in early OA to correct bony alignment deformities. Arthrodesis in neutral dorsiflexion with roughly 5 degrees of external rotation is reserved for end-stage ankle OA to allow for near normal gait and pain relief. Total ankle arthroplasty is an emerging option for severe ankle OA, resulting in improved pain relief, gait, and patient satisfaction, but potentially has a higher reoperation rate when compared with arthrodesis.1,2
CASE › We prescribed short-term immobilization with a controlled ankle motion boot and administered an intra-articular corticosteroid injection. At the patient’s follow-up visit 6 weeks later, he reported only moderate improvement in pain. We then advised physical therapy at a specialty ankle rehabilitation program to focus on mobilization, strengthening, and gait training. Nearly one year after his initial visit to our clinic, he is doing well. He understands, however, that the nature of his ankle arthrosis may necessitate surgical intervention in the future.
CORRESPONDENCE
Adam Bitterman, DO, Department of Orthopedic Surgery, Hofstra Northwell School of Medicine at Huntington Hospital, 155 East Main Street, Huntington, NY 11743; [email protected].
1. Valderrabano V, Horisberger M, Russell I, et al. Etiology of ankle osteoarthritis. Clin Orthop Relat Res. 2009;467:1800-1806.
2. Huch K, Kuettner KE, Dieppe P. Osteoarthritis in ankle and knee joints. Semin Arthritis Rheum. 1997;26:667-674.
3. Kempson GE. Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint. Biochim Biophys Acta. 1991;1075:223-230.
4. Saltzman CL, Salamon ML, Blanchard GM, et al. Epidemiology of ankle arthritis: Report of a consecutive series of 639 patients from a tertiary orthopaedic center. Iowa Orthop J. 2005;25:44-46.
5. Brown T, Johnston R, Saltzman C, et al. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20:739-744.
6. Barg A, Pagenstert G, Hügle T, et al. Ankle osteoarthritis etiology, diagnostics and classification. Foot Ankle Clin. 2013;18:411-426.
7. Schenker M, Mauck R, Ahn J, et al. Pathogenesis and prevention of posttraumatic osteoarthritis after intra-articular fracture. J Am Acad Orthop Surg. 2014;22:20-28.
8. Ramsey PL, Hamilton W. Changes in tibiotalar area of contact caused by lateral talar shift. J Bone Joint Surg Am. 1976;58:356-357.
9. Hayes BJ, Gonzalez T, Smith JT, et al. Ankle arthritis: you can’t always replace it. J Am Acad Orthop Surg. 2016;24:e29-e38.
10. Thomas R, Daniels T. Current concepts review ankle arthritis. J Bone Joint Surg Am. 2003;85A:923-936.
11. Martin RL, Stewart GW, Conti SF. Posttraumatic ankle arthritis: an update on conservative and surgical management. J Orthop Sports Phys Ther. 2007:37:253-259.
12. Pekarek B, Osher L, Buck S, et al. Intra-articular corticosteroid injections: a critical literature review with up-to-date findings. Foot. 2011;21:66-70.
13. Abate M, Schiavone C, Salini V. Hyaluronic acid in ankle arthritis: why evidence of efficacy is still lacking? Clin Exp Rheumatol. 2012;30:277-281.
14. Witteveen AG, Hofstad CJ, Kerkhoffs GM. Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle. Cochrane Database Syst Rev. 2015;(10):CD010643.
15. Rao S, Ellis SJ, Deland JT, et al. Nonmedicinal therapy in the management of ankle arthritis. Curr Opin Rheumatol. 2010;22:223-228.
1. Valderrabano V, Horisberger M, Russell I, et al. Etiology of ankle osteoarthritis. Clin Orthop Relat Res. 2009;467:1800-1806.
2. Huch K, Kuettner KE, Dieppe P. Osteoarthritis in ankle and knee joints. Semin Arthritis Rheum. 1997;26:667-674.
3. Kempson GE. Age-related changes in the tensile properties of human articular cartilage: a comparative study between the femoral head of the hip joint and the talus of the ankle joint. Biochim Biophys Acta. 1991;1075:223-230.
4. Saltzman CL, Salamon ML, Blanchard GM, et al. Epidemiology of ankle arthritis: Report of a consecutive series of 639 patients from a tertiary orthopaedic center. Iowa Orthop J. 2005;25:44-46.
5. Brown T, Johnston R, Saltzman C, et al. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006;20:739-744.
6. Barg A, Pagenstert G, Hügle T, et al. Ankle osteoarthritis etiology, diagnostics and classification. Foot Ankle Clin. 2013;18:411-426.
7. Schenker M, Mauck R, Ahn J, et al. Pathogenesis and prevention of posttraumatic osteoarthritis after intra-articular fracture. J Am Acad Orthop Surg. 2014;22:20-28.
8. Ramsey PL, Hamilton W. Changes in tibiotalar area of contact caused by lateral talar shift. J Bone Joint Surg Am. 1976;58:356-357.
9. Hayes BJ, Gonzalez T, Smith JT, et al. Ankle arthritis: you can’t always replace it. J Am Acad Orthop Surg. 2016;24:e29-e38.
10. Thomas R, Daniels T. Current concepts review ankle arthritis. J Bone Joint Surg Am. 2003;85A:923-936.
11. Martin RL, Stewart GW, Conti SF. Posttraumatic ankle arthritis: an update on conservative and surgical management. J Orthop Sports Phys Ther. 2007:37:253-259.
12. Pekarek B, Osher L, Buck S, et al. Intra-articular corticosteroid injections: a critical literature review with up-to-date findings. Foot. 2011;21:66-70.
13. Abate M, Schiavone C, Salini V. Hyaluronic acid in ankle arthritis: why evidence of efficacy is still lacking? Clin Exp Rheumatol. 2012;30:277-281.
14. Witteveen AG, Hofstad CJ, Kerkhoffs GM. Hyaluronic acid and other conservative treatment options for osteoarthritis of the ankle. Cochrane Database Syst Rev. 2015;(10):CD010643.
15. Rao S, Ellis SJ, Deland JT, et al. Nonmedicinal therapy in the management of ankle arthritis. Curr Opin Rheumatol. 2010;22:223-228.
PRACTICE RECOMMENDATIONS
› Always ask that the foot be included in ankle x-rays to aid in identifying malalignment, deformity, or joint arthritis. C
› Use anti-inflammatory medications, orthotic devices, and footwear modifications, as needed, for ankle osteoarthritis. C
› Avoid ankle immobilization except, perhaps, during arthritic flare. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
A stepwise approach to pediatric asthma
Pediatric asthma is the most commonly encountered childhood chronic disease, occurring in approximately 13.5% of children.1 Due to the interplay between patient, family physician (FP), and the environment, asthma often proves challenging to control. Although national guidelines for the treatment of asthma have not changed since 2007, significant research continues to examine the optimal means of preventing, controlling, and treating asthma in children. This review summarizes the evidence to date so that you can maximize your care for these young patients.
A stepwise approach to asthma control
The 2007 National Heart, Lung, and Blood Institute (NHLBI) guidelines provide a common pathway for the management of asthma (FIGURE).2 These guidelines emphasize stepwise treatment, based on symptom severity, which maximizes quality of life while minimizing morbidity. Treatment is escalated after careful assessment of frequency of daytime symptoms, frequency of nighttime symptoms, forced expiratory volume in one second (FEV1), and the number of exacerbations requiring systemic steroids over the past year. It’s also appropriate to de-escalate care when symptoms are controlled to minimize adverse effects.
The 2017 Global Initiative for Asthma (GINA) guidelines recommend a similar stepwise approach, with generally the same progression of control medications as the NHLBI guidelines. One variation is that GINA guidelines recommend considering inhaled corticosteroids (ICS) for all asthma patients—even those with intermittent symptoms.3
The Asthma Control Test and Asthma Control Questionnaire are also available for assessment of efficacy of asthma control and can help guide FPs with the decision of when to escalate control medications. (They are available at: http://bit.ly/2o3CzGX and http://bit.ly/2p1LvAc, respectively.)
A systematic review found that both tools were effective in determining if a patient was well controlled vs not well controlled.4 Similarly, a 2012 study found that using the Asthma Control Test score was useful for assessing control and directing changes to treatment.5 In addition, using these tools consistently in a primary care setting increased the frequency of assessment without negatively impacting patient flow through a clinic.6
Short-acting beta-agonists: A mainstay for intermittent asthma
Inhaled short-acting beta-agonists (SABAs) are the mainstay of treatment for intermittent asthma as well as asthma exacerbations. Short-acting beta-agonists are effective for symptomatic relief and preventing exacerbations prior to known exposures because they dilate smooth muscle in bronchioles and relieve bronchospasm.
Albuterol, the most commonly used SABA, is a mixture of the active R-enantiomer and inactive L-enantiomer. Levalbuterol, which consists of only the active R-enantiomer, is also available and is theoretically more effective with fewer adverse effects. Studies examining the difference in efficacy between albuterol and levalbuterol, however, have been mixed, and current guidelines do not recommend one over the other.7
Metered-dose inhalers vs nebulizers
SABAs are typically prescribed in metered-dose inhalers (MDIs), dry powder inhalers, or nebulizers. A meta-analysis comparing the efficacy of nebulizers to MDIs with spacers in both the outpatient and emergency department (ED) settings indicated that MDIs work at least as well as nebulizers and may also reduce length of ED stay.8 This trend appears consistent even with children younger than 24 months.9
If you are prescribing an MDI, be sure to routinely prescribe spacers to help ensure the medication is properly administered. Various types of spacers are available; some consist of an extension of the mouthpiece, while others serve as a chamber with a one-way valve to help improve the ability of the child to inhale the medication. Spacers that do not have antistatic coating should be gently washed with water and detergent.
Masks are also available for younger children and should be properly sized. The same spacer can be used for multiple medications, although they should be administered one at a time. Generally, albuterol should be administered prior to other medications to maximize distribution of subsequent inhaled medications.
Start low with inhaled corticosteroids
Treatment of persistent asthma consists of regular use of inhaled corticosteroids (ICSs; first line) with SABAs, as needed, for exacerbations. Guidelines recommend starting at a low dose and increasing the dose based on symptom control. Patients must consistently use ICSs for one to 2 weeks prior to obtaining full effect of the medication, and parents should be counseled to set appropriate expectations.2,3 ICSs are dispensed as MDIs, dry powder inhalers, and nebulizers; spacers should be considered.
Studies have shown a slight decrease in height for children on ICSs, with long-term studies indicating a persistent 1- to 2-cm decrease in adult height.10,11
Patient isn’t well controlled? Time for a long-acting beta-agonist
For patients not well controlled on low-dose ICSs, the dose can be increased or a long-acting beta-agonist (LABA) or leukotriene receptor antagonist (LTRA) can be added. A recent meta-analysis examining children not well controlled with ICSs, found that the addition of LABAs resulted in improved FEV1 and nighttime symptoms, and reduced the requirement for rescue inhalers when compared to increasing the ICS dose alone.12 In addition, there was no difference in adverse events between the 2 agents, although patients taking ICSs and LABAs had greater growth in height than those with an increased dose of ICS.12 Adding a LABA, however, did not decrease the need for systemic steroids and also did not reduce the number of exacerbations requiring hospitalizations.12
Another recent study demonstrated that the combination of ICSs and LABAs was noninferior to ICSs alone in preventing hospitalizations, intubations, and deaths.13 There are limited data on whether patients already on LABAs and ICSs should be continued on dual medications. Additionally, there is no clear method describing how to de-escalate therapy for those patients who are well controlled on ICSs and LABAs. A reasonable approach is to reduce doses of both medications and discontinue the LABA if tolerated.14,15 The US Food and Drug Administration has issued a black box warning that LABAs should not be used as a single controller medication because patients may be at increased risk of asthma-related deaths.16,17
What role for leukotriene receptor antagonists?
According to NHLBI guidelines, LTRAs can be considered as an alternative to ICSs when starting a control medication for mild persistent asthma.2 A recent meta-analysis, however, showed that there were increased rates of hospitalizations with LTRAs alone when compared to ICSs.18 The NHLBI guidelines also suggest that LTRAs can be used as adjunctive medication for those patients not well controlled on ICSs rather than increasing the ICS dose or adding a LABA.2
A 2011 clinical trial found no difference in quality of life measures between LTRAs and LABAs as adjunctive therapy at 2 months, but LABAs were more effective when patients were reassessed in 2 years.19 Similarly, the same study also found that adding LTRAs to low-dose ICSs rather than increasing the ICS dose was equivalent in the short term but not at 2 years.19
2 other adjunctive therapy options: Xanthines, cromolyn
Similar to LTRAs, xanthines can be considered as adjunctive therapy for children older than 5 years who are not well controlled on a low-dose ICS. Although xanthines decrease asthma symptoms when compared to placebo alone, they are not more effective than ICSs alone and should be considered only as adjunctive therapy.2,20 There have been few studies comparing xanthines to other adjunctive medications.21
Cromolyn is another adjunctive medication cited in the NHLBI guidelines for escalation of therapy.2 Although the medication has few adverse effects, its use is generally limited in the United States because data supporting its efficacy are lacking.
Omalizumab for allergy-related asthma exacerbations
Omalizumab, an anti-IgE antibody injected every 2 to 4 weeks, is available for children older than 6 years with moderate to severe asthma that is not responsive to ICSs and LABAs.22 The medication is effective in reducing allergy-related asthma exacerbations and hospitalizations, but data comparing it to other adjunctive medications are limited.22 Due to their significant systemic effects, the role of oral steroids as control medications is reserved for patients with severe asthma who are refractory to other medications. Children should be placed on oral steroids for the least amount of time required to achieve symptom control.
Acute exacerbation treatment: What to consider
Although there is no agreed-upon definition for an acute asthma exacerbation, the American Thoracic Society defines it as "an event characterized by a change from the patient’s previous status."23 All patients should be given an asthma action plan that clearly delineates the escalation of therapy in the event of an exacerbation, although only half of all patients report experiencing one.24 Symptom-based plans may prevent more acute care visits when compared to plans that use peak-flow measurements, although children on peak-flow plans may have fewer symptomatic days.25
Start with short-acting beta-agonists
The SABAs serve as the initial treatment of choice for management of asthma exacerbations. In young children (0-3 years), SABAs delivered by MDI with a spacer were more effective in reducing admission rates (11.3% vs 21.7%) when compared to SABAs delivered by nebulizers, resulting in a number needed to treat to prevent one admission of 10.26
In older children (3-18 years), SABAs delivered via spacer reduced ED length of stay, but did not significantly affect hospitalization rates. Additionally, SABAs administered with anticholinergics such as ipratropium bromide were more effective than SABAs alone in reducing admissions (16.9% vs 23.2%), particularly in older children with moderate to severe asthma, while also minimizing adverse effects.8,26
Corticosteroids: A mainstay in the ED
In addition to albuterol administration, corticosteroids remain the mainstay of ED management for asthma exacerbations. Administration of systemic steroids has been shown to reduce hospitalizations in children under 6 years, although, paradoxically, studies examining outpatient administration have demonstrated an increase in hospitalizations when compared to placebo.27
Dexamethasone and prednisone are the 2 most commonly used systemic steroids, and studies haven't indicated superiority of either.28,29 There is no difference in efficacy between oral and intravenous steroids.30 A recent clinical trial found a 2-day course of dexamethasone (0.6 mg/kg) had similar efficacy with fewer adverse effects when compared to a 5-day course of prednisone (1-2 mg/kg/day).28
Patient isn’t responding? Try IV magnesium
For patients who don't respond to corticosteroids and albuterol treatments, IV magnesium sulfate (usual dose, 25-75 mg/kg/d; maximum dose, 2000 mg/d) has been shown to improve respiratory function, but not necessarily decrease admission rates.31 Inhaled magnesium sulfate hasn't been shown to be more effective than IV administration and isn'trecommended.32
Evidence doesn’t support use of heliox
Heliox, which consists of 80% helium, is theorized to be effective in the treatment of asthma by increasing laminar flow and increasing the delivery of medications to the alveoli.32 Overall, the evidence does not support the use of heliox, which is typically restricted to patients with severe asthma exacerbations.33
Is it worth considering noninvasive positive pressure ventilation?
If patients don't improve with medical treatment, noninvasive positive pressure ventilation can be considered. A recent meta-analysis suggests that there is no definitive benefit or harm from this treatment, although several studies have indicated a decrease in symptom severity.34
Intubation should be considered for hypoxemia unresponsive to medications, or in cases of exhaustion, worsening mental status, or respiratory acidosis unresponsive to medication. Ventilation should allow for a permissive respiratory acidosis (pH, 7.2), while maintaining adequate oxygenation.35
Reducing the burden of asthma
Due to the complex task of reducing triggers and providing effective controller medications, working with parents and children is integral to improving the quality of life for patients with asthma. Although there is an obvious genetic predisposition, family physicians can help reduce the risk of developing asthma by encouraging healthy behaviors at home before the child is born. In the prenatal period, this includes avoiding tobacco-smoke exposure, lessening maternal obesity, decreasing maternal antibiotic and acetaminophen use, and curtailing stress.
Evidence suggests that after birth, breastfeeding and reducing childhood obesity can help lower the risk of asthma.36 Atopic disease, in general, can be reduced by breastfeeding until at least 4 months, as well as encouraging a varied diet that does not restrict potential allergens during pregnancy or lactation, and introducing foods (including potential allergens) after the age of 4 months.
The risk of atopic disease can also be lowered by lessening potential triggers at home. These include restricting exposure to cats (but not dogs), reducing home mold by decreasing humidity and ensuring adequate ventilation, avoiding volatile organic compounds, such as chlorine, and curtailing exposure to vehicle emissions. Although often marketed to be effective in reducing allergies, dust-mite covers and soy-based formulas don't prevent or minimize allergies and are often costly.37,38 In addition, there is no evidence that vaccinations areassociated with allergies.39
CORRESPONDENCE
Douglas M. Maurer, 9040A Jackson Ave, Joint-Base Lewis-McChord, WA 98431; [email protected].
1. US Department of Health and Human Services. Centers for Disease Control and Prevention. Asthma and Schools. Available at: www.cdc.gov/healthyschools/asthma/index.htm. Updated June 17, 2015. Accessed September 28, 2016.
2. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. Bethesda, Md: National Heart, Lung, and Blood Institute; 2007. Report No.:07-4051.
3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. Available at: www.ginasthma.org. Accessed April 11, 2017.
4. Jia CE, Zhang HP, Lv Y, et al. The asthma control test and asthma control questionnaire for assessing asthma control: systematic review and meta-analysis. J Allergy Clin Immunol. 2013;131:695-703.
5. Ko FW, Hui DS, Leung TS, et al. Evaluation of the asthma control test: a reliable determinant of disease stability and a predictor of future exacerbations. Respirology. 2012;17: 370-378.
6. Sudhanthar S, Thakur K, Sigal Y, et al. Improving asthma severity and control screening in a primary care pediatric practice. BMJ Qual Improv Rep. 2016;5
7. Wilkinson M, Bulloch B, Garcia-Filion P, et al. Efficacy of racemic albuterol versus levalbuterol used as a continuous nebulization for the treatment of acute asthma exacerbations: a randomized, double-blind, clinical trial. J Asthma. 2011;48:188-193.
8. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;19.
9. Delgado A, Chou KJ, Silver EJ, et al. Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department. Arch Pediatr Adolesc Med. 2003;157:76-80.
10. Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904-912.
11. Loke YK, Blanco P, Thavarajh M, et al. Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis. PLoS ONE. 2015;10:e0133428.
12. Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015;24:CD007949.
13. Stempel DA, Szefler SJ, Pedersen S, et al; VESTRI Investigators. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016;375:840-849.
14. Blair MM. PL Detail-Document, Safety of long-acting beta-agonists in asthma. Pharmacist’s Letter/Prescriber’s Letter. November 2012.
15. Kew KM, Beggs S, Ahmad S. Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015;5:CD011316.
16. Nelson HS, Weiss ST, Bleecker ER, et al; SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.
17. US Food and Drug Administration. FDA Drug Safety Communication: new safety requirements for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs). Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200776.htm. Accessed December 23, 2016.
18. Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev. 2012;5:CD002314.
19. Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med. 2011;364:1695-1707.
20. Seddon P, Bara A, Ducharme FM, et al. Oral xanthines as maintenance treatment for asthma in children. Cochrane Database Syst Rev. 2006;1:CD002885.
21. van der Mark LB, Lyklema PHE, Geskus RB, et al. A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four. BMC Pulm Med. 2012;12:63.
22. Normansell R, Walker S, Milan SJ. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.
23. Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society Statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180:59-99.
24. Simon AE, Akinbami LJ. Asthma action plan receipt among children with asthma 2-17 years of age, United States, 2002-2013. J Pediatr. 2016;171:283-289.
25. Bhogal SK, Zemek R, Ducharme FM. Written action plans for asthma in children. Cochrane Database Syst Rev. 2006;3: CD005306.
26. Pollock M, Sinha IP, Hartling L, et al. Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews. Allergy. 2017;72:183-200.
27. Castro-Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: systematic review with meta-analysis. Pediatr Pulmonol. 2016;51:868-876.
28. Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133:493-499.
29. Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev. 2016;5:CD011801.
30. Rowe BH, Keller JL, Oxman AD. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med. 1992;10:301-310.
31. Rowe BH, Bretzlaff J, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000;1:CD001490.
32. Powell C, Dwan K, Milan SJ, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2012;12:CD003898.
33. Rodrigo GJ, Pollack CV, Rodrigo C, et al. Heliox for non-intubated acute asthma patients. Cochrane Database Syst Rev. 2006;4:CD002884.
34. Korang SK, Feinberg J, Wetterslev J, et al. Non-invasive positive pressure ventilation for acute asthma in children. Cochrane Database System Rev. 2016;9:CD012067.
35. Kline-Krammes S, Patel NH, Robinson S. Childhood asthma: a guide for pediatric emergency medicine providers. Emerg Med Clin North Am. 2013;31:705-732.
36. Castro-Rodriguez JA, Forno E, Rodriguez-Martinez CE, et al. Risk and protective factors for childhood asthma: what is the evidence? J Allergy Clin Immunol Pract. 2016;4:1111-1122.
37. Gøtzsche P, Johansen HK. House dust mite control measures for asthma. Cochrane Database Syst Rev. 2008;2:1465-1858.
38. Osborn DA, Sinn JKH. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database of Syst Rev. 2006;4:1465-1858.
39. Schäfer T, Bauer CP, Beyer K, et al. S3-Guideline on allergy prevention: 2014 update: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German society for Pediatric and Adolescent Medicine (DGKJ). Allegro J Int. 2014;23:186-199.
Pediatric asthma is the most commonly encountered childhood chronic disease, occurring in approximately 13.5% of children.1 Due to the interplay between patient, family physician (FP), and the environment, asthma often proves challenging to control. Although national guidelines for the treatment of asthma have not changed since 2007, significant research continues to examine the optimal means of preventing, controlling, and treating asthma in children. This review summarizes the evidence to date so that you can maximize your care for these young patients.
A stepwise approach to asthma control
The 2007 National Heart, Lung, and Blood Institute (NHLBI) guidelines provide a common pathway for the management of asthma (FIGURE).2 These guidelines emphasize stepwise treatment, based on symptom severity, which maximizes quality of life while minimizing morbidity. Treatment is escalated after careful assessment of frequency of daytime symptoms, frequency of nighttime symptoms, forced expiratory volume in one second (FEV1), and the number of exacerbations requiring systemic steroids over the past year. It’s also appropriate to de-escalate care when symptoms are controlled to minimize adverse effects.
The 2017 Global Initiative for Asthma (GINA) guidelines recommend a similar stepwise approach, with generally the same progression of control medications as the NHLBI guidelines. One variation is that GINA guidelines recommend considering inhaled corticosteroids (ICS) for all asthma patients—even those with intermittent symptoms.3
The Asthma Control Test and Asthma Control Questionnaire are also available for assessment of efficacy of asthma control and can help guide FPs with the decision of when to escalate control medications. (They are available at: http://bit.ly/2o3CzGX and http://bit.ly/2p1LvAc, respectively.)
A systematic review found that both tools were effective in determining if a patient was well controlled vs not well controlled.4 Similarly, a 2012 study found that using the Asthma Control Test score was useful for assessing control and directing changes to treatment.5 In addition, using these tools consistently in a primary care setting increased the frequency of assessment without negatively impacting patient flow through a clinic.6
Short-acting beta-agonists: A mainstay for intermittent asthma
Inhaled short-acting beta-agonists (SABAs) are the mainstay of treatment for intermittent asthma as well as asthma exacerbations. Short-acting beta-agonists are effective for symptomatic relief and preventing exacerbations prior to known exposures because they dilate smooth muscle in bronchioles and relieve bronchospasm.
Albuterol, the most commonly used SABA, is a mixture of the active R-enantiomer and inactive L-enantiomer. Levalbuterol, which consists of only the active R-enantiomer, is also available and is theoretically more effective with fewer adverse effects. Studies examining the difference in efficacy between albuterol and levalbuterol, however, have been mixed, and current guidelines do not recommend one over the other.7
Metered-dose inhalers vs nebulizers
SABAs are typically prescribed in metered-dose inhalers (MDIs), dry powder inhalers, or nebulizers. A meta-analysis comparing the efficacy of nebulizers to MDIs with spacers in both the outpatient and emergency department (ED) settings indicated that MDIs work at least as well as nebulizers and may also reduce length of ED stay.8 This trend appears consistent even with children younger than 24 months.9
If you are prescribing an MDI, be sure to routinely prescribe spacers to help ensure the medication is properly administered. Various types of spacers are available; some consist of an extension of the mouthpiece, while others serve as a chamber with a one-way valve to help improve the ability of the child to inhale the medication. Spacers that do not have antistatic coating should be gently washed with water and detergent.
Masks are also available for younger children and should be properly sized. The same spacer can be used for multiple medications, although they should be administered one at a time. Generally, albuterol should be administered prior to other medications to maximize distribution of subsequent inhaled medications.
Start low with inhaled corticosteroids
Treatment of persistent asthma consists of regular use of inhaled corticosteroids (ICSs; first line) with SABAs, as needed, for exacerbations. Guidelines recommend starting at a low dose and increasing the dose based on symptom control. Patients must consistently use ICSs for one to 2 weeks prior to obtaining full effect of the medication, and parents should be counseled to set appropriate expectations.2,3 ICSs are dispensed as MDIs, dry powder inhalers, and nebulizers; spacers should be considered.
Studies have shown a slight decrease in height for children on ICSs, with long-term studies indicating a persistent 1- to 2-cm decrease in adult height.10,11
Patient isn’t well controlled? Time for a long-acting beta-agonist
For patients not well controlled on low-dose ICSs, the dose can be increased or a long-acting beta-agonist (LABA) or leukotriene receptor antagonist (LTRA) can be added. A recent meta-analysis examining children not well controlled with ICSs, found that the addition of LABAs resulted in improved FEV1 and nighttime symptoms, and reduced the requirement for rescue inhalers when compared to increasing the ICS dose alone.12 In addition, there was no difference in adverse events between the 2 agents, although patients taking ICSs and LABAs had greater growth in height than those with an increased dose of ICS.12 Adding a LABA, however, did not decrease the need for systemic steroids and also did not reduce the number of exacerbations requiring hospitalizations.12
Another recent study demonstrated that the combination of ICSs and LABAs was noninferior to ICSs alone in preventing hospitalizations, intubations, and deaths.13 There are limited data on whether patients already on LABAs and ICSs should be continued on dual medications. Additionally, there is no clear method describing how to de-escalate therapy for those patients who are well controlled on ICSs and LABAs. A reasonable approach is to reduce doses of both medications and discontinue the LABA if tolerated.14,15 The US Food and Drug Administration has issued a black box warning that LABAs should not be used as a single controller medication because patients may be at increased risk of asthma-related deaths.16,17
What role for leukotriene receptor antagonists?
According to NHLBI guidelines, LTRAs can be considered as an alternative to ICSs when starting a control medication for mild persistent asthma.2 A recent meta-analysis, however, showed that there were increased rates of hospitalizations with LTRAs alone when compared to ICSs.18 The NHLBI guidelines also suggest that LTRAs can be used as adjunctive medication for those patients not well controlled on ICSs rather than increasing the ICS dose or adding a LABA.2
A 2011 clinical trial found no difference in quality of life measures between LTRAs and LABAs as adjunctive therapy at 2 months, but LABAs were more effective when patients were reassessed in 2 years.19 Similarly, the same study also found that adding LTRAs to low-dose ICSs rather than increasing the ICS dose was equivalent in the short term but not at 2 years.19
2 other adjunctive therapy options: Xanthines, cromolyn
Similar to LTRAs, xanthines can be considered as adjunctive therapy for children older than 5 years who are not well controlled on a low-dose ICS. Although xanthines decrease asthma symptoms when compared to placebo alone, they are not more effective than ICSs alone and should be considered only as adjunctive therapy.2,20 There have been few studies comparing xanthines to other adjunctive medications.21
Cromolyn is another adjunctive medication cited in the NHLBI guidelines for escalation of therapy.2 Although the medication has few adverse effects, its use is generally limited in the United States because data supporting its efficacy are lacking.
Omalizumab for allergy-related asthma exacerbations
Omalizumab, an anti-IgE antibody injected every 2 to 4 weeks, is available for children older than 6 years with moderate to severe asthma that is not responsive to ICSs and LABAs.22 The medication is effective in reducing allergy-related asthma exacerbations and hospitalizations, but data comparing it to other adjunctive medications are limited.22 Due to their significant systemic effects, the role of oral steroids as control medications is reserved for patients with severe asthma who are refractory to other medications. Children should be placed on oral steroids for the least amount of time required to achieve symptom control.
Acute exacerbation treatment: What to consider
Although there is no agreed-upon definition for an acute asthma exacerbation, the American Thoracic Society defines it as "an event characterized by a change from the patient’s previous status."23 All patients should be given an asthma action plan that clearly delineates the escalation of therapy in the event of an exacerbation, although only half of all patients report experiencing one.24 Symptom-based plans may prevent more acute care visits when compared to plans that use peak-flow measurements, although children on peak-flow plans may have fewer symptomatic days.25
Start with short-acting beta-agonists
The SABAs serve as the initial treatment of choice for management of asthma exacerbations. In young children (0-3 years), SABAs delivered by MDI with a spacer were more effective in reducing admission rates (11.3% vs 21.7%) when compared to SABAs delivered by nebulizers, resulting in a number needed to treat to prevent one admission of 10.26
In older children (3-18 years), SABAs delivered via spacer reduced ED length of stay, but did not significantly affect hospitalization rates. Additionally, SABAs administered with anticholinergics such as ipratropium bromide were more effective than SABAs alone in reducing admissions (16.9% vs 23.2%), particularly in older children with moderate to severe asthma, while also minimizing adverse effects.8,26
Corticosteroids: A mainstay in the ED
In addition to albuterol administration, corticosteroids remain the mainstay of ED management for asthma exacerbations. Administration of systemic steroids has been shown to reduce hospitalizations in children under 6 years, although, paradoxically, studies examining outpatient administration have demonstrated an increase in hospitalizations when compared to placebo.27
Dexamethasone and prednisone are the 2 most commonly used systemic steroids, and studies haven't indicated superiority of either.28,29 There is no difference in efficacy between oral and intravenous steroids.30 A recent clinical trial found a 2-day course of dexamethasone (0.6 mg/kg) had similar efficacy with fewer adverse effects when compared to a 5-day course of prednisone (1-2 mg/kg/day).28
Patient isn’t responding? Try IV magnesium
For patients who don't respond to corticosteroids and albuterol treatments, IV magnesium sulfate (usual dose, 25-75 mg/kg/d; maximum dose, 2000 mg/d) has been shown to improve respiratory function, but not necessarily decrease admission rates.31 Inhaled magnesium sulfate hasn't been shown to be more effective than IV administration and isn'trecommended.32
Evidence doesn’t support use of heliox
Heliox, which consists of 80% helium, is theorized to be effective in the treatment of asthma by increasing laminar flow and increasing the delivery of medications to the alveoli.32 Overall, the evidence does not support the use of heliox, which is typically restricted to patients with severe asthma exacerbations.33
Is it worth considering noninvasive positive pressure ventilation?
If patients don't improve with medical treatment, noninvasive positive pressure ventilation can be considered. A recent meta-analysis suggests that there is no definitive benefit or harm from this treatment, although several studies have indicated a decrease in symptom severity.34
Intubation should be considered for hypoxemia unresponsive to medications, or in cases of exhaustion, worsening mental status, or respiratory acidosis unresponsive to medication. Ventilation should allow for a permissive respiratory acidosis (pH, 7.2), while maintaining adequate oxygenation.35
Reducing the burden of asthma
Due to the complex task of reducing triggers and providing effective controller medications, working with parents and children is integral to improving the quality of life for patients with asthma. Although there is an obvious genetic predisposition, family physicians can help reduce the risk of developing asthma by encouraging healthy behaviors at home before the child is born. In the prenatal period, this includes avoiding tobacco-smoke exposure, lessening maternal obesity, decreasing maternal antibiotic and acetaminophen use, and curtailing stress.
Evidence suggests that after birth, breastfeeding and reducing childhood obesity can help lower the risk of asthma.36 Atopic disease, in general, can be reduced by breastfeeding until at least 4 months, as well as encouraging a varied diet that does not restrict potential allergens during pregnancy or lactation, and introducing foods (including potential allergens) after the age of 4 months.
The risk of atopic disease can also be lowered by lessening potential triggers at home. These include restricting exposure to cats (but not dogs), reducing home mold by decreasing humidity and ensuring adequate ventilation, avoiding volatile organic compounds, such as chlorine, and curtailing exposure to vehicle emissions. Although often marketed to be effective in reducing allergies, dust-mite covers and soy-based formulas don't prevent or minimize allergies and are often costly.37,38 In addition, there is no evidence that vaccinations areassociated with allergies.39
CORRESPONDENCE
Douglas M. Maurer, 9040A Jackson Ave, Joint-Base Lewis-McChord, WA 98431; [email protected].
Pediatric asthma is the most commonly encountered childhood chronic disease, occurring in approximately 13.5% of children.1 Due to the interplay between patient, family physician (FP), and the environment, asthma often proves challenging to control. Although national guidelines for the treatment of asthma have not changed since 2007, significant research continues to examine the optimal means of preventing, controlling, and treating asthma in children. This review summarizes the evidence to date so that you can maximize your care for these young patients.
A stepwise approach to asthma control
The 2007 National Heart, Lung, and Blood Institute (NHLBI) guidelines provide a common pathway for the management of asthma (FIGURE).2 These guidelines emphasize stepwise treatment, based on symptom severity, which maximizes quality of life while minimizing morbidity. Treatment is escalated after careful assessment of frequency of daytime symptoms, frequency of nighttime symptoms, forced expiratory volume in one second (FEV1), and the number of exacerbations requiring systemic steroids over the past year. It’s also appropriate to de-escalate care when symptoms are controlled to minimize adverse effects.
The 2017 Global Initiative for Asthma (GINA) guidelines recommend a similar stepwise approach, with generally the same progression of control medications as the NHLBI guidelines. One variation is that GINA guidelines recommend considering inhaled corticosteroids (ICS) for all asthma patients—even those with intermittent symptoms.3
The Asthma Control Test and Asthma Control Questionnaire are also available for assessment of efficacy of asthma control and can help guide FPs with the decision of when to escalate control medications. (They are available at: http://bit.ly/2o3CzGX and http://bit.ly/2p1LvAc, respectively.)
A systematic review found that both tools were effective in determining if a patient was well controlled vs not well controlled.4 Similarly, a 2012 study found that using the Asthma Control Test score was useful for assessing control and directing changes to treatment.5 In addition, using these tools consistently in a primary care setting increased the frequency of assessment without negatively impacting patient flow through a clinic.6
Short-acting beta-agonists: A mainstay for intermittent asthma
Inhaled short-acting beta-agonists (SABAs) are the mainstay of treatment for intermittent asthma as well as asthma exacerbations. Short-acting beta-agonists are effective for symptomatic relief and preventing exacerbations prior to known exposures because they dilate smooth muscle in bronchioles and relieve bronchospasm.
Albuterol, the most commonly used SABA, is a mixture of the active R-enantiomer and inactive L-enantiomer. Levalbuterol, which consists of only the active R-enantiomer, is also available and is theoretically more effective with fewer adverse effects. Studies examining the difference in efficacy between albuterol and levalbuterol, however, have been mixed, and current guidelines do not recommend one over the other.7
Metered-dose inhalers vs nebulizers
SABAs are typically prescribed in metered-dose inhalers (MDIs), dry powder inhalers, or nebulizers. A meta-analysis comparing the efficacy of nebulizers to MDIs with spacers in both the outpatient and emergency department (ED) settings indicated that MDIs work at least as well as nebulizers and may also reduce length of ED stay.8 This trend appears consistent even with children younger than 24 months.9
If you are prescribing an MDI, be sure to routinely prescribe spacers to help ensure the medication is properly administered. Various types of spacers are available; some consist of an extension of the mouthpiece, while others serve as a chamber with a one-way valve to help improve the ability of the child to inhale the medication. Spacers that do not have antistatic coating should be gently washed with water and detergent.
Masks are also available for younger children and should be properly sized. The same spacer can be used for multiple medications, although they should be administered one at a time. Generally, albuterol should be administered prior to other medications to maximize distribution of subsequent inhaled medications.
Start low with inhaled corticosteroids
Treatment of persistent asthma consists of regular use of inhaled corticosteroids (ICSs; first line) with SABAs, as needed, for exacerbations. Guidelines recommend starting at a low dose and increasing the dose based on symptom control. Patients must consistently use ICSs for one to 2 weeks prior to obtaining full effect of the medication, and parents should be counseled to set appropriate expectations.2,3 ICSs are dispensed as MDIs, dry powder inhalers, and nebulizers; spacers should be considered.
Studies have shown a slight decrease in height for children on ICSs, with long-term studies indicating a persistent 1- to 2-cm decrease in adult height.10,11
Patient isn’t well controlled? Time for a long-acting beta-agonist
For patients not well controlled on low-dose ICSs, the dose can be increased or a long-acting beta-agonist (LABA) or leukotriene receptor antagonist (LTRA) can be added. A recent meta-analysis examining children not well controlled with ICSs, found that the addition of LABAs resulted in improved FEV1 and nighttime symptoms, and reduced the requirement for rescue inhalers when compared to increasing the ICS dose alone.12 In addition, there was no difference in adverse events between the 2 agents, although patients taking ICSs and LABAs had greater growth in height than those with an increased dose of ICS.12 Adding a LABA, however, did not decrease the need for systemic steroids and also did not reduce the number of exacerbations requiring hospitalizations.12
Another recent study demonstrated that the combination of ICSs and LABAs was noninferior to ICSs alone in preventing hospitalizations, intubations, and deaths.13 There are limited data on whether patients already on LABAs and ICSs should be continued on dual medications. Additionally, there is no clear method describing how to de-escalate therapy for those patients who are well controlled on ICSs and LABAs. A reasonable approach is to reduce doses of both medications and discontinue the LABA if tolerated.14,15 The US Food and Drug Administration has issued a black box warning that LABAs should not be used as a single controller medication because patients may be at increased risk of asthma-related deaths.16,17
What role for leukotriene receptor antagonists?
According to NHLBI guidelines, LTRAs can be considered as an alternative to ICSs when starting a control medication for mild persistent asthma.2 A recent meta-analysis, however, showed that there were increased rates of hospitalizations with LTRAs alone when compared to ICSs.18 The NHLBI guidelines also suggest that LTRAs can be used as adjunctive medication for those patients not well controlled on ICSs rather than increasing the ICS dose or adding a LABA.2
A 2011 clinical trial found no difference in quality of life measures between LTRAs and LABAs as adjunctive therapy at 2 months, but LABAs were more effective when patients were reassessed in 2 years.19 Similarly, the same study also found that adding LTRAs to low-dose ICSs rather than increasing the ICS dose was equivalent in the short term but not at 2 years.19
2 other adjunctive therapy options: Xanthines, cromolyn
Similar to LTRAs, xanthines can be considered as adjunctive therapy for children older than 5 years who are not well controlled on a low-dose ICS. Although xanthines decrease asthma symptoms when compared to placebo alone, they are not more effective than ICSs alone and should be considered only as adjunctive therapy.2,20 There have been few studies comparing xanthines to other adjunctive medications.21
Cromolyn is another adjunctive medication cited in the NHLBI guidelines for escalation of therapy.2 Although the medication has few adverse effects, its use is generally limited in the United States because data supporting its efficacy are lacking.
Omalizumab for allergy-related asthma exacerbations
Omalizumab, an anti-IgE antibody injected every 2 to 4 weeks, is available for children older than 6 years with moderate to severe asthma that is not responsive to ICSs and LABAs.22 The medication is effective in reducing allergy-related asthma exacerbations and hospitalizations, but data comparing it to other adjunctive medications are limited.22 Due to their significant systemic effects, the role of oral steroids as control medications is reserved for patients with severe asthma who are refractory to other medications. Children should be placed on oral steroids for the least amount of time required to achieve symptom control.
Acute exacerbation treatment: What to consider
Although there is no agreed-upon definition for an acute asthma exacerbation, the American Thoracic Society defines it as "an event characterized by a change from the patient’s previous status."23 All patients should be given an asthma action plan that clearly delineates the escalation of therapy in the event of an exacerbation, although only half of all patients report experiencing one.24 Symptom-based plans may prevent more acute care visits when compared to plans that use peak-flow measurements, although children on peak-flow plans may have fewer symptomatic days.25
Start with short-acting beta-agonists
The SABAs serve as the initial treatment of choice for management of asthma exacerbations. In young children (0-3 years), SABAs delivered by MDI with a spacer were more effective in reducing admission rates (11.3% vs 21.7%) when compared to SABAs delivered by nebulizers, resulting in a number needed to treat to prevent one admission of 10.26
In older children (3-18 years), SABAs delivered via spacer reduced ED length of stay, but did not significantly affect hospitalization rates. Additionally, SABAs administered with anticholinergics such as ipratropium bromide were more effective than SABAs alone in reducing admissions (16.9% vs 23.2%), particularly in older children with moderate to severe asthma, while also minimizing adverse effects.8,26
Corticosteroids: A mainstay in the ED
In addition to albuterol administration, corticosteroids remain the mainstay of ED management for asthma exacerbations. Administration of systemic steroids has been shown to reduce hospitalizations in children under 6 years, although, paradoxically, studies examining outpatient administration have demonstrated an increase in hospitalizations when compared to placebo.27
Dexamethasone and prednisone are the 2 most commonly used systemic steroids, and studies haven't indicated superiority of either.28,29 There is no difference in efficacy between oral and intravenous steroids.30 A recent clinical trial found a 2-day course of dexamethasone (0.6 mg/kg) had similar efficacy with fewer adverse effects when compared to a 5-day course of prednisone (1-2 mg/kg/day).28
Patient isn’t responding? Try IV magnesium
For patients who don't respond to corticosteroids and albuterol treatments, IV magnesium sulfate (usual dose, 25-75 mg/kg/d; maximum dose, 2000 mg/d) has been shown to improve respiratory function, but not necessarily decrease admission rates.31 Inhaled magnesium sulfate hasn't been shown to be more effective than IV administration and isn'trecommended.32
Evidence doesn’t support use of heliox
Heliox, which consists of 80% helium, is theorized to be effective in the treatment of asthma by increasing laminar flow and increasing the delivery of medications to the alveoli.32 Overall, the evidence does not support the use of heliox, which is typically restricted to patients with severe asthma exacerbations.33
Is it worth considering noninvasive positive pressure ventilation?
If patients don't improve with medical treatment, noninvasive positive pressure ventilation can be considered. A recent meta-analysis suggests that there is no definitive benefit or harm from this treatment, although several studies have indicated a decrease in symptom severity.34
Intubation should be considered for hypoxemia unresponsive to medications, or in cases of exhaustion, worsening mental status, or respiratory acidosis unresponsive to medication. Ventilation should allow for a permissive respiratory acidosis (pH, 7.2), while maintaining adequate oxygenation.35
Reducing the burden of asthma
Due to the complex task of reducing triggers and providing effective controller medications, working with parents and children is integral to improving the quality of life for patients with asthma. Although there is an obvious genetic predisposition, family physicians can help reduce the risk of developing asthma by encouraging healthy behaviors at home before the child is born. In the prenatal period, this includes avoiding tobacco-smoke exposure, lessening maternal obesity, decreasing maternal antibiotic and acetaminophen use, and curtailing stress.
Evidence suggests that after birth, breastfeeding and reducing childhood obesity can help lower the risk of asthma.36 Atopic disease, in general, can be reduced by breastfeeding until at least 4 months, as well as encouraging a varied diet that does not restrict potential allergens during pregnancy or lactation, and introducing foods (including potential allergens) after the age of 4 months.
The risk of atopic disease can also be lowered by lessening potential triggers at home. These include restricting exposure to cats (but not dogs), reducing home mold by decreasing humidity and ensuring adequate ventilation, avoiding volatile organic compounds, such as chlorine, and curtailing exposure to vehicle emissions. Although often marketed to be effective in reducing allergies, dust-mite covers and soy-based formulas don't prevent or minimize allergies and are often costly.37,38 In addition, there is no evidence that vaccinations areassociated with allergies.39
CORRESPONDENCE
Douglas M. Maurer, 9040A Jackson Ave, Joint-Base Lewis-McChord, WA 98431; [email protected].
1. US Department of Health and Human Services. Centers for Disease Control and Prevention. Asthma and Schools. Available at: www.cdc.gov/healthyschools/asthma/index.htm. Updated June 17, 2015. Accessed September 28, 2016.
2. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. Bethesda, Md: National Heart, Lung, and Blood Institute; 2007. Report No.:07-4051.
3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. Available at: www.ginasthma.org. Accessed April 11, 2017.
4. Jia CE, Zhang HP, Lv Y, et al. The asthma control test and asthma control questionnaire for assessing asthma control: systematic review and meta-analysis. J Allergy Clin Immunol. 2013;131:695-703.
5. Ko FW, Hui DS, Leung TS, et al. Evaluation of the asthma control test: a reliable determinant of disease stability and a predictor of future exacerbations. Respirology. 2012;17: 370-378.
6. Sudhanthar S, Thakur K, Sigal Y, et al. Improving asthma severity and control screening in a primary care pediatric practice. BMJ Qual Improv Rep. 2016;5
7. Wilkinson M, Bulloch B, Garcia-Filion P, et al. Efficacy of racemic albuterol versus levalbuterol used as a continuous nebulization for the treatment of acute asthma exacerbations: a randomized, double-blind, clinical trial. J Asthma. 2011;48:188-193.
8. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;19.
9. Delgado A, Chou KJ, Silver EJ, et al. Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department. Arch Pediatr Adolesc Med. 2003;157:76-80.
10. Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904-912.
11. Loke YK, Blanco P, Thavarajh M, et al. Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis. PLoS ONE. 2015;10:e0133428.
12. Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015;24:CD007949.
13. Stempel DA, Szefler SJ, Pedersen S, et al; VESTRI Investigators. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016;375:840-849.
14. Blair MM. PL Detail-Document, Safety of long-acting beta-agonists in asthma. Pharmacist’s Letter/Prescriber’s Letter. November 2012.
15. Kew KM, Beggs S, Ahmad S. Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015;5:CD011316.
16. Nelson HS, Weiss ST, Bleecker ER, et al; SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.
17. US Food and Drug Administration. FDA Drug Safety Communication: new safety requirements for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs). Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200776.htm. Accessed December 23, 2016.
18. Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev. 2012;5:CD002314.
19. Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med. 2011;364:1695-1707.
20. Seddon P, Bara A, Ducharme FM, et al. Oral xanthines as maintenance treatment for asthma in children. Cochrane Database Syst Rev. 2006;1:CD002885.
21. van der Mark LB, Lyklema PHE, Geskus RB, et al. A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four. BMC Pulm Med. 2012;12:63.
22. Normansell R, Walker S, Milan SJ. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.
23. Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society Statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180:59-99.
24. Simon AE, Akinbami LJ. Asthma action plan receipt among children with asthma 2-17 years of age, United States, 2002-2013. J Pediatr. 2016;171:283-289.
25. Bhogal SK, Zemek R, Ducharme FM. Written action plans for asthma in children. Cochrane Database Syst Rev. 2006;3: CD005306.
26. Pollock M, Sinha IP, Hartling L, et al. Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews. Allergy. 2017;72:183-200.
27. Castro-Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: systematic review with meta-analysis. Pediatr Pulmonol. 2016;51:868-876.
28. Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133:493-499.
29. Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev. 2016;5:CD011801.
30. Rowe BH, Keller JL, Oxman AD. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med. 1992;10:301-310.
31. Rowe BH, Bretzlaff J, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000;1:CD001490.
32. Powell C, Dwan K, Milan SJ, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2012;12:CD003898.
33. Rodrigo GJ, Pollack CV, Rodrigo C, et al. Heliox for non-intubated acute asthma patients. Cochrane Database Syst Rev. 2006;4:CD002884.
34. Korang SK, Feinberg J, Wetterslev J, et al. Non-invasive positive pressure ventilation for acute asthma in children. Cochrane Database System Rev. 2016;9:CD012067.
35. Kline-Krammes S, Patel NH, Robinson S. Childhood asthma: a guide for pediatric emergency medicine providers. Emerg Med Clin North Am. 2013;31:705-732.
36. Castro-Rodriguez JA, Forno E, Rodriguez-Martinez CE, et al. Risk and protective factors for childhood asthma: what is the evidence? J Allergy Clin Immunol Pract. 2016;4:1111-1122.
37. Gøtzsche P, Johansen HK. House dust mite control measures for asthma. Cochrane Database Syst Rev. 2008;2:1465-1858.
38. Osborn DA, Sinn JKH. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database of Syst Rev. 2006;4:1465-1858.
39. Schäfer T, Bauer CP, Beyer K, et al. S3-Guideline on allergy prevention: 2014 update: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German society for Pediatric and Adolescent Medicine (DGKJ). Allegro J Int. 2014;23:186-199.
1. US Department of Health and Human Services. Centers for Disease Control and Prevention. Asthma and Schools. Available at: www.cdc.gov/healthyschools/asthma/index.htm. Updated June 17, 2015. Accessed September 28, 2016.
2. National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. Bethesda, Md: National Heart, Lung, and Blood Institute; 2007. Report No.:07-4051.
3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. Available at: www.ginasthma.org. Accessed April 11, 2017.
4. Jia CE, Zhang HP, Lv Y, et al. The asthma control test and asthma control questionnaire for assessing asthma control: systematic review and meta-analysis. J Allergy Clin Immunol. 2013;131:695-703.
5. Ko FW, Hui DS, Leung TS, et al. Evaluation of the asthma control test: a reliable determinant of disease stability and a predictor of future exacerbations. Respirology. 2012;17: 370-378.
6. Sudhanthar S, Thakur K, Sigal Y, et al. Improving asthma severity and control screening in a primary care pediatric practice. BMJ Qual Improv Rep. 2016;5
7. Wilkinson M, Bulloch B, Garcia-Filion P, et al. Efficacy of racemic albuterol versus levalbuterol used as a continuous nebulization for the treatment of acute asthma exacerbations: a randomized, double-blind, clinical trial. J Asthma. 2011;48:188-193.
8. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;19.
9. Delgado A, Chou KJ, Silver EJ, et al. Nebulizers vs metered-dose inhalers with spacers for bronchodilator therapy to treat wheezing in children aged 2 to 24 months in a pediatric emergency department. Arch Pediatr Adolesc Med. 2003;157:76-80.
10. Kelly HW, Sternberg AL, Lescher R, et al. Effect of inhaled glucocorticoids in childhood on adult height. N Engl J Med. 2012;367:904-912.
11. Loke YK, Blanco P, Thavarajh M, et al. Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis. PLoS ONE. 2015;10:e0133428.
12. Chauhan BF, Chartrand C, Ni Chroinin M, et al. Addition of long-acting beta2-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst Rev. 2015;24:CD007949.
13. Stempel DA, Szefler SJ, Pedersen S, et al; VESTRI Investigators. Safety of adding salmeterol to fluticasone propionate in children with asthma. N Engl J Med. 2016;375:840-849.
14. Blair MM. PL Detail-Document, Safety of long-acting beta-agonists in asthma. Pharmacist’s Letter/Prescriber’s Letter. November 2012.
15. Kew KM, Beggs S, Ahmad S. Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids. Cochrane Database Syst Rev. 2015;5:CD011316.
16. Nelson HS, Weiss ST, Bleecker ER, et al; SMART Study Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15-26.
17. US Food and Drug Administration. FDA Drug Safety Communication: new safety requirements for long-acting inhaled asthma medications called long-acting beta-agonists (LABAs). Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200776.htm. Accessed December 23, 2016.
18. Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev. 2012;5:CD002314.
19. Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med. 2011;364:1695-1707.
20. Seddon P, Bara A, Ducharme FM, et al. Oral xanthines as maintenance treatment for asthma in children. Cochrane Database Syst Rev. 2006;1:CD002885.
21. van der Mark LB, Lyklema PHE, Geskus RB, et al. A systematic review with attempted network meta-analysis of asthma therapy recommended for five to eighteen year olds in GINA steps three and four. BMC Pulm Med. 2012;12:63.
22. Normansell R, Walker S, Milan SJ. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;1:CD003559.
23. Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society Statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180:59-99.
24. Simon AE, Akinbami LJ. Asthma action plan receipt among children with asthma 2-17 years of age, United States, 2002-2013. J Pediatr. 2016;171:283-289.
25. Bhogal SK, Zemek R, Ducharme FM. Written action plans for asthma in children. Cochrane Database Syst Rev. 2006;3: CD005306.
26. Pollock M, Sinha IP, Hartling L, et al. Inhaled short-acting bronchodilators for managing emergency childhood asthma: an overview of reviews. Allergy. 2017;72:183-200.
27. Castro-Rodriguez JA, Beckhaus AA, Forno E. Efficacy of oral corticosteroids in the treatment of acute wheezing episodes in asthmatic preschoolers: systematic review with meta-analysis. Pediatr Pulmonol. 2016;51:868-876.
28. Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133:493-499.
29. Normansell R, Kew KM, Mansour G. Different oral corticosteroid regimens for acute asthma. Cochrane Database Syst Rev. 2016;5:CD011801.
30. Rowe BH, Keller JL, Oxman AD. Effectiveness of steroid therapy in acute exacerbations of asthma: a meta-analysis. Am J Emerg Med. 1992;10:301-310.
31. Rowe BH, Bretzlaff J, Bourdon C, et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst Rev. 2000;1:CD001490.
32. Powell C, Dwan K, Milan SJ, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2012;12:CD003898.
33. Rodrigo GJ, Pollack CV, Rodrigo C, et al. Heliox for non-intubated acute asthma patients. Cochrane Database Syst Rev. 2006;4:CD002884.
34. Korang SK, Feinberg J, Wetterslev J, et al. Non-invasive positive pressure ventilation for acute asthma in children. Cochrane Database System Rev. 2016;9:CD012067.
35. Kline-Krammes S, Patel NH, Robinson S. Childhood asthma: a guide for pediatric emergency medicine providers. Emerg Med Clin North Am. 2013;31:705-732.
36. Castro-Rodriguez JA, Forno E, Rodriguez-Martinez CE, et al. Risk and protective factors for childhood asthma: what is the evidence? J Allergy Clin Immunol Pract. 2016;4:1111-1122.
37. Gøtzsche P, Johansen HK. House dust mite control measures for asthma. Cochrane Database Syst Rev. 2008;2:1465-1858.
38. Osborn DA, Sinn JKH. Soy formula for prevention of allergy and food intolerance in infants. Cochrane Database of Syst Rev. 2006;4:1465-1858.
39. Schäfer T, Bauer CP, Beyer K, et al. S3-Guideline on allergy prevention: 2014 update: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German society for Pediatric and Adolescent Medicine (DGKJ). Allegro J Int. 2014;23:186-199.
PRACTICE RECOMMENDATIONS
› Reassure parents that metered-dose inhalers are as effective as nebulizers for asthma exacerbations. A
› Use a 2-day course of systemic steroids for asthma exacerbations rather than extended regimens. B
› Develop an asthma action plan for every patient with asthma to decrease acute care visits. B
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
These agents do double duty by reducing CV risk in diabetes
In this issue of JFP, Skolnik et al discuss ways we can assist patients with type 2 diabetes mellitus (T2DM) in lowering their cardiovascular (CV) risk. It is well established that the main predictors of the development of CV disease in patients with T2DM are blood pressure (BP) and lipid levels. Many randomized controlled trials (RCTs) have demonstrated the benefit of lowering BP and lipid levels on reducing CV disease in these patients.
The problem has been that other than a modest CV benefit from metformin, no glucose-lowering drug has been shown to have a significant effect on CV outcomes—until recently. Now there is solid evidence from RCTs that treatment with one of 3 newer agents—empagliflozin (a sodium-glucose cotransporter [SGLT]-2 inhibitor), liraglutide, and semaglutide (both glucagon-like peptide [GLP]-1 receptor agonists)—is associated with reductions in CV morbidity and mortality for patients with T2DM who have established, or are at high risk for, CV disease. (Of note: Semaglutide is not yet on the market. Its manufacturer submitted a New Drug Application late last year.)
For empagliflozin, an RCT involving more than 7000 patients calculated that the number needed to treat (NNT) over a 3-year period to prevent one CV event was 63 and the NNT to prevent one death from any cause was 38.1 For liraglutide, a double-blind trial involving over 9000 patients reported the NNT to prevent one CV event in 3 years was 53, and the NNT to prevent one death from any cause was 71.2 The RCT for semaglutide involved more than 3000 patients and reported the NNT to prevent one major CVD event was 43, but there was no significant difference in CV mortality between the semaglutide and placebo groups in that clinical trial.3
1. Zinman B, Wanner C, Lachin JM, et al, for the EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.
2. Marso SP, Daniels GH, Brown-Frandsen K, et al, for the LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.
3. Marso SP, Bain SC, Consoli A, et al, for the SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844.
4. Ebell MH, Siwek J, Weiss BD, et al. Simplifying the language of evidence to improve patient care: Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in medical literature. J Fam Pract. 2004;53:111-120.
Editor-in-Chief
Dr. Hickner reported no potential conflict of interest relevant to this article.
Editor-in-Chief
Dr. Hickner reported no potential conflict of interest relevant to this article.
Editor-in-Chief
Dr. Hickner reported no potential conflict of interest relevant to this article.
In this issue of JFP, Skolnik et al discuss ways we can assist patients with type 2 diabetes mellitus (T2DM) in lowering their cardiovascular (CV) risk. It is well established that the main predictors of the development of CV disease in patients with T2DM are blood pressure (BP) and lipid levels. Many randomized controlled trials (RCTs) have demonstrated the benefit of lowering BP and lipid levels on reducing CV disease in these patients.
The problem has been that other than a modest CV benefit from metformin, no glucose-lowering drug has been shown to have a significant effect on CV outcomes—until recently. Now there is solid evidence from RCTs that treatment with one of 3 newer agents—empagliflozin (a sodium-glucose cotransporter [SGLT]-2 inhibitor), liraglutide, and semaglutide (both glucagon-like peptide [GLP]-1 receptor agonists)—is associated with reductions in CV morbidity and mortality for patients with T2DM who have established, or are at high risk for, CV disease. (Of note: Semaglutide is not yet on the market. Its manufacturer submitted a New Drug Application late last year.)
For empagliflozin, an RCT involving more than 7000 patients calculated that the number needed to treat (NNT) over a 3-year period to prevent one CV event was 63 and the NNT to prevent one death from any cause was 38.1 For liraglutide, a double-blind trial involving over 9000 patients reported the NNT to prevent one CV event in 3 years was 53, and the NNT to prevent one death from any cause was 71.2 The RCT for semaglutide involved more than 3000 patients and reported the NNT to prevent one major CVD event was 43, but there was no significant difference in CV mortality between the semaglutide and placebo groups in that clinical trial.3
In this issue of JFP, Skolnik et al discuss ways we can assist patients with type 2 diabetes mellitus (T2DM) in lowering their cardiovascular (CV) risk. It is well established that the main predictors of the development of CV disease in patients with T2DM are blood pressure (BP) and lipid levels. Many randomized controlled trials (RCTs) have demonstrated the benefit of lowering BP and lipid levels on reducing CV disease in these patients.
The problem has been that other than a modest CV benefit from metformin, no glucose-lowering drug has been shown to have a significant effect on CV outcomes—until recently. Now there is solid evidence from RCTs that treatment with one of 3 newer agents—empagliflozin (a sodium-glucose cotransporter [SGLT]-2 inhibitor), liraglutide, and semaglutide (both glucagon-like peptide [GLP]-1 receptor agonists)—is associated with reductions in CV morbidity and mortality for patients with T2DM who have established, or are at high risk for, CV disease. (Of note: Semaglutide is not yet on the market. Its manufacturer submitted a New Drug Application late last year.)
For empagliflozin, an RCT involving more than 7000 patients calculated that the number needed to treat (NNT) over a 3-year period to prevent one CV event was 63 and the NNT to prevent one death from any cause was 38.1 For liraglutide, a double-blind trial involving over 9000 patients reported the NNT to prevent one CV event in 3 years was 53, and the NNT to prevent one death from any cause was 71.2 The RCT for semaglutide involved more than 3000 patients and reported the NNT to prevent one major CVD event was 43, but there was no significant difference in CV mortality between the semaglutide and placebo groups in that clinical trial.3
1. Zinman B, Wanner C, Lachin JM, et al, for the EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.
2. Marso SP, Daniels GH, Brown-Frandsen K, et al, for the LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.
3. Marso SP, Bain SC, Consoli A, et al, for the SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844.
4. Ebell MH, Siwek J, Weiss BD, et al. Simplifying the language of evidence to improve patient care: Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in medical literature. J Fam Pract. 2004;53:111-120.
1. Zinman B, Wanner C, Lachin JM, et al, for the EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128.
2. Marso SP, Daniels GH, Brown-Frandsen K, et al, for the LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322.
3. Marso SP, Bain SC, Consoli A, et al, for the SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844.
4. Ebell MH, Siwek J, Weiss BD, et al. Simplifying the language of evidence to improve patient care: Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in medical literature. J Fam Pract. 2004;53:111-120.
USPSTF changes stance on routine pelvic exams
AGA Guideline: Transient elastography in liver fibrosis, most used and most accurate
Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).
However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.
When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.
For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”
For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.
Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.
For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.
The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.
The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.
Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”
Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.
Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).
However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.
When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.
For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”
For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.
Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.
For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.
The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.
The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.
Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”
Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.
Vibration-controlled transient elastography (VCTE) can accurately diagnose cirrhosis in most patients with chronic liver disease, particularly those with chronic hepatitis B or C, states a new guideline from the AGA Institute, published in the May issue of Gastroenterology (doi: 10.1053/j.gastro.2017.03.017).
However, magnetic resonance elastography (MRE) is somewhat more accurate for detecting cirrhosis in nonalcoholic fatty liver disease, wrote Joseph K. Lim, MD, AGAF, of Yale University in New Haven, Conn., with his associates from the Clinical Guidelines Committee of the AGA. VCTE is convenient but performs unevenly in some liver conditions and is especially unreliable in patients with acute hepatitis, alcohol abuse, food intake within 2-3 hours, congestive heart failure, or extrahepatic cholestasis, the guideline notes. Yet, VCTE remains the most common imaging tool for diagnosing fibrosis in the United States, and the guideline addresses “focused, clinically relevant questions” to guide its use.
When possible, clinicians should use VCTE instead of noninvasive serum tests for cirrhosis in patients with chronic hepatitis C, the guideline asserts. In pooled analyses of 62 studies, VCTE detected about 89% of cirrhosis cases (95% confidence interval, 84%-92%), Fibrosis-4 test (FIB-4) detected 87% (95% CI, 74%-94%), and aspartate aminotransferase to platelet ratio index (APRI) detected 77% (95% CI, 73%-81%). The specificity of VCTE (91%) also equaled or exceeded that of FIB-4 (91%) or APRI (78%), the guideline noted.
For chronic hepatitis C, MRE had “poorer specificity with higher false-positive rates, suggesting poorer diagnostic performance,” compared with VCTE. Lower cost and lower point-of-care availability make VCTE “an attractive solution compared to MRE,” the guideline adds. It conditionally recommends VCTE cutoffs of 12.5 kPa for cirrhosis and 9.5 kPa for advanced (F3-F4) liver fibrosis after patients have a sustained virologic response to therapy. The 9.5-kPa cutoff would misclassify only 1% of low-risk patients and 7% of high-risk patients, but noncirrhotic patients (less than 9.5 kPa) may reasonably choose to continue specialty care if they prioritize avoiding “the small risk” of hepatocellular carcinoma over the “inconvenience and risks of continued laboratory and fibrosis testing.”
For chronic hepatitis B, the guideline conditionally recommends VCTE with an 11.0-kPa cutoff over APRI or FIB-4. In a pooled analysis of 28 studies, VCTE detected cirrhosis with a sensitivity of 86% and a specificity of 85%, compared with 66% and 74%, respectively, for APRI, and 87% and 65%, respectively, for FIB-4. However, the overall diagnostic performance of VCTE resembled that of the serum tests, and clinicians should interpret VCTE in the context of other clinical cirrhosis data, the guideline states.
Among 17 studies of VCTE cutoffs in hepatitis B, an 11.0-kPa threshold diagnosed cirrhosis with a sensitivity of 81% and a specificity of 83%. This cutoff would miss cirrhosis in less than 1% of low-risk patients and about 5% of high-risk patients and would yield false positives in 10%-15% of patients. Thus, its cutoff minimizes false negatives, reflecting “a judgment that the harm of missing cirrhosis is greater than the harm of over diagnosis,” the authors write.
For chronic alcoholic liver disease, the AGA conditionally recommends VCTE with a cirrhosis cutoff of 12.5 kPa. In pooled analyses, this value had a sensitivity of 95% and a specificity of 71%. For suspected compensated cirrhosis, the guideline conditionally suggests a 19.5-kPa cutoff when assessing the need for esophagogastroduodenoscopy (EGD) to identify high-risk esophageal varices. Patients who fall below this cutoff can reasonably pursue screening endoscopy if they are concerned about the small risk of acute variceal hemorrhage, the guideline adds.
The guideline also conditionally recommends a 17-kPa cutoff to detect clinically significant portal hypertension in patients with suspected chronic liver disease who are undergoing elective nonhepatic surgeries. This cutoff will miss about 0.1% of very low-risk patients, 0.8% of low-risk patients, and 7% of high-risk patients. Because the failure to detect portal hypertension contributes to operative morbidity and mortality, higher-risk patients might “reasonably” pursue screening endoscopy even if their kPa is below the cutoff, the guideline states.
The guideline made no recommendation about VCTE versus APRI or FIB-4 in adults with nonalcoholic fatty liver disease (NAFLD), citing “unacceptable bias” in 12 studies that excluded obese patients, used per-protocol rather than intention-to-diagnose analyses, and ignored “unsuccessful or inadequate” liver stiffness measurements, which are relatively common in NAFLD, the guideline notes. It conditionally recommends MRE over VCTE in high-risk adults with NAFLD, including those who are older, diabetic, or obese (especially with central adiposity) or who have alanine levels more than twice the upper limit of normal. However, it cites insufficient evidence to extend this recommendation to low-risk patients who only have imaging evidence of fatty liver.
Overall, the guideline focuses on “routine clinical management issues, and [does] not address comparisons with proprietary serum fibrosis assays, other emerging imaging-based fibrosis assessment techniques, or combinations of more than one noninvasive fibrosis test,” the authors note. They also limited VCTE cutoffs to single thresholds that prioritized sensitivity over specificity. “Additional studies are needed to further define the role of VCTE, MRE, and emerging diagnostic studies in the assessment of liver fibrosis, for which a significant unmet medical need remains, particularly in conditions such as NAFLD/[nonalcoholic steatohepatitis],” they add. “In particular, defining the implications for serial liver stiffness measurements over time on management decisions is of great interest.”
Dr. Muir has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead, and Merck. Dr. Lim has served as a consultant for Bristol Myers-Squibb, Gilead, Merck, and Boehringer Ingelheim. Dr. Flamm has served as a consultant or received research support from Gilead, Bristol-Myers Squibb, AbbVie, Salix Pharmaceuticals, and Intercept Pharmaceuticals. Dr. Dieterich has presented lectures for Gilead and Merck products. The rest of the authors disclosed no conflicts related to the content of this guideline.
FROM GASTROENTEROLOGY