The Journal of Family Practice is a peer-reviewed and indexed journal that provides its 95,000 family physician readers with timely, practical, and evidence-based information that they can immediately put into practice. Research and applied evidence articles, plus patient-oriented departments like Practice Alert, PURLs, and Clinical Inquiries can be found in print and at jfponline.com. The Web site, which logs an average of 125,000 visitors every month, also offers audiocasts by physician specialists and interactive features like Instant Polls and Photo Rounds Friday—a weekly diagnostic puzzle.

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Proclivity ID
18805001
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Citation Name
J Fam Pract
Negative Keywords
gaming
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
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ISIL
ISIS
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Popliteal plaques

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Popliteal plaques

Popliteal plaques

Both a Wood lamp examination and a potassium hydroxide (KOH) prep returned negative results. Those findings, combined with the patient’s month-long antifungal medication adherence, helped to rule out other diagnoses. Based on history and examination, the patient was diagnosed with erythrasma.

Erythrasma is a skin infection caused by the gram-positive bacteria Corynebacterium minutissimum1 that usually manifests in moist intertriginous areas. Sometimes it is secondary to fungal or yeast infections, local skin irritation due to friction, or due to maceration of the skin from persistent moisture. The Wood lamp examination can show coral-red fluorescence in erythrasma, but recent bathing (as in this case) may limit this finding.1

The differential diagnosis of erythematous plaques in an intertriginous area includes inverse psoriasis. However, this patient had no nail changes, joint difficulties, or other rashes consistent with psoriasis. Macerated, erythematous inflammatory changes in intertriginous areas are always concerning for fungal infections (eg, yeast infection, tinea corporis), especially with the presence of any scale. In this case, the patient’s medication regimen helped to rule out these types of conditions.

First-line therapy for erythrasma includes topical antibiotics: clindamycin, erythromycin, mupirocin, and fusidic acid. Systemic antibiotics in the tetracycline family and macrolides may also be used but have a higher risk of adverse effects. Keeping the affected area dry is a useful adjunct to pharmacologic therapy.

The patient was treated with topical clindamycin bid for 7 days. By her 2-month follow-up appointment, there were no residual skin changes. Had the plaques persisted, the possibility of inverse psoriasis would have been revisited, with either presumptive treatment prescribed or biopsy performed to establish the diagnosis.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733

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Popliteal plaques

Both a Wood lamp examination and a potassium hydroxide (KOH) prep returned negative results. Those findings, combined with the patient’s month-long antifungal medication adherence, helped to rule out other diagnoses. Based on history and examination, the patient was diagnosed with erythrasma.

Erythrasma is a skin infection caused by the gram-positive bacteria Corynebacterium minutissimum1 that usually manifests in moist intertriginous areas. Sometimes it is secondary to fungal or yeast infections, local skin irritation due to friction, or due to maceration of the skin from persistent moisture. The Wood lamp examination can show coral-red fluorescence in erythrasma, but recent bathing (as in this case) may limit this finding.1

The differential diagnosis of erythematous plaques in an intertriginous area includes inverse psoriasis. However, this patient had no nail changes, joint difficulties, or other rashes consistent with psoriasis. Macerated, erythematous inflammatory changes in intertriginous areas are always concerning for fungal infections (eg, yeast infection, tinea corporis), especially with the presence of any scale. In this case, the patient’s medication regimen helped to rule out these types of conditions.

First-line therapy for erythrasma includes topical antibiotics: clindamycin, erythromycin, mupirocin, and fusidic acid. Systemic antibiotics in the tetracycline family and macrolides may also be used but have a higher risk of adverse effects. Keeping the affected area dry is a useful adjunct to pharmacologic therapy.

The patient was treated with topical clindamycin bid for 7 days. By her 2-month follow-up appointment, there were no residual skin changes. Had the plaques persisted, the possibility of inverse psoriasis would have been revisited, with either presumptive treatment prescribed or biopsy performed to establish the diagnosis.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Popliteal plaques

Both a Wood lamp examination and a potassium hydroxide (KOH) prep returned negative results. Those findings, combined with the patient’s month-long antifungal medication adherence, helped to rule out other diagnoses. Based on history and examination, the patient was diagnosed with erythrasma.

Erythrasma is a skin infection caused by the gram-positive bacteria Corynebacterium minutissimum1 that usually manifests in moist intertriginous areas. Sometimes it is secondary to fungal or yeast infections, local skin irritation due to friction, or due to maceration of the skin from persistent moisture. The Wood lamp examination can show coral-red fluorescence in erythrasma, but recent bathing (as in this case) may limit this finding.1

The differential diagnosis of erythematous plaques in an intertriginous area includes inverse psoriasis. However, this patient had no nail changes, joint difficulties, or other rashes consistent with psoriasis. Macerated, erythematous inflammatory changes in intertriginous areas are always concerning for fungal infections (eg, yeast infection, tinea corporis), especially with the presence of any scale. In this case, the patient’s medication regimen helped to rule out these types of conditions.

First-line therapy for erythrasma includes topical antibiotics: clindamycin, erythromycin, mupirocin, and fusidic acid. Systemic antibiotics in the tetracycline family and macrolides may also be used but have a higher risk of adverse effects. Keeping the affected area dry is a useful adjunct to pharmacologic therapy.

The patient was treated with topical clindamycin bid for 7 days. By her 2-month follow-up appointment, there were no residual skin changes. Had the plaques persisted, the possibility of inverse psoriasis would have been revisited, with either presumptive treatment prescribed or biopsy performed to establish the diagnosis.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733

References

1. Forouzan P, Cohen PR. Erythrasma revisited: diagnosis, differential diagnoses, and comprehensive review of treatment. Cureus. 2020;12:e10733. doi: 10.7759/cureus.10733

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Linear leg rash

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Linear leg rash

A 4-mm punch biopsy confirmed that this was a case of blaschkitis. This uncommon condition is referred to as adult blaschkitis because it resembles lichen striatus, a linear erythematous papular eruption usually seen in children younger than 15 years of age that erupts along Blaschko lines. The biopsy in this case helped to rule out lichen planus, which can also manifest with an erythematous papular eruption along Blaschko lines.

Adult blaschkitis is thought to be a hypersensitivity reaction involving T cells. It has been linked to medication use, insect stings, trauma, and autoimmune disease.1 The characteristic linear pattern is due to the inflammatory response following the Blaschko lines of keratinocytes that migrated during the embryonic phase.1 Post-inflammatory hyperpigmentation is a frequent complication. Topical steroids often help with the itching, but do not usually make the lesions go away. There have been better results in reducing itching and lesion prominence with intralesional steroid injections, topical calcipotriol, or calcineurin inhibitors.1 The inflammation usually spontaneously resolves over 3 to 12 months.

The patient was advised that the condition is benign and would likely resolve on its own over time. She was counseled that since the clobetasol was helping with her itching, she could use it (sparingly) as needed. She was cautioned that prolonged usage could lead to skin atrophy.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Al-Balbeesi A. Adult blaschkitis with lichenoid features and blood eosinophilia. Cureus. 2021;13:e16846. doi: 10.7759/cureus.16846

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The Journal of Family Practice - 71(6)
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Linear leg rash

A 4-mm punch biopsy confirmed that this was a case of blaschkitis. This uncommon condition is referred to as adult blaschkitis because it resembles lichen striatus, a linear erythematous papular eruption usually seen in children younger than 15 years of age that erupts along Blaschko lines. The biopsy in this case helped to rule out lichen planus, which can also manifest with an erythematous papular eruption along Blaschko lines.

Adult blaschkitis is thought to be a hypersensitivity reaction involving T cells. It has been linked to medication use, insect stings, trauma, and autoimmune disease.1 The characteristic linear pattern is due to the inflammatory response following the Blaschko lines of keratinocytes that migrated during the embryonic phase.1 Post-inflammatory hyperpigmentation is a frequent complication. Topical steroids often help with the itching, but do not usually make the lesions go away. There have been better results in reducing itching and lesion prominence with intralesional steroid injections, topical calcipotriol, or calcineurin inhibitors.1 The inflammation usually spontaneously resolves over 3 to 12 months.

The patient was advised that the condition is benign and would likely resolve on its own over time. She was counseled that since the clobetasol was helping with her itching, she could use it (sparingly) as needed. She was cautioned that prolonged usage could lead to skin atrophy.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Linear leg rash

A 4-mm punch biopsy confirmed that this was a case of blaschkitis. This uncommon condition is referred to as adult blaschkitis because it resembles lichen striatus, a linear erythematous papular eruption usually seen in children younger than 15 years of age that erupts along Blaschko lines. The biopsy in this case helped to rule out lichen planus, which can also manifest with an erythematous papular eruption along Blaschko lines.

Adult blaschkitis is thought to be a hypersensitivity reaction involving T cells. It has been linked to medication use, insect stings, trauma, and autoimmune disease.1 The characteristic linear pattern is due to the inflammatory response following the Blaschko lines of keratinocytes that migrated during the embryonic phase.1 Post-inflammatory hyperpigmentation is a frequent complication. Topical steroids often help with the itching, but do not usually make the lesions go away. There have been better results in reducing itching and lesion prominence with intralesional steroid injections, topical calcipotriol, or calcineurin inhibitors.1 The inflammation usually spontaneously resolves over 3 to 12 months.

The patient was advised that the condition is benign and would likely resolve on its own over time. She was counseled that since the clobetasol was helping with her itching, she could use it (sparingly) as needed. She was cautioned that prolonged usage could lead to skin atrophy.

Photo courtesy of Daniel Stulberg, MD. Text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References

1. Al-Balbeesi A. Adult blaschkitis with lichenoid features and blood eosinophilia. Cureus. 2021;13:e16846. doi: 10.7759/cureus.16846

References

1. Al-Balbeesi A. Adult blaschkitis with lichenoid features and blood eosinophilia. Cureus. 2021;13:e16846. doi: 10.7759/cureus.16846

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Vitamins and CVD, cancer prevention: USPSTF says evidence isn’t there

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Vitamins and CVD, cancer prevention: USPSTF says evidence isn’t there

The leading causes of death in the United States are cardiovascular disease (CVD) and cancer. CVD causes about 800,00 deaths per year (30% of all deaths), and cancer is responsible for about 600,000 deaths annually (21%).1 Many adults—more than 50%—report regular use of dietary supplements, including multivitamins and minerals, to improve their overall health, believing that these supplements’ anti-inflammatory and antioxidative properties help prevent CVD and cancer.2 However, this belief is not supported by evidence, according to the US Preventive Services Task Force.

What did the Task Force find? After a recent reassessment of the topic of vitamin and mineral supplementation, the Task Force reaffirmed its position from 2014: There is insufficient evidence to recommend the use of vitamins and minerals to prevent CVD and cancer.3

For most of the vitamins and minerals included in the systematic review—vitamins A, C, D, E, and K; B vitamins; calcium; iron; zinc; and selenium—the Task Force could not find sufficient evidence to make a recommendation. It is important to note that if any of these are taken at the recommended levels, there is no evidence of serious harm from using them.

However, there is good evidence to recommend against the use of beta carotene and vitamin E.3 For beta carotene, the harms outweigh the benefits: Its use is associated with an increase in the risk of CVD death, as well as an increased incidence of lung cancer in smokers and those with occupational exposure to asbestos. The evidence on vitamin E indicates that it simply does not provide any cancer or CVD mortality benefit.

How to advise patients. Both the US Department of Health and Human Services (DHHS) and the American Heart Association state that most nutritional needs can be met through the consumption of nutritional foods and beverages; supplements do not add any benefit for those who consume a healthy diet.4 The updated USPSTF recommendations support this approach for community-dwelling, nonpregnant adults.

For those adults who want to supplement their diets—or who need to do so because of an inability to achieve an adequate diet—urge them to follow the recommendations found in DHHS’s Dietary Guidelines for Americans, 2020-2025.4

References

1. Murphy SL, Xu J, Kochanek KD, et al. Deaths: final data for 2018. Natl Vital Stat Rep. 2021;69:1-83.

2. Cowan AE, Jun S, Gahche JJ, et al. Dietary supplement use differs by socioeconomic and health-related characteristics among US adults, NHANES 2011-2014. Nutrients. 2018;10:1114. doi: 10.3390/nu10081114

3. USPSTF. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force recommendation statement. JAMA. 2022;327:2326-2333. doi: 10.1001/jama.2022.8970

4. US Department of Agriculture and US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. Published December 2020. Accessed July 13, 2022. www.dietaryguidelines.gov/current-dietary-guidelines

Author and Disclosure Information

Doug Campos-Outcalt, MD, MPA, is a clinical professor at the University of Arizona College of Medicine and a senior lecturer with the University of Arizona College of Public Health. He’s also an assistant editor at The Journal of Family Practice.

The author reported no potential conflict of interest relevant to this article.

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Doug Campos-Outcalt, MD, MPA, is a clinical professor at the University of Arizona College of Medicine and a senior lecturer with the University of Arizona College of Public Health. He’s also an assistant editor at The Journal of Family Practice.

The author reported no potential conflict of interest relevant to this article.

Author and Disclosure Information

Doug Campos-Outcalt, MD, MPA, is a clinical professor at the University of Arizona College of Medicine and a senior lecturer with the University of Arizona College of Public Health. He’s also an assistant editor at The Journal of Family Practice.

The author reported no potential conflict of interest relevant to this article.

The leading causes of death in the United States are cardiovascular disease (CVD) and cancer. CVD causes about 800,00 deaths per year (30% of all deaths), and cancer is responsible for about 600,000 deaths annually (21%).1 Many adults—more than 50%—report regular use of dietary supplements, including multivitamins and minerals, to improve their overall health, believing that these supplements’ anti-inflammatory and antioxidative properties help prevent CVD and cancer.2 However, this belief is not supported by evidence, according to the US Preventive Services Task Force.

What did the Task Force find? After a recent reassessment of the topic of vitamin and mineral supplementation, the Task Force reaffirmed its position from 2014: There is insufficient evidence to recommend the use of vitamins and minerals to prevent CVD and cancer.3

For most of the vitamins and minerals included in the systematic review—vitamins A, C, D, E, and K; B vitamins; calcium; iron; zinc; and selenium—the Task Force could not find sufficient evidence to make a recommendation. It is important to note that if any of these are taken at the recommended levels, there is no evidence of serious harm from using them.

However, there is good evidence to recommend against the use of beta carotene and vitamin E.3 For beta carotene, the harms outweigh the benefits: Its use is associated with an increase in the risk of CVD death, as well as an increased incidence of lung cancer in smokers and those with occupational exposure to asbestos. The evidence on vitamin E indicates that it simply does not provide any cancer or CVD mortality benefit.

How to advise patients. Both the US Department of Health and Human Services (DHHS) and the American Heart Association state that most nutritional needs can be met through the consumption of nutritional foods and beverages; supplements do not add any benefit for those who consume a healthy diet.4 The updated USPSTF recommendations support this approach for community-dwelling, nonpregnant adults.

For those adults who want to supplement their diets—or who need to do so because of an inability to achieve an adequate diet—urge them to follow the recommendations found in DHHS’s Dietary Guidelines for Americans, 2020-2025.4

The leading causes of death in the United States are cardiovascular disease (CVD) and cancer. CVD causes about 800,00 deaths per year (30% of all deaths), and cancer is responsible for about 600,000 deaths annually (21%).1 Many adults—more than 50%—report regular use of dietary supplements, including multivitamins and minerals, to improve their overall health, believing that these supplements’ anti-inflammatory and antioxidative properties help prevent CVD and cancer.2 However, this belief is not supported by evidence, according to the US Preventive Services Task Force.

What did the Task Force find? After a recent reassessment of the topic of vitamin and mineral supplementation, the Task Force reaffirmed its position from 2014: There is insufficient evidence to recommend the use of vitamins and minerals to prevent CVD and cancer.3

For most of the vitamins and minerals included in the systematic review—vitamins A, C, D, E, and K; B vitamins; calcium; iron; zinc; and selenium—the Task Force could not find sufficient evidence to make a recommendation. It is important to note that if any of these are taken at the recommended levels, there is no evidence of serious harm from using them.

However, there is good evidence to recommend against the use of beta carotene and vitamin E.3 For beta carotene, the harms outweigh the benefits: Its use is associated with an increase in the risk of CVD death, as well as an increased incidence of lung cancer in smokers and those with occupational exposure to asbestos. The evidence on vitamin E indicates that it simply does not provide any cancer or CVD mortality benefit.

How to advise patients. Both the US Department of Health and Human Services (DHHS) and the American Heart Association state that most nutritional needs can be met through the consumption of nutritional foods and beverages; supplements do not add any benefit for those who consume a healthy diet.4 The updated USPSTF recommendations support this approach for community-dwelling, nonpregnant adults.

For those adults who want to supplement their diets—or who need to do so because of an inability to achieve an adequate diet—urge them to follow the recommendations found in DHHS’s Dietary Guidelines for Americans, 2020-2025.4

References

1. Murphy SL, Xu J, Kochanek KD, et al. Deaths: final data for 2018. Natl Vital Stat Rep. 2021;69:1-83.

2. Cowan AE, Jun S, Gahche JJ, et al. Dietary supplement use differs by socioeconomic and health-related characteristics among US adults, NHANES 2011-2014. Nutrients. 2018;10:1114. doi: 10.3390/nu10081114

3. USPSTF. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force recommendation statement. JAMA. 2022;327:2326-2333. doi: 10.1001/jama.2022.8970

4. US Department of Agriculture and US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. Published December 2020. Accessed July 13, 2022. www.dietaryguidelines.gov/current-dietary-guidelines

References

1. Murphy SL, Xu J, Kochanek KD, et al. Deaths: final data for 2018. Natl Vital Stat Rep. 2021;69:1-83.

2. Cowan AE, Jun S, Gahche JJ, et al. Dietary supplement use differs by socioeconomic and health-related characteristics among US adults, NHANES 2011-2014. Nutrients. 2018;10:1114. doi: 10.3390/nu10081114

3. USPSTF. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force recommendation statement. JAMA. 2022;327:2326-2333. doi: 10.1001/jama.2022.8970

4. US Department of Agriculture and US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. Published December 2020. Accessed July 13, 2022. www.dietaryguidelines.gov/current-dietary-guidelines

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Toe growth

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Toe growth

Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.

Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.

In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.1 Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.2 While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.

The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

References

1. Tisa LM, Iurcotta A. Solitary periungual angiofibroma. An unusual case report. J Am Podiatr Med Assoc. 1993;83:679-80. doi: 10.7547/87507315-83-12-679

2. Boixeda P, Sánchez-Miralles E, Azaña JM, et al. CO2, argon, and pulsed dye laser treatment of angiofibromas. J Dermatol Surg Oncol. 1994;20:808-812. doi: 10.1111/j.1524- 4725.1994.tb03709.x

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Toe growth

Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.

Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.

In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.1 Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.2 While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.

The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Toe growth

Shave biopsy was consistent with a solitary periungual angiofibroma, often termed a Koenen tumor. These can manifest as a soft pink papule (as with this patient), sometimes with a distal keratinaceous tip. At times, the nail bed and nail plate may be deformed because of the angiofibroma.

Periungual angiofibromas can occur sporadically in children and adults, it was a solitary finding in this case. Importantly, periungual angiofibromas may also occur as a visible sign of a multisystem genetic disorder known as tuberous sclerosis complex (TSC). TSC causes benign tumors to develop throughout the body (eg, skin, brain, heart, lungs). The condition can be mild or lead to serious disabilities, including seizures and developmental delays.

In isolation, periungual angiofibromas are benign but occasionally hurt or bleed from light trauma. In such cases, or for cosmetic reasons, patients may seek treatments. Complete excision of the lesion may include the affected portion of the nail bed or matrix. This is more easily repaired when the lesion is on the lateral nail fold, facilitating an en bloc fusiform excision and matrixectomy.1 Surgical excision of a lesion in the mid-proximal nail fold is much more likely to result in long-term nail deformity. Electrosurgery and various laser modalities have been successful as less invasive removal options.2 While expensive, topical sirolimus 1% has been used successfully in sporadic angiofibromas and those associated with TSC.

The patient in this case underwent lateral nail fold excision with complete removal of the tumor and repair with a side-to-side closure.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

References

1. Tisa LM, Iurcotta A. Solitary periungual angiofibroma. An unusual case report. J Am Podiatr Med Assoc. 1993;83:679-80. doi: 10.7547/87507315-83-12-679

2. Boixeda P, Sánchez-Miralles E, Azaña JM, et al. CO2, argon, and pulsed dye laser treatment of angiofibromas. J Dermatol Surg Oncol. 1994;20:808-812. doi: 10.1111/j.1524- 4725.1994.tb03709.x

References

1. Tisa LM, Iurcotta A. Solitary periungual angiofibroma. An unusual case report. J Am Podiatr Med Assoc. 1993;83:679-80. doi: 10.7547/87507315-83-12-679

2. Boixeda P, Sánchez-Miralles E, Azaña JM, et al. CO2, argon, and pulsed dye laser treatment of angiofibromas. J Dermatol Surg Oncol. 1994;20:808-812. doi: 10.1111/j.1524- 4725.1994.tb03709.x

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A Special Supplement on Hot Topics in Primary Care 2022

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Hot Topics in Primary Care 2022 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice. 

Click on the link below to access the entire supplement. You can also click on the video panes below to view brief summaries of individual chapters. Titles above the video panes link directly to each article.

  • A Paradigm Shift for Asthma Care
  • Common Questions on Continuous Glucose Monitoring in Primary Care 
  • Detecting and Managing ASCVD in Women: A Focus on Statins
  • Improving Detection and Management of Anemia in CKD
  • OTC Analgesics vs Opioids for Pain Management
  • Practical Considerations for Use of Insulin/Glucagon-Like Peptide 1 Receptor Agonist Combinations in Older Adults With Type 2 Diabetes
  • Practical Screening for Islet Autoantibodies: The Time Has Come
  • Reducing Thrombotic Risk From Polyvascular Disease in Primary Care
  • Strategies to Improve Outcomes in COPD
  • The Evolving Landscape of ASCVD Risk Among Patients With HIV
  • The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines
  • The Role of Eggs in Healthy Diets
  • Update on the Gut Microbiome for the Primary Care Clinician
  • Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease
  • Use of SGLT-2 Inhibitors for Chronic Kidney Disease in Primary Care

This supplement offers the opportunity to earn a total of 4 continuing medical education (CME) credits. Credit is awarded for successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered. 
 

Click here to read Hot Topics in Primary Care 2022


This supplement to The Journal of Family Practice was sponsored by the Primary Care Education Consortium and Primary Care Metabolic Group.
Check out these short video segments, which were prepared by the supplement authors and summarize the individual articles. 
The title above each video links to the related article.

 

A Paradigm Shift for Asthma Care, Njira Lugogo, MD; Neil Skolnik, MD; Yihui Jiang, DO

 

Common Questions on Continuous Glucose Monitoring in Primary Care, Eden M. Miller, DO

 

Detecting and Managing ASCVD in Women: A Focus on Statins, Pam Kushner, MD

 

Improving Detection and Management of Anemia in CKD, Steven Fishbane, MD; Stephen Brunton, MD, FAAFP

 

OTC Analgesics vs Opioids for Pain Management, Gary M. Ruoff, MD

 

Practical Considerations for Use of Insulin/Glucagon-Like Peptide 1 Receptor Agonist Combinations in Older Adults With Type 2 Diabetes, Jacqueline M. Champlain, MD

 

Practical Screening for Islet Autoantibodies: The Time Has Come, Timothy Reid, MD

 

Reducing Thrombotic Risk From Polyvascular Disease in Primary Care, Stephen Brunton, MD, FAAFP

 

Strategies to Improve Outcomes in COPD, Barbara Yawn, MD, MSc, FAAFP

 

The Evolving Landscape of ASCVD Risk Among Patients With HIV, Carlos Malvestutto, MD, MPH

 

The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines, Lawrence Eichenfield, MD; Adelaide Hebert, MD; Seemal R. Desai, MD; Moise L. Levy, MD; Anthony J. Mancini, MD; Zakiya Pressley Rice, MD; Jeffrey Sugarman, MD, PhD; Andrea Zaenglein, MD

 

The Role of Eggs in Healthy Diets, Maria Luz Fernandez, PhD

 

Update on the Gut Microbiome for the Primary Care Clinician, Eden M. Miller, DO

 

Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease, Gary Small, MD

 

Use of SGLT-2 Inhibitors for Chronic Kidney Disease in Primary Care, George Bakris, MD

Sponsor
This supplement was sponsored by Primary Care Education Consortium and Primary …
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This supplement was sponsored by Primary Care Education Consortium and Primary …
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This supplement was sponsored by Primary Care Education Consortium and Primary …



Hot Topics in Primary Care 2022 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice. 

Click on the link below to access the entire supplement. You can also click on the video panes below to view brief summaries of individual chapters. Titles above the video panes link directly to each article.

  • A Paradigm Shift for Asthma Care
  • Common Questions on Continuous Glucose Monitoring in Primary Care 
  • Detecting and Managing ASCVD in Women: A Focus on Statins
  • Improving Detection and Management of Anemia in CKD
  • OTC Analgesics vs Opioids for Pain Management
  • Practical Considerations for Use of Insulin/Glucagon-Like Peptide 1 Receptor Agonist Combinations in Older Adults With Type 2 Diabetes
  • Practical Screening for Islet Autoantibodies: The Time Has Come
  • Reducing Thrombotic Risk From Polyvascular Disease in Primary Care
  • Strategies to Improve Outcomes in COPD
  • The Evolving Landscape of ASCVD Risk Among Patients With HIV
  • The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines
  • The Role of Eggs in Healthy Diets
  • Update on the Gut Microbiome for the Primary Care Clinician
  • Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease
  • Use of SGLT-2 Inhibitors for Chronic Kidney Disease in Primary Care

This supplement offers the opportunity to earn a total of 4 continuing medical education (CME) credits. Credit is awarded for successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered. 
 

Click here to read Hot Topics in Primary Care 2022


This supplement to The Journal of Family Practice was sponsored by the Primary Care Education Consortium and Primary Care Metabolic Group.
Check out these short video segments, which were prepared by the supplement authors and summarize the individual articles. 
The title above each video links to the related article.

 

A Paradigm Shift for Asthma Care, Njira Lugogo, MD; Neil Skolnik, MD; Yihui Jiang, DO

 

Common Questions on Continuous Glucose Monitoring in Primary Care, Eden M. Miller, DO

 

Detecting and Managing ASCVD in Women: A Focus on Statins, Pam Kushner, MD

 

Improving Detection and Management of Anemia in CKD, Steven Fishbane, MD; Stephen Brunton, MD, FAAFP

 

OTC Analgesics vs Opioids for Pain Management, Gary M. Ruoff, MD

 

Practical Considerations for Use of Insulin/Glucagon-Like Peptide 1 Receptor Agonist Combinations in Older Adults With Type 2 Diabetes, Jacqueline M. Champlain, MD

 

Practical Screening for Islet Autoantibodies: The Time Has Come, Timothy Reid, MD

 

Reducing Thrombotic Risk From Polyvascular Disease in Primary Care, Stephen Brunton, MD, FAAFP

 

Strategies to Improve Outcomes in COPD, Barbara Yawn, MD, MSc, FAAFP

 

The Evolving Landscape of ASCVD Risk Among Patients With HIV, Carlos Malvestutto, MD, MPH

 

The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines, Lawrence Eichenfield, MD; Adelaide Hebert, MD; Seemal R. Desai, MD; Moise L. Levy, MD; Anthony J. Mancini, MD; Zakiya Pressley Rice, MD; Jeffrey Sugarman, MD, PhD; Andrea Zaenglein, MD

 

The Role of Eggs in Healthy Diets, Maria Luz Fernandez, PhD

 

Update on the Gut Microbiome for the Primary Care Clinician, Eden M. Miller, DO

 

Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease, Gary Small, MD

 

Use of SGLT-2 Inhibitors for Chronic Kidney Disease in Primary Care, George Bakris, MD



Hot Topics in Primary Care 2022 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice. 

Click on the link below to access the entire supplement. You can also click on the video panes below to view brief summaries of individual chapters. Titles above the video panes link directly to each article.

  • A Paradigm Shift for Asthma Care
  • Common Questions on Continuous Glucose Monitoring in Primary Care 
  • Detecting and Managing ASCVD in Women: A Focus on Statins
  • Improving Detection and Management of Anemia in CKD
  • OTC Analgesics vs Opioids for Pain Management
  • Practical Considerations for Use of Insulin/Glucagon-Like Peptide 1 Receptor Agonist Combinations in Older Adults With Type 2 Diabetes
  • Practical Screening for Islet Autoantibodies: The Time Has Come
  • Reducing Thrombotic Risk From Polyvascular Disease in Primary Care
  • Strategies to Improve Outcomes in COPD
  • The Evolving Landscape of ASCVD Risk Among Patients With HIV
  • The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines
  • The Role of Eggs in Healthy Diets
  • Update on the Gut Microbiome for the Primary Care Clinician
  • Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease
  • Use of SGLT-2 Inhibitors for Chronic Kidney Disease in Primary Care

This supplement offers the opportunity to earn a total of 4 continuing medical education (CME) credits. Credit is awarded for successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered. 
 

Click here to read Hot Topics in Primary Care 2022


This supplement to The Journal of Family Practice was sponsored by the Primary Care Education Consortium and Primary Care Metabolic Group.
Check out these short video segments, which were prepared by the supplement authors and summarize the individual articles. 
The title above each video links to the related article.

 

A Paradigm Shift for Asthma Care, Njira Lugogo, MD; Neil Skolnik, MD; Yihui Jiang, DO

 

Common Questions on Continuous Glucose Monitoring in Primary Care, Eden M. Miller, DO

 

Detecting and Managing ASCVD in Women: A Focus on Statins, Pam Kushner, MD

 

Improving Detection and Management of Anemia in CKD, Steven Fishbane, MD; Stephen Brunton, MD, FAAFP

 

OTC Analgesics vs Opioids for Pain Management, Gary M. Ruoff, MD

 

Practical Considerations for Use of Insulin/Glucagon-Like Peptide 1 Receptor Agonist Combinations in Older Adults With Type 2 Diabetes, Jacqueline M. Champlain, MD

 

Practical Screening for Islet Autoantibodies: The Time Has Come, Timothy Reid, MD

 

Reducing Thrombotic Risk From Polyvascular Disease in Primary Care, Stephen Brunton, MD, FAAFP

 

Strategies to Improve Outcomes in COPD, Barbara Yawn, MD, MSc, FAAFP

 

The Evolving Landscape of ASCVD Risk Among Patients With HIV, Carlos Malvestutto, MD, MPH

 

The New Face of Preadolescent and Adolescent Acne: Beyond the Guidelines, Lawrence Eichenfield, MD; Adelaide Hebert, MD; Seemal R. Desai, MD; Moise L. Levy, MD; Anthony J. Mancini, MD; Zakiya Pressley Rice, MD; Jeffrey Sugarman, MD, PhD; Andrea Zaenglein, MD

 

The Role of Eggs in Healthy Diets, Maria Luz Fernandez, PhD

 

Update on the Gut Microbiome for the Primary Care Clinician, Eden M. Miller, DO

 

Updates in the Management of Mild Cognitive Impairment and Alzheimer Disease, Gary Small, MD

 

Use of SGLT-2 Inhibitors for Chronic Kidney Disease in Primary Care, George Bakris, MD

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Leg lesions

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Leg lesions

Leg lesions

A 4-mm punch biopsy performed on the central portion of a lesion revealed thickening of the epidermis and altered collagen in the dermis consistent with acquired reactive perforating collagenosis (ARPC).

ARPC is strongly associated with diabetes, renal disease, and malignancy. ARPC manifests as an eruption of intensely pruritic papules to small plaques (with a central plug or firm dry depression) on the trunk, or more commonly, on the extremities. The etiology is unclear but altered collagen from systemic disease, trauma, or cold exposure may trigger collagen elimination.1 Secondary infection may occur due to the intensity of itching. ARPC develops in adulthood; epidemiologic data are lacking and prevalence has not been systematically assessed.2

Treatment approaches are based on small case reports and case series. Common antipruritic therapies, such as topical and intralesional steroids, oral antihistamines, and vitamin-D analogues, have had mixed success. UV therapy is effective for nephrogenic pruritus; case reports suggest it has also been helpful for ARPC. Similarly, keratolytics and topical and systemic retinoids have shown promise. Allopurinol, which reduces free radicals, has also demonstrated its utility.3

This patient was started on topical triamcinolone 0.1% cream bid and narrowband UV-B phototherapy 3 times weekly with marked improvement in her itching. Lesions decreased in number over 3 months of follow-up but did not completely resolve.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

References

1. Zhang X, Yang Y, Shao S. Acquired reactive perforating collagenosis: a case report and review of the literature. Medicine (Baltimore). 2020;99:e20391. doi: 10.1097/MD.0000000000020391

2. Karpouzis A, Giatromanolaki A, Sivridis E, et al. Acquired reactive perforating collagenosis: current status. J Dermatol. 2010;37:585-592. doi: 10.1111/j.1346-8138.2010.00918.x

3. Lukács J, Schliemann S, Elsner P. Treatment of acquired reactive perforating dermatosis - a systematic review. J Dtsch Dermatol Ges. 2018;16:825-842. doi: 10.1111/ddg.13561

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Leg lesions

A 4-mm punch biopsy performed on the central portion of a lesion revealed thickening of the epidermis and altered collagen in the dermis consistent with acquired reactive perforating collagenosis (ARPC).

ARPC is strongly associated with diabetes, renal disease, and malignancy. ARPC manifests as an eruption of intensely pruritic papules to small plaques (with a central plug or firm dry depression) on the trunk, or more commonly, on the extremities. The etiology is unclear but altered collagen from systemic disease, trauma, or cold exposure may trigger collagen elimination.1 Secondary infection may occur due to the intensity of itching. ARPC develops in adulthood; epidemiologic data are lacking and prevalence has not been systematically assessed.2

Treatment approaches are based on small case reports and case series. Common antipruritic therapies, such as topical and intralesional steroids, oral antihistamines, and vitamin-D analogues, have had mixed success. UV therapy is effective for nephrogenic pruritus; case reports suggest it has also been helpful for ARPC. Similarly, keratolytics and topical and systemic retinoids have shown promise. Allopurinol, which reduces free radicals, has also demonstrated its utility.3

This patient was started on topical triamcinolone 0.1% cream bid and narrowband UV-B phototherapy 3 times weekly with marked improvement in her itching. Lesions decreased in number over 3 months of follow-up but did not completely resolve.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Leg lesions

A 4-mm punch biopsy performed on the central portion of a lesion revealed thickening of the epidermis and altered collagen in the dermis consistent with acquired reactive perforating collagenosis (ARPC).

ARPC is strongly associated with diabetes, renal disease, and malignancy. ARPC manifests as an eruption of intensely pruritic papules to small plaques (with a central plug or firm dry depression) on the trunk, or more commonly, on the extremities. The etiology is unclear but altered collagen from systemic disease, trauma, or cold exposure may trigger collagen elimination.1 Secondary infection may occur due to the intensity of itching. ARPC develops in adulthood; epidemiologic data are lacking and prevalence has not been systematically assessed.2

Treatment approaches are based on small case reports and case series. Common antipruritic therapies, such as topical and intralesional steroids, oral antihistamines, and vitamin-D analogues, have had mixed success. UV therapy is effective for nephrogenic pruritus; case reports suggest it has also been helpful for ARPC. Similarly, keratolytics and topical and systemic retinoids have shown promise. Allopurinol, which reduces free radicals, has also demonstrated its utility.3

This patient was started on topical triamcinolone 0.1% cream bid and narrowband UV-B phototherapy 3 times weekly with marked improvement in her itching. Lesions decreased in number over 3 months of follow-up but did not completely resolve.

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

References

1. Zhang X, Yang Y, Shao S. Acquired reactive perforating collagenosis: a case report and review of the literature. Medicine (Baltimore). 2020;99:e20391. doi: 10.1097/MD.0000000000020391

2. Karpouzis A, Giatromanolaki A, Sivridis E, et al. Acquired reactive perforating collagenosis: current status. J Dermatol. 2010;37:585-592. doi: 10.1111/j.1346-8138.2010.00918.x

3. Lukács J, Schliemann S, Elsner P. Treatment of acquired reactive perforating dermatosis - a systematic review. J Dtsch Dermatol Ges. 2018;16:825-842. doi: 10.1111/ddg.13561

References

1. Zhang X, Yang Y, Shao S. Acquired reactive perforating collagenosis: a case report and review of the literature. Medicine (Baltimore). 2020;99:e20391. doi: 10.1097/MD.0000000000020391

2. Karpouzis A, Giatromanolaki A, Sivridis E, et al. Acquired reactive perforating collagenosis: current status. J Dermatol. 2010;37:585-592. doi: 10.1111/j.1346-8138.2010.00918.x

3. Lukács J, Schliemann S, Elsner P. Treatment of acquired reactive perforating dermatosis - a systematic review. J Dtsch Dermatol Ges. 2018;16:825-842. doi: 10.1111/ddg.13561

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The testing we order should help, not hurt

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The testing we order should help, not hurt

Ordering and interpreting tests is at the heart of what we do as family physicians. Ordering tests judiciously and interpreting them accurately is not easy. The Choosing Wisely campaign1 has focused our attention on the need to think carefully before ordering tests, whether they be laboratory tests or imaging. Before ordering any test, one should always ask: Is the result of this test going to help me make better decisions about managing this patient?

I would like to highlight and expand on 2 problematic issues Kaminski and Venkat raise in their excellent article on testing in this issue of JFP.2

One should always ask: Is the result of this test going to help me make better decisions?

First, they advise us to know the pretest probability of a disease before we order a test. If we order a test on a patient for whom the probability of disease is very low, a positive result is likely to be a false-positive and mislead us into thinking the patient has the disease when he does not. If we order a test for a patient with a high probability of disease and the result is negative, there is great danger of a false-­negative. We might think the patient does not have the disease, but she does.

There is a deeper problem here, however. Primary care physicians are notorious for overestimating disease probability. In a recent study, primary care clinicians overestimated the pretest probability of disease 2- to 10-fold in scenarios involving 4 common diagnoses: breast cancer, coronary artery disease (CAD), pneumonia, and urinary tract infection.3 Even after receiving a negative test result, clinicians still overestimated the chance of disease in all the scenarios. For example, when presented with a 43-year-old premenopausal woman with atypical chest pain and a normal electrocardiogram, clinicians’ average estimate of the probability of CAD was 10%—considerably higher than true estimates of 1% to 4.4%.3

To improve your accuracy in judging pretest probabilities, see the diagnostic test calculators in Essential Evidence Plus (www.essentialevidenceplus.com/).

Secondly, Kaminski and Venkat advise us to try to avoid the testing cascade.2 The associated dangers to patients are considerable. For a cautionary tale, I recommend you read the essay by Michael B. Rothberg, MD, MPH, called “The $50,000 Physical”.4 Dr. Rothberg describes the testing cascade his 85-year-old father experienced, which led to a liver biopsy that nearly killed him from post-biopsy bleeding. Always remember: Testing is a double-edged sword. It can help—or harm—your patients.

References

1. American Board of Internal Medicine Foundation. Choosing Wisely. Accessed June 30, 2022. www.choosingwisely.org/

2. Kaminski M, Venkat N. A judicious approach to ordering lab tests. J Fam Pract. 2022;71:245-250. doi: 10.12788/jfp.0444

3. Morgan DJ, Pineles L, Owczarzak J, et al. Accuracy of practitioner estimates of probability of diagnosis before and after testing. JAMA Intern Med. 2021;181:747-755. doi: 10.1001/jamainternmed.2021.0269

4. Rothberg MB. The $50 000 physical. JAMA. 2020;323:1682-1683. doi: 10.1001/jama.2020.2866

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Ordering and interpreting tests is at the heart of what we do as family physicians. Ordering tests judiciously and interpreting them accurately is not easy. The Choosing Wisely campaign1 has focused our attention on the need to think carefully before ordering tests, whether they be laboratory tests or imaging. Before ordering any test, one should always ask: Is the result of this test going to help me make better decisions about managing this patient?

I would like to highlight and expand on 2 problematic issues Kaminski and Venkat raise in their excellent article on testing in this issue of JFP.2

One should always ask: Is the result of this test going to help me make better decisions?

First, they advise us to know the pretest probability of a disease before we order a test. If we order a test on a patient for whom the probability of disease is very low, a positive result is likely to be a false-positive and mislead us into thinking the patient has the disease when he does not. If we order a test for a patient with a high probability of disease and the result is negative, there is great danger of a false-­negative. We might think the patient does not have the disease, but she does.

There is a deeper problem here, however. Primary care physicians are notorious for overestimating disease probability. In a recent study, primary care clinicians overestimated the pretest probability of disease 2- to 10-fold in scenarios involving 4 common diagnoses: breast cancer, coronary artery disease (CAD), pneumonia, and urinary tract infection.3 Even after receiving a negative test result, clinicians still overestimated the chance of disease in all the scenarios. For example, when presented with a 43-year-old premenopausal woman with atypical chest pain and a normal electrocardiogram, clinicians’ average estimate of the probability of CAD was 10%—considerably higher than true estimates of 1% to 4.4%.3

To improve your accuracy in judging pretest probabilities, see the diagnostic test calculators in Essential Evidence Plus (www.essentialevidenceplus.com/).

Secondly, Kaminski and Venkat advise us to try to avoid the testing cascade.2 The associated dangers to patients are considerable. For a cautionary tale, I recommend you read the essay by Michael B. Rothberg, MD, MPH, called “The $50,000 Physical”.4 Dr. Rothberg describes the testing cascade his 85-year-old father experienced, which led to a liver biopsy that nearly killed him from post-biopsy bleeding. Always remember: Testing is a double-edged sword. It can help—or harm—your patients.

Ordering and interpreting tests is at the heart of what we do as family physicians. Ordering tests judiciously and interpreting them accurately is not easy. The Choosing Wisely campaign1 has focused our attention on the need to think carefully before ordering tests, whether they be laboratory tests or imaging. Before ordering any test, one should always ask: Is the result of this test going to help me make better decisions about managing this patient?

I would like to highlight and expand on 2 problematic issues Kaminski and Venkat raise in their excellent article on testing in this issue of JFP.2

One should always ask: Is the result of this test going to help me make better decisions?

First, they advise us to know the pretest probability of a disease before we order a test. If we order a test on a patient for whom the probability of disease is very low, a positive result is likely to be a false-positive and mislead us into thinking the patient has the disease when he does not. If we order a test for a patient with a high probability of disease and the result is negative, there is great danger of a false-­negative. We might think the patient does not have the disease, but she does.

There is a deeper problem here, however. Primary care physicians are notorious for overestimating disease probability. In a recent study, primary care clinicians overestimated the pretest probability of disease 2- to 10-fold in scenarios involving 4 common diagnoses: breast cancer, coronary artery disease (CAD), pneumonia, and urinary tract infection.3 Even after receiving a negative test result, clinicians still overestimated the chance of disease in all the scenarios. For example, when presented with a 43-year-old premenopausal woman with atypical chest pain and a normal electrocardiogram, clinicians’ average estimate of the probability of CAD was 10%—considerably higher than true estimates of 1% to 4.4%.3

To improve your accuracy in judging pretest probabilities, see the diagnostic test calculators in Essential Evidence Plus (www.essentialevidenceplus.com/).

Secondly, Kaminski and Venkat advise us to try to avoid the testing cascade.2 The associated dangers to patients are considerable. For a cautionary tale, I recommend you read the essay by Michael B. Rothberg, MD, MPH, called “The $50,000 Physical”.4 Dr. Rothberg describes the testing cascade his 85-year-old father experienced, which led to a liver biopsy that nearly killed him from post-biopsy bleeding. Always remember: Testing is a double-edged sword. It can help—or harm—your patients.

References

1. American Board of Internal Medicine Foundation. Choosing Wisely. Accessed June 30, 2022. www.choosingwisely.org/

2. Kaminski M, Venkat N. A judicious approach to ordering lab tests. J Fam Pract. 2022;71:245-250. doi: 10.12788/jfp.0444

3. Morgan DJ, Pineles L, Owczarzak J, et al. Accuracy of practitioner estimates of probability of diagnosis before and after testing. JAMA Intern Med. 2021;181:747-755. doi: 10.1001/jamainternmed.2021.0269

4. Rothberg MB. The $50 000 physical. JAMA. 2020;323:1682-1683. doi: 10.1001/jama.2020.2866

References

1. American Board of Internal Medicine Foundation. Choosing Wisely. Accessed June 30, 2022. www.choosingwisely.org/

2. Kaminski M, Venkat N. A judicious approach to ordering lab tests. J Fam Pract. 2022;71:245-250. doi: 10.12788/jfp.0444

3. Morgan DJ, Pineles L, Owczarzak J, et al. Accuracy of practitioner estimates of probability of diagnosis before and after testing. JAMA Intern Med. 2021;181:747-755. doi: 10.1001/jamainternmed.2021.0269

4. Rothberg MB. The $50 000 physical. JAMA. 2020;323:1682-1683. doi: 10.1001/jama.2020.2866

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Milium cysts on hands; hypertrichosis on face

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Milium cysts on hands; hypertrichosis on face

A 55-YEAR-OLD MAN with hypertension and untreated hepatitis C virus (HCV) was referred to the Dermatology Clinic after reporting a 2-year history of photosensitivity and intermittent episodes of blistering and scars on the dorsal side of his hands and feet. No alcohol consumption or drug use was reported.

Physical examination revealed small and shallow erosions on the dorsal aspect of the hands and feet (but no visible blisters) and milium cysts (FIGURE 1A). Additionally, hypertrichosis and hyperpigmentation were observed in the zygomatic areas (FIGURE 1B). Complete blood count and kidney function test results were within normal ranges. Liver function tests showed slightly elevated levels of alanine aminotransferase (79 U/L; normal range, 0-41 U/L), aspartate aminotransferase (62 U/L; normal range, 0-40 U/L), and ferritin (121 ng/mL; normal range, 30-100 ng/mL). Serologies for syphilis, HIV, and hepatitis B virus were negative.

Telltale signs on hands and face

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Porphyria cutanea tarda

The clinical presentation, along with the elevated laboratory values, suggested that this might be a case of porphyria cutanea tarda (PCT). Therefore, a sample of the patient’s urine was examined under Wood lamp and compared to a sample from a healthy control. In the sample of urine from our patient, a vivid red-pink fluorescence could be visualized under the lamp (FIGURE 2), confirming the diagnosis.

Wood lamp confirmed the diagnosis

The porphyrias are a group of metabolic diseases that affect the heme biosynthesis. They can be classified into 1 of 3 groups, according to clinical features:

  • acute hepatic porphyrias, with neurovisceral symptoms (eg, acute intermittent porphyria),
  • nonblistering cutaneous porphyrias, with severe photosensitivity but without bullae formation (eg, erythropoietic protoporphyria), or
  • blistering cutaneous porphyrias (eg, PCT, hepatoerythropoietic porphyria, and variegate porphyria).

PCT is the most common type of porphyria, with a global prevalence of 1 per 10,000 people.1,2 It affects adults after the third or fourth decade of life.

Porphyria cutanea tarda has a global prevalance of 1 per 10,000 people.

PCT involves dysfunction of the uroporphyrinogen decarboxylase enzyme (UROD), the fifth enzyme in heme biosynthesis, which catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. This dysfunction causes the accumulation of porphyrinogens that are auto-oxidized to photosensitizing porphyrins.1-4 PCT can be classified as “sporadic” or “familial” based on the absence or presence of UROD mutation. Approximately 80% of cases of PCT are sporadic.2

In sporadic PCT, triggers for UROD dysfunction include alcohol use, use of estrogens, hemochromatosis or iron overload, chronic HCV infection, and HIV infection.1-4 HCV (which this patient had) is the most common infection associated with sporadic PCT, with a prevalence of about 50% among these patients.5

Continue to: Dermatologic manifestations of PCT

 

 

Dermatologic manifestations of PCT include photosensitivity, skin fragility, vesicles, bullae, erosions, and crusts observed in sun-exposed areas. A nonvirilizing type of hypertrichosis may appear prominently on the temples and the cheeks.2-4 After blisters rupture, atrophy and scarring occur. Milia cysts can form on the dorsal side of the hands and fingers. Less common manifestations include pruritus, scarring alopecia, sclerodermatous changes, and periorbital purple-red suffusion.

Hepatic involvement is demonstrated with elevated serum transaminases and ­gamma-glutamyl transpeptidase. Hepatomegaly is common, and cirrhosis manifests in 30% to 40% of patients.2-5 On liver biopsy, some degree of siderosis is found in 80% of patients with PCT, and most of them have increased levels of serum iron. The incidence of hepatocellular carcinoma in patients with PCT is greater than in patients with other liver diseases.2

A Wood lamp can be a useful diagnostic first step

Plasma or urine porphyrin lab tests are the gold standard for PCT diagnosis. These tests can be followed by more specific tests (eg, porphyrin fractionation) to exclude other forms of porphyria. However, if plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam, which can be performed on urine or stool. (Plasma or urine porphyrin testing may ultimately be necessary if there is doubt about the diagnosis following the Wood lamp screening.) Histopathologic examination does not confirm the diagnosis of PCT4; however, it can be helpful in differential diagnosis.

Wood lamp is a source of long-wave UV light (320 to 400 nm), visualized as a purple or violet light. When porphyrins are present in a urine sample, a red-pink fluorescence may be seen.3,4,6 The Wood lamp examination should be performed in a completely dark room after the lamp has been warmed up for about 1 minute; time should be allowed for the clinician’s vision to adapt to the dark.6 There are no data regarding the sensitivity or specificity of the Wood lamp test in the diagnosis of PCT.

These conditions also cause skin fragility and photosensitivity

The differential diagnosis for PCT includes diseases that also cause skin fragility, blistering, or photosensitivity, such as pseudoporphyria, bullous systemic lupus erythematosus (SLE), and epidermolysis bullosa acquisita (EBA).3

Continue to: In pseudoporphyria

 

 

In pseudoporphyria, the clinical findings may be indistinguishable from PCT. Thus, the patient’s history will be especially important; suspect pseudoporphyria if the patient has a history of chronic renal failure or use of a photosensitizing drug.1,3

Bullous SLE usually manifests with systemic involvement and widespread, tense bullae. Serologic investigation will demonstrate the presence of antinuclear antibodies in high titers (> 1:80), as well as other circulating autoantibodies.

Skin lesions of EBA usually manifest with skin fragility and noninflammatory tense bullae in traumatized skin, such as the extensor surfaces of the hands, feet, and fingers.

None of the above-mentioned diagnoses manifest with hypertrichosis or red-pink fluorescent urine on Wood lamp, and results of porphyrin studies would be normal.3

Address triggers, provide treatment

Once the diagnosis is confirmed, steps must be taken to avoid triggering factors, such as any alcohol consumption, use of estrogen, sun exposure (until plasma porphyrin levels are normal), and potential sources of excessive iron intake.

If plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam.

Two therapeutic options are available for treating PCT—whether it’s sporadic or familial. Phlebotomy sessions reduce iron overload and iron depletion and may prevent the formation of a porphomethene inhibitor of UROD. The other treatment option is antimalarial agents—usually hydroxychloroquine— and is indicated for patients with lower serum ferritin levels.1-4 In patients with HCV-associated PCT, effective treatment of the infection has resulted in resolution of the PCT, in some cases.3

Treatment involving phlebotomy or an antimalarial agent can be stopped when plasma porphyrins reach normal levels.

Our patient was initially managed with 2 sessions of phlebotomy. He subsequently received treatment for the HCV infection at another hospital.

References

1. Handler NS, Handler MZ, Stephany MP, et. Porphyria cutanea tarda: an intriguing genetic disease and marker. Int J Dermatol. 2017;56:e106-e117.doi: 10.1111/ijd.13580

2. Lambrecht RW, Thapar M, Bonkovsky HL. Genetic aspects of porphyria cutanea tarda. Semin Liver Dis. 2007;27:99-108.doi: 10.1055/s-2006-960173

3. Callen JP. Hepatitis C viral infection and porphyria cutanea tarda. Am J Med Sci. 2017;354:5-6. doi: 10.1016/j.amjms.2017.06.009

4. Frank J, Poblete-Gutiérrez P. Porphyria cutanea tarda—when skin meets liver. Best Pract Res Clin Gastroenterol. 2010;24:735-745. doi: 10.1016/j.bpg.2010.07.002

5. Gisbert JP, García-Buey L, Pajares JM, et al. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol. 2003;39:620-627.doi: 10.1016/s0168-8278(03)00346-5

6. Asawanonda P, Taylor CR. Wood’s light in dermatology. Int J Dermatol. 1999;38:801-807. doi: 10.1046/j.1365-4362.1999.00794.x

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University of Texas Health, San Antonio

The authors reported no potential conflict of interest relevant to this article.

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A 55-YEAR-OLD MAN with hypertension and untreated hepatitis C virus (HCV) was referred to the Dermatology Clinic after reporting a 2-year history of photosensitivity and intermittent episodes of blistering and scars on the dorsal side of his hands and feet. No alcohol consumption or drug use was reported.

Physical examination revealed small and shallow erosions on the dorsal aspect of the hands and feet (but no visible blisters) and milium cysts (FIGURE 1A). Additionally, hypertrichosis and hyperpigmentation were observed in the zygomatic areas (FIGURE 1B). Complete blood count and kidney function test results were within normal ranges. Liver function tests showed slightly elevated levels of alanine aminotransferase (79 U/L; normal range, 0-41 U/L), aspartate aminotransferase (62 U/L; normal range, 0-40 U/L), and ferritin (121 ng/mL; normal range, 30-100 ng/mL). Serologies for syphilis, HIV, and hepatitis B virus were negative.

Telltale signs on hands and face

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Porphyria cutanea tarda

The clinical presentation, along with the elevated laboratory values, suggested that this might be a case of porphyria cutanea tarda (PCT). Therefore, a sample of the patient’s urine was examined under Wood lamp and compared to a sample from a healthy control. In the sample of urine from our patient, a vivid red-pink fluorescence could be visualized under the lamp (FIGURE 2), confirming the diagnosis.

Wood lamp confirmed the diagnosis

The porphyrias are a group of metabolic diseases that affect the heme biosynthesis. They can be classified into 1 of 3 groups, according to clinical features:

  • acute hepatic porphyrias, with neurovisceral symptoms (eg, acute intermittent porphyria),
  • nonblistering cutaneous porphyrias, with severe photosensitivity but without bullae formation (eg, erythropoietic protoporphyria), or
  • blistering cutaneous porphyrias (eg, PCT, hepatoerythropoietic porphyria, and variegate porphyria).

PCT is the most common type of porphyria, with a global prevalence of 1 per 10,000 people.1,2 It affects adults after the third or fourth decade of life.

Porphyria cutanea tarda has a global prevalance of 1 per 10,000 people.

PCT involves dysfunction of the uroporphyrinogen decarboxylase enzyme (UROD), the fifth enzyme in heme biosynthesis, which catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. This dysfunction causes the accumulation of porphyrinogens that are auto-oxidized to photosensitizing porphyrins.1-4 PCT can be classified as “sporadic” or “familial” based on the absence or presence of UROD mutation. Approximately 80% of cases of PCT are sporadic.2

In sporadic PCT, triggers for UROD dysfunction include alcohol use, use of estrogens, hemochromatosis or iron overload, chronic HCV infection, and HIV infection.1-4 HCV (which this patient had) is the most common infection associated with sporadic PCT, with a prevalence of about 50% among these patients.5

Continue to: Dermatologic manifestations of PCT

 

 

Dermatologic manifestations of PCT include photosensitivity, skin fragility, vesicles, bullae, erosions, and crusts observed in sun-exposed areas. A nonvirilizing type of hypertrichosis may appear prominently on the temples and the cheeks.2-4 After blisters rupture, atrophy and scarring occur. Milia cysts can form on the dorsal side of the hands and fingers. Less common manifestations include pruritus, scarring alopecia, sclerodermatous changes, and periorbital purple-red suffusion.

Hepatic involvement is demonstrated with elevated serum transaminases and ­gamma-glutamyl transpeptidase. Hepatomegaly is common, and cirrhosis manifests in 30% to 40% of patients.2-5 On liver biopsy, some degree of siderosis is found in 80% of patients with PCT, and most of them have increased levels of serum iron. The incidence of hepatocellular carcinoma in patients with PCT is greater than in patients with other liver diseases.2

A Wood lamp can be a useful diagnostic first step

Plasma or urine porphyrin lab tests are the gold standard for PCT diagnosis. These tests can be followed by more specific tests (eg, porphyrin fractionation) to exclude other forms of porphyria. However, if plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam, which can be performed on urine or stool. (Plasma or urine porphyrin testing may ultimately be necessary if there is doubt about the diagnosis following the Wood lamp screening.) Histopathologic examination does not confirm the diagnosis of PCT4; however, it can be helpful in differential diagnosis.

Wood lamp is a source of long-wave UV light (320 to 400 nm), visualized as a purple or violet light. When porphyrins are present in a urine sample, a red-pink fluorescence may be seen.3,4,6 The Wood lamp examination should be performed in a completely dark room after the lamp has been warmed up for about 1 minute; time should be allowed for the clinician’s vision to adapt to the dark.6 There are no data regarding the sensitivity or specificity of the Wood lamp test in the diagnosis of PCT.

These conditions also cause skin fragility and photosensitivity

The differential diagnosis for PCT includes diseases that also cause skin fragility, blistering, or photosensitivity, such as pseudoporphyria, bullous systemic lupus erythematosus (SLE), and epidermolysis bullosa acquisita (EBA).3

Continue to: In pseudoporphyria

 

 

In pseudoporphyria, the clinical findings may be indistinguishable from PCT. Thus, the patient’s history will be especially important; suspect pseudoporphyria if the patient has a history of chronic renal failure or use of a photosensitizing drug.1,3

Bullous SLE usually manifests with systemic involvement and widespread, tense bullae. Serologic investigation will demonstrate the presence of antinuclear antibodies in high titers (> 1:80), as well as other circulating autoantibodies.

Skin lesions of EBA usually manifest with skin fragility and noninflammatory tense bullae in traumatized skin, such as the extensor surfaces of the hands, feet, and fingers.

None of the above-mentioned diagnoses manifest with hypertrichosis or red-pink fluorescent urine on Wood lamp, and results of porphyrin studies would be normal.3

Address triggers, provide treatment

Once the diagnosis is confirmed, steps must be taken to avoid triggering factors, such as any alcohol consumption, use of estrogen, sun exposure (until plasma porphyrin levels are normal), and potential sources of excessive iron intake.

If plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam.

Two therapeutic options are available for treating PCT—whether it’s sporadic or familial. Phlebotomy sessions reduce iron overload and iron depletion and may prevent the formation of a porphomethene inhibitor of UROD. The other treatment option is antimalarial agents—usually hydroxychloroquine— and is indicated for patients with lower serum ferritin levels.1-4 In patients with HCV-associated PCT, effective treatment of the infection has resulted in resolution of the PCT, in some cases.3

Treatment involving phlebotomy or an antimalarial agent can be stopped when plasma porphyrins reach normal levels.

Our patient was initially managed with 2 sessions of phlebotomy. He subsequently received treatment for the HCV infection at another hospital.

A 55-YEAR-OLD MAN with hypertension and untreated hepatitis C virus (HCV) was referred to the Dermatology Clinic after reporting a 2-year history of photosensitivity and intermittent episodes of blistering and scars on the dorsal side of his hands and feet. No alcohol consumption or drug use was reported.

Physical examination revealed small and shallow erosions on the dorsal aspect of the hands and feet (but no visible blisters) and milium cysts (FIGURE 1A). Additionally, hypertrichosis and hyperpigmentation were observed in the zygomatic areas (FIGURE 1B). Complete blood count and kidney function test results were within normal ranges. Liver function tests showed slightly elevated levels of alanine aminotransferase (79 U/L; normal range, 0-41 U/L), aspartate aminotransferase (62 U/L; normal range, 0-40 U/L), and ferritin (121 ng/mL; normal range, 30-100 ng/mL). Serologies for syphilis, HIV, and hepatitis B virus were negative.

Telltale signs on hands and face

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Porphyria cutanea tarda

The clinical presentation, along with the elevated laboratory values, suggested that this might be a case of porphyria cutanea tarda (PCT). Therefore, a sample of the patient’s urine was examined under Wood lamp and compared to a sample from a healthy control. In the sample of urine from our patient, a vivid red-pink fluorescence could be visualized under the lamp (FIGURE 2), confirming the diagnosis.

Wood lamp confirmed the diagnosis

The porphyrias are a group of metabolic diseases that affect the heme biosynthesis. They can be classified into 1 of 3 groups, according to clinical features:

  • acute hepatic porphyrias, with neurovisceral symptoms (eg, acute intermittent porphyria),
  • nonblistering cutaneous porphyrias, with severe photosensitivity but without bullae formation (eg, erythropoietic protoporphyria), or
  • blistering cutaneous porphyrias (eg, PCT, hepatoerythropoietic porphyria, and variegate porphyria).

PCT is the most common type of porphyria, with a global prevalence of 1 per 10,000 people.1,2 It affects adults after the third or fourth decade of life.

Porphyria cutanea tarda has a global prevalance of 1 per 10,000 people.

PCT involves dysfunction of the uroporphyrinogen decarboxylase enzyme (UROD), the fifth enzyme in heme biosynthesis, which catalyzes the conversion of uroporphyrinogen to coproporphyrinogen. This dysfunction causes the accumulation of porphyrinogens that are auto-oxidized to photosensitizing porphyrins.1-4 PCT can be classified as “sporadic” or “familial” based on the absence or presence of UROD mutation. Approximately 80% of cases of PCT are sporadic.2

In sporadic PCT, triggers for UROD dysfunction include alcohol use, use of estrogens, hemochromatosis or iron overload, chronic HCV infection, and HIV infection.1-4 HCV (which this patient had) is the most common infection associated with sporadic PCT, with a prevalence of about 50% among these patients.5

Continue to: Dermatologic manifestations of PCT

 

 

Dermatologic manifestations of PCT include photosensitivity, skin fragility, vesicles, bullae, erosions, and crusts observed in sun-exposed areas. A nonvirilizing type of hypertrichosis may appear prominently on the temples and the cheeks.2-4 After blisters rupture, atrophy and scarring occur. Milia cysts can form on the dorsal side of the hands and fingers. Less common manifestations include pruritus, scarring alopecia, sclerodermatous changes, and periorbital purple-red suffusion.

Hepatic involvement is demonstrated with elevated serum transaminases and ­gamma-glutamyl transpeptidase. Hepatomegaly is common, and cirrhosis manifests in 30% to 40% of patients.2-5 On liver biopsy, some degree of siderosis is found in 80% of patients with PCT, and most of them have increased levels of serum iron. The incidence of hepatocellular carcinoma in patients with PCT is greater than in patients with other liver diseases.2

A Wood lamp can be a useful diagnostic first step

Plasma or urine porphyrin lab tests are the gold standard for PCT diagnosis. These tests can be followed by more specific tests (eg, porphyrin fractionation) to exclude other forms of porphyria. However, if plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam, which can be performed on urine or stool. (Plasma or urine porphyrin testing may ultimately be necessary if there is doubt about the diagnosis following the Wood lamp screening.) Histopathologic examination does not confirm the diagnosis of PCT4; however, it can be helpful in differential diagnosis.

Wood lamp is a source of long-wave UV light (320 to 400 nm), visualized as a purple or violet light. When porphyrins are present in a urine sample, a red-pink fluorescence may be seen.3,4,6 The Wood lamp examination should be performed in a completely dark room after the lamp has been warmed up for about 1 minute; time should be allowed for the clinician’s vision to adapt to the dark.6 There are no data regarding the sensitivity or specificity of the Wood lamp test in the diagnosis of PCT.

These conditions also cause skin fragility and photosensitivity

The differential diagnosis for PCT includes diseases that also cause skin fragility, blistering, or photosensitivity, such as pseudoporphyria, bullous systemic lupus erythematosus (SLE), and epidermolysis bullosa acquisita (EBA).3

Continue to: In pseudoporphyria

 

 

In pseudoporphyria, the clinical findings may be indistinguishable from PCT. Thus, the patient’s history will be especially important; suspect pseudoporphyria if the patient has a history of chronic renal failure or use of a photosensitizing drug.1,3

Bullous SLE usually manifests with systemic involvement and widespread, tense bullae. Serologic investigation will demonstrate the presence of antinuclear antibodies in high titers (> 1:80), as well as other circulating autoantibodies.

Skin lesions of EBA usually manifest with skin fragility and noninflammatory tense bullae in traumatized skin, such as the extensor surfaces of the hands, feet, and fingers.

None of the above-mentioned diagnoses manifest with hypertrichosis or red-pink fluorescent urine on Wood lamp, and results of porphyrin studies would be normal.3

Address triggers, provide treatment

Once the diagnosis is confirmed, steps must be taken to avoid triggering factors, such as any alcohol consumption, use of estrogen, sun exposure (until plasma porphyrin levels are normal), and potential sources of excessive iron intake.

If plasma or urine porphyrin testing is not readily available, a good first step is a Wood lamp exam.

Two therapeutic options are available for treating PCT—whether it’s sporadic or familial. Phlebotomy sessions reduce iron overload and iron depletion and may prevent the formation of a porphomethene inhibitor of UROD. The other treatment option is antimalarial agents—usually hydroxychloroquine— and is indicated for patients with lower serum ferritin levels.1-4 In patients with HCV-associated PCT, effective treatment of the infection has resulted in resolution of the PCT, in some cases.3

Treatment involving phlebotomy or an antimalarial agent can be stopped when plasma porphyrins reach normal levels.

Our patient was initially managed with 2 sessions of phlebotomy. He subsequently received treatment for the HCV infection at another hospital.

References

1. Handler NS, Handler MZ, Stephany MP, et. Porphyria cutanea tarda: an intriguing genetic disease and marker. Int J Dermatol. 2017;56:e106-e117.doi: 10.1111/ijd.13580

2. Lambrecht RW, Thapar M, Bonkovsky HL. Genetic aspects of porphyria cutanea tarda. Semin Liver Dis. 2007;27:99-108.doi: 10.1055/s-2006-960173

3. Callen JP. Hepatitis C viral infection and porphyria cutanea tarda. Am J Med Sci. 2017;354:5-6. doi: 10.1016/j.amjms.2017.06.009

4. Frank J, Poblete-Gutiérrez P. Porphyria cutanea tarda—when skin meets liver. Best Pract Res Clin Gastroenterol. 2010;24:735-745. doi: 10.1016/j.bpg.2010.07.002

5. Gisbert JP, García-Buey L, Pajares JM, et al. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol. 2003;39:620-627.doi: 10.1016/s0168-8278(03)00346-5

6. Asawanonda P, Taylor CR. Wood’s light in dermatology. Int J Dermatol. 1999;38:801-807. doi: 10.1046/j.1365-4362.1999.00794.x

References

1. Handler NS, Handler MZ, Stephany MP, et. Porphyria cutanea tarda: an intriguing genetic disease and marker. Int J Dermatol. 2017;56:e106-e117.doi: 10.1111/ijd.13580

2. Lambrecht RW, Thapar M, Bonkovsky HL. Genetic aspects of porphyria cutanea tarda. Semin Liver Dis. 2007;27:99-108.doi: 10.1055/s-2006-960173

3. Callen JP. Hepatitis C viral infection and porphyria cutanea tarda. Am J Med Sci. 2017;354:5-6. doi: 10.1016/j.amjms.2017.06.009

4. Frank J, Poblete-Gutiérrez P. Porphyria cutanea tarda—when skin meets liver. Best Pract Res Clin Gastroenterol. 2010;24:735-745. doi: 10.1016/j.bpg.2010.07.002

5. Gisbert JP, García-Buey L, Pajares JM, et al. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol. 2003;39:620-627.doi: 10.1016/s0168-8278(03)00346-5

6. Asawanonda P, Taylor CR. Wood’s light in dermatology. Int J Dermatol. 1999;38:801-807. doi: 10.1046/j.1365-4362.1999.00794.x

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Can early introduction of gluten reduce risk of celiac disease?

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Can early introduction of gluten reduce risk of celiac disease?

ILLUSTRATIVE CASE

You are seeing a 2-month-old female infant for a routine well-child visit. The birth history was unremarkable. The infant is meeting appropriate developmental milestones. Growth is appropriate at the 40th percentile. The infant is exclusively breastfed. The parents report that they have heard confusing information about when to introduce solid foods, including bread, to their child’s diet. There is no known family history of CD. What anticipatory guidance can you offer regarding gluten introduction and the risk of CD?

CD is an inflammatory disease of the small intestine caused by an immune-based reaction to dietary gluten. The worldwide incidence of CD in children younger than 15 years is 21.3 per 100,000 person-years; this incidence has increased by 7.5% per year over the past several decades.2 CD has a range of both gastrointestinal and nongastrointestinal manifestations, including diarrhea, weight loss, abdominal pain, abnormal liver function test results, and iron deficiency anemia.

Diagnosis of CD in adults is based on a combination of clinical symptoms, elevated levels of immunoglobulin A anti-tissue transglutaminase antibody (tTG-IgA), and biopsy-confirmed villous atrophy of the duodenum on upper endoscopy.3 European pediatric guidelines suggest that use of certain criteria, including very high results of tTG-IgA antibody testing (> 10 times the upper limit of normal), can help to avoid endoscopic biopsies and/or human leukocyte antigens (HLA) testing for diagnosis in children.4

The mainstay of CD management is strict adherence to a gluten-free diet.3 Because this can be difficult, and yield an incomplete disease response, emphasis has been placed on primary prevention by modifying introduction of dietary gluten. Multiple prior studies examining the risk of CD have failed to demonstrate a significant association between timing of gluten introduction and development of CD among high-risk infants (eg, those with HLA-DR3 alleles or first-degree relatives with CD or type 1 diabetes).5-7 A 2016 meta-analysis concluded that there was not enough evidence to support early introduction of gluten (at 4-6 months).8 RCTs have not previously been conducted to examine the timing of gluten introduction on CD prevalence for infants at average risk, using age-appropriate doses of gluten prior to age 6 months.

Current dietary guidelines in the United States and the United Kingdom recommend introduction of nutrient-dense foods, including potentially allergenic foods, at about age 6 months to complement human milk or infant formula feedings.9,10 These guidelines do not specify the exact timing or quantity of gluten- containing food introduction for infants. A 2016 position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition indicated that gluten could be introduced into the infant’s diet any time between 4 and 12 months. They did indicate that the amount of gluten introduced into the diet should be low to start and then increased, and that infants at high risk for CD should wait longer for gluten introduction (4 vs 6 months or 6 vs 12 months).11

STUDY SUMMARY

Gluten introduced at 4 months may be linked to lower occurrence of CD

The Enquiring About Tolerance (EAT) Study was an open-label RCT (N = 1303) with children from the general population in England and Wales. The EAT Study sought to test the prevention of food allergy by introducing allergenic foods to infants at age 4 months compared with exclusively breastfeeding until age 6 months. The median age at enrollment was 3.4 months, but allergenic food was not started until age 4 months.1,12 Most patients were White (84.%-85.4%) and lived in an urban area (77.3%-77.4%). The mean gestational age at delivery was 39.7 to 39.9 weeks.12

Infants were exclusively breastfed until age 13 weeks, at which time they were randomized into an early introduction group (EIG) or a standard introduction group (SIG). In addition to breast milk, infants in the EIG consumed 6 allergenic foods (peanut, sesame, hen’s egg, cow’s milk, cod fish, and wheat [gluten]) in a specified pattern per protocol, starting at age 4 months. Wheat (gluten) was introduced during Week 5 of the EIG protocol (median age, 20.6 weeks).12 The recommended minimum dose of gluten was 3.2 g/wk from age 16 weeks, or 4 g/wk of wheat protein (given as 2 cereal biscuits or the equivalent). Infants in the SIG avoided allergenic foods, following UK infant feeding recommendations for exclusive breastfeeding until about age 6 months. The EIG had a significantly higher rate of cesarean births than the SIG, but the study groups were otherwise balanced.13

Continue to: Families completed monthly...

 

 

Families completed monthly questionnaires on infant gluten intake and symptoms (eg, gastrointestinal, fatigue) through age 1 year, and then every 3 months through age 3 years. All children were tested for anti-transglutaminase type 2 (anti-TG2) antibodies at age 3 years as a screen for CD. Children with antibody levels > 20 IU/L were referred to independent gastroenterologists for further evaluation, which could include HLA (DQ-2/DQ-8) testing and biopsy in accordance with current European diagnostic guidelines.4

Introducing gluten as a complement to breast milk or infant formula from age 4 months may reduce the risk of celiac disease at age 3 years.

In an intention-to-treat analysis for the primary outcome, 595 children in the SIG (91.4%) and 567 in the EIG (87.0%) were included. Between ages 4 and 6 months, the mean (SD) quantity of gluten consumed in the SIG was 0.49 (1.40) g/wk; in the EIG, the mean quantity was 2.66 (1.85) g/wk (P < .001). At age 3 years, of a total of 1004 children tested for anti-TG2 antibodies, 9 had anti-TG2 levels requiring referral (7 in the SIG and 2 in the EIG). A diagnosis of CD was confirmed in 7 of 516 children in the SIG (1.4%) vs none of the 488 children in the EIG (P = .02). Using bootstrap resampling, the risk difference between the groups was 1.4% (95% CI, 0.6%-2.6%).

WHAT’S NEW

Findings have potential to change nutritional guidance

This study demonstrated that introduction of age-appropriate portions of gluten-containing products at age 4 months, in addition to breast milk, may reduce the risk of CD at 3 years in children at average risk. This finding has the potential to change anticipatory guidance given to parents regarding infant nutrition recommendations.

CAVEATS

More studies needed to confirm prevention vs delay of CD

The homogeneous study population may limit generalizability. Infants in this study were from England and Wales (84.3% were White), born at term, and were exclusively breastfed until age 13 weeks. Further studies are required to determine whether these findings can be applied to infants who are no longer breastfeeding, are more racially diverse, or are preterm in gestational age at birth. Additionally, the study followed the participants only until age 3 years. Given that the onset of CD after this age is likely, further research is needed to support that CD is truly prevented rather than delayed.

CHALLENGES TO IMPLEMENTATION

Guidance on allergen introduction may be unclear

The EAT Study protocol required parents in the EIG to sequentially introduce a minimum amount of the 6 allergenic foods specified. Only 42% of the EIG cohort reported adherence to the protocol.12 It is unclear how important this specific regimen is to the study results and whether introduction of all 6 allergenic foods simultaneously modifies the immune response to gluten. Therefore, there may be challenges to implementation if physicians do not know how to provide anticipatory guidance on the appropriate steps for allergen introduction.

References

1. Logan K, Perkin MR, Marrs T, et al. Early gluten introduction and celiac disease in the EAT Study: a prespecified analysis of the EAT randomized clinical trial. JAMA Pediatr. 2020;174:1041-1047. doi: 10.1001/jamapediatrics.2020.2893

2. King JA, Jeong J, Underwood FE, et al. Incidence of celiac disease is increasing over time: a systematic review and meta-analysis. Am J Gastroenterol. 2020;115:507-525. doi: 10.14309/ajg.0000000000000523

3. Rubio-Tapia A, Hill ID, Kelly CP, et al; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656-676; quiz 677. doi: 10.1038/ajg.2013.79

4. Husby S, Koletzko S, Korponay-Szabó I, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr. 2020;70:141-156. doi: 10.1097/MPG.0000000000002497

5. Vriezinga SL, Auricchio R, Bravi E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med. 2014;371:1304-1315. doi: 10.1056/NEJMoa1404172

6. Beyerlein A, Chmiel R, Hummel S, et al. Timing of gluten introduction and islet autoimmunity in young children: updated results from the BABYDIET study. Diabetes Care. 2014;37:e194-e195. doi: 10.2337/dc14-1208

7. Lionetti E, Castellaneta S, Francavilla R, et al; SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371:1295-1303. doi: 10.1056/NEJMoa1400697

8. Pinto-Sánchez MI, Verdu EF, Liu E, et al. Gluten introduction to infant feeding and risk of celiac disease: systematic review and meta-analysis. J Pediatr. 2016;168:132-143.e3. doi: 10.1016/j.jpeds.2015.09.032

9. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th ed. December 2020. Accessed June 8, 2022. www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf

10. NHS. Food allergies in babies and young children. Last reviewed November 5, 2021. Accessed June 8, 2022. www.nhs.uk/conditions/baby/weaning-and-feeding/food-allergies-in-babies-and-young-children/

11. Szajewska H, Shamir R, Mearin L, et al. Gluten introduction and the risk of coeliac disease: a position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2016;62:507-513. doi: 10.1097/MPG.0000000000001105

12. Perkin MR, Logan K, Marrs T, et al; EAT Study Team. Enquiring About Tolerance (EAT) study: feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137:1477-1486.e8. doi: 10.1016/j.jaci.2015.12.1322

13. Perkin MR, Logan K, Tseng A, et al; EAT Study Team. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733-1743. doi: 10.1056/NEJMoa1514210

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ILLUSTRATIVE CASE

You are seeing a 2-month-old female infant for a routine well-child visit. The birth history was unremarkable. The infant is meeting appropriate developmental milestones. Growth is appropriate at the 40th percentile. The infant is exclusively breastfed. The parents report that they have heard confusing information about when to introduce solid foods, including bread, to their child’s diet. There is no known family history of CD. What anticipatory guidance can you offer regarding gluten introduction and the risk of CD?

CD is an inflammatory disease of the small intestine caused by an immune-based reaction to dietary gluten. The worldwide incidence of CD in children younger than 15 years is 21.3 per 100,000 person-years; this incidence has increased by 7.5% per year over the past several decades.2 CD has a range of both gastrointestinal and nongastrointestinal manifestations, including diarrhea, weight loss, abdominal pain, abnormal liver function test results, and iron deficiency anemia.

Diagnosis of CD in adults is based on a combination of clinical symptoms, elevated levels of immunoglobulin A anti-tissue transglutaminase antibody (tTG-IgA), and biopsy-confirmed villous atrophy of the duodenum on upper endoscopy.3 European pediatric guidelines suggest that use of certain criteria, including very high results of tTG-IgA antibody testing (> 10 times the upper limit of normal), can help to avoid endoscopic biopsies and/or human leukocyte antigens (HLA) testing for diagnosis in children.4

The mainstay of CD management is strict adherence to a gluten-free diet.3 Because this can be difficult, and yield an incomplete disease response, emphasis has been placed on primary prevention by modifying introduction of dietary gluten. Multiple prior studies examining the risk of CD have failed to demonstrate a significant association between timing of gluten introduction and development of CD among high-risk infants (eg, those with HLA-DR3 alleles or first-degree relatives with CD or type 1 diabetes).5-7 A 2016 meta-analysis concluded that there was not enough evidence to support early introduction of gluten (at 4-6 months).8 RCTs have not previously been conducted to examine the timing of gluten introduction on CD prevalence for infants at average risk, using age-appropriate doses of gluten prior to age 6 months.

Current dietary guidelines in the United States and the United Kingdom recommend introduction of nutrient-dense foods, including potentially allergenic foods, at about age 6 months to complement human milk or infant formula feedings.9,10 These guidelines do not specify the exact timing or quantity of gluten- containing food introduction for infants. A 2016 position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition indicated that gluten could be introduced into the infant’s diet any time between 4 and 12 months. They did indicate that the amount of gluten introduced into the diet should be low to start and then increased, and that infants at high risk for CD should wait longer for gluten introduction (4 vs 6 months or 6 vs 12 months).11

STUDY SUMMARY

Gluten introduced at 4 months may be linked to lower occurrence of CD

The Enquiring About Tolerance (EAT) Study was an open-label RCT (N = 1303) with children from the general population in England and Wales. The EAT Study sought to test the prevention of food allergy by introducing allergenic foods to infants at age 4 months compared with exclusively breastfeeding until age 6 months. The median age at enrollment was 3.4 months, but allergenic food was not started until age 4 months.1,12 Most patients were White (84.%-85.4%) and lived in an urban area (77.3%-77.4%). The mean gestational age at delivery was 39.7 to 39.9 weeks.12

Infants were exclusively breastfed until age 13 weeks, at which time they were randomized into an early introduction group (EIG) or a standard introduction group (SIG). In addition to breast milk, infants in the EIG consumed 6 allergenic foods (peanut, sesame, hen’s egg, cow’s milk, cod fish, and wheat [gluten]) in a specified pattern per protocol, starting at age 4 months. Wheat (gluten) was introduced during Week 5 of the EIG protocol (median age, 20.6 weeks).12 The recommended minimum dose of gluten was 3.2 g/wk from age 16 weeks, or 4 g/wk of wheat protein (given as 2 cereal biscuits or the equivalent). Infants in the SIG avoided allergenic foods, following UK infant feeding recommendations for exclusive breastfeeding until about age 6 months. The EIG had a significantly higher rate of cesarean births than the SIG, but the study groups were otherwise balanced.13

Continue to: Families completed monthly...

 

 

Families completed monthly questionnaires on infant gluten intake and symptoms (eg, gastrointestinal, fatigue) through age 1 year, and then every 3 months through age 3 years. All children were tested for anti-transglutaminase type 2 (anti-TG2) antibodies at age 3 years as a screen for CD. Children with antibody levels > 20 IU/L were referred to independent gastroenterologists for further evaluation, which could include HLA (DQ-2/DQ-8) testing and biopsy in accordance with current European diagnostic guidelines.4

Introducing gluten as a complement to breast milk or infant formula from age 4 months may reduce the risk of celiac disease at age 3 years.

In an intention-to-treat analysis for the primary outcome, 595 children in the SIG (91.4%) and 567 in the EIG (87.0%) were included. Between ages 4 and 6 months, the mean (SD) quantity of gluten consumed in the SIG was 0.49 (1.40) g/wk; in the EIG, the mean quantity was 2.66 (1.85) g/wk (P < .001). At age 3 years, of a total of 1004 children tested for anti-TG2 antibodies, 9 had anti-TG2 levels requiring referral (7 in the SIG and 2 in the EIG). A diagnosis of CD was confirmed in 7 of 516 children in the SIG (1.4%) vs none of the 488 children in the EIG (P = .02). Using bootstrap resampling, the risk difference between the groups was 1.4% (95% CI, 0.6%-2.6%).

WHAT’S NEW

Findings have potential to change nutritional guidance

This study demonstrated that introduction of age-appropriate portions of gluten-containing products at age 4 months, in addition to breast milk, may reduce the risk of CD at 3 years in children at average risk. This finding has the potential to change anticipatory guidance given to parents regarding infant nutrition recommendations.

CAVEATS

More studies needed to confirm prevention vs delay of CD

The homogeneous study population may limit generalizability. Infants in this study were from England and Wales (84.3% were White), born at term, and were exclusively breastfed until age 13 weeks. Further studies are required to determine whether these findings can be applied to infants who are no longer breastfeeding, are more racially diverse, or are preterm in gestational age at birth. Additionally, the study followed the participants only until age 3 years. Given that the onset of CD after this age is likely, further research is needed to support that CD is truly prevented rather than delayed.

CHALLENGES TO IMPLEMENTATION

Guidance on allergen introduction may be unclear

The EAT Study protocol required parents in the EIG to sequentially introduce a minimum amount of the 6 allergenic foods specified. Only 42% of the EIG cohort reported adherence to the protocol.12 It is unclear how important this specific regimen is to the study results and whether introduction of all 6 allergenic foods simultaneously modifies the immune response to gluten. Therefore, there may be challenges to implementation if physicians do not know how to provide anticipatory guidance on the appropriate steps for allergen introduction.

ILLUSTRATIVE CASE

You are seeing a 2-month-old female infant for a routine well-child visit. The birth history was unremarkable. The infant is meeting appropriate developmental milestones. Growth is appropriate at the 40th percentile. The infant is exclusively breastfed. The parents report that they have heard confusing information about when to introduce solid foods, including bread, to their child’s diet. There is no known family history of CD. What anticipatory guidance can you offer regarding gluten introduction and the risk of CD?

CD is an inflammatory disease of the small intestine caused by an immune-based reaction to dietary gluten. The worldwide incidence of CD in children younger than 15 years is 21.3 per 100,000 person-years; this incidence has increased by 7.5% per year over the past several decades.2 CD has a range of both gastrointestinal and nongastrointestinal manifestations, including diarrhea, weight loss, abdominal pain, abnormal liver function test results, and iron deficiency anemia.

Diagnosis of CD in adults is based on a combination of clinical symptoms, elevated levels of immunoglobulin A anti-tissue transglutaminase antibody (tTG-IgA), and biopsy-confirmed villous atrophy of the duodenum on upper endoscopy.3 European pediatric guidelines suggest that use of certain criteria, including very high results of tTG-IgA antibody testing (> 10 times the upper limit of normal), can help to avoid endoscopic biopsies and/or human leukocyte antigens (HLA) testing for diagnosis in children.4

The mainstay of CD management is strict adherence to a gluten-free diet.3 Because this can be difficult, and yield an incomplete disease response, emphasis has been placed on primary prevention by modifying introduction of dietary gluten. Multiple prior studies examining the risk of CD have failed to demonstrate a significant association between timing of gluten introduction and development of CD among high-risk infants (eg, those with HLA-DR3 alleles or first-degree relatives with CD or type 1 diabetes).5-7 A 2016 meta-analysis concluded that there was not enough evidence to support early introduction of gluten (at 4-6 months).8 RCTs have not previously been conducted to examine the timing of gluten introduction on CD prevalence for infants at average risk, using age-appropriate doses of gluten prior to age 6 months.

Current dietary guidelines in the United States and the United Kingdom recommend introduction of nutrient-dense foods, including potentially allergenic foods, at about age 6 months to complement human milk or infant formula feedings.9,10 These guidelines do not specify the exact timing or quantity of gluten- containing food introduction for infants. A 2016 position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition indicated that gluten could be introduced into the infant’s diet any time between 4 and 12 months. They did indicate that the amount of gluten introduced into the diet should be low to start and then increased, and that infants at high risk for CD should wait longer for gluten introduction (4 vs 6 months or 6 vs 12 months).11

STUDY SUMMARY

Gluten introduced at 4 months may be linked to lower occurrence of CD

The Enquiring About Tolerance (EAT) Study was an open-label RCT (N = 1303) with children from the general population in England and Wales. The EAT Study sought to test the prevention of food allergy by introducing allergenic foods to infants at age 4 months compared with exclusively breastfeeding until age 6 months. The median age at enrollment was 3.4 months, but allergenic food was not started until age 4 months.1,12 Most patients were White (84.%-85.4%) and lived in an urban area (77.3%-77.4%). The mean gestational age at delivery was 39.7 to 39.9 weeks.12

Infants were exclusively breastfed until age 13 weeks, at which time they were randomized into an early introduction group (EIG) or a standard introduction group (SIG). In addition to breast milk, infants in the EIG consumed 6 allergenic foods (peanut, sesame, hen’s egg, cow’s milk, cod fish, and wheat [gluten]) in a specified pattern per protocol, starting at age 4 months. Wheat (gluten) was introduced during Week 5 of the EIG protocol (median age, 20.6 weeks).12 The recommended minimum dose of gluten was 3.2 g/wk from age 16 weeks, or 4 g/wk of wheat protein (given as 2 cereal biscuits or the equivalent). Infants in the SIG avoided allergenic foods, following UK infant feeding recommendations for exclusive breastfeeding until about age 6 months. The EIG had a significantly higher rate of cesarean births than the SIG, but the study groups were otherwise balanced.13

Continue to: Families completed monthly...

 

 

Families completed monthly questionnaires on infant gluten intake and symptoms (eg, gastrointestinal, fatigue) through age 1 year, and then every 3 months through age 3 years. All children were tested for anti-transglutaminase type 2 (anti-TG2) antibodies at age 3 years as a screen for CD. Children with antibody levels > 20 IU/L were referred to independent gastroenterologists for further evaluation, which could include HLA (DQ-2/DQ-8) testing and biopsy in accordance with current European diagnostic guidelines.4

Introducing gluten as a complement to breast milk or infant formula from age 4 months may reduce the risk of celiac disease at age 3 years.

In an intention-to-treat analysis for the primary outcome, 595 children in the SIG (91.4%) and 567 in the EIG (87.0%) were included. Between ages 4 and 6 months, the mean (SD) quantity of gluten consumed in the SIG was 0.49 (1.40) g/wk; in the EIG, the mean quantity was 2.66 (1.85) g/wk (P < .001). At age 3 years, of a total of 1004 children tested for anti-TG2 antibodies, 9 had anti-TG2 levels requiring referral (7 in the SIG and 2 in the EIG). A diagnosis of CD was confirmed in 7 of 516 children in the SIG (1.4%) vs none of the 488 children in the EIG (P = .02). Using bootstrap resampling, the risk difference between the groups was 1.4% (95% CI, 0.6%-2.6%).

WHAT’S NEW

Findings have potential to change nutritional guidance

This study demonstrated that introduction of age-appropriate portions of gluten-containing products at age 4 months, in addition to breast milk, may reduce the risk of CD at 3 years in children at average risk. This finding has the potential to change anticipatory guidance given to parents regarding infant nutrition recommendations.

CAVEATS

More studies needed to confirm prevention vs delay of CD

The homogeneous study population may limit generalizability. Infants in this study were from England and Wales (84.3% were White), born at term, and were exclusively breastfed until age 13 weeks. Further studies are required to determine whether these findings can be applied to infants who are no longer breastfeeding, are more racially diverse, or are preterm in gestational age at birth. Additionally, the study followed the participants only until age 3 years. Given that the onset of CD after this age is likely, further research is needed to support that CD is truly prevented rather than delayed.

CHALLENGES TO IMPLEMENTATION

Guidance on allergen introduction may be unclear

The EAT Study protocol required parents in the EIG to sequentially introduce a minimum amount of the 6 allergenic foods specified. Only 42% of the EIG cohort reported adherence to the protocol.12 It is unclear how important this specific regimen is to the study results and whether introduction of all 6 allergenic foods simultaneously modifies the immune response to gluten. Therefore, there may be challenges to implementation if physicians do not know how to provide anticipatory guidance on the appropriate steps for allergen introduction.

References

1. Logan K, Perkin MR, Marrs T, et al. Early gluten introduction and celiac disease in the EAT Study: a prespecified analysis of the EAT randomized clinical trial. JAMA Pediatr. 2020;174:1041-1047. doi: 10.1001/jamapediatrics.2020.2893

2. King JA, Jeong J, Underwood FE, et al. Incidence of celiac disease is increasing over time: a systematic review and meta-analysis. Am J Gastroenterol. 2020;115:507-525. doi: 10.14309/ajg.0000000000000523

3. Rubio-Tapia A, Hill ID, Kelly CP, et al; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656-676; quiz 677. doi: 10.1038/ajg.2013.79

4. Husby S, Koletzko S, Korponay-Szabó I, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr. 2020;70:141-156. doi: 10.1097/MPG.0000000000002497

5. Vriezinga SL, Auricchio R, Bravi E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med. 2014;371:1304-1315. doi: 10.1056/NEJMoa1404172

6. Beyerlein A, Chmiel R, Hummel S, et al. Timing of gluten introduction and islet autoimmunity in young children: updated results from the BABYDIET study. Diabetes Care. 2014;37:e194-e195. doi: 10.2337/dc14-1208

7. Lionetti E, Castellaneta S, Francavilla R, et al; SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371:1295-1303. doi: 10.1056/NEJMoa1400697

8. Pinto-Sánchez MI, Verdu EF, Liu E, et al. Gluten introduction to infant feeding and risk of celiac disease: systematic review and meta-analysis. J Pediatr. 2016;168:132-143.e3. doi: 10.1016/j.jpeds.2015.09.032

9. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th ed. December 2020. Accessed June 8, 2022. www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf

10. NHS. Food allergies in babies and young children. Last reviewed November 5, 2021. Accessed June 8, 2022. www.nhs.uk/conditions/baby/weaning-and-feeding/food-allergies-in-babies-and-young-children/

11. Szajewska H, Shamir R, Mearin L, et al. Gluten introduction and the risk of coeliac disease: a position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2016;62:507-513. doi: 10.1097/MPG.0000000000001105

12. Perkin MR, Logan K, Marrs T, et al; EAT Study Team. Enquiring About Tolerance (EAT) study: feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137:1477-1486.e8. doi: 10.1016/j.jaci.2015.12.1322

13. Perkin MR, Logan K, Tseng A, et al; EAT Study Team. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733-1743. doi: 10.1056/NEJMoa1514210

References

1. Logan K, Perkin MR, Marrs T, et al. Early gluten introduction and celiac disease in the EAT Study: a prespecified analysis of the EAT randomized clinical trial. JAMA Pediatr. 2020;174:1041-1047. doi: 10.1001/jamapediatrics.2020.2893

2. King JA, Jeong J, Underwood FE, et al. Incidence of celiac disease is increasing over time: a systematic review and meta-analysis. Am J Gastroenterol. 2020;115:507-525. doi: 10.14309/ajg.0000000000000523

3. Rubio-Tapia A, Hill ID, Kelly CP, et al; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656-676; quiz 677. doi: 10.1038/ajg.2013.79

4. Husby S, Koletzko S, Korponay-Szabó I, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition guidelines for diagnosing coeliac disease 2020. J Pediatr Gastroenterol Nutr. 2020;70:141-156. doi: 10.1097/MPG.0000000000002497

5. Vriezinga SL, Auricchio R, Bravi E, et al. Randomized feeding intervention in infants at high risk for celiac disease. N Engl J Med. 2014;371:1304-1315. doi: 10.1056/NEJMoa1404172

6. Beyerlein A, Chmiel R, Hummel S, et al. Timing of gluten introduction and islet autoimmunity in young children: updated results from the BABYDIET study. Diabetes Care. 2014;37:e194-e195. doi: 10.2337/dc14-1208

7. Lionetti E, Castellaneta S, Francavilla R, et al; SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition) Working Group on Weaning and CD Risk. Introduction of gluten, HLA status, and the risk of celiac disease in children. N Engl J Med. 2014;371:1295-1303. doi: 10.1056/NEJMoa1400697

8. Pinto-Sánchez MI, Verdu EF, Liu E, et al. Gluten introduction to infant feeding and risk of celiac disease: systematic review and meta-analysis. J Pediatr. 2016;168:132-143.e3. doi: 10.1016/j.jpeds.2015.09.032

9. US Department of Agriculture, US Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th ed. December 2020. Accessed June 8, 2022. www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf

10. NHS. Food allergies in babies and young children. Last reviewed November 5, 2021. Accessed June 8, 2022. www.nhs.uk/conditions/baby/weaning-and-feeding/food-allergies-in-babies-and-young-children/

11. Szajewska H, Shamir R, Mearin L, et al. Gluten introduction and the risk of coeliac disease: a position paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2016;62:507-513. doi: 10.1097/MPG.0000000000001105

12. Perkin MR, Logan K, Marrs T, et al; EAT Study Team. Enquiring About Tolerance (EAT) study: feasibility of an early allergenic food introduction regimen. J Allergy Clin Immunol. 2016;137:1477-1486.e8. doi: 10.1016/j.jaci.2015.12.1322

13. Perkin MR, Logan K, Tseng A, et al; EAT Study Team. Randomized trial of introduction of allergenic foods in breast-fed infants. N Engl J Med. 2016;374:1733-1743. doi: 10.1056/NEJMoa1514210

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Inside the Article

PRACTICE CHANGER

Consider introducing gluten (wheat) in addition to breast milk or infant formula from age 4 months to potentially reduce the risk of celiac disease (CD) at age 3 years.1

STRENGTH OF RECOMMENDATION

B: Based on a single randomized controlled trial (RCT) with a patient-oriented outcome of CD diagnosis.1

Logan K, Perkin MR, Marrs T, et al. Early gluten introduction and celiac disease in the EAT Study: a prespecified analysis of the EAT randomized clinical trial. JAMA Pediatr. 2020;174:1041-1047.

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A judicious approach to ordering lab tests

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A judicious approach to ordering lab tests

CASE

A 35-year-old man arrives for an annual wellness visit with no specific complaints and no significant personal or family history. His normal exam includes a blood pressure of 110/74 mm Hg and a body mass index (BMI) of 23.6. You order “routine labs” for prevention, which include a comprehensive metabolic panel (CMP), fasting lipid profile, and thyroid-stimulating hormone (TSH) and 25(OH) vitamin D tests. Are you practicing value-based laboratory testing?

The answer to this question appears in the Case discussion at the end of the article.

Value-based care, including care provided through laboratory testing, can achieve the Institute for Healthcare Improvement’s Triple Aim of improving population health, improving the patient experience of care (including quality and satisfaction), and reducing cost: Value = (Quality x Patient experience) / Cost.1

As quality and patient experience rise and cost falls, the value of care increases. Unnecessary lab testing, however, can negatively impact this equation:

  • Error introduced by unnecessary testing can adversely affect quality.
  • Patients experience inconvenience and sometimes cascades of testing, in addition to financial responsibility, from unnecessary testing.
  • Low-value testing also contributes to work burden and provider burnout by requiring additional review and follow-up.

Rising health care costs are approaching 18% of the US gross domestic product, driven in large part by a wasteful and inefficient care delivery system.2 One review of “waste domains” identified by the Institute of Medicine estimates that approximately one-quarter of health care costs represent waste, including overtreatment, breakdowns of care coordination, and pricing that fails to correlate to the level of care received.3 High-volume, low-cost testing contributes more to total cost than low-volume, high-cost tests.4

Provider and system factors that contribute to ongoing waste

A lack of awareness of waste and how to reduce it contribute to the problem, as does an underappreciation of the harmful effects caused by incidental abnormal results.

Provider intolerance of diagnostic uncertainty often leads to ordering even more tests.

Continue to: Also, a hope of avoiding...

 

 

Do not order tests just to reassure the patient; unnecessary tests with insignificant results do little to reduce patient anxiety.

Also, a hope of avoiding missed diagnoses and potential lawsuits leads to defensive practice and more testing. In addition, patients and family members can exert pressure based on a belief that more testing represents better care. Of course, financial revenues from testing may come into play, with few disincentives to forgo testing. Something that also comes into play is that evidence-based guidance on cost-­effective laboratory testing may be lacking, or there may be a lack of knowledge on how to access existing evidence.

Automated systems can facilitate wasteful laboratory testing, and the heavy testing practices of hospitals and specialists may be inappropriately applied to outpatient primary care.

Factors affecting the cost of laboratory testing

Laboratory test results drive 70% of today’s medical decisions.5 Negotiated insurance payment for tests is usually much less than the direct out-of-pocket costs charged to the patient. Without insurance, lab tests can cost patients between $100 and $1000.6 If multiple tests are ordered, the costs could likely be many thousands of dollars.

Actual costs typically vary by the testing facility, the patient’s health plan, and location in the United States; hospital-based testing tends to be the most expensive. Insurers will pay for lab tests with appropriate indications that are covered in the contract with the provider.6

Choosing Wisely initiative weighs in on lab testing

Choosing Wisely, a prominent initiative of the American Board of Internal Medicine Foundation, promotes appropriate resource utilization through educational campaigns that detail how to avoid unnecessary medical tests, treatments, and procedures.7 Recommendations are based largely on specialty society consensus and disease-oriented evidence. Choosing Wisely recommendations advise against the following7:

  • performing laboratory blood testing unless clinically indicated or necessary for diagnosis or management, in order to avoid iatrogenic anemia. (American Academy of Family Physicians; Society for the Advancement of Patient Blood Management)
  • requesting just a serum creatinine to test adult patients with diabetes and/or hypertension for chronic kidney disease. Use the kidney profile: serum creatinine with estimated glomerular filtration rate and urinary albumin-creatinine ratio. (American Society for Clinical Pathology)
  • routinely screening for prostate cancer using a prostate-specific antigen test. It should be performed only after engaging in shared decision-making with the patient. (American Academy of Family Physicians; American Urological Association)
  • screening for genital herpes simplex virus infectionFrutiger LT Std in asymptomatic adults, including pregnant women. (American Academy of Family Physicians)
  • performing preoperative medical tests for eye surgery unless there are specific medical indications. (American Academy of Ophthalmology)

Sequential steps to takefor value-based lab ordering

Ask the question: “How will ordering this specific test change the management of my patient?” From there, take sequential steps using sound, evidence-based pathways. Morgan and colleagues8 outline the following practical approaches to rational test ordering:

  • Perform a thorough clinical assessment.
  • Consider the probability and implications of a positive test result.
  • Practice patient-centered communication: address the patient’s concerns and discuss the risks and benefits of tests and how they will influence management.
  • Follow clinical guidelines when available.
  • Avoid ordering tests to reassure the patient; unnecessary tests with insignificant results do little to reduce patient anxieties.
  • Avoid letting uncertainty drive unnecessary testing. Watchful waiting can allow time for the illness to resolve or declare itself.

Let’s consider this approach in the context of 4 areas: preventive care, diagnostic evaluation, ongoing management of chronic conditions, and preoperative testing.

Continue to: Preventive guidance from the USPSTF

 

 

Preventive guidance from the USPSTF

An independent volunteer panel of 16 national experts in prevention and evidence-based medicine develop recommendations for the US Preventive Services Task Force (USPSTF).9 These guidelines are based on evidence and are updated as new evidence surfaces. Thirteen recommendations, some of which advise avoiding preventive procedures that could cause harm to patients, cover laboratory tests used in screening for conditions such as hyperlipidemia10 and prostate cancer.11 We review the ones pertinent to our patient later at the end of the Case.

While the target audience for USPSTF recommendations is clinicians who provide preventive care, the recommendations are widely followed by policymakers, managed care organizations, public and private payers, quality improvement organizations, research institutions, and patients.

Take a critical look at how you approach the diagnostic evaluation

To reduce unnecessary testing in the diagnostic evaluation of patients, first consider pretest probability, test sensitivity and specificity, narrowly out-of-range tests, habitually paired tests, and repetitive laboratory testing.

Pretest probability, and test sensitivity and specificity. Pretest probability is the estimated chance that the patient has the disease before the test result is known. In a patient with low pretest probability of a disease, the ability to conclusively arrive at the diagnosis with one positive result is limited. Similarly, for tests in patients with high pretest probability of disease, a negative test cannot be used to firmly rule out a diagnosis.12

Reliability also depends on test sensitivity (the proportion of true positive results) and specificity (the proportion of true negative results). A test with high sensitivity but low specificity will generate more false-positive results, with potential harm to patients who do not have a disease.

Reflexively ordering tests together (eg, C-reactive protein with erythrocyte sedimentation rate) often contributes to unnecessary testing.

The pretest probability along with test sensitivity and specificity help a clinician to interpret a test result, and even decide whether to order the test at all. For example, the anti-nuclear antibody (ANA) test for systemic lupus erythematosus (SLE) has a sensitivity of 100% and a specificity of 86%13; it will always be positive in a patient with SLE. But when applied to individuals with low likelihood of SLE, false-positives are more common; the ANA is falsely positive in up to 14% of healthy individuals, depending on the population studied.13

Ordering a test may be unnecessary if the results will not change the treatment plan. For example, in a female patient with classic symptoms of an uncomplicated urinary tract infection, a urine culture and even a urinalysis may not change treatment.

Continue to: Narrowly out-of-range tests

 

 

Narrowly out-of-range tests. Test results that fall just outside the “normal” range may be of questionable significance. When an asymptomatic patient has mildly elevated liver enzymes, should additional tests be ordered to avoid missing a treatable disorder? In these scenarios, a history, including possible contributing factors such as alcohol or substance misuse, must be paired with the clinical presentation to assess pre-test probability of a particular condition.14 Repeating a narrowly out-of-range test is an option in patients when follow-up is possible. Alternatively, you could pursue watchful waiting and monitor a minor abnormality over time while being vigilant for clinical changes. This whole-patient approach will guide the decision of whether to order additional testing.

Habitually paired tests. Reflexively ordering tests together often contributes to unnecessary testing. Examples of commonly paired tests are serum lipase with amylase, C-reactive protein (CRP) with erythrocyte sedimentation rate (ESR), and TSH with free T4 to monitor patients with treated hypothyroidism. These tests add minimal value together and can be decoupled.15-17 Evidence supports ordering serum lipase alone, CRP instead of ESR, and TSH alone for monitoring thyroid status.

Unnecessary routine preoperative testing and testing sequelae for cataract surgery was calculated to cost Medicare up to $45.4 million annually

Some commonly paired tests may not even be necessary for diagnosis. The well-established Rotterdam Criteria for diagnosing polycystic ovary syndrome specify clinical features and ovarian ultrasound for diagnosis.18 They do not require measurement of commonly ordered follicle-­stimulating hormone and luteinizing hormone for diagnosis.

Serial rather than parallel testing, a “2-step approach,” is a strategy made easier with the advent of the electronic medical record (EMR) and computerized lab systems.8 These records and lab systems allow providers to order reflex tests, and to add on additional tests, if necessary, to an existing blood specimen.

Repetitive laboratory testing. Repetitive inpatient laboratory testing in patients who are clinically stable is wasteful and potentially harmful. Interventions involving physician education alone show mixed results, but combining education with clinician audit and feedback, along with EMR-enabled restrictive ordering, have resulted in significant and sustained reductions in repetitive laboratory testing.19

Continue to: Ongoing management of chronic conditions

 

 

Ongoing management of chronic conditions

Evidence-based guidelines support choices of tests and testing intervals for ongoing management of chronic conditions such as diabetes, hyperlipidemia, and hypertension.

Diabetes. Guidelines also define quality standards that are applied to value-based contracts. For example, the American Diabetes Association recommends assessing A1C every 6 months in patients whose type 2 diabetes is under stable control.20

Hyperlipidemia. For patients diagnosed with hyperlipidemia, 2018 clinical practice guidelines published by multiple specialty societies recommend assessing adherence and response to lifestyle changes and LDL-C–lowering medications with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed.21

Hypertension. With a new diagnosis of hypertension, guidelines advise an initial assessment for comorbidities and end-organ damage with an electrocardiogram, urinalysis, glucose level, blood count, electrolytes, creatinine, calcium, lipids, and urinary albumin/creatinine ratio. For ongoing monitoring, guidelines recommend assessment for end-organ damage through regular measurements of creatinine, glomerular filtration rate, and urinary microalbumin/creatinine ratio. Initiation and alteration of medications should prompt appropriate additional lab follow-up—eg, a measurement of serum potassium after starting a diuretic.22

Preoperative testing

Preoperative testing is overused in low-risk, ambulatory surgery. And testing, even with abnormal results, does not affect postoperative outcomes.23

Continue to: The American Society of Anesthesiologists (ASA) Physical Status Classification System

 

 

The American Society of Anesthesiologists (ASA) Physical Status Classification System, which has been in use for more than 60 years, considers the patient’s physical status (ASA grades I-VI),24 and when paired with surgery grades of minor, intermediate, and major/complex, can help assess preoperative risk and guide preoperative testing (TABLE).24-26

ASA recommendations for preoperative testing: Complete blood count and kidney function

Preoperative medical testing did not reduce the risk of medical adverse events during or after cataract surgery when compared with selective or no testing.27 Unnecessary preoperative testing can lead to a nonproductive cascade of additional investigations. In a 2018 study of Medicare beneficiaries, unnecessary routine preoperative testing and testing sequelae for cataract surgery was calculated to cost Medicare up to $45.4 million annually.28

CASE

You would not be practicing value-based laboratory testing, according to the USPSTF, if you ordered a CMP, fasting lipid profile, and TSH and 25(OH) vitamin D tests for this healthy 35-year-old man whose family history, blood pressure, and BMI do not put him at elevated risk. Universal lipid screening (Grade Ba) is recommended for all adults ages 40 to 75. Thyroid screening tests and measurement of 25(OH) vitamin D level (I statementsa) are not recommended. The USPSTF has not evaluated chemistry panels for screening.

The USPSTF would recommend the following actions for this patient:

  • Screen for HIV (ages 15 to 65 years; and younger or older if patient is at risk). (A recommendationa,29)
  • Screen for hepatitis C virus (in those ages 18 to 79). (B recommendation30)

The following USPSTF recommendations might have come into play if this patient had certain risk factors, or if the patient had been a woman:

  • Screen for diabetes if the patient is overweight or obese (B recommendation).
  • Screen for hepatitis B in adults at risk (B recommendation).
  • Screen for gonorrhea and chlamydia in women at risk (B recommendation). Such screening has an “I”statement for screening men at risk.

Continue to: As noted, costs of laboratory...

 

 

As noted, costs of laboratory testing vary widely, depending upon what tests are ordered, what type of insurance the patient has, and which tests the patient’s insurance covers. Who performs the testing also factors into the cost. Payers negotiate reduced fees for commercial lab testing, but potential out-of-­pocket costs to patients are much higher.

For our healthy 35-year-old man, the cost of the initially proposed testing (CMP, lipid panel, TSH, and 25[OH] vitamin D level) ranges from a negotiated payer cost of $85 to potential patient out-of-pocket cost of more than $400.6

Insurance would cover the USPSTF-­recommended testing (HIV and hepatitis C screening tests), which might incur only a patient co-pay, and cost the system about $65.

The USPSTF home page, found at www.uspreventiveservicestaskforce.org/uspstf/ includes recommendations that can be sorted for your patients. A web and mobile device application is also available through the website.

a USPSTF grade definitions:

A: There is high certainty that the net benefit is substantial. Offer service.

B: There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. Offer service.

C: There is at least moderate certainty that the net benefit is small. Offer service selectively.

D: There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Don’t offer service.

I: Current evidence is insufficient to assess the balance of benefits and harms of the service.

CORRESPONDENCE
Mitchell Kaminski, MD, MBA, 901 Walnut Street, 10th Floor, Jefferson College of Population Health, Philadelphia, PA 19107; [email protected]

References

1. IHI. What is the Triple Aim? Accessed June 20, 2022. http://www.ihi.org/Topics/TripleAim/Pages/Overview.aspx#:~:text=It%20is%20IHI’s%20belief%20that,capita%20cost%20of%20health%20care

2. Papanicolas I, Woskie LR, Jha AK. Health care spending in the United States and other high-income countries. JAMA. 2018;319:1024-1039. doi: 10.1001/jama.2018.1150

3. Shrank WH, Rogstad TL, Parekh N. Waste in the US health care system estimated costs and potential for savings. JAMA. 2019;322:1501-1509. doi:10.1001/jama.2019.13978

4. Mafi JN, Russell K, Bortz BA, et al. Low-cost, high-volume health services contribute the most to unnecessary health spending. Health Aff. 2017;36:1701-1704. doi: 10.1377/hlthaff.2017.0385

5. CDC. Strengthening clinical laboratories. 2018. Accessed June 2020, 2022. www.cdc.gov/csels/dls/strengthening-clinical-labs.html

6. Vuong KT. How much do lab tests cost without insurance in 2022? Accessed May 11, 2022. www.talktomira.com/post/how-much-do-lab-test-cost-without-insurance

7. Choosing Wisely: Promoting conversations between providers and patients. Accessed June 20, 2022. www.choosingwisely.org

8. Morgan S, van Driel M, Coleman J, et al. Rational test ordering in family medicine. Can Fam Physician. 2015;61:535-537.

9. US Preventive Services Taskforce. Screening for glaucoma and impaired vision. Accessed June 20, 2022. www.uspreventiveservicestaskforce.org/uspstf

10. Arnold MJ, O’Malley PG, Downs JR. Key recommendations on managing dyslipidemia for cardiovascular risk reduction: stopping where the evidence does. Am Fam Physician. 2021;103:455-458.

11. Welch HG, Albertsen PC. Reconsidering prostate cancer mortality—the future of PSA screening. N Engl J Med. 2020;382:1557-1563. doi: 10.1056/NEJMms1914228

12. American Society for Microbiology. Why pretest and posttest probability matter in the time of COVID-19. Accessed June 20, 2022. https://asm.org/Articles/2020/June/Why-Pretest-and-Posttest-Probability-Matter-in-the

13. Slater CA, Davis RB, Shmerling RH. Antinuclear antibody testing. A study of clinical utility. Arch Intern Med. 1996;156:1421-1425.

14. Aragon G, Younossi ZM. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleve Clin J Med. 2010;77:195-204. doi: 10.3949/ccjm.77a.09064

15. Ismail OZ, Bhayana V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem. 2017;50:1275-1280. doi: 10.1016/j.clinbiochem.2017.07.003.

16. Gottheil S, Khemani E, Copley K, et al. Reducing inappropriate ESR testing with computerized clinical decision support. BMJ Quality Improvement Reports, 2016;5:u211376.w4582. doi: 10.1136/bmjquality.u211376.w4582

17. Schneider C, Feller M, Bauer DC, et al. Initial evaluation of thyroid dysfunction - are simultaneous TSH and fT4 tests necessary? PloS One. 2018;13:e0196631–e0196631. doi: 10.1371/journal.pone.0196631

18. Williams T, Mortada R, Porter S. Diagnosis and treatment of polycystic ovary syndrome. Am Fam Physician. 2016;94:106-113.

19. Eaton KP, Levy K, Soong C et.al. Evidence-Based Guidelines to Eliminate Repetitive Laboratory Testing. JAMA Intern Med. 2017;177:1833-1839. doi: 10.1001/jamainternmed.2017.5152

20. ADA. Glycemic targets: standards of medical care in diabetes—2021. Diabetes Care. 2021;44:S73-S84. doi: 10.2337/dc21-S006

21. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139:e1082-e1143. doi: 10.1161/CIR.0000000000000625

22. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75:1334-1357. doi: 10.1161/­HYPERTENSIONAHA.120.15026.

23. Benarroch-Gampel J, Sheffield KM, Duncan CB, et al. Preoperative laboratory testing in patients undergoing elective, low-risk ambulatory surgery. Ann Surg. 2012;256:518-528. doi: 10.1097/SLA.0b013e318265bcdb

24. ASA. ASA physical status classification system. Accessed June 22,2022. www.asahq.org/standards-and-guidelines/asa-­physical-status-classification-system

25. NLM. Preoperative tests (update): routine preoperative tests for elective surgery. Accessed June 22, 2022. www.ncbi.nlm.nih.gov/books/NBK367919/

26. ASA. American Society of Anesthesiologists releases list of commonly used tests and treatments to question-AS PART OF CHOOSING WISELY® CAMPAIGN. Accessed June 22, 2022. www.asahq.org/about-asa/newsroom/news-­releases/2013/10/choosing-wisely

27. Keay L, Lindsley K, Tielsch J, et al. Routine preoperative medical testing for cataract surgery. Cochrane Database Syst Rev. 2019;1:CD007293. doi: 10.1002/14651858.CD007293.pub4

28. Chen CL, Clay TH, McLeod S, et al. A revised estimate of costs associated with routine preoperative testing in Medicare cataract patients with a procedure-specific indicator. JAMA Ophthalmol. 2018;136:231-238. doi:10.1001/jamaophthalmol.2017.6372

29. USPSTF. Human immunodeficiency virus (HIV) infection: screening. Accessed May 16, 2022. www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening

30. USPSTF. Hepatitis C virus infection in adolescents and adults: screening. Accessed June 20, 2022. www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-c-screening

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CASE

A 35-year-old man arrives for an annual wellness visit with no specific complaints and no significant personal or family history. His normal exam includes a blood pressure of 110/74 mm Hg and a body mass index (BMI) of 23.6. You order “routine labs” for prevention, which include a comprehensive metabolic panel (CMP), fasting lipid profile, and thyroid-stimulating hormone (TSH) and 25(OH) vitamin D tests. Are you practicing value-based laboratory testing?

The answer to this question appears in the Case discussion at the end of the article.

Value-based care, including care provided through laboratory testing, can achieve the Institute for Healthcare Improvement’s Triple Aim of improving population health, improving the patient experience of care (including quality and satisfaction), and reducing cost: Value = (Quality x Patient experience) / Cost.1

As quality and patient experience rise and cost falls, the value of care increases. Unnecessary lab testing, however, can negatively impact this equation:

  • Error introduced by unnecessary testing can adversely affect quality.
  • Patients experience inconvenience and sometimes cascades of testing, in addition to financial responsibility, from unnecessary testing.
  • Low-value testing also contributes to work burden and provider burnout by requiring additional review and follow-up.

Rising health care costs are approaching 18% of the US gross domestic product, driven in large part by a wasteful and inefficient care delivery system.2 One review of “waste domains” identified by the Institute of Medicine estimates that approximately one-quarter of health care costs represent waste, including overtreatment, breakdowns of care coordination, and pricing that fails to correlate to the level of care received.3 High-volume, low-cost testing contributes more to total cost than low-volume, high-cost tests.4

Provider and system factors that contribute to ongoing waste

A lack of awareness of waste and how to reduce it contribute to the problem, as does an underappreciation of the harmful effects caused by incidental abnormal results.

Provider intolerance of diagnostic uncertainty often leads to ordering even more tests.

Continue to: Also, a hope of avoiding...

 

 

Do not order tests just to reassure the patient; unnecessary tests with insignificant results do little to reduce patient anxiety.

Also, a hope of avoiding missed diagnoses and potential lawsuits leads to defensive practice and more testing. In addition, patients and family members can exert pressure based on a belief that more testing represents better care. Of course, financial revenues from testing may come into play, with few disincentives to forgo testing. Something that also comes into play is that evidence-based guidance on cost-­effective laboratory testing may be lacking, or there may be a lack of knowledge on how to access existing evidence.

Automated systems can facilitate wasteful laboratory testing, and the heavy testing practices of hospitals and specialists may be inappropriately applied to outpatient primary care.

Factors affecting the cost of laboratory testing

Laboratory test results drive 70% of today’s medical decisions.5 Negotiated insurance payment for tests is usually much less than the direct out-of-pocket costs charged to the patient. Without insurance, lab tests can cost patients between $100 and $1000.6 If multiple tests are ordered, the costs could likely be many thousands of dollars.

Actual costs typically vary by the testing facility, the patient’s health plan, and location in the United States; hospital-based testing tends to be the most expensive. Insurers will pay for lab tests with appropriate indications that are covered in the contract with the provider.6

Choosing Wisely initiative weighs in on lab testing

Choosing Wisely, a prominent initiative of the American Board of Internal Medicine Foundation, promotes appropriate resource utilization through educational campaigns that detail how to avoid unnecessary medical tests, treatments, and procedures.7 Recommendations are based largely on specialty society consensus and disease-oriented evidence. Choosing Wisely recommendations advise against the following7:

  • performing laboratory blood testing unless clinically indicated or necessary for diagnosis or management, in order to avoid iatrogenic anemia. (American Academy of Family Physicians; Society for the Advancement of Patient Blood Management)
  • requesting just a serum creatinine to test adult patients with diabetes and/or hypertension for chronic kidney disease. Use the kidney profile: serum creatinine with estimated glomerular filtration rate and urinary albumin-creatinine ratio. (American Society for Clinical Pathology)
  • routinely screening for prostate cancer using a prostate-specific antigen test. It should be performed only after engaging in shared decision-making with the patient. (American Academy of Family Physicians; American Urological Association)
  • screening for genital herpes simplex virus infectionFrutiger LT Std in asymptomatic adults, including pregnant women. (American Academy of Family Physicians)
  • performing preoperative medical tests for eye surgery unless there are specific medical indications. (American Academy of Ophthalmology)

Sequential steps to takefor value-based lab ordering

Ask the question: “How will ordering this specific test change the management of my patient?” From there, take sequential steps using sound, evidence-based pathways. Morgan and colleagues8 outline the following practical approaches to rational test ordering:

  • Perform a thorough clinical assessment.
  • Consider the probability and implications of a positive test result.
  • Practice patient-centered communication: address the patient’s concerns and discuss the risks and benefits of tests and how they will influence management.
  • Follow clinical guidelines when available.
  • Avoid ordering tests to reassure the patient; unnecessary tests with insignificant results do little to reduce patient anxieties.
  • Avoid letting uncertainty drive unnecessary testing. Watchful waiting can allow time for the illness to resolve or declare itself.

Let’s consider this approach in the context of 4 areas: preventive care, diagnostic evaluation, ongoing management of chronic conditions, and preoperative testing.

Continue to: Preventive guidance from the USPSTF

 

 

Preventive guidance from the USPSTF

An independent volunteer panel of 16 national experts in prevention and evidence-based medicine develop recommendations for the US Preventive Services Task Force (USPSTF).9 These guidelines are based on evidence and are updated as new evidence surfaces. Thirteen recommendations, some of which advise avoiding preventive procedures that could cause harm to patients, cover laboratory tests used in screening for conditions such as hyperlipidemia10 and prostate cancer.11 We review the ones pertinent to our patient later at the end of the Case.

While the target audience for USPSTF recommendations is clinicians who provide preventive care, the recommendations are widely followed by policymakers, managed care organizations, public and private payers, quality improvement organizations, research institutions, and patients.

Take a critical look at how you approach the diagnostic evaluation

To reduce unnecessary testing in the diagnostic evaluation of patients, first consider pretest probability, test sensitivity and specificity, narrowly out-of-range tests, habitually paired tests, and repetitive laboratory testing.

Pretest probability, and test sensitivity and specificity. Pretest probability is the estimated chance that the patient has the disease before the test result is known. In a patient with low pretest probability of a disease, the ability to conclusively arrive at the diagnosis with one positive result is limited. Similarly, for tests in patients with high pretest probability of disease, a negative test cannot be used to firmly rule out a diagnosis.12

Reliability also depends on test sensitivity (the proportion of true positive results) and specificity (the proportion of true negative results). A test with high sensitivity but low specificity will generate more false-positive results, with potential harm to patients who do not have a disease.

Reflexively ordering tests together (eg, C-reactive protein with erythrocyte sedimentation rate) often contributes to unnecessary testing.

The pretest probability along with test sensitivity and specificity help a clinician to interpret a test result, and even decide whether to order the test at all. For example, the anti-nuclear antibody (ANA) test for systemic lupus erythematosus (SLE) has a sensitivity of 100% and a specificity of 86%13; it will always be positive in a patient with SLE. But when applied to individuals with low likelihood of SLE, false-positives are more common; the ANA is falsely positive in up to 14% of healthy individuals, depending on the population studied.13

Ordering a test may be unnecessary if the results will not change the treatment plan. For example, in a female patient with classic symptoms of an uncomplicated urinary tract infection, a urine culture and even a urinalysis may not change treatment.

Continue to: Narrowly out-of-range tests

 

 

Narrowly out-of-range tests. Test results that fall just outside the “normal” range may be of questionable significance. When an asymptomatic patient has mildly elevated liver enzymes, should additional tests be ordered to avoid missing a treatable disorder? In these scenarios, a history, including possible contributing factors such as alcohol or substance misuse, must be paired with the clinical presentation to assess pre-test probability of a particular condition.14 Repeating a narrowly out-of-range test is an option in patients when follow-up is possible. Alternatively, you could pursue watchful waiting and monitor a minor abnormality over time while being vigilant for clinical changes. This whole-patient approach will guide the decision of whether to order additional testing.

Habitually paired tests. Reflexively ordering tests together often contributes to unnecessary testing. Examples of commonly paired tests are serum lipase with amylase, C-reactive protein (CRP) with erythrocyte sedimentation rate (ESR), and TSH with free T4 to monitor patients with treated hypothyroidism. These tests add minimal value together and can be decoupled.15-17 Evidence supports ordering serum lipase alone, CRP instead of ESR, and TSH alone for monitoring thyroid status.

Unnecessary routine preoperative testing and testing sequelae for cataract surgery was calculated to cost Medicare up to $45.4 million annually

Some commonly paired tests may not even be necessary for diagnosis. The well-established Rotterdam Criteria for diagnosing polycystic ovary syndrome specify clinical features and ovarian ultrasound for diagnosis.18 They do not require measurement of commonly ordered follicle-­stimulating hormone and luteinizing hormone for diagnosis.

Serial rather than parallel testing, a “2-step approach,” is a strategy made easier with the advent of the electronic medical record (EMR) and computerized lab systems.8 These records and lab systems allow providers to order reflex tests, and to add on additional tests, if necessary, to an existing blood specimen.

Repetitive laboratory testing. Repetitive inpatient laboratory testing in patients who are clinically stable is wasteful and potentially harmful. Interventions involving physician education alone show mixed results, but combining education with clinician audit and feedback, along with EMR-enabled restrictive ordering, have resulted in significant and sustained reductions in repetitive laboratory testing.19

Continue to: Ongoing management of chronic conditions

 

 

Ongoing management of chronic conditions

Evidence-based guidelines support choices of tests and testing intervals for ongoing management of chronic conditions such as diabetes, hyperlipidemia, and hypertension.

Diabetes. Guidelines also define quality standards that are applied to value-based contracts. For example, the American Diabetes Association recommends assessing A1C every 6 months in patients whose type 2 diabetes is under stable control.20

Hyperlipidemia. For patients diagnosed with hyperlipidemia, 2018 clinical practice guidelines published by multiple specialty societies recommend assessing adherence and response to lifestyle changes and LDL-C–lowering medications with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed.21

Hypertension. With a new diagnosis of hypertension, guidelines advise an initial assessment for comorbidities and end-organ damage with an electrocardiogram, urinalysis, glucose level, blood count, electrolytes, creatinine, calcium, lipids, and urinary albumin/creatinine ratio. For ongoing monitoring, guidelines recommend assessment for end-organ damage through regular measurements of creatinine, glomerular filtration rate, and urinary microalbumin/creatinine ratio. Initiation and alteration of medications should prompt appropriate additional lab follow-up—eg, a measurement of serum potassium after starting a diuretic.22

Preoperative testing

Preoperative testing is overused in low-risk, ambulatory surgery. And testing, even with abnormal results, does not affect postoperative outcomes.23

Continue to: The American Society of Anesthesiologists (ASA) Physical Status Classification System

 

 

The American Society of Anesthesiologists (ASA) Physical Status Classification System, which has been in use for more than 60 years, considers the patient’s physical status (ASA grades I-VI),24 and when paired with surgery grades of minor, intermediate, and major/complex, can help assess preoperative risk and guide preoperative testing (TABLE).24-26

ASA recommendations for preoperative testing: Complete blood count and kidney function

Preoperative medical testing did not reduce the risk of medical adverse events during or after cataract surgery when compared with selective or no testing.27 Unnecessary preoperative testing can lead to a nonproductive cascade of additional investigations. In a 2018 study of Medicare beneficiaries, unnecessary routine preoperative testing and testing sequelae for cataract surgery was calculated to cost Medicare up to $45.4 million annually.28

CASE

You would not be practicing value-based laboratory testing, according to the USPSTF, if you ordered a CMP, fasting lipid profile, and TSH and 25(OH) vitamin D tests for this healthy 35-year-old man whose family history, blood pressure, and BMI do not put him at elevated risk. Universal lipid screening (Grade Ba) is recommended for all adults ages 40 to 75. Thyroid screening tests and measurement of 25(OH) vitamin D level (I statementsa) are not recommended. The USPSTF has not evaluated chemistry panels for screening.

The USPSTF would recommend the following actions for this patient:

  • Screen for HIV (ages 15 to 65 years; and younger or older if patient is at risk). (A recommendationa,29)
  • Screen for hepatitis C virus (in those ages 18 to 79). (B recommendation30)

The following USPSTF recommendations might have come into play if this patient had certain risk factors, or if the patient had been a woman:

  • Screen for diabetes if the patient is overweight or obese (B recommendation).
  • Screen for hepatitis B in adults at risk (B recommendation).
  • Screen for gonorrhea and chlamydia in women at risk (B recommendation). Such screening has an “I”statement for screening men at risk.

Continue to: As noted, costs of laboratory...

 

 

As noted, costs of laboratory testing vary widely, depending upon what tests are ordered, what type of insurance the patient has, and which tests the patient’s insurance covers. Who performs the testing also factors into the cost. Payers negotiate reduced fees for commercial lab testing, but potential out-of-­pocket costs to patients are much higher.

For our healthy 35-year-old man, the cost of the initially proposed testing (CMP, lipid panel, TSH, and 25[OH] vitamin D level) ranges from a negotiated payer cost of $85 to potential patient out-of-pocket cost of more than $400.6

Insurance would cover the USPSTF-­recommended testing (HIV and hepatitis C screening tests), which might incur only a patient co-pay, and cost the system about $65.

The USPSTF home page, found at www.uspreventiveservicestaskforce.org/uspstf/ includes recommendations that can be sorted for your patients. A web and mobile device application is also available through the website.

a USPSTF grade definitions:

A: There is high certainty that the net benefit is substantial. Offer service.

B: There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. Offer service.

C: There is at least moderate certainty that the net benefit is small. Offer service selectively.

D: There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Don’t offer service.

I: Current evidence is insufficient to assess the balance of benefits and harms of the service.

CORRESPONDENCE
Mitchell Kaminski, MD, MBA, 901 Walnut Street, 10th Floor, Jefferson College of Population Health, Philadelphia, PA 19107; [email protected]

CASE

A 35-year-old man arrives for an annual wellness visit with no specific complaints and no significant personal or family history. His normal exam includes a blood pressure of 110/74 mm Hg and a body mass index (BMI) of 23.6. You order “routine labs” for prevention, which include a comprehensive metabolic panel (CMP), fasting lipid profile, and thyroid-stimulating hormone (TSH) and 25(OH) vitamin D tests. Are you practicing value-based laboratory testing?

The answer to this question appears in the Case discussion at the end of the article.

Value-based care, including care provided through laboratory testing, can achieve the Institute for Healthcare Improvement’s Triple Aim of improving population health, improving the patient experience of care (including quality and satisfaction), and reducing cost: Value = (Quality x Patient experience) / Cost.1

As quality and patient experience rise and cost falls, the value of care increases. Unnecessary lab testing, however, can negatively impact this equation:

  • Error introduced by unnecessary testing can adversely affect quality.
  • Patients experience inconvenience and sometimes cascades of testing, in addition to financial responsibility, from unnecessary testing.
  • Low-value testing also contributes to work burden and provider burnout by requiring additional review and follow-up.

Rising health care costs are approaching 18% of the US gross domestic product, driven in large part by a wasteful and inefficient care delivery system.2 One review of “waste domains” identified by the Institute of Medicine estimates that approximately one-quarter of health care costs represent waste, including overtreatment, breakdowns of care coordination, and pricing that fails to correlate to the level of care received.3 High-volume, low-cost testing contributes more to total cost than low-volume, high-cost tests.4

Provider and system factors that contribute to ongoing waste

A lack of awareness of waste and how to reduce it contribute to the problem, as does an underappreciation of the harmful effects caused by incidental abnormal results.

Provider intolerance of diagnostic uncertainty often leads to ordering even more tests.

Continue to: Also, a hope of avoiding...

 

 

Do not order tests just to reassure the patient; unnecessary tests with insignificant results do little to reduce patient anxiety.

Also, a hope of avoiding missed diagnoses and potential lawsuits leads to defensive practice and more testing. In addition, patients and family members can exert pressure based on a belief that more testing represents better care. Of course, financial revenues from testing may come into play, with few disincentives to forgo testing. Something that also comes into play is that evidence-based guidance on cost-­effective laboratory testing may be lacking, or there may be a lack of knowledge on how to access existing evidence.

Automated systems can facilitate wasteful laboratory testing, and the heavy testing practices of hospitals and specialists may be inappropriately applied to outpatient primary care.

Factors affecting the cost of laboratory testing

Laboratory test results drive 70% of today’s medical decisions.5 Negotiated insurance payment for tests is usually much less than the direct out-of-pocket costs charged to the patient. Without insurance, lab tests can cost patients between $100 and $1000.6 If multiple tests are ordered, the costs could likely be many thousands of dollars.

Actual costs typically vary by the testing facility, the patient’s health plan, and location in the United States; hospital-based testing tends to be the most expensive. Insurers will pay for lab tests with appropriate indications that are covered in the contract with the provider.6

Choosing Wisely initiative weighs in on lab testing

Choosing Wisely, a prominent initiative of the American Board of Internal Medicine Foundation, promotes appropriate resource utilization through educational campaigns that detail how to avoid unnecessary medical tests, treatments, and procedures.7 Recommendations are based largely on specialty society consensus and disease-oriented evidence. Choosing Wisely recommendations advise against the following7:

  • performing laboratory blood testing unless clinically indicated or necessary for diagnosis or management, in order to avoid iatrogenic anemia. (American Academy of Family Physicians; Society for the Advancement of Patient Blood Management)
  • requesting just a serum creatinine to test adult patients with diabetes and/or hypertension for chronic kidney disease. Use the kidney profile: serum creatinine with estimated glomerular filtration rate and urinary albumin-creatinine ratio. (American Society for Clinical Pathology)
  • routinely screening for prostate cancer using a prostate-specific antigen test. It should be performed only after engaging in shared decision-making with the patient. (American Academy of Family Physicians; American Urological Association)
  • screening for genital herpes simplex virus infectionFrutiger LT Std in asymptomatic adults, including pregnant women. (American Academy of Family Physicians)
  • performing preoperative medical tests for eye surgery unless there are specific medical indications. (American Academy of Ophthalmology)

Sequential steps to takefor value-based lab ordering

Ask the question: “How will ordering this specific test change the management of my patient?” From there, take sequential steps using sound, evidence-based pathways. Morgan and colleagues8 outline the following practical approaches to rational test ordering:

  • Perform a thorough clinical assessment.
  • Consider the probability and implications of a positive test result.
  • Practice patient-centered communication: address the patient’s concerns and discuss the risks and benefits of tests and how they will influence management.
  • Follow clinical guidelines when available.
  • Avoid ordering tests to reassure the patient; unnecessary tests with insignificant results do little to reduce patient anxieties.
  • Avoid letting uncertainty drive unnecessary testing. Watchful waiting can allow time for the illness to resolve or declare itself.

Let’s consider this approach in the context of 4 areas: preventive care, diagnostic evaluation, ongoing management of chronic conditions, and preoperative testing.

Continue to: Preventive guidance from the USPSTF

 

 

Preventive guidance from the USPSTF

An independent volunteer panel of 16 national experts in prevention and evidence-based medicine develop recommendations for the US Preventive Services Task Force (USPSTF).9 These guidelines are based on evidence and are updated as new evidence surfaces. Thirteen recommendations, some of which advise avoiding preventive procedures that could cause harm to patients, cover laboratory tests used in screening for conditions such as hyperlipidemia10 and prostate cancer.11 We review the ones pertinent to our patient later at the end of the Case.

While the target audience for USPSTF recommendations is clinicians who provide preventive care, the recommendations are widely followed by policymakers, managed care organizations, public and private payers, quality improvement organizations, research institutions, and patients.

Take a critical look at how you approach the diagnostic evaluation

To reduce unnecessary testing in the diagnostic evaluation of patients, first consider pretest probability, test sensitivity and specificity, narrowly out-of-range tests, habitually paired tests, and repetitive laboratory testing.

Pretest probability, and test sensitivity and specificity. Pretest probability is the estimated chance that the patient has the disease before the test result is known. In a patient with low pretest probability of a disease, the ability to conclusively arrive at the diagnosis with one positive result is limited. Similarly, for tests in patients with high pretest probability of disease, a negative test cannot be used to firmly rule out a diagnosis.12

Reliability also depends on test sensitivity (the proportion of true positive results) and specificity (the proportion of true negative results). A test with high sensitivity but low specificity will generate more false-positive results, with potential harm to patients who do not have a disease.

Reflexively ordering tests together (eg, C-reactive protein with erythrocyte sedimentation rate) often contributes to unnecessary testing.

The pretest probability along with test sensitivity and specificity help a clinician to interpret a test result, and even decide whether to order the test at all. For example, the anti-nuclear antibody (ANA) test for systemic lupus erythematosus (SLE) has a sensitivity of 100% and a specificity of 86%13; it will always be positive in a patient with SLE. But when applied to individuals with low likelihood of SLE, false-positives are more common; the ANA is falsely positive in up to 14% of healthy individuals, depending on the population studied.13

Ordering a test may be unnecessary if the results will not change the treatment plan. For example, in a female patient with classic symptoms of an uncomplicated urinary tract infection, a urine culture and even a urinalysis may not change treatment.

Continue to: Narrowly out-of-range tests

 

 

Narrowly out-of-range tests. Test results that fall just outside the “normal” range may be of questionable significance. When an asymptomatic patient has mildly elevated liver enzymes, should additional tests be ordered to avoid missing a treatable disorder? In these scenarios, a history, including possible contributing factors such as alcohol or substance misuse, must be paired with the clinical presentation to assess pre-test probability of a particular condition.14 Repeating a narrowly out-of-range test is an option in patients when follow-up is possible. Alternatively, you could pursue watchful waiting and monitor a minor abnormality over time while being vigilant for clinical changes. This whole-patient approach will guide the decision of whether to order additional testing.

Habitually paired tests. Reflexively ordering tests together often contributes to unnecessary testing. Examples of commonly paired tests are serum lipase with amylase, C-reactive protein (CRP) with erythrocyte sedimentation rate (ESR), and TSH with free T4 to monitor patients with treated hypothyroidism. These tests add minimal value together and can be decoupled.15-17 Evidence supports ordering serum lipase alone, CRP instead of ESR, and TSH alone for monitoring thyroid status.

Unnecessary routine preoperative testing and testing sequelae for cataract surgery was calculated to cost Medicare up to $45.4 million annually

Some commonly paired tests may not even be necessary for diagnosis. The well-established Rotterdam Criteria for diagnosing polycystic ovary syndrome specify clinical features and ovarian ultrasound for diagnosis.18 They do not require measurement of commonly ordered follicle-­stimulating hormone and luteinizing hormone for diagnosis.

Serial rather than parallel testing, a “2-step approach,” is a strategy made easier with the advent of the electronic medical record (EMR) and computerized lab systems.8 These records and lab systems allow providers to order reflex tests, and to add on additional tests, if necessary, to an existing blood specimen.

Repetitive laboratory testing. Repetitive inpatient laboratory testing in patients who are clinically stable is wasteful and potentially harmful. Interventions involving physician education alone show mixed results, but combining education with clinician audit and feedback, along with EMR-enabled restrictive ordering, have resulted in significant and sustained reductions in repetitive laboratory testing.19

Continue to: Ongoing management of chronic conditions

 

 

Ongoing management of chronic conditions

Evidence-based guidelines support choices of tests and testing intervals for ongoing management of chronic conditions such as diabetes, hyperlipidemia, and hypertension.

Diabetes. Guidelines also define quality standards that are applied to value-based contracts. For example, the American Diabetes Association recommends assessing A1C every 6 months in patients whose type 2 diabetes is under stable control.20

Hyperlipidemia. For patients diagnosed with hyperlipidemia, 2018 clinical practice guidelines published by multiple specialty societies recommend assessing adherence and response to lifestyle changes and LDL-C–lowering medications with repeat lipid measurement 4 to 12 weeks after statin initiation or dose adjustment, repeated every 3 to 12 months as needed.21

Hypertension. With a new diagnosis of hypertension, guidelines advise an initial assessment for comorbidities and end-organ damage with an electrocardiogram, urinalysis, glucose level, blood count, electrolytes, creatinine, calcium, lipids, and urinary albumin/creatinine ratio. For ongoing monitoring, guidelines recommend assessment for end-organ damage through regular measurements of creatinine, glomerular filtration rate, and urinary microalbumin/creatinine ratio. Initiation and alteration of medications should prompt appropriate additional lab follow-up—eg, a measurement of serum potassium after starting a diuretic.22

Preoperative testing

Preoperative testing is overused in low-risk, ambulatory surgery. And testing, even with abnormal results, does not affect postoperative outcomes.23

Continue to: The American Society of Anesthesiologists (ASA) Physical Status Classification System

 

 

The American Society of Anesthesiologists (ASA) Physical Status Classification System, which has been in use for more than 60 years, considers the patient’s physical status (ASA grades I-VI),24 and when paired with surgery grades of minor, intermediate, and major/complex, can help assess preoperative risk and guide preoperative testing (TABLE).24-26

ASA recommendations for preoperative testing: Complete blood count and kidney function

Preoperative medical testing did not reduce the risk of medical adverse events during or after cataract surgery when compared with selective or no testing.27 Unnecessary preoperative testing can lead to a nonproductive cascade of additional investigations. In a 2018 study of Medicare beneficiaries, unnecessary routine preoperative testing and testing sequelae for cataract surgery was calculated to cost Medicare up to $45.4 million annually.28

CASE

You would not be practicing value-based laboratory testing, according to the USPSTF, if you ordered a CMP, fasting lipid profile, and TSH and 25(OH) vitamin D tests for this healthy 35-year-old man whose family history, blood pressure, and BMI do not put him at elevated risk. Universal lipid screening (Grade Ba) is recommended for all adults ages 40 to 75. Thyroid screening tests and measurement of 25(OH) vitamin D level (I statementsa) are not recommended. The USPSTF has not evaluated chemistry panels for screening.

The USPSTF would recommend the following actions for this patient:

  • Screen for HIV (ages 15 to 65 years; and younger or older if patient is at risk). (A recommendationa,29)
  • Screen for hepatitis C virus (in those ages 18 to 79). (B recommendation30)

The following USPSTF recommendations might have come into play if this patient had certain risk factors, or if the patient had been a woman:

  • Screen for diabetes if the patient is overweight or obese (B recommendation).
  • Screen for hepatitis B in adults at risk (B recommendation).
  • Screen for gonorrhea and chlamydia in women at risk (B recommendation). Such screening has an “I”statement for screening men at risk.

Continue to: As noted, costs of laboratory...

 

 

As noted, costs of laboratory testing vary widely, depending upon what tests are ordered, what type of insurance the patient has, and which tests the patient’s insurance covers. Who performs the testing also factors into the cost. Payers negotiate reduced fees for commercial lab testing, but potential out-of-­pocket costs to patients are much higher.

For our healthy 35-year-old man, the cost of the initially proposed testing (CMP, lipid panel, TSH, and 25[OH] vitamin D level) ranges from a negotiated payer cost of $85 to potential patient out-of-pocket cost of more than $400.6

Insurance would cover the USPSTF-­recommended testing (HIV and hepatitis C screening tests), which might incur only a patient co-pay, and cost the system about $65.

The USPSTF home page, found at www.uspreventiveservicestaskforce.org/uspstf/ includes recommendations that can be sorted for your patients. A web and mobile device application is also available through the website.

a USPSTF grade definitions:

A: There is high certainty that the net benefit is substantial. Offer service.

B: There is high certainty that the net benefit is moderate, or there is moderate certainty that the net benefit is moderate to substantial. Offer service.

C: There is at least moderate certainty that the net benefit is small. Offer service selectively.

D: There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. Don’t offer service.

I: Current evidence is insufficient to assess the balance of benefits and harms of the service.

CORRESPONDENCE
Mitchell Kaminski, MD, MBA, 901 Walnut Street, 10th Floor, Jefferson College of Population Health, Philadelphia, PA 19107; [email protected]

References

1. IHI. What is the Triple Aim? Accessed June 20, 2022. http://www.ihi.org/Topics/TripleAim/Pages/Overview.aspx#:~:text=It%20is%20IHI’s%20belief%20that,capita%20cost%20of%20health%20care

2. Papanicolas I, Woskie LR, Jha AK. Health care spending in the United States and other high-income countries. JAMA. 2018;319:1024-1039. doi: 10.1001/jama.2018.1150

3. Shrank WH, Rogstad TL, Parekh N. Waste in the US health care system estimated costs and potential for savings. JAMA. 2019;322:1501-1509. doi:10.1001/jama.2019.13978

4. Mafi JN, Russell K, Bortz BA, et al. Low-cost, high-volume health services contribute the most to unnecessary health spending. Health Aff. 2017;36:1701-1704. doi: 10.1377/hlthaff.2017.0385

5. CDC. Strengthening clinical laboratories. 2018. Accessed June 2020, 2022. www.cdc.gov/csels/dls/strengthening-clinical-labs.html

6. Vuong KT. How much do lab tests cost without insurance in 2022? Accessed May 11, 2022. www.talktomira.com/post/how-much-do-lab-test-cost-without-insurance

7. Choosing Wisely: Promoting conversations between providers and patients. Accessed June 20, 2022. www.choosingwisely.org

8. Morgan S, van Driel M, Coleman J, et al. Rational test ordering in family medicine. Can Fam Physician. 2015;61:535-537.

9. US Preventive Services Taskforce. Screening for glaucoma and impaired vision. Accessed June 20, 2022. www.uspreventiveservicestaskforce.org/uspstf

10. Arnold MJ, O’Malley PG, Downs JR. Key recommendations on managing dyslipidemia for cardiovascular risk reduction: stopping where the evidence does. Am Fam Physician. 2021;103:455-458.

11. Welch HG, Albertsen PC. Reconsidering prostate cancer mortality—the future of PSA screening. N Engl J Med. 2020;382:1557-1563. doi: 10.1056/NEJMms1914228

12. American Society for Microbiology. Why pretest and posttest probability matter in the time of COVID-19. Accessed June 20, 2022. https://asm.org/Articles/2020/June/Why-Pretest-and-Posttest-Probability-Matter-in-the

13. Slater CA, Davis RB, Shmerling RH. Antinuclear antibody testing. A study of clinical utility. Arch Intern Med. 1996;156:1421-1425.

14. Aragon G, Younossi ZM. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleve Clin J Med. 2010;77:195-204. doi: 10.3949/ccjm.77a.09064

15. Ismail OZ, Bhayana V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem. 2017;50:1275-1280. doi: 10.1016/j.clinbiochem.2017.07.003.

16. Gottheil S, Khemani E, Copley K, et al. Reducing inappropriate ESR testing with computerized clinical decision support. BMJ Quality Improvement Reports, 2016;5:u211376.w4582. doi: 10.1136/bmjquality.u211376.w4582

17. Schneider C, Feller M, Bauer DC, et al. Initial evaluation of thyroid dysfunction - are simultaneous TSH and fT4 tests necessary? PloS One. 2018;13:e0196631–e0196631. doi: 10.1371/journal.pone.0196631

18. Williams T, Mortada R, Porter S. Diagnosis and treatment of polycystic ovary syndrome. Am Fam Physician. 2016;94:106-113.

19. Eaton KP, Levy K, Soong C et.al. Evidence-Based Guidelines to Eliminate Repetitive Laboratory Testing. JAMA Intern Med. 2017;177:1833-1839. doi: 10.1001/jamainternmed.2017.5152

20. ADA. Glycemic targets: standards of medical care in diabetes—2021. Diabetes Care. 2021;44:S73-S84. doi: 10.2337/dc21-S006

21. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139:e1082-e1143. doi: 10.1161/CIR.0000000000000625

22. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75:1334-1357. doi: 10.1161/­HYPERTENSIONAHA.120.15026.

23. Benarroch-Gampel J, Sheffield KM, Duncan CB, et al. Preoperative laboratory testing in patients undergoing elective, low-risk ambulatory surgery. Ann Surg. 2012;256:518-528. doi: 10.1097/SLA.0b013e318265bcdb

24. ASA. ASA physical status classification system. Accessed June 22,2022. www.asahq.org/standards-and-guidelines/asa-­physical-status-classification-system

25. NLM. Preoperative tests (update): routine preoperative tests for elective surgery. Accessed June 22, 2022. www.ncbi.nlm.nih.gov/books/NBK367919/

26. ASA. American Society of Anesthesiologists releases list of commonly used tests and treatments to question-AS PART OF CHOOSING WISELY® CAMPAIGN. Accessed June 22, 2022. www.asahq.org/about-asa/newsroom/news-­releases/2013/10/choosing-wisely

27. Keay L, Lindsley K, Tielsch J, et al. Routine preoperative medical testing for cataract surgery. Cochrane Database Syst Rev. 2019;1:CD007293. doi: 10.1002/14651858.CD007293.pub4

28. Chen CL, Clay TH, McLeod S, et al. A revised estimate of costs associated with routine preoperative testing in Medicare cataract patients with a procedure-specific indicator. JAMA Ophthalmol. 2018;136:231-238. doi:10.1001/jamaophthalmol.2017.6372

29. USPSTF. Human immunodeficiency virus (HIV) infection: screening. Accessed May 16, 2022. www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening

30. USPSTF. Hepatitis C virus infection in adolescents and adults: screening. Accessed June 20, 2022. www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-c-screening

References

1. IHI. What is the Triple Aim? Accessed June 20, 2022. http://www.ihi.org/Topics/TripleAim/Pages/Overview.aspx#:~:text=It%20is%20IHI’s%20belief%20that,capita%20cost%20of%20health%20care

2. Papanicolas I, Woskie LR, Jha AK. Health care spending in the United States and other high-income countries. JAMA. 2018;319:1024-1039. doi: 10.1001/jama.2018.1150

3. Shrank WH, Rogstad TL, Parekh N. Waste in the US health care system estimated costs and potential for savings. JAMA. 2019;322:1501-1509. doi:10.1001/jama.2019.13978

4. Mafi JN, Russell K, Bortz BA, et al. Low-cost, high-volume health services contribute the most to unnecessary health spending. Health Aff. 2017;36:1701-1704. doi: 10.1377/hlthaff.2017.0385

5. CDC. Strengthening clinical laboratories. 2018. Accessed June 2020, 2022. www.cdc.gov/csels/dls/strengthening-clinical-labs.html

6. Vuong KT. How much do lab tests cost without insurance in 2022? Accessed May 11, 2022. www.talktomira.com/post/how-much-do-lab-test-cost-without-insurance

7. Choosing Wisely: Promoting conversations between providers and patients. Accessed June 20, 2022. www.choosingwisely.org

8. Morgan S, van Driel M, Coleman J, et al. Rational test ordering in family medicine. Can Fam Physician. 2015;61:535-537.

9. US Preventive Services Taskforce. Screening for glaucoma and impaired vision. Accessed June 20, 2022. www.uspreventiveservicestaskforce.org/uspstf

10. Arnold MJ, O’Malley PG, Downs JR. Key recommendations on managing dyslipidemia for cardiovascular risk reduction: stopping where the evidence does. Am Fam Physician. 2021;103:455-458.

11. Welch HG, Albertsen PC. Reconsidering prostate cancer mortality—the future of PSA screening. N Engl J Med. 2020;382:1557-1563. doi: 10.1056/NEJMms1914228

12. American Society for Microbiology. Why pretest and posttest probability matter in the time of COVID-19. Accessed June 20, 2022. https://asm.org/Articles/2020/June/Why-Pretest-and-Posttest-Probability-Matter-in-the

13. Slater CA, Davis RB, Shmerling RH. Antinuclear antibody testing. A study of clinical utility. Arch Intern Med. 1996;156:1421-1425.

14. Aragon G, Younossi ZM. When and how to evaluate mildly elevated liver enzymes in apparently healthy patients. Cleve Clin J Med. 2010;77:195-204. doi: 10.3949/ccjm.77a.09064

15. Ismail OZ, Bhayana V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem. 2017;50:1275-1280. doi: 10.1016/j.clinbiochem.2017.07.003.

16. Gottheil S, Khemani E, Copley K, et al. Reducing inappropriate ESR testing with computerized clinical decision support. BMJ Quality Improvement Reports, 2016;5:u211376.w4582. doi: 10.1136/bmjquality.u211376.w4582

17. Schneider C, Feller M, Bauer DC, et al. Initial evaluation of thyroid dysfunction - are simultaneous TSH and fT4 tests necessary? PloS One. 2018;13:e0196631–e0196631. doi: 10.1371/journal.pone.0196631

18. Williams T, Mortada R, Porter S. Diagnosis and treatment of polycystic ovary syndrome. Am Fam Physician. 2016;94:106-113.

19. Eaton KP, Levy K, Soong C et.al. Evidence-Based Guidelines to Eliminate Repetitive Laboratory Testing. JAMA Intern Med. 2017;177:1833-1839. doi: 10.1001/jamainternmed.2017.5152

20. ADA. Glycemic targets: standards of medical care in diabetes—2021. Diabetes Care. 2021;44:S73-S84. doi: 10.2337/dc21-S006

21. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. Circulation. 2019;139:e1082-e1143. doi: 10.1161/CIR.0000000000000625

22. Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension. 2020;75:1334-1357. doi: 10.1161/­HYPERTENSIONAHA.120.15026.

23. Benarroch-Gampel J, Sheffield KM, Duncan CB, et al. Preoperative laboratory testing in patients undergoing elective, low-risk ambulatory surgery. Ann Surg. 2012;256:518-528. doi: 10.1097/SLA.0b013e318265bcdb

24. ASA. ASA physical status classification system. Accessed June 22,2022. www.asahq.org/standards-and-guidelines/asa-­physical-status-classification-system

25. NLM. Preoperative tests (update): routine preoperative tests for elective surgery. Accessed June 22, 2022. www.ncbi.nlm.nih.gov/books/NBK367919/

26. ASA. American Society of Anesthesiologists releases list of commonly used tests and treatments to question-AS PART OF CHOOSING WISELY® CAMPAIGN. Accessed June 22, 2022. www.asahq.org/about-asa/newsroom/news-­releases/2013/10/choosing-wisely

27. Keay L, Lindsley K, Tielsch J, et al. Routine preoperative medical testing for cataract surgery. Cochrane Database Syst Rev. 2019;1:CD007293. doi: 10.1002/14651858.CD007293.pub4

28. Chen CL, Clay TH, McLeod S, et al. A revised estimate of costs associated with routine preoperative testing in Medicare cataract patients with a procedure-specific indicator. JAMA Ophthalmol. 2018;136:231-238. doi:10.1001/jamaophthalmol.2017.6372

29. USPSTF. Human immunodeficiency virus (HIV) infection: screening. Accessed May 16, 2022. www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening

30. USPSTF. Hepatitis C virus infection in adolescents and adults: screening. Accessed June 20, 2022. www.uspreventiveservicestaskforce.org/uspstf/recommendation/hepatitis-c-screening

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The Journal of Family Practice - 71(6)
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The Journal of Family Practice - 71(6)
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A judicious approach to ordering lab tests
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A judicious approach to ordering lab tests
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PRACTICE RECOMMENDATIONS

› Follow US Preventive Services Task Force and professional society recommendations for laboratory testing, including choice and frequency of tests. A

› Consider the pretest probability of your patient having a disease, and order the most sensitive and specific test to diagnose a new condition. Employ a 2-step approach with a second laboratory test when the first is outside the reference range. B

› Refrain from ordering routine preoperative testing for patients undergoing low-risk surgeries; these data do not improve postoperative outcomes, can lead to costly testing cascades, and may delay necessary surgical care for patients. A

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

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