The low molecular weight heparin dalteparin and unfractionated heparin are associated with similar rates of thrombosis and major bleeding, but dalteparin is associated with lower rates of pulmonary embolus and heparin-induced thrombocytopenia, based on results from a prospective randomized study.

Given for prevention of venous thromboembolism, median hospital costs per patient were $39,508 for dalteparin users and $40,805 for unfractionated heparin users. Dalteparin remained the least costly strategy until its acquisition costs rose from $8 per dose to $179, as reported online 1 November in the Journal of the American Medical Association [doi:10.1001/jama.2014.15101].

CDC/Janice Carr

The economic analysis—conducted alongside the multi-centre, randomized PROTECT trial in 2344 critically-ill medical-surgical patients— showed no matter how low the acquisition cost of unfractionated heparin, there was no threshold that favored that form of prophylaxis, according to data also presented at the Critical Care Canada Forum.

“From a health care payer perspective, VTE prophylaxis with the LMWH [low molecular weight heparin] dalteparin in critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH [unfractionated heparin],” wrote Dr. Robert A. Fowler, from the Sunnybrook Health Sciences Centre, University of Toronto, and colleagues.The E-PROTECT study was funded by the Heart and Stroke Foundation (Ontario, Canada), the University of Toronto, and the Canadian Intensive Care Foundation. PROTECT was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (Canada), and the Australian and New Zealand College of Anesthetists Research Foundation. Some authors reported fees, support, and consultancies from the pharmaceutical industry.

The low molecular weight heparin dalteparin and unfractionated heparin are associated with similar rates of thrombosis and major bleeding, but dalteparin is associated with lower rates of pulmonary embolus and heparin-induced thrombocytopenia, based on results from a prospective randomized study.

Given for prevention of venous thromboembolism, median hospital costs per patient were $39,508 for dalteparin users and $40,805 for unfractionated heparin users. Dalteparin remained the least costly strategy until its acquisition costs rose from $8 per dose to $179, as reported online 1 November in the Journal of the American Medical Association [doi:10.1001/jama.2014.15101].

CDC/Janice Carr

The economic analysis—conducted alongside the multi-centre, randomized PROTECT trial in 2344 critically-ill medical-surgical patients— showed no matter how low the acquisition cost of unfractionated heparin, there was no threshold that favored that form of prophylaxis, according to data also presented at the Critical Care Canada Forum.

“From a health care payer perspective, VTE prophylaxis with the LMWH [low molecular weight heparin] dalteparin in critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH [unfractionated heparin],” wrote Dr. Robert A. Fowler, from the Sunnybrook Health Sciences Centre, University of Toronto, and colleagues.The E-PROTECT study was funded by the Heart and Stroke Foundation (Ontario, Canada), the University of Toronto, and the Canadian Intensive Care Foundation. PROTECT was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (Canada), and the Australian and New Zealand College of Anesthetists Research Foundation. Some authors reported fees, support, and consultancies from the pharmaceutical industry.

The low molecular weight heparin dalteparin and unfractionated heparin are associated with similar rates of thrombosis and major bleeding, but dalteparin is associated with lower rates of pulmonary embolus and heparin-induced thrombocytopenia, based on results from a prospective randomized study.

Given for prevention of venous thromboembolism, median hospital costs per patient were $39,508 for dalteparin users and $40,805 for unfractionated heparin users. Dalteparin remained the least costly strategy until its acquisition costs rose from $8 per dose to $179, as reported online 1 November in the Journal of the American Medical Association [doi:10.1001/jama.2014.15101].

CDC/Janice Carr

The economic analysis—conducted alongside the multi-centre, randomized PROTECT trial in 2344 critically-ill medical-surgical patients— showed no matter how low the acquisition cost of unfractionated heparin, there was no threshold that favored that form of prophylaxis, according to data also presented at the Critical Care Canada Forum.

“From a health care payer perspective, VTE prophylaxis with the LMWH [low molecular weight heparin] dalteparin in critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH [unfractionated heparin],” wrote Dr. Robert A. Fowler, from the Sunnybrook Health Sciences Centre, University of Toronto, and colleagues.The E-PROTECT study was funded by the Heart and Stroke Foundation (Ontario, Canada), the University of Toronto, and the Canadian Intensive Care Foundation. PROTECT was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation (Canada), and the Australian and New Zealand College of Anesthetists Research Foundation. Some authors reported fees, support, and consultancies from the pharmaceutical industry.

As a generalist specialty, family medicine faces more diagnostic challenges than any other specialty because we see so many undifferentiated problems. However, only 2 family physicians attended this meeting: I was one, because of my research interests in proper use of lab testing, and John Ely, MD, from the University of Iowa, was the other. He has been researching diagnostic errors for most of his career. One physician/researcher has developed a note card diagnostic checklist that he goes through like a pilot before takeoff. Dr. Ely has been testing an idea borrowed from aviation: using a diagnostic checklist. He developed a packet of note cards that lists the top 10 to 20 diagnoses for complaints commonly seen in family medicine, such as headache and abdominal pain. Before the patient leaves the exam room, he pulls out the appropriate checklist and goes through it out loud, just like a pilot before takeoff. He says for most patients, this process is pretty quick and it reassures both them and him that he has not missed an important diagnosis. (You can download Dr. Ely’s checklists from http://www.improvediagnosis.org/resource/resmgr/docs/diffdx.doc.)

How are the rest of us avoiding diagnostic errors? Some day IBM’s Watson or another diagnostic software program embedded in the electronic health record will guide us to the right diagnosis. In the meantime, I have developed a list of 7 low-tech ways to arrive at the correct diagnosis (and to rapidly correct a diagnostic error, should one occur):

As a generalist specialty, family medicine faces more diagnostic challenges than any other specialty because we see so many undifferentiated problems. However, only 2 family physicians attended this meeting: I was one, because of my research interests in proper use of lab testing, and John Ely, MD, from the University of Iowa, was the other. He has been researching diagnostic errors for most of his career. One physician/researcher has developed a note card diagnostic checklist that he goes through like a pilot before takeoff. Dr. Ely has been testing an idea borrowed from aviation: using a diagnostic checklist. He developed a packet of note cards that lists the top 10 to 20 diagnoses for complaints commonly seen in family medicine, such as headache and abdominal pain. Before the patient leaves the exam room, he pulls out the appropriate checklist and goes through it out loud, just like a pilot before takeoff. He says for most patients, this process is pretty quick and it reassures both them and him that he has not missed an important diagnosis. (You can download Dr. Ely’s checklists from http://www.improvediagnosis.org/resource/resmgr/docs/diffdx.doc.)

How are the rest of us avoiding diagnostic errors? Some day IBM’s Watson or another diagnostic software program embedded in the electronic health record will guide us to the right diagnosis. In the meantime, I have developed a list of 7 low-tech ways to arrive at the correct diagnosis (and to rapidly correct a diagnostic error, should one occur):

As a generalist specialty, family medicine faces more diagnostic challenges than any other specialty because we see so many undifferentiated problems. However, only 2 family physicians attended this meeting: I was one, because of my research interests in proper use of lab testing, and John Ely, MD, from the University of Iowa, was the other. He has been researching diagnostic errors for most of his career. One physician/researcher has developed a note card diagnostic checklist that he goes through like a pilot before takeoff. Dr. Ely has been testing an idea borrowed from aviation: using a diagnostic checklist. He developed a packet of note cards that lists the top 10 to 20 diagnoses for complaints commonly seen in family medicine, such as headache and abdominal pain. Before the patient leaves the exam room, he pulls out the appropriate checklist and goes through it out loud, just like a pilot before takeoff. He says for most patients, this process is pretty quick and it reassures both them and him that he has not missed an important diagnosis. (You can download Dr. Ely’s checklists from http://www.improvediagnosis.org/resource/resmgr/docs/diffdx.doc.)

How are the rest of us avoiding diagnostic errors? Some day IBM’s Watson or another diagnostic software program embedded in the electronic health record will guide us to the right diagnosis. In the meantime, I have developed a list of 7 low-tech ways to arrive at the correct diagnosis (and to rapidly correct a diagnostic error, should one occur):

THE CASES

CASE 1 › A 32-year-old G2P1 with an uncomplicated prenatal course presented for induction at 41 weeks and 2 days of gestation. Fetal heart tracing showed no abnormalities. A compound presentation and a prolonged second stage of labor made vacuum assistance necessary. The infant had both a true umbilical cord knot (TUCK) (FIGURE 1A) and double nuchal cord.

CASE 2 › A 46-year-old G3P0 at 38 weeks of gestation by in vitro fertilization underwent an uncomplicated primary low transverse cesarean (C-section) delivery of dichorionic/diamniotic twins. The C-section had been necessary because baby A had been in the breech position. Fetal heart tracing showed no abnormalities. Baby A had a velamentous cord insertion, and baby B had a succenturiate lobe and a TUCK.

CASE 3 › A 23-year-old G2P1 with an uncomplicated prenatal course chose to have a repeat C-section and delivered at 41 weeks in active labor. Fetal heart monitoring showed no abnormalities. Umbilical artery pH and venous pH were normal. A TUCK was noted at time of delivery.

CASE 4 › A 30-year-old G1P0 with an uncomplicated prenatal course presented in active labor at 40 weeks and 4 days of gestation. At 7 cm cervical dilation, monitoring showed repeated deep variable fetal heart rate decelerations. The patient underwent an uncomplicated primary C-section. Umbilical artery pH and venous pH were normal. A TUCK (FIGURE 1B) and double nuchal cord were found at time of delivery.

DISCUSSION

TUCKs are thought to occur when a fetus passes through a loop in the umbilical cord. They occur in <2% of term deliveries.^1,2 TUCKs differ from false knots. False knots are exaggerated loops of cord vasculature.

Risk factors that have been independently associated with TUCK include advanced maternal age (AMA; >35 years), multiparity, diabetes mellitus, gestational diabetes, polyhydramnios, and previous spontaneous abortion.^1-3 In one study, 72% of women with a TUCK were multiparous.³ Hershkovitz et al² suggested that laxity of uterine and abdominal musculature in multiparous patients may contribute to increased room for TUCK formation.

The adjusted odds ratio of having a TUCK is 2.53 in women with diabetes mellitus.³ Hyperglycemia can contribute to increased fetal movements, thereby increasing the risk of TUCK development.² Polyhydramnios is often found in patients with diabetes mellitus and gestational diabetes.³ The incidence is higher in monoamniotic twins.⁴

Being a male and having a longer umbilical cord may also increase the risk of TUCK. On average, male infants have longer cords than females, which may predispose them to TUCKs.³ Räisänen et al³ found that the mean cord length in TUCK infants was 16.9 cm longer than in infants without a TUCK.

Of our 4 patients, one was of AMA, 2 were multiparous, and 3 of the 4 infants who developed TUCK were male.

TUCK is usually
 diagnosed at delivery


Most cases of TUCK are found incidentally at the time of delivery. Antenatal diagnosis is difficult, because loops of cord lying together are easily mistaken for knots on ultrasound.⁵ Sepulveda et al⁶ evaluated the use of 3D power Doppler in 8 cases of suspected TUCK; only 63% were confirmed at delivery. Some researchers have found improved detection of TUCK with color Doppler and 4D ultrasound, which have demonstrated a “hanging noose sign” (a transverse section of umbilical cord surrounded by a loop of cord) as well as views of the cord under pressure.^7-10

Outcomes associated with TUCK vary greatly. Neonates affected by TUCK have a 4% to 10% increased risk of stillbirth, usually attributed to knot tightening.^2,4,11,12

In addition, there is an increased incidence of fetal heart rate abnormalities during labor.^1,3,12,13

Infants with true umbilical cord knots have an increased incidence of heart rate abnormalities during labor. There is no increase in the incidence of assisted vaginal or C-section delivery.¹² And as for whether TUCK affects an infant’s size or weight, one study found TUCK infants had a 3.2-fold higher risk of measuring small for gestational age, potentially due to chronic umbilical cord compromise; however, mean birth weight between study and control groups did not differ significantly.³

Outcomes for our patients and their infants. All 4 cases had good outcomes (TABLE). The umbilical cord knot produced no detectable fetal compromise in cases 1 through 3. In Case 4, electronic fetal monitoring showed repeated variable fetal heart rate decelerations, presumably associated with cord compression.

THE TAKEAWAY

Pregnant women who may be at risk for experiencing a TUCK include those who are older than age 35, multiparous, carrying a boy, or have diabetes mellitus, gestational diabetes, or polyhydramnios. While it is good to be aware of these risk factors, there are no recommended changes in management based on risk or ultrasound findings unless there is additional concern for fetal compromise.

Antenatal diagnosis of TUCK is challenging, but Doppler ultrasound may be able to identify the condition. Most cases of TUCK are noted on delivery, and outcomes are generally positive, although infants in whom the TUCK tightens may have an increased risk of heart rate abnormalities or stillbirth. 

THE CASES

CASE 1 › A 32-year-old G2P1 with an uncomplicated prenatal course presented for induction at 41 weeks and 2 days of gestation. Fetal heart tracing showed no abnormalities. A compound presentation and a prolonged second stage of labor made vacuum assistance necessary. The infant had both a true umbilical cord knot (TUCK) (FIGURE 1A) and double nuchal cord.

CASE 2 › A 46-year-old G3P0 at 38 weeks of gestation by in vitro fertilization underwent an uncomplicated primary low transverse cesarean (C-section) delivery of dichorionic/diamniotic twins. The C-section had been necessary because baby A had been in the breech position. Fetal heart tracing showed no abnormalities. Baby A had a velamentous cord insertion, and baby B had a succenturiate lobe and a TUCK.

CASE 3 › A 23-year-old G2P1 with an uncomplicated prenatal course chose to have a repeat C-section and delivered at 41 weeks in active labor. Fetal heart monitoring showed no abnormalities. Umbilical artery pH and venous pH were normal. A TUCK was noted at time of delivery.

CASE 4 › A 30-year-old G1P0 with an uncomplicated prenatal course presented in active labor at 40 weeks and 4 days of gestation. At 7 cm cervical dilation, monitoring showed repeated deep variable fetal heart rate decelerations. The patient underwent an uncomplicated primary C-section. Umbilical artery pH and venous pH were normal. A TUCK (FIGURE 1B) and double nuchal cord were found at time of delivery.

DISCUSSION

TUCKs are thought to occur when a fetus passes through a loop in the umbilical cord. They occur in <2% of term deliveries.^1,2 TUCKs differ from false knots. False knots are exaggerated loops of cord vasculature.

Risk factors that have been independently associated with TUCK include advanced maternal age (AMA; >35 years), multiparity, diabetes mellitus, gestational diabetes, polyhydramnios, and previous spontaneous abortion.^1-3 In one study, 72% of women with a TUCK were multiparous.³ Hershkovitz et al² suggested that laxity of uterine and abdominal musculature in multiparous patients may contribute to increased room for TUCK formation.

The adjusted odds ratio of having a TUCK is 2.53 in women with diabetes mellitus.³ Hyperglycemia can contribute to increased fetal movements, thereby increasing the risk of TUCK development.² Polyhydramnios is often found in patients with diabetes mellitus and gestational diabetes.³ The incidence is higher in monoamniotic twins.⁴

Being a male and having a longer umbilical cord may also increase the risk of TUCK. On average, male infants have longer cords than females, which may predispose them to TUCKs.³ Räisänen et al³ found that the mean cord length in TUCK infants was 16.9 cm longer than in infants without a TUCK.

Of our 4 patients, one was of AMA, 2 were multiparous, and 3 of the 4 infants who developed TUCK were male.

TUCK is usually
 diagnosed at delivery


Most cases of TUCK are found incidentally at the time of delivery. Antenatal diagnosis is difficult, because loops of cord lying together are easily mistaken for knots on ultrasound.⁵ Sepulveda et al⁶ evaluated the use of 3D power Doppler in 8 cases of suspected TUCK; only 63% were confirmed at delivery. Some researchers have found improved detection of TUCK with color Doppler and 4D ultrasound, which have demonstrated a “hanging noose sign” (a transverse section of umbilical cord surrounded by a loop of cord) as well as views of the cord under pressure.^7-10

Outcomes associated with TUCK vary greatly. Neonates affected by TUCK have a 4% to 10% increased risk of stillbirth, usually attributed to knot tightening.^2,4,11,12

In addition, there is an increased incidence of fetal heart rate abnormalities during labor.^1,3,12,13

Infants with true umbilical cord knots have an increased incidence of heart rate abnormalities during labor. There is no increase in the incidence of assisted vaginal or C-section delivery.¹² And as for whether TUCK affects an infant’s size or weight, one study found TUCK infants had a 3.2-fold higher risk of measuring small for gestational age, potentially due to chronic umbilical cord compromise; however, mean birth weight between study and control groups did not differ significantly.³

Outcomes for our patients and their infants. All 4 cases had good outcomes (TABLE). The umbilical cord knot produced no detectable fetal compromise in cases 1 through 3. In Case 4, electronic fetal monitoring showed repeated variable fetal heart rate decelerations, presumably associated with cord compression.

THE TAKEAWAY

Pregnant women who may be at risk for experiencing a TUCK include those who are older than age 35, multiparous, carrying a boy, or have diabetes mellitus, gestational diabetes, or polyhydramnios. While it is good to be aware of these risk factors, there are no recommended changes in management based on risk or ultrasound findings unless there is additional concern for fetal compromise.

Antenatal diagnosis of TUCK is challenging, but Doppler ultrasound may be able to identify the condition. Most cases of TUCK are noted on delivery, and outcomes are generally positive, although infants in whom the TUCK tightens may have an increased risk of heart rate abnormalities or stillbirth. 

THE CASES

CASE 1 › A 32-year-old G2P1 with an uncomplicated prenatal course presented for induction at 41 weeks and 2 days of gestation. Fetal heart tracing showed no abnormalities. A compound presentation and a prolonged second stage of labor made vacuum assistance necessary. The infant had both a true umbilical cord knot (TUCK) (FIGURE 1A) and double nuchal cord.

CASE 2 › A 46-year-old G3P0 at 38 weeks of gestation by in vitro fertilization underwent an uncomplicated primary low transverse cesarean (C-section) delivery of dichorionic/diamniotic twins. The C-section had been necessary because baby A had been in the breech position. Fetal heart tracing showed no abnormalities. Baby A had a velamentous cord insertion, and baby B had a succenturiate lobe and a TUCK.

CASE 3 › A 23-year-old G2P1 with an uncomplicated prenatal course chose to have a repeat C-section and delivered at 41 weeks in active labor. Fetal heart monitoring showed no abnormalities. Umbilical artery pH and venous pH were normal. A TUCK was noted at time of delivery.

CASE 4 › A 30-year-old G1P0 with an uncomplicated prenatal course presented in active labor at 40 weeks and 4 days of gestation. At 7 cm cervical dilation, monitoring showed repeated deep variable fetal heart rate decelerations. The patient underwent an uncomplicated primary C-section. Umbilical artery pH and venous pH were normal. A TUCK (FIGURE 1B) and double nuchal cord were found at time of delivery.

DISCUSSION

TUCKs are thought to occur when a fetus passes through a loop in the umbilical cord. They occur in <2% of term deliveries.^1,2 TUCKs differ from false knots. False knots are exaggerated loops of cord vasculature.

Risk factors that have been independently associated with TUCK include advanced maternal age (AMA; >35 years), multiparity, diabetes mellitus, gestational diabetes, polyhydramnios, and previous spontaneous abortion.^1-3 In one study, 72% of women with a TUCK were multiparous.³ Hershkovitz et al² suggested that laxity of uterine and abdominal musculature in multiparous patients may contribute to increased room for TUCK formation.

The adjusted odds ratio of having a TUCK is 2.53 in women with diabetes mellitus.³ Hyperglycemia can contribute to increased fetal movements, thereby increasing the risk of TUCK development.² Polyhydramnios is often found in patients with diabetes mellitus and gestational diabetes.³ The incidence is higher in monoamniotic twins.⁴

Being a male and having a longer umbilical cord may also increase the risk of TUCK. On average, male infants have longer cords than females, which may predispose them to TUCKs.³ Räisänen et al³ found that the mean cord length in TUCK infants was 16.9 cm longer than in infants without a TUCK.

Of our 4 patients, one was of AMA, 2 were multiparous, and 3 of the 4 infants who developed TUCK were male.

TUCK is usually
 diagnosed at delivery


Most cases of TUCK are found incidentally at the time of delivery. Antenatal diagnosis is difficult, because loops of cord lying together are easily mistaken for knots on ultrasound.⁵ Sepulveda et al⁶ evaluated the use of 3D power Doppler in 8 cases of suspected TUCK; only 63% were confirmed at delivery. Some researchers have found improved detection of TUCK with color Doppler and 4D ultrasound, which have demonstrated a “hanging noose sign” (a transverse section of umbilical cord surrounded by a loop of cord) as well as views of the cord under pressure.^7-10

Outcomes associated with TUCK vary greatly. Neonates affected by TUCK have a 4% to 10% increased risk of stillbirth, usually attributed to knot tightening.^2,4,11,12

In addition, there is an increased incidence of fetal heart rate abnormalities during labor.^1,3,12,13

Infants with true umbilical cord knots have an increased incidence of heart rate abnormalities during labor. There is no increase in the incidence of assisted vaginal or C-section delivery.¹² And as for whether TUCK affects an infant’s size or weight, one study found TUCK infants had a 3.2-fold higher risk of measuring small for gestational age, potentially due to chronic umbilical cord compromise; however, mean birth weight between study and control groups did not differ significantly.³

Outcomes for our patients and their infants. All 4 cases had good outcomes (TABLE). The umbilical cord knot produced no detectable fetal compromise in cases 1 through 3. In Case 4, electronic fetal monitoring showed repeated variable fetal heart rate decelerations, presumably associated with cord compression.

THE TAKEAWAY

Pregnant women who may be at risk for experiencing a TUCK include those who are older than age 35, multiparous, carrying a boy, or have diabetes mellitus, gestational diabetes, or polyhydramnios. While it is good to be aware of these risk factors, there are no recommended changes in management based on risk or ultrasound findings unless there is additional concern for fetal compromise.

Antenatal diagnosis of TUCK is challenging, but Doppler ultrasound may be able to identify the condition. Most cases of TUCK are noted on delivery, and outcomes are generally positive, although infants in whom the TUCK tightens may have an increased risk of heart rate abnormalities or stillbirth. 

THE CASE

A 23-year-old immunocompetent woman was referred to our spinal clinic with a 6-month history of low back pain that radiated to her right flank, buttock, and groin. She’d had intermittent urinary problems, including mild dysuria and frequency, and had been treated with antibiotics for a presumed urinary tract infection on 3 previous occasions, but her pain gradually increased and eventually became constant.

The patient had no history of fever, malaise, or weight loss. She denied consuming unpasteurized milk or undercooked poultry, and hadn’t recently experienced diarrhea or vomiting.

Eight years earlier, she had undergone anterior fusion of her spine for idiopathic scoliosis. At that time, she was at Risser grade 1, and her Cobb angle was 50°; metallic instrumentation was implanted at T10 to L3 to prevent progression of the scoliosis. Her recovery had been uneventful.

During examination, her temperature, pulse, respiratory rate, blood pressure, and nervous system were all normal. Her hips appeared normal, as well, and a straight leg raise was negative bilaterally. The patient had mild midline lumbar tenderness. Spinal range of movement revealed decreased flexion and mild pain.

X-rays (FIGURE 1) showed no changes in the previous metalwork in her spine. There was decreased disk height at the L3/4 level, but no significant bony erosion or soft-tissue shadows. Laboratory testing revealed a C-reactive protein (CRP) level of 240 mg/dL (normal, <1 mg/dL) and her erythrocyte sedimentation rate (ESR) was 102 mm/h—more than 5 times higher than it should have been.¹ The patient had a normal peripheral white cell count (WCC). Midstream urine cultures were negative.


The patient was admitted to the hospital for further work-up. Magnetic resonance imaging (MRI) of the lumbar spine showed gross abnormality at the L3-L4 disk level with erosion of the end plates, fluid in the disk space, marked enhancing edema, and mild surrounding soft-tissue edematous changes, but no evidence of any epidural abscess (FIGURE 2). The patient had a fluoroscopy-guided needle biopsy of the disk on the same day and received intravenous (IV) ceftriaxone 2 g twice a day. Blood and urine cultures were negative.

THE DIAGNOSIS

We suspected our patient had spondylodiscitis, an infection of the spine that includes spondylitis (inflammation of the vertebrae) and discitis (inflammation of the vertebral disk space). After 48 hours, the biopsy sample grew Salmonella typhimurium and confirmed the diagnosis. The organism was sensitive to ceftriaxone and ciprofloxacin; parenteral ceftriaxone was continued and the patient wore a thoracolumbar brace for immobilization. For 3 days, her inflammatory marker levels were checked daily, then every other day for the rest of that first week, and then 2 more times in the following week.

DISCUSSION

Thoracic and lumbar vertebrae are the most common sites of spondylodiscitis.² Spondylodiscitis accounts for 3% to 5% of pyogenic osteomyelitis in patients in developed countries.³ The incidence of pyogenic spondylodiscitis may be rising due to an increase in the number of elderly and immunocompromised patients, as well as a rise in invasive medical procedures.^4-6

If left untreated, spondylodiscitis can spread longitudinally (involving the adjacent levels), posteriorly (causing bacterial meningitis, abscess formation, and cord compromise), or anteriorly (causing paravertebral abscess). Untreated spondylodiscitis can also send distant infective emboli and cause endocarditis^7-9 or mycotic abdominal aneurysm.¹⁰

Historically, mortality in patients with vertebral osteomyelitis has been as high as 25%.¹¹ The combination of earlier diagnosis, antibiotics, and surgical debridement and stabilization has decreased mortality to less than 15%.^12-14

Risk factors for spondylodiscitis include male sex, IV drug abuse, diabetes, morbid obesity, having had a genitourinary or spinal procedure, and being immunocompromised (eg, from alcohol abuse, malignancy, organ transplantation, chemotherapy, or corticosteroid use).^12,15,16

Gram-positive organisms cause most spine infections in both adults and children, with 40% to 90% caused by Staphylococcus aureus.¹⁷ Gram-negative organisms (Escherichia coli, Pseudomonas, and Proteus), which can also cause spondylodiscitis, typically occur after genitourinary infections or procedures. IV drug abusers are prone to Pseudomonas infections.¹⁸ Anaerobic infections may be seen in patients with diabetes or after penetrating trauma.¹⁵ Salmonella species can cause spondylodiscitis, especially in patients with sickle cell disease from an intestinal source.¹⁹

Mycobacterium tuberculosis is the most common nonpyogenic infecting agent that also can cause spondylodiscitis. Infection caused by tuberculosis (TB) has had a recent resurgence with resistant strains, especially in patients with human immunodeficiency virus.¹⁵ Although less than 10% of patients with TB have skeletal involvement, 50% of the skeletal involvement occurs in the spine.¹⁵

The clinical presentation of spondylodiscitis depends on the location of the infection, the virulence of the organism, and the immune status of the patient. Discitis can present as pain in the back, hip, abdomen (especially in children²⁰) and, occasionally, with meningeal involvement.¹¹ Patients with discitis often have a normal temperature.^15,21 In patients with discitis, the patient’s WCC will be normal, but the ESR is almost always elevated.^15,22 Suspect spondylodiscitis in patients who present with persistent or increasing pain 3 to 4 weeks after back surgery. For such patients, measure inflammatory markers and order imaging of the spine.

Risk factors for spondylodiscitis include IV drug abuse, diabetes, morbid obesity, and having had a genitourinary or spinal procedure. X-ray findings for patients with spondylodiscitis will include osteolysis and end plate erosions (early) and narrowing and collapse of the disk space (late). (In TB, relative preservation of the disk spaces is seen, with significant vertebral destruction.)

MRI is the modality of choice for diagnosis and assessment of suspected spondylodiscitis because it can provide imaging of the soft tissue, neural elements, and bony changes with a high sensitivity and specificity.²³ Once infection is suspected, the diagnosis should be confirmed by fluoroscopic- or computed tomography-guided biopsy before starting antibiotic treatment.

Long-term antibiotics
 are required to prevent recurrence


IV antibiotics are the mainstay of treatment for spondylodiscitis;²⁴ the specific drug used will depend upon the organism identified. Patients typically receive 2 to 6 weeks of IV therapy. Then, once the patient improves and inflammatory markers return to normal levels, the patient receives a course of oral antibiotics for 2 to 6 more weeks. Grados et al¹⁹ found recurrence rates of 10% to 15% for patients who were treated 4 to 8 weeks compared to 3.9% in those treated for 12 weeks or longer; therefore, a total duration of 12 weeks is commonly chosen.^25-28

To minimize the risk of spondylolisthesis, kyphosis, and fractures of the infected bone, patients are advised to rest and the spine is often immobilized with a spinal brace. Surgery may be needed if antibiotics are not effective, or for patients who develop complications such as fluid collection, neurologic deficits, or deformity.

Our patient’s pain improved after 2 weeks and she became more comfortable wearing the thoracolumbar brace. Her CRP and ESR also improved and there was no radiologic evidence of fluid collection. The patient was discharged with a peripherally inserted central catheter in place and received IV ceftriaxone for 6 more weeks at home. This was followed by 4 weeks of oral ciprofloxacin 750 mg twice daily, thereby completing a 12-week course of antibiotics.

Our patient’s response to treatment was monitored clinically and the inflammatory markers were checked weekly after discharge until the end of treatment and at 6 and 12 months after start of treatment. At 12 months, our patient’s CRP was <1 mg/dL and ESR was 22 mm/h. One year later, our patient remained asymptomatic with normal inflammatory marker levels and no evidence of recurrence.

THE TAKEAWAY

Spondylodiscitis is an important differential diagnosis of lower back, flank, groin, and buttock pain. It’s important to be aware of this diagnosis, especially in patients who have risk factors such as IV drug abuse, diabetes, and morbid obesity. Although previous spinal surgery is a risk factor, spondylodiscitis should be considered in patients with persistent back pain even if they haven’t had spinal surgery. It can be present even when there is no tenderness over the spinous process or any fever.

Checking inflammatory markers is a reasonable next step if a patient’s pain does not resolve after at least 4 weeks. If levels of inflammatory markers such as CRP and ESR are elevated and symptoms continue, MRI can confirm or rule out the presence of spondylodiscitis. Treatments include orthotic support, antibiotics, and surgical intervention when complications arise.

THE CASE

A 23-year-old immunocompetent woman was referred to our spinal clinic with a 6-month history of low back pain that radiated to her right flank, buttock, and groin. She’d had intermittent urinary problems, including mild dysuria and frequency, and had been treated with antibiotics for a presumed urinary tract infection on 3 previous occasions, but her pain gradually increased and eventually became constant.

The patient had no history of fever, malaise, or weight loss. She denied consuming unpasteurized milk or undercooked poultry, and hadn’t recently experienced diarrhea or vomiting.

Eight years earlier, she had undergone anterior fusion of her spine for idiopathic scoliosis. At that time, she was at Risser grade 1, and her Cobb angle was 50°; metallic instrumentation was implanted at T10 to L3 to prevent progression of the scoliosis. Her recovery had been uneventful.

During examination, her temperature, pulse, respiratory rate, blood pressure, and nervous system were all normal. Her hips appeared normal, as well, and a straight leg raise was negative bilaterally. The patient had mild midline lumbar tenderness. Spinal range of movement revealed decreased flexion and mild pain.

X-rays (FIGURE 1) showed no changes in the previous metalwork in her spine. There was decreased disk height at the L3/4 level, but no significant bony erosion or soft-tissue shadows. Laboratory testing revealed a C-reactive protein (CRP) level of 240 mg/dL (normal, <1 mg/dL) and her erythrocyte sedimentation rate (ESR) was 102 mm/h—more than 5 times higher than it should have been.¹ The patient had a normal peripheral white cell count (WCC). Midstream urine cultures were negative.


The patient was admitted to the hospital for further work-up. Magnetic resonance imaging (MRI) of the lumbar spine showed gross abnormality at the L3-L4 disk level with erosion of the end plates, fluid in the disk space, marked enhancing edema, and mild surrounding soft-tissue edematous changes, but no evidence of any epidural abscess (FIGURE 2). The patient had a fluoroscopy-guided needle biopsy of the disk on the same day and received intravenous (IV) ceftriaxone 2 g twice a day. Blood and urine cultures were negative.

THE DIAGNOSIS

We suspected our patient had spondylodiscitis, an infection of the spine that includes spondylitis (inflammation of the vertebrae) and discitis (inflammation of the vertebral disk space). After 48 hours, the biopsy sample grew Salmonella typhimurium and confirmed the diagnosis. The organism was sensitive to ceftriaxone and ciprofloxacin; parenteral ceftriaxone was continued and the patient wore a thoracolumbar brace for immobilization. For 3 days, her inflammatory marker levels were checked daily, then every other day for the rest of that first week, and then 2 more times in the following week.

DISCUSSION

Thoracic and lumbar vertebrae are the most common sites of spondylodiscitis.² Spondylodiscitis accounts for 3% to 5% of pyogenic osteomyelitis in patients in developed countries.³ The incidence of pyogenic spondylodiscitis may be rising due to an increase in the number of elderly and immunocompromised patients, as well as a rise in invasive medical procedures.^4-6

If left untreated, spondylodiscitis can spread longitudinally (involving the adjacent levels), posteriorly (causing bacterial meningitis, abscess formation, and cord compromise), or anteriorly (causing paravertebral abscess). Untreated spondylodiscitis can also send distant infective emboli and cause endocarditis^7-9 or mycotic abdominal aneurysm.¹⁰

Historically, mortality in patients with vertebral osteomyelitis has been as high as 25%.¹¹ The combination of earlier diagnosis, antibiotics, and surgical debridement and stabilization has decreased mortality to less than 15%.^12-14

Risk factors for spondylodiscitis include male sex, IV drug abuse, diabetes, morbid obesity, having had a genitourinary or spinal procedure, and being immunocompromised (eg, from alcohol abuse, malignancy, organ transplantation, chemotherapy, or corticosteroid use).^12,15,16

Gram-positive organisms cause most spine infections in both adults and children, with 40% to 90% caused by Staphylococcus aureus.¹⁷ Gram-negative organisms (Escherichia coli, Pseudomonas, and Proteus), which can also cause spondylodiscitis, typically occur after genitourinary infections or procedures. IV drug abusers are prone to Pseudomonas infections.¹⁸ Anaerobic infections may be seen in patients with diabetes or after penetrating trauma.¹⁵ Salmonella species can cause spondylodiscitis, especially in patients with sickle cell disease from an intestinal source.¹⁹

Mycobacterium tuberculosis is the most common nonpyogenic infecting agent that also can cause spondylodiscitis. Infection caused by tuberculosis (TB) has had a recent resurgence with resistant strains, especially in patients with human immunodeficiency virus.¹⁵ Although less than 10% of patients with TB have skeletal involvement, 50% of the skeletal involvement occurs in the spine.¹⁵

The clinical presentation of spondylodiscitis depends on the location of the infection, the virulence of the organism, and the immune status of the patient. Discitis can present as pain in the back, hip, abdomen (especially in children²⁰) and, occasionally, with meningeal involvement.¹¹ Patients with discitis often have a normal temperature.^15,21 In patients with discitis, the patient’s WCC will be normal, but the ESR is almost always elevated.^15,22 Suspect spondylodiscitis in patients who present with persistent or increasing pain 3 to 4 weeks after back surgery. For such patients, measure inflammatory markers and order imaging of the spine.

Risk factors for spondylodiscitis include IV drug abuse, diabetes, morbid obesity, and having had a genitourinary or spinal procedure. X-ray findings for patients with spondylodiscitis will include osteolysis and end plate erosions (early) and narrowing and collapse of the disk space (late). (In TB, relative preservation of the disk spaces is seen, with significant vertebral destruction.)

MRI is the modality of choice for diagnosis and assessment of suspected spondylodiscitis because it can provide imaging of the soft tissue, neural elements, and bony changes with a high sensitivity and specificity.²³ Once infection is suspected, the diagnosis should be confirmed by fluoroscopic- or computed tomography-guided biopsy before starting antibiotic treatment.

Long-term antibiotics
 are required to prevent recurrence


IV antibiotics are the mainstay of treatment for spondylodiscitis;²⁴ the specific drug used will depend upon the organism identified. Patients typically receive 2 to 6 weeks of IV therapy. Then, once the patient improves and inflammatory markers return to normal levels, the patient receives a course of oral antibiotics for 2 to 6 more weeks. Grados et al¹⁹ found recurrence rates of 10% to 15% for patients who were treated 4 to 8 weeks compared to 3.9% in those treated for 12 weeks or longer; therefore, a total duration of 12 weeks is commonly chosen.^25-28

To minimize the risk of spondylolisthesis, kyphosis, and fractures of the infected bone, patients are advised to rest and the spine is often immobilized with a spinal brace. Surgery may be needed if antibiotics are not effective, or for patients who develop complications such as fluid collection, neurologic deficits, or deformity.

Our patient’s pain improved after 2 weeks and she became more comfortable wearing the thoracolumbar brace. Her CRP and ESR also improved and there was no radiologic evidence of fluid collection. The patient was discharged with a peripherally inserted central catheter in place and received IV ceftriaxone for 6 more weeks at home. This was followed by 4 weeks of oral ciprofloxacin 750 mg twice daily, thereby completing a 12-week course of antibiotics.

Our patient’s response to treatment was monitored clinically and the inflammatory markers were checked weekly after discharge until the end of treatment and at 6 and 12 months after start of treatment. At 12 months, our patient’s CRP was <1 mg/dL and ESR was 22 mm/h. One year later, our patient remained asymptomatic with normal inflammatory marker levels and no evidence of recurrence.

THE TAKEAWAY

Spondylodiscitis is an important differential diagnosis of lower back, flank, groin, and buttock pain. It’s important to be aware of this diagnosis, especially in patients who have risk factors such as IV drug abuse, diabetes, and morbid obesity. Although previous spinal surgery is a risk factor, spondylodiscitis should be considered in patients with persistent back pain even if they haven’t had spinal surgery. It can be present even when there is no tenderness over the spinous process or any fever.

Checking inflammatory markers is a reasonable next step if a patient’s pain does not resolve after at least 4 weeks. If levels of inflammatory markers such as CRP and ESR are elevated and symptoms continue, MRI can confirm or rule out the presence of spondylodiscitis. Treatments include orthotic support, antibiotics, and surgical intervention when complications arise.

THE CASE

A 23-year-old immunocompetent woman was referred to our spinal clinic with a 6-month history of low back pain that radiated to her right flank, buttock, and groin. She’d had intermittent urinary problems, including mild dysuria and frequency, and had been treated with antibiotics for a presumed urinary tract infection on 3 previous occasions, but her pain gradually increased and eventually became constant.

The patient had no history of fever, malaise, or weight loss. She denied consuming unpasteurized milk or undercooked poultry, and hadn’t recently experienced diarrhea or vomiting.

Eight years earlier, she had undergone anterior fusion of her spine for idiopathic scoliosis. At that time, she was at Risser grade 1, and her Cobb angle was 50°; metallic instrumentation was implanted at T10 to L3 to prevent progression of the scoliosis. Her recovery had been uneventful.

During examination, her temperature, pulse, respiratory rate, blood pressure, and nervous system were all normal. Her hips appeared normal, as well, and a straight leg raise was negative bilaterally. The patient had mild midline lumbar tenderness. Spinal range of movement revealed decreased flexion and mild pain.

X-rays (FIGURE 1) showed no changes in the previous metalwork in her spine. There was decreased disk height at the L3/4 level, but no significant bony erosion or soft-tissue shadows. Laboratory testing revealed a C-reactive protein (CRP) level of 240 mg/dL (normal, <1 mg/dL) and her erythrocyte sedimentation rate (ESR) was 102 mm/h—more than 5 times higher than it should have been.¹ The patient had a normal peripheral white cell count (WCC). Midstream urine cultures were negative.


The patient was admitted to the hospital for further work-up. Magnetic resonance imaging (MRI) of the lumbar spine showed gross abnormality at the L3-L4 disk level with erosion of the end plates, fluid in the disk space, marked enhancing edema, and mild surrounding soft-tissue edematous changes, but no evidence of any epidural abscess (FIGURE 2). The patient had a fluoroscopy-guided needle biopsy of the disk on the same day and received intravenous (IV) ceftriaxone 2 g twice a day. Blood and urine cultures were negative.

THE DIAGNOSIS

We suspected our patient had spondylodiscitis, an infection of the spine that includes spondylitis (inflammation of the vertebrae) and discitis (inflammation of the vertebral disk space). After 48 hours, the biopsy sample grew Salmonella typhimurium and confirmed the diagnosis. The organism was sensitive to ceftriaxone and ciprofloxacin; parenteral ceftriaxone was continued and the patient wore a thoracolumbar brace for immobilization. For 3 days, her inflammatory marker levels were checked daily, then every other day for the rest of that first week, and then 2 more times in the following week.

DISCUSSION

Thoracic and lumbar vertebrae are the most common sites of spondylodiscitis.² Spondylodiscitis accounts for 3% to 5% of pyogenic osteomyelitis in patients in developed countries.³ The incidence of pyogenic spondylodiscitis may be rising due to an increase in the number of elderly and immunocompromised patients, as well as a rise in invasive medical procedures.^4-6

If left untreated, spondylodiscitis can spread longitudinally (involving the adjacent levels), posteriorly (causing bacterial meningitis, abscess formation, and cord compromise), or anteriorly (causing paravertebral abscess). Untreated spondylodiscitis can also send distant infective emboli and cause endocarditis^7-9 or mycotic abdominal aneurysm.¹⁰

Historically, mortality in patients with vertebral osteomyelitis has been as high as 25%.¹¹ The combination of earlier diagnosis, antibiotics, and surgical debridement and stabilization has decreased mortality to less than 15%.^12-14

Risk factors for spondylodiscitis include male sex, IV drug abuse, diabetes, morbid obesity, having had a genitourinary or spinal procedure, and being immunocompromised (eg, from alcohol abuse, malignancy, organ transplantation, chemotherapy, or corticosteroid use).^12,15,16

Gram-positive organisms cause most spine infections in both adults and children, with 40% to 90% caused by Staphylococcus aureus.¹⁷ Gram-negative organisms (Escherichia coli, Pseudomonas, and Proteus), which can also cause spondylodiscitis, typically occur after genitourinary infections or procedures. IV drug abusers are prone to Pseudomonas infections.¹⁸ Anaerobic infections may be seen in patients with diabetes or after penetrating trauma.¹⁵ Salmonella species can cause spondylodiscitis, especially in patients with sickle cell disease from an intestinal source.¹⁹

Mycobacterium tuberculosis is the most common nonpyogenic infecting agent that also can cause spondylodiscitis. Infection caused by tuberculosis (TB) has had a recent resurgence with resistant strains, especially in patients with human immunodeficiency virus.¹⁵ Although less than 10% of patients with TB have skeletal involvement, 50% of the skeletal involvement occurs in the spine.¹⁵

The clinical presentation of spondylodiscitis depends on the location of the infection, the virulence of the organism, and the immune status of the patient. Discitis can present as pain in the back, hip, abdomen (especially in children²⁰) and, occasionally, with meningeal involvement.¹¹ Patients with discitis often have a normal temperature.^15,21 In patients with discitis, the patient’s WCC will be normal, but the ESR is almost always elevated.^15,22 Suspect spondylodiscitis in patients who present with persistent or increasing pain 3 to 4 weeks after back surgery. For such patients, measure inflammatory markers and order imaging of the spine.

Risk factors for spondylodiscitis include IV drug abuse, diabetes, morbid obesity, and having had a genitourinary or spinal procedure. X-ray findings for patients with spondylodiscitis will include osteolysis and end plate erosions (early) and narrowing and collapse of the disk space (late). (In TB, relative preservation of the disk spaces is seen, with significant vertebral destruction.)

MRI is the modality of choice for diagnosis and assessment of suspected spondylodiscitis because it can provide imaging of the soft tissue, neural elements, and bony changes with a high sensitivity and specificity.²³ Once infection is suspected, the diagnosis should be confirmed by fluoroscopic- or computed tomography-guided biopsy before starting antibiotic treatment.

Long-term antibiotics
 are required to prevent recurrence


IV antibiotics are the mainstay of treatment for spondylodiscitis;²⁴ the specific drug used will depend upon the organism identified. Patients typically receive 2 to 6 weeks of IV therapy. Then, once the patient improves and inflammatory markers return to normal levels, the patient receives a course of oral antibiotics for 2 to 6 more weeks. Grados et al¹⁹ found recurrence rates of 10% to 15% for patients who were treated 4 to 8 weeks compared to 3.9% in those treated for 12 weeks or longer; therefore, a total duration of 12 weeks is commonly chosen.^25-28

To minimize the risk of spondylolisthesis, kyphosis, and fractures of the infected bone, patients are advised to rest and the spine is often immobilized with a spinal brace. Surgery may be needed if antibiotics are not effective, or for patients who develop complications such as fluid collection, neurologic deficits, or deformity.

Our patient’s pain improved after 2 weeks and she became more comfortable wearing the thoracolumbar brace. Her CRP and ESR also improved and there was no radiologic evidence of fluid collection. The patient was discharged with a peripherally inserted central catheter in place and received IV ceftriaxone for 6 more weeks at home. This was followed by 4 weeks of oral ciprofloxacin 750 mg twice daily, thereby completing a 12-week course of antibiotics.

Our patient’s response to treatment was monitored clinically and the inflammatory markers were checked weekly after discharge until the end of treatment and at 6 and 12 months after start of treatment. At 12 months, our patient’s CRP was <1 mg/dL and ESR was 22 mm/h. One year later, our patient remained asymptomatic with normal inflammatory marker levels and no evidence of recurrence.

THE TAKEAWAY

Spondylodiscitis is an important differential diagnosis of lower back, flank, groin, and buttock pain. It’s important to be aware of this diagnosis, especially in patients who have risk factors such as IV drug abuse, diabetes, and morbid obesity. Although previous spinal surgery is a risk factor, spondylodiscitis should be considered in patients with persistent back pain even if they haven’t had spinal surgery. It can be present even when there is no tenderness over the spinous process or any fever.

Checking inflammatory markers is a reasonable next step if a patient’s pain does not resolve after at least 4 weeks. If levels of inflammatory markers such as CRP and ESR are elevated and symptoms continue, MRI can confirm or rule out the presence of spondylodiscitis. Treatments include orthotic support, antibiotics, and surgical intervention when complications arise.

CASE › Marie C, a 75-year-old Asian woman, reports weakness in her legs and arms with unsteadiness when walking. She has a vague but persistent ache in her large muscles. Her symptoms have developed slowly over the past 3 months. She denies recent signs or symptoms of infection or other illness. Her medical history includes hypertension, hyperlipidemia, osteopenia, and obesity. Ms. C takes lisinopril 10 mg/d and atorvastatin, which was recently increased from 10 to 20 mg/d.

What would your next steps be in caring for this patient?

Patients who experience muscle-related symptoms such as pain, fatigue, or weakness often seek help from their family physician (FP). The list of possible causes of these complaints can be lengthy and vary greatly, from nonmyopathic conditions such as fibromyalgia to worrisome forms of myopathy such as inclusion body myositis or polymyositis. This article will help you to quickly identify which patients with muscle-related complaints should be evaluated for myopathy and what your work-up should include.

Myopathy or not?

Distinguishing between myopathy and nonmyopathic muscle pain or weakness is the first step in evaluating patients with muscle-related complaints. Many conditions share muscle-related symptoms, but actual muscle damage is not always present (eg, fibromyalgia, chronic pain, and chronic fatigue syndromes).¹ While there is some overlap in presentation between patients with myopathy and nonmyopathic conditions, there are important differences in symptoms, physical exam findings, and lab test results (TABLE 1^1-4). Notably, in myopathic disease, patients’ symptoms are usually progressive, vital signs are abnormal, and weakness is common, whereas patients with nonmyopathic disease typically have remitting and relapsing symptoms, normal vital signs, and no weakness.

Myopathy itself is divided into 3 categories—myositic, intrinsic, and toxic—which reflect the condition, or medication, that brought on the muscle damage (TABLE 2^2,4-15). Placing patients into one of these categories based on their risk factors, history, and physical exam findings can help to focus the diagnostic work-up on areas most likely to provide useful information.

Myositic myopathy can be caused by infection or autoimmunity

Myositic myopathies result in inflammatory destruction of muscle tissue. Patients with myositic myopathy often exhibit fever, malaise, weight loss, and general fatigue. Though weakness and pain are common, both can be variable or even absent in myositic myopathy.^2,5 Myositic myopathy can be caused by infectious agents or can develop from an autoimmune disease.

Infectious myositic myopathy is one of the more common types of myopathy that FPs will encounter.² Viruses such as influenza, parainfluenza, coxsackievirus, human immunodeficiency virus, cytomegalovirus, echovirus, adenovirus, Epstein-Barr, and hepatitis C are common causes.^2,4,16 Patients with 
a viral myositis often report prodromal symptoms such as fever, upper respiratory illness, or GI distress one to 2 weeks before the onset of muscle complaints. Bacterial and fungal myositides are relatively rare. Both most often occur as the result of penetrating trauma or immunocompromise, and are generally not subtle.² Parasitic myopathy can occur from the invasion of skeletal muscle by trichinella after ingesting undercooked, infected meat.² Although previously a more common problem, currently only 10 to 20 cases of trichinellosis are reported in the United States each year.¹⁷ Due to their rarity, bacterial, fungal, and parasitic myositides are not reviewed here.

Patients with a viral myositis often report prodromal symptoms such as fever, upper respiratory illness, or gastrointestinal distress one to 2 weeks before the onset of muscle complaints. Muscle pain is usually multifocal, involving larger, bilateral muscle groups, and may be associated with swelling.

Patients with viral myositis may exhibit diffusely painful, swollen, or boggy-feeling muscles as well as weakness and pain with exertion. Other signs of viral infection such as rash, fever, upper respiratory symptoms, or meningeal signs may be present. Severe signs include arrhythmia or respiratory failure due to cardiac muscle or diaphragm involvement, or signs of renal failure due to precipitation of myoglobin in the renal system (ie, rhabdomyolysis).² If the infection affects the heart, patients may develop palpitations, pleuritic chest pain, or shortness of breath.²

Diagnosis of viral myositis relies heavily on clinical suspicion in patients with a fitting history and physical exam findings. Helpful lab tests include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), creatine kinase (CK), and liver function tests (LFTs), all of which can be abnormal in viral myositis. Viral polymerase chain reaction, culture, or antigen testing may be helpful in severe or confusing cases, but in most cases such testing is unnecessary. Muscle biopsy is not recommended except in persistent cases, where definitive identification of the causative agent might alter treatment or when nonviral infection is suspected.²

Autoimmune myositic myopathy. Unlike infectious myopathies, autoimmune myopathies are usually chronic, subtle, and relatively rare. The 3 most common autoimmune myopathies—polymyositis, dermatomyositis, and inclusion body myositis—have a combined prevalence of approximately 10:100,000.⁶ Although these types of myopathies are uncommon, FPs will likely be the first to evaluate a patient with one of them.

Patients with an autoimmune myopathy typically complain of weakness and mild to moderate muscle pain, although pain may be absent. Compared to infectious myopathies, autoimmune myopathies usually exhibit a more indolent course. Patients with advanced disease may report fever, weight loss, shortness of breath from cardiomyopathy, heartburn from a weakened lower esophageal sphincter, and/or a rash.⁵

A patient
 with mild
 to moderate electrolyte problems may complain of muscle fatigue, weakness,
 or pain. Physical examination may reveal symmetric, proximal muscle weakness. Atrophy is typically not seen until late in the disease. Skin exam usually is normal in patients with inclusion body myositis and polymyositis. The typical rash of dermatomyositis is a heliotrope (blue-purple) discoloration on the upper eyelids and a raised, violaceous, scaly eruption on the knuckles (Gottron’s papules).

Laboratory tests that can be helpful include CK, lactate dehydrogenase (LDH), aldolase, and LFTs (reflecting muscle injury, not liver involvement). For polymyositis and dermatomyositis, CK is the most sensitive lab test and often exhibits the highest elevation above normal.⁶ Conversely, CK is often normal or only mildly elevated in inclusion body myositis. Up to 80% of patients with autoimmune myopathy will have antinuclear antibodies.^3,5 ESR and CRP levels are also often elevated.

Both electromyography (EMG) and muscle biopsy may be required to diagnose autoimmune myopathy, but these are typically done under the direction of a rheumatologist after an FP’s initial work-up is inconclusive.

Intrinsic myopathy: Suspect electrolyte problems, other causes

Intrinsic myopathy occurs in patients with electrolyte disorders, diseases of the endocrine system, or underlying metabolic dysfunction.

Electrolyte disorders. Muscle-related symptoms are unlikely to be the chief complaint of patients with severe electrolyte imbalance. However, a patient with mild to moderate electrolyte problems may develop muscle fatigue, weakness, or pain. TABLE 3 reviews other signs and symptoms of electrolyte abnormalities that may be helpful in establishing a diagnosis in a patient with muscle complaints.

Ordering a complete metabolic panel (CMP), CK, and urinalysis (UA) can help rule out electrolyte disorders. If electrolyte disorders are detected, an electrocardiogram is useful to evaluate for cardiac dysfunction. Once an electrolyte disorder is identified, investigate its underlying cause. Correcting the electrolyte disorder should help improve symptoms of myopathy.

Endocrine myopathy can be associated with hypothyroidism, hyperthyroidism, parathyroid disease, vitamin D deficiency, or Cushing syndrome.^8-10,18,19 Although less common than some other causes, identifying endocrine myopathy is crucial because correcting the underlying disease will often improve multiple aspects of the patient’s health.

The presentation of endocrine myopathy may be subtle. Patients with hypothyroidism may experience muscle pain or weakness, fatigue, cold sensitivity, constipation, and dry skin.²⁰ Muscle-related symptoms may be the only sign of endocrine myopathy in a patient who would otherwise be considered to have subclinical hypothyroidism.^8,18 Hyperthyroidism can present with weight loss, heat intolerance, frequent bowel movements, tachycardia, and muscle weakness.²¹

Patients with parathyroid disease— especially patients with chronic renal failure—may report proximal muscle weakness, often in the lower extremities.¹⁹ Complaints of muscle weakness or pain can occur with severe vitamin D deficiency.¹⁰ Patients with Cushing syndrome often experience proximal weakness and weight gain.⁹

Patients with a personal or family history of endocrine disorders, previous thyroid surgery, or those taking medications that can impair thyroid function, such as lithium, amiodarone, or interferon, are at risk for endocrine myopathy.^18-20 Suspect hyperparathyroidism in patients with chronic kidney disease who complain of weakness.

Vitamin D deficiency is relatively common, with at minimum 20% of elderly adults estimated to be deficient.¹⁰ Patients at risk for Cushing disease are most likely receiving pharmacologic doses of glucocorticoids, which can increase their risk of myopathy, or to have ectopic adrenocorticotropic hormone secretion.

Metabolic myopathy results from a lack of sufficient energy production in the muscle. The 3 main groups of metabolic myopathy are impaired muscle glycogenoses, disorders of fatty acid oxidation, and mitochondrial myopathies.⁷

Because metabolic myopathy can occur at any age, a thorough history and physical is crucial for diagnosis. Proximal weakness in metabolic myopathy is often associated with exercise intolerance, stressful illness, or fasting. Patients often present with dynamic abnormalities such as fatigue, muscle cramping, and even rhabdomyolysis during exertion.⁷

When evaluating patients you suspect may have metabolic myopathy, a physical exam may reveal muscle contractures, muscle swelling, or proximal muscle weakness. Patients with certain types of fatty acid oxidation disorders or mitochondrial disorders may also exhibit cardiomyopathy, neuropathy, retinopathy, ataxia, hearing loss, or other systemic manifestations.⁷

Basic labs for investigating suspected metabolic myopathy include serum electrolytes, glucose, LFTs, CK (which may or may not be elevated), lactate, ammonia, and UA for myoglobinuria. More advanced labs, such as serum total carnitine and acylcarnitine as well as urinary levels of dicarboxylic acids and acylglycines, may be needed if a metabolic disorder is strongly suspected.⁷ Muscle biopsy, EMG, and genetic testing can also prove helpful in diagnosis. Definitive diagnosis and treatment of metabolic myopathy usually requires a multidisciplinary team of providers, including subspecialty referral.

Toxic myopathy

The symptoms of drug-induced toxic myopathy are usually more insidious and lab abnormalities are usually more subtle than for other forms
 of myopathy. Toxic myopathy refers to muscle damage caused by an exogenous chemical agent, most often a drug. The mechanism of toxicity is not always clear and may result from the activation of inflammatory responses similar to autoimmune myopathy.²² Toxic myopathies may result from several commonly used medications; cholesterol-lowering medications are a common culprit.^13-15,23-25 Drug-induced myopathies vary in frequency and severity. For instance, in patients taking statins, the rate of myalgias is 6%, while the incidence of rhabdomyolysis is estimated to be 4 per 100,000, and is found most often in patients taking concomitant fibrates.²³

Drug-induced toxic myopathy differs from previously discussed myopathies in that symptoms are usually more insidious, findings on exam are more often mixed muscular and neurologic, and lab abnormalities are usually more subtle.^11,12 Symptoms of myopathy typically occur weeks or months after initiating a drug and usually improve or resolve within weeks after discontinuing the offending agent. Knowing the patient’s medication list and which medications cause certain patterns of myopathy symptoms can help guide the differential diagnosis (TABLE 4^11-15,22-25).

Cholesterol-lowering medications such as statins are a common cause of toxic myopathy. Risk factors for most medication-related myopathies are polypharmacy, renal or liver disease, and age over 50 years^13-15,23-25 The physical exam for patients with drug- or toxin-related myopathy will most often reveal relatively minor abnormalities such as muscle tenderness and mild weakness, except for the most severe or advanced cases. Most patients will not have physical signs that suggest an underlying illness. CK levels and LFTs should be obtained. Basic chemistry and UA may also be helpful in patients with risk factors for renal disease.

CASE › Ms. C has been taking a statin for more than 10 years, and the dose was recently increased. You are aware that statin-related muscle injury can develop even after years of use, and suspect the statin may be causing her myopathy. You order a CK test, which is mildly elevated. You recommend discontinuing the statin. After 8 weeks off her statin, Ms. C’s Symptoms do not improve. Given her lack of systemic complaints, myositic myopathy from an infectious or rheumatologic cause seems unlikely. You begin to consider an intrinsic cause of myopathy, and order the following tests: a CMP, UA, thyroid-stimulating hormone, repeat CK, and vitamin D level. This testing reveals a vitamin D deficiency at 17 ng/ml (normal range: 30-74 ng/ml). You recommend vitamin D, 50,000 IU per week for 8 weeks. At follow-up, Ms. C's vitamin D level is 40. She says she feels better and her muscle complaints have resolved.

CORRESPONDENCE
Brent W. Smith, MD, Travis Air Force Base Family Medicine Residency, 101 Bodin Circle, Travis Air Force Base, CA 94535; [email protected]

CASE › Marie C, a 75-year-old Asian woman, reports weakness in her legs and arms with unsteadiness when walking. She has a vague but persistent ache in her large muscles. Her symptoms have developed slowly over the past 3 months. She denies recent signs or symptoms of infection or other illness. Her medical history includes hypertension, hyperlipidemia, osteopenia, and obesity. Ms. C takes lisinopril 10 mg/d and atorvastatin, which was recently increased from 10 to 20 mg/d.

What would your next steps be in caring for this patient?

Patients who experience muscle-related symptoms such as pain, fatigue, or weakness often seek help from their family physician (FP). The list of possible causes of these complaints can be lengthy and vary greatly, from nonmyopathic conditions such as fibromyalgia to worrisome forms of myopathy such as inclusion body myositis or polymyositis. This article will help you to quickly identify which patients with muscle-related complaints should be evaluated for myopathy and what your work-up should include.

Myopathy or not?

Distinguishing between myopathy and nonmyopathic muscle pain or weakness is the first step in evaluating patients with muscle-related complaints. Many conditions share muscle-related symptoms, but actual muscle damage is not always present (eg, fibromyalgia, chronic pain, and chronic fatigue syndromes).¹ While there is some overlap in presentation between patients with myopathy and nonmyopathic conditions, there are important differences in symptoms, physical exam findings, and lab test results (TABLE 1^1-4). Notably, in myopathic disease, patients’ symptoms are usually progressive, vital signs are abnormal, and weakness is common, whereas patients with nonmyopathic disease typically have remitting and relapsing symptoms, normal vital signs, and no weakness.

Myopathy itself is divided into 3 categories—myositic, intrinsic, and toxic—which reflect the condition, or medication, that brought on the muscle damage (TABLE 2^2,4-15). Placing patients into one of these categories based on their risk factors, history, and physical exam findings can help to focus the diagnostic work-up on areas most likely to provide useful information.

Myositic myopathy can be caused by infection or autoimmunity

Myositic myopathies result in inflammatory destruction of muscle tissue. Patients with myositic myopathy often exhibit fever, malaise, weight loss, and general fatigue. Though weakness and pain are common, both can be variable or even absent in myositic myopathy.^2,5 Myositic myopathy can be caused by infectious agents or can develop from an autoimmune disease.

Infectious myositic myopathy is one of the more common types of myopathy that FPs will encounter.² Viruses such as influenza, parainfluenza, coxsackievirus, human immunodeficiency virus, cytomegalovirus, echovirus, adenovirus, Epstein-Barr, and hepatitis C are common causes.^2,4,16 Patients with 
a viral myositis often report prodromal symptoms such as fever, upper respiratory illness, or GI distress one to 2 weeks before the onset of muscle complaints. Bacterial and fungal myositides are relatively rare. Both most often occur as the result of penetrating trauma or immunocompromise, and are generally not subtle.² Parasitic myopathy can occur from the invasion of skeletal muscle by trichinella after ingesting undercooked, infected meat.² Although previously a more common problem, currently only 10 to 20 cases of trichinellosis are reported in the United States each year.¹⁷ Due to their rarity, bacterial, fungal, and parasitic myositides are not reviewed here.

Patients with a viral myositis often report prodromal symptoms such as fever, upper respiratory illness, or gastrointestinal distress one to 2 weeks before the onset of muscle complaints. Muscle pain is usually multifocal, involving larger, bilateral muscle groups, and may be associated with swelling.

Patients with viral myositis may exhibit diffusely painful, swollen, or boggy-feeling muscles as well as weakness and pain with exertion. Other signs of viral infection such as rash, fever, upper respiratory symptoms, or meningeal signs may be present. Severe signs include arrhythmia or respiratory failure due to cardiac muscle or diaphragm involvement, or signs of renal failure due to precipitation of myoglobin in the renal system (ie, rhabdomyolysis).² If the infection affects the heart, patients may develop palpitations, pleuritic chest pain, or shortness of breath.²

Diagnosis of viral myositis relies heavily on clinical suspicion in patients with a fitting history and physical exam findings. Helpful lab tests include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), creatine kinase (CK), and liver function tests (LFTs), all of which can be abnormal in viral myositis. Viral polymerase chain reaction, culture, or antigen testing may be helpful in severe or confusing cases, but in most cases such testing is unnecessary. Muscle biopsy is not recommended except in persistent cases, where definitive identification of the causative agent might alter treatment or when nonviral infection is suspected.²

Autoimmune myositic myopathy. Unlike infectious myopathies, autoimmune myopathies are usually chronic, subtle, and relatively rare. The 3 most common autoimmune myopathies—polymyositis, dermatomyositis, and inclusion body myositis—have a combined prevalence of approximately 10:100,000.⁶ Although these types of myopathies are uncommon, FPs will likely be the first to evaluate a patient with one of them.

Patients with an autoimmune myopathy typically complain of weakness and mild to moderate muscle pain, although pain may be absent. Compared to infectious myopathies, autoimmune myopathies usually exhibit a more indolent course. Patients with advanced disease may report fever, weight loss, shortness of breath from cardiomyopathy, heartburn from a weakened lower esophageal sphincter, and/or a rash.⁵

A patient
 with mild
 to moderate electrolyte problems may complain of muscle fatigue, weakness,
 or pain. Physical examination may reveal symmetric, proximal muscle weakness. Atrophy is typically not seen until late in the disease. Skin exam usually is normal in patients with inclusion body myositis and polymyositis. The typical rash of dermatomyositis is a heliotrope (blue-purple) discoloration on the upper eyelids and a raised, violaceous, scaly eruption on the knuckles (Gottron’s papules).

Laboratory tests that can be helpful include CK, lactate dehydrogenase (LDH), aldolase, and LFTs (reflecting muscle injury, not liver involvement). For polymyositis and dermatomyositis, CK is the most sensitive lab test and often exhibits the highest elevation above normal.⁶ Conversely, CK is often normal or only mildly elevated in inclusion body myositis. Up to 80% of patients with autoimmune myopathy will have antinuclear antibodies.^3,5 ESR and CRP levels are also often elevated.

Both electromyography (EMG) and muscle biopsy may be required to diagnose autoimmune myopathy, but these are typically done under the direction of a rheumatologist after an FP’s initial work-up is inconclusive.

Intrinsic myopathy: Suspect electrolyte problems, other causes

Intrinsic myopathy occurs in patients with electrolyte disorders, diseases of the endocrine system, or underlying metabolic dysfunction.

Electrolyte disorders. Muscle-related symptoms are unlikely to be the chief complaint of patients with severe electrolyte imbalance. However, a patient with mild to moderate electrolyte problems may develop muscle fatigue, weakness, or pain. TABLE 3 reviews other signs and symptoms of electrolyte abnormalities that may be helpful in establishing a diagnosis in a patient with muscle complaints.

Ordering a complete metabolic panel (CMP), CK, and urinalysis (UA) can help rule out electrolyte disorders. If electrolyte disorders are detected, an electrocardiogram is useful to evaluate for cardiac dysfunction. Once an electrolyte disorder is identified, investigate its underlying cause. Correcting the electrolyte disorder should help improve symptoms of myopathy.

Endocrine myopathy can be associated with hypothyroidism, hyperthyroidism, parathyroid disease, vitamin D deficiency, or Cushing syndrome.^8-10,18,19 Although less common than some other causes, identifying endocrine myopathy is crucial because correcting the underlying disease will often improve multiple aspects of the patient’s health.

The presentation of endocrine myopathy may be subtle. Patients with hypothyroidism may experience muscle pain or weakness, fatigue, cold sensitivity, constipation, and dry skin.²⁰ Muscle-related symptoms may be the only sign of endocrine myopathy in a patient who would otherwise be considered to have subclinical hypothyroidism.^8,18 Hyperthyroidism can present with weight loss, heat intolerance, frequent bowel movements, tachycardia, and muscle weakness.²¹

Patients with parathyroid disease— especially patients with chronic renal failure—may report proximal muscle weakness, often in the lower extremities.¹⁹ Complaints of muscle weakness or pain can occur with severe vitamin D deficiency.¹⁰ Patients with Cushing syndrome often experience proximal weakness and weight gain.⁹

Patients with a personal or family history of endocrine disorders, previous thyroid surgery, or those taking medications that can impair thyroid function, such as lithium, amiodarone, or interferon, are at risk for endocrine myopathy.^18-20 Suspect hyperparathyroidism in patients with chronic kidney disease who complain of weakness.

Vitamin D deficiency is relatively common, with at minimum 20% of elderly adults estimated to be deficient.¹⁰ Patients at risk for Cushing disease are most likely receiving pharmacologic doses of glucocorticoids, which can increase their risk of myopathy, or to have ectopic adrenocorticotropic hormone secretion.

Metabolic myopathy results from a lack of sufficient energy production in the muscle. The 3 main groups of metabolic myopathy are impaired muscle glycogenoses, disorders of fatty acid oxidation, and mitochondrial myopathies.⁷

Because metabolic myopathy can occur at any age, a thorough history and physical is crucial for diagnosis. Proximal weakness in metabolic myopathy is often associated with exercise intolerance, stressful illness, or fasting. Patients often present with dynamic abnormalities such as fatigue, muscle cramping, and even rhabdomyolysis during exertion.⁷

When evaluating patients you suspect may have metabolic myopathy, a physical exam may reveal muscle contractures, muscle swelling, or proximal muscle weakness. Patients with certain types of fatty acid oxidation disorders or mitochondrial disorders may also exhibit cardiomyopathy, neuropathy, retinopathy, ataxia, hearing loss, or other systemic manifestations.⁷

Basic labs for investigating suspected metabolic myopathy include serum electrolytes, glucose, LFTs, CK (which may or may not be elevated), lactate, ammonia, and UA for myoglobinuria. More advanced labs, such as serum total carnitine and acylcarnitine as well as urinary levels of dicarboxylic acids and acylglycines, may be needed if a metabolic disorder is strongly suspected.⁷ Muscle biopsy, EMG, and genetic testing can also prove helpful in diagnosis. Definitive diagnosis and treatment of metabolic myopathy usually requires a multidisciplinary team of providers, including subspecialty referral.

Toxic myopathy

The symptoms of drug-induced toxic myopathy are usually more insidious and lab abnormalities are usually more subtle than for other forms
 of myopathy. Toxic myopathy refers to muscle damage caused by an exogenous chemical agent, most often a drug. The mechanism of toxicity is not always clear and may result from the activation of inflammatory responses similar to autoimmune myopathy.²² Toxic myopathies may result from several commonly used medications; cholesterol-lowering medications are a common culprit.^13-15,23-25 Drug-induced myopathies vary in frequency and severity. For instance, in patients taking statins, the rate of myalgias is 6%, while the incidence of rhabdomyolysis is estimated to be 4 per 100,000, and is found most often in patients taking concomitant fibrates.²³

Drug-induced toxic myopathy differs from previously discussed myopathies in that symptoms are usually more insidious, findings on exam are more often mixed muscular and neurologic, and lab abnormalities are usually more subtle.^11,12 Symptoms of myopathy typically occur weeks or months after initiating a drug and usually improve or resolve within weeks after discontinuing the offending agent. Knowing the patient’s medication list and which medications cause certain patterns of myopathy symptoms can help guide the differential diagnosis (TABLE 4^11-15,22-25).

Cholesterol-lowering medications such as statins are a common cause of toxic myopathy. Risk factors for most medication-related myopathies are polypharmacy, renal or liver disease, and age over 50 years^13-15,23-25 The physical exam for patients with drug- or toxin-related myopathy will most often reveal relatively minor abnormalities such as muscle tenderness and mild weakness, except for the most severe or advanced cases. Most patients will not have physical signs that suggest an underlying illness. CK levels and LFTs should be obtained. Basic chemistry and UA may also be helpful in patients with risk factors for renal disease.

CASE › Ms. C has been taking a statin for more than 10 years, and the dose was recently increased. You are aware that statin-related muscle injury can develop even after years of use, and suspect the statin may be causing her myopathy. You order a CK test, which is mildly elevated. You recommend discontinuing the statin. After 8 weeks off her statin, Ms. C’s Symptoms do not improve. Given her lack of systemic complaints, myositic myopathy from an infectious or rheumatologic cause seems unlikely. You begin to consider an intrinsic cause of myopathy, and order the following tests: a CMP, UA, thyroid-stimulating hormone, repeat CK, and vitamin D level. This testing reveals a vitamin D deficiency at 17 ng/ml (normal range: 30-74 ng/ml). You recommend vitamin D, 50,000 IU per week for 8 weeks. At follow-up, Ms. C's vitamin D level is 40. She says she feels better and her muscle complaints have resolved.

CORRESPONDENCE
Brent W. Smith, MD, Travis Air Force Base Family Medicine Residency, 101 Bodin Circle, Travis Air Force Base, CA 94535; [email protected]

CASE › Marie C, a 75-year-old Asian woman, reports weakness in her legs and arms with unsteadiness when walking. She has a vague but persistent ache in her large muscles. Her symptoms have developed slowly over the past 3 months. She denies recent signs or symptoms of infection or other illness. Her medical history includes hypertension, hyperlipidemia, osteopenia, and obesity. Ms. C takes lisinopril 10 mg/d and atorvastatin, which was recently increased from 10 to 20 mg/d.

What would your next steps be in caring for this patient?

Patients who experience muscle-related symptoms such as pain, fatigue, or weakness often seek help from their family physician (FP). The list of possible causes of these complaints can be lengthy and vary greatly, from nonmyopathic conditions such as fibromyalgia to worrisome forms of myopathy such as inclusion body myositis or polymyositis. This article will help you to quickly identify which patients with muscle-related complaints should be evaluated for myopathy and what your work-up should include.

Myopathy or not?

Distinguishing between myopathy and nonmyopathic muscle pain or weakness is the first step in evaluating patients with muscle-related complaints. Many conditions share muscle-related symptoms, but actual muscle damage is not always present (eg, fibromyalgia, chronic pain, and chronic fatigue syndromes).¹ While there is some overlap in presentation between patients with myopathy and nonmyopathic conditions, there are important differences in symptoms, physical exam findings, and lab test results (TABLE 1^1-4). Notably, in myopathic disease, patients’ symptoms are usually progressive, vital signs are abnormal, and weakness is common, whereas patients with nonmyopathic disease typically have remitting and relapsing symptoms, normal vital signs, and no weakness.

Myopathy itself is divided into 3 categories—myositic, intrinsic, and toxic—which reflect the condition, or medication, that brought on the muscle damage (TABLE 2^2,4-15). Placing patients into one of these categories based on their risk factors, history, and physical exam findings can help to focus the diagnostic work-up on areas most likely to provide useful information.

Myositic myopathy can be caused by infection or autoimmunity

Myositic myopathies result in inflammatory destruction of muscle tissue. Patients with myositic myopathy often exhibit fever, malaise, weight loss, and general fatigue. Though weakness and pain are common, both can be variable or even absent in myositic myopathy.^2,5 Myositic myopathy can be caused by infectious agents or can develop from an autoimmune disease.

Infectious myositic myopathy is one of the more common types of myopathy that FPs will encounter.² Viruses such as influenza, parainfluenza, coxsackievirus, human immunodeficiency virus, cytomegalovirus, echovirus, adenovirus, Epstein-Barr, and hepatitis C are common causes.^2,4,16 Patients with 
a viral myositis often report prodromal symptoms such as fever, upper respiratory illness, or GI distress one to 2 weeks before the onset of muscle complaints. Bacterial and fungal myositides are relatively rare. Both most often occur as the result of penetrating trauma or immunocompromise, and are generally not subtle.² Parasitic myopathy can occur from the invasion of skeletal muscle by trichinella after ingesting undercooked, infected meat.² Although previously a more common problem, currently only 10 to 20 cases of trichinellosis are reported in the United States each year.¹⁷ Due to their rarity, bacterial, fungal, and parasitic myositides are not reviewed here.

Patients with a viral myositis often report prodromal symptoms such as fever, upper respiratory illness, or gastrointestinal distress one to 2 weeks before the onset of muscle complaints. Muscle pain is usually multifocal, involving larger, bilateral muscle groups, and may be associated with swelling.

Patients with viral myositis may exhibit diffusely painful, swollen, or boggy-feeling muscles as well as weakness and pain with exertion. Other signs of viral infection such as rash, fever, upper respiratory symptoms, or meningeal signs may be present. Severe signs include arrhythmia or respiratory failure due to cardiac muscle or diaphragm involvement, or signs of renal failure due to precipitation of myoglobin in the renal system (ie, rhabdomyolysis).² If the infection affects the heart, patients may develop palpitations, pleuritic chest pain, or shortness of breath.²

Diagnosis of viral myositis relies heavily on clinical suspicion in patients with a fitting history and physical exam findings. Helpful lab tests include a complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), creatine kinase (CK), and liver function tests (LFTs), all of which can be abnormal in viral myositis. Viral polymerase chain reaction, culture, or antigen testing may be helpful in severe or confusing cases, but in most cases such testing is unnecessary. Muscle biopsy is not recommended except in persistent cases, where definitive identification of the causative agent might alter treatment or when nonviral infection is suspected.²

Autoimmune myositic myopathy. Unlike infectious myopathies, autoimmune myopathies are usually chronic, subtle, and relatively rare. The 3 most common autoimmune myopathies—polymyositis, dermatomyositis, and inclusion body myositis—have a combined prevalence of approximately 10:100,000.⁶ Although these types of myopathies are uncommon, FPs will likely be the first to evaluate a patient with one of them.

Patients with an autoimmune myopathy typically complain of weakness and mild to moderate muscle pain, although pain may be absent. Compared to infectious myopathies, autoimmune myopathies usually exhibit a more indolent course. Patients with advanced disease may report fever, weight loss, shortness of breath from cardiomyopathy, heartburn from a weakened lower esophageal sphincter, and/or a rash.⁵

A patient
 with mild
 to moderate electrolyte problems may complain of muscle fatigue, weakness,
 or pain. Physical examination may reveal symmetric, proximal muscle weakness. Atrophy is typically not seen until late in the disease. Skin exam usually is normal in patients with inclusion body myositis and polymyositis. The typical rash of dermatomyositis is a heliotrope (blue-purple) discoloration on the upper eyelids and a raised, violaceous, scaly eruption on the knuckles (Gottron’s papules).

Laboratory tests that can be helpful include CK, lactate dehydrogenase (LDH), aldolase, and LFTs (reflecting muscle injury, not liver involvement). For polymyositis and dermatomyositis, CK is the most sensitive lab test and often exhibits the highest elevation above normal.⁶ Conversely, CK is often normal or only mildly elevated in inclusion body myositis. Up to 80% of patients with autoimmune myopathy will have antinuclear antibodies.^3,5 ESR and CRP levels are also often elevated.

Both electromyography (EMG) and muscle biopsy may be required to diagnose autoimmune myopathy, but these are typically done under the direction of a rheumatologist after an FP’s initial work-up is inconclusive.

Intrinsic myopathy: Suspect electrolyte problems, other causes

Intrinsic myopathy occurs in patients with electrolyte disorders, diseases of the endocrine system, or underlying metabolic dysfunction.

Electrolyte disorders. Muscle-related symptoms are unlikely to be the chief complaint of patients with severe electrolyte imbalance. However, a patient with mild to moderate electrolyte problems may develop muscle fatigue, weakness, or pain. TABLE 3 reviews other signs and symptoms of electrolyte abnormalities that may be helpful in establishing a diagnosis in a patient with muscle complaints.

Ordering a complete metabolic panel (CMP), CK, and urinalysis (UA) can help rule out electrolyte disorders. If electrolyte disorders are detected, an electrocardiogram is useful to evaluate for cardiac dysfunction. Once an electrolyte disorder is identified, investigate its underlying cause. Correcting the electrolyte disorder should help improve symptoms of myopathy.

Endocrine myopathy can be associated with hypothyroidism, hyperthyroidism, parathyroid disease, vitamin D deficiency, or Cushing syndrome.^8-10,18,19 Although less common than some other causes, identifying endocrine myopathy is crucial because correcting the underlying disease will often improve multiple aspects of the patient’s health.

The presentation of endocrine myopathy may be subtle. Patients with hypothyroidism may experience muscle pain or weakness, fatigue, cold sensitivity, constipation, and dry skin.²⁰ Muscle-related symptoms may be the only sign of endocrine myopathy in a patient who would otherwise be considered to have subclinical hypothyroidism.^8,18 Hyperthyroidism can present with weight loss, heat intolerance, frequent bowel movements, tachycardia, and muscle weakness.²¹

Patients with parathyroid disease— especially patients with chronic renal failure—may report proximal muscle weakness, often in the lower extremities.¹⁹ Complaints of muscle weakness or pain can occur with severe vitamin D deficiency.¹⁰ Patients with Cushing syndrome often experience proximal weakness and weight gain.⁹

Patients with a personal or family history of endocrine disorders, previous thyroid surgery, or those taking medications that can impair thyroid function, such as lithium, amiodarone, or interferon, are at risk for endocrine myopathy.^18-20 Suspect hyperparathyroidism in patients with chronic kidney disease who complain of weakness.

Vitamin D deficiency is relatively common, with at minimum 20% of elderly adults estimated to be deficient.¹⁰ Patients at risk for Cushing disease are most likely receiving pharmacologic doses of glucocorticoids, which can increase their risk of myopathy, or to have ectopic adrenocorticotropic hormone secretion.

Metabolic myopathy results from a lack of sufficient energy production in the muscle. The 3 main groups of metabolic myopathy are impaired muscle glycogenoses, disorders of fatty acid oxidation, and mitochondrial myopathies.⁷

Because metabolic myopathy can occur at any age, a thorough history and physical is crucial for diagnosis. Proximal weakness in metabolic myopathy is often associated with exercise intolerance, stressful illness, or fasting. Patients often present with dynamic abnormalities such as fatigue, muscle cramping, and even rhabdomyolysis during exertion.⁷

When evaluating patients you suspect may have metabolic myopathy, a physical exam may reveal muscle contractures, muscle swelling, or proximal muscle weakness. Patients with certain types of fatty acid oxidation disorders or mitochondrial disorders may also exhibit cardiomyopathy, neuropathy, retinopathy, ataxia, hearing loss, or other systemic manifestations.⁷

Basic labs for investigating suspected metabolic myopathy include serum electrolytes, glucose, LFTs, CK (which may or may not be elevated), lactate, ammonia, and UA for myoglobinuria. More advanced labs, such as serum total carnitine and acylcarnitine as well as urinary levels of dicarboxylic acids and acylglycines, may be needed if a metabolic disorder is strongly suspected.⁷ Muscle biopsy, EMG, and genetic testing can also prove helpful in diagnosis. Definitive diagnosis and treatment of metabolic myopathy usually requires a multidisciplinary team of providers, including subspecialty referral.

Toxic myopathy

The symptoms of drug-induced toxic myopathy are usually more insidious and lab abnormalities are usually more subtle than for other forms
 of myopathy. Toxic myopathy refers to muscle damage caused by an exogenous chemical agent, most often a drug. The mechanism of toxicity is not always clear and may result from the activation of inflammatory responses similar to autoimmune myopathy.²² Toxic myopathies may result from several commonly used medications; cholesterol-lowering medications are a common culprit.^13-15,23-25 Drug-induced myopathies vary in frequency and severity. For instance, in patients taking statins, the rate of myalgias is 6%, while the incidence of rhabdomyolysis is estimated to be 4 per 100,000, and is found most often in patients taking concomitant fibrates.²³

Drug-induced toxic myopathy differs from previously discussed myopathies in that symptoms are usually more insidious, findings on exam are more often mixed muscular and neurologic, and lab abnormalities are usually more subtle.^11,12 Symptoms of myopathy typically occur weeks or months after initiating a drug and usually improve or resolve within weeks after discontinuing the offending agent. Knowing the patient’s medication list and which medications cause certain patterns of myopathy symptoms can help guide the differential diagnosis (TABLE 4^11-15,22-25).

Cholesterol-lowering medications such as statins are a common cause of toxic myopathy. Risk factors for most medication-related myopathies are polypharmacy, renal or liver disease, and age over 50 years^13-15,23-25 The physical exam for patients with drug- or toxin-related myopathy will most often reveal relatively minor abnormalities such as muscle tenderness and mild weakness, except for the most severe or advanced cases. Most patients will not have physical signs that suggest an underlying illness. CK levels and LFTs should be obtained. Basic chemistry and UA may also be helpful in patients with risk factors for renal disease.

CASE › Ms. C has been taking a statin for more than 10 years, and the dose was recently increased. You are aware that statin-related muscle injury can develop even after years of use, and suspect the statin may be causing her myopathy. You order a CK test, which is mildly elevated. You recommend discontinuing the statin. After 8 weeks off her statin, Ms. C’s Symptoms do not improve. Given her lack of systemic complaints, myositic myopathy from an infectious or rheumatologic cause seems unlikely. You begin to consider an intrinsic cause of myopathy, and order the following tests: a CMP, UA, thyroid-stimulating hormone, repeat CK, and vitamin D level. This testing reveals a vitamin D deficiency at 17 ng/ml (normal range: 30-74 ng/ml). You recommend vitamin D, 50,000 IU per week for 8 weeks. At follow-up, Ms. C's vitamin D level is 40. She says she feels better and her muscle complaints have resolved.

CORRESPONDENCE
Brent W. Smith, MD, Travis Air Force Base Family Medicine Residency, 101 Bodin Circle, Travis Air Force Base, CA 94535; [email protected]

Premature infant has CP: $14.5M verdict
After learning that, 14 years earlier, a 36-year-old woman had undergone an emergency cesarean delivery at 32 weeks’ gestation, her health-care providers planned a cesarean delivery for the new pregnancy. The woman was admitted to the hospital in preterm labor. Three days later, she was discharged, but readmitted twice more over a 2-week period. At each admission, preterm labor was halted using medication and bed rest.

The patient’s water broke and she was admitted to the hospital at 25 weeks’ gestation, about a week after the previous admission. Shortly after admission, the patient asked about a cesarean delivery, but no action was taken. When her ObGyn arrived at the hospital 5 hours later, the patient asked for a cesarean delivery; the ObGyn said he wanted to wait to see how her labor was progressing. After 3 hours, the fetus showed signs of distress, and an emergency cesarean delivery was undertaken. The infant experienced a massive brain hemorrhage, resulting in cerebral palsy (CP). The child has cognitive delays, visual impairment, and additional problems; he will require lifelong care.

PARENTS’ CLAIM The ObGyn and hospital were negligent in discharging the woman from admission for preterm labor. Cesarean delivery should have been performed much earlier due to nonreassuring fetal heart tones. Severe variable decelerations caused cerebral blood flow fluctuations that led to the hemorrhage.

DEFENDANTS’ DEFENSE The child’s prematurity and a severe placental infection led to the injuries. Nothing would have changed the outcome.

VERDICT A $14.5 million Ohio verdict was returned, including $1.5 million for the mother.

_______________

Costs returned afterverdict for the defense
A 65-year-old woman underwent a hysterectomy for treatment of uterine cancer performed by a gynecologic oncologist. Postoperatively, the patient developed an infection. A small-bowel injury was surgically repaired. The patient was hospitalized for 4 months for treatment of sepsis.

PARENTS’ CLAIM The physician was negligent for injuring the patient’s bowel and then failing to identify and repair the injury during surgery.

PHYSICIAN’S DEFENSE There was no negligence. The patient had significant adhesions from prior surgeries. The physician noted minor serosal tears of the bowel, several of which were repaired during surgery. He checked the length of the bowel for tears/perforations several times during the procedure, but found none. The patient had areas of weakness in her bowel, one of which broke down after surgery. The perforation was repaired in a timely manner.

VERDICT A Michigan defense verdict was returned. The physician was awarded $14,535 in costs.

_______________

Colon injury after cystectomy
A 21-year-old woman underwent laparoscopic ovarian cystectomy, performed by her gynecologist, and was discharged the next day. Eight days later, the patient went to the emergency department (ED) with pelvic pain. Testing revealed a perforated colon with peritonitis. She underwent repair by laparotomy, including bowel resection and colostomy, which was reversed several months later. She has not regained regular bowel function, cannot digest food that has not been finely sliced, and constantly uses laxatives.

PARENTS’ CLAIM The colon injury occurred during cystectomy because the gynecologist was negligent in failing to maintain proper anatomical landmarks. The injury should have been recognized at the time of surgery by injecting saline solution into the colon. She had not been informed of the risk of colon injury.

DEFENDANTS’ DEFENSE Colon injury is a known complication of cystectomy. The injury could have occurred after surgery due to a minor nick of the colon that was undetectable during surgery. Proper informed consent was acquired.

VERDICT A $340,000 New York settlement was reached.

_______________

Mother hemorrhages, dies after delivery: $1M settlement
A 19-year-old woman presented at full term to a community hospital. After several hours of labor, an emergency cesarean delivery was performed due to arrested descent.

Fifteen minutes after delivery, the mother exhibited moderate bleeding with decreasing blood pressure and tachycardia. The post-anesthesia care unit nurse assessed the patient’s uterus as “boggy,” and alerted the ObGyn, who immediately reacted by expressing clots from the uterus. He noted that the fundus was firm. He ordered intravenous (IV) oxytocin, but the patient continued to hemorrhage. Fifteen minutes later, the patient’s vital signs worsened. The ObGyn ordered blood products, uterotonics, and an additional IV line for fluid resuscitation. He began to massage the fundus and expressed clots.

When the patient did not stabilize, she was returned to the OR. After attempting to stop the bleeding with O’Leary stitches, the ObGyn performed a hysterectomy. Six hours after surgery, and after transfusion of a total of 12 units of blood, the woman coded multiple times. She died 14 hours after delivery. Cause of death was disseminated intravascular coagulopathy caused by an atonic uterus.

ESTATE’S CLAIM The ObGyn failed to recognize the extent of the postpartum hemorrhage and should have acted more aggressively with resuscitation. He should have returned her to the OR earlier. The ObGyn was negligent in waiting 45 minutes for cross-matched blood rather than using universal donor O-negative blood that was readily available.

PHYSICIAN’S DEFENSE The ObGyn denied negligence and maintained that he had acted properly. He returned the patient to the OR within 90 minutes of first learning of the hemorrhage.

VERDICT A $1 million Virginia settlement was reached.

_______________

Infant born with broken arms, collarbone, facial bones
A 23-year-old woman had gestational diabetes. She is 5’9” tall and weighed 300 lb while pregnant. She went to the hospital in labor.

During delivery, shoulder dystocia was encountered. The ObGyn performed a variety of techniques, including the McRobert’s maneuver. Forceps were eventually used for delivery.

Both of the newborn’s arms were broken, and she had a broken collarbone and facial fractures. The mother also suffered significant vaginal lacerations and required an episiotomy. She continues to complain of bladder and bowel problems.

PARENTS’ CLAIM A vaginal delivery should not have been attempted due to the mother’s gestational diabetes and the risk of having a macrosomic baby. A cesarean delivery should have been performed. The ObGyn did not use the proper techniques when delivering the child after shoulder dystocia was encountered.

PHYSICIAN’S DEFENSE The ObGyn denied negligence. He claimed that the baby recovered well from her injuries. The mother underwent surgery and now has excellent bladder and bowel control.

VERDICT A confidential Louisiana settlement was reached with the hospital before trial. A defense verdict was returned for the ObGyn.

_______________

Protein found in urine at 39 weeks’ gestation: mother and child die
At 39 weeks' gestation, a woman saw her ObGyn for a prenatal visit. During the examination, the ObGyn found high levels of protein in the woman’s urine, an accumulation of fluid in her ankles, and the highest blood pressure (BP) reading of the woman’s pregnancy. However, because the BP reading was lower than that required to diagnose preeclampsia, the ObGyn sent the patient home and scheduled the next prenatal visit for the following week. The woman and her unborn child died 5 days later.

ESTATE’S CLAIM The ObGyn was negligent in failing to order a urine study and more closely monitor the mother’s symptoms when signs of preeclampsia were evident at 39 weeks’ gestation. Delivery of the child would have resolved the problem and saved both lives.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $3 million Illinois settlement was reached.

_______________

Baby dies from group B strep
A 16-year-old woman planned delivery at a local hospital. Her ObGyn’s practice regularly sends the hospital its patients’ prenatal records, starting at 25 weeks’ gestation. At 33 weeks, the ObGyn took a vaginal culture to test for group B Streptococcus (GBS) bacteria. The laboratory reported positive GBS results to a computer in the ObGyn’s office, but the results were not entered into the patient’s chart.

The mother went to the ED in labor a week later; she was evaluated and discharged. Several days later, she returned to the ED, but was again discharged. She returned the next day, now in gestational week 36. An on-call ObGyn admitted her. A labor and delivery nurse claimed that the ObGyn’s office reported that the mother was GBS negative, so the nurse placed a negative sign in the prenatal record in the chart. When the patient’s ObGyn arrived at the hospital, he noticed the negative sign in the chart.

At birth, the baby’s Apgar scores were 7 at 1 minute and 7 at 5 minutes. She appeared limp and was grunting. A pediatrician diagnosed transient respiratory problems related to prematurity. The baby continued to deteriorate; antibiotics were ordered 7 hours after birth. After the child was transported to another facility, she died. The cause of death was GBS sepsis and pneumonia.

PARENTS’ CLAIM The ObGyn was negligent in failing to properly and timely note the positive GBS test result in the mother’s chart. The ObGyn’s office staff was negligent in miscommunicating the GBS status to the nurse.

DEFENDANTS’ DEFENSE The ObGyn usually noted laboratory results at the next prenatal visit, but the mother gave birth before that occurred. The on-call ObGyn failed to give antibiotics when the mother presented in preterm labor with unknown GBS status. The hospital did not have a protocol that required the on-call ObGyn to prescribe prophylactic antibiotics in this context. The nurse was negligent for failing to verify the oral telephone report of GBS-negative status with a written or faxed laboratory report.

The ObGyn surmised that the infection had occurred in utero, not during birth; antibiotics would not have changed the outcome.

VERDICT The parents settled with the hospital for a confidential amount. An Arizona defense verdict was returned for the ObGyn. 

_______________

Child has quadraparetic CP after oxytocin-augmented delivery
A pregnant woman was hospitalized for 23-hour observation with blood work and obstetric ultrasonography. The admitting nurse noted that the patient was having mild contractions and that fetal heart tones were 130 bpm with moderate variability. The mother’s cervix was dilated to 2.5 cm, 70% effaced, at –1 station, with intact and bulging membranes and normal maternal vital signs. The ObGyn ordered intravenous ampicillin and sent the mother to labor and delivery. He prescribed oxytocin (6 mU/min), but, after its initiation, oxytocin was discontinued for almost 2 hours. When the mother had five contractions in 10 minutes, oxytocin was restarted at 8 mU/min. The oxytocin dosage was later increased to 10 mU/min, and then to 12 mU/min.

When shoulder dystocia was encountered, various maneuvers were performed. The baby was delivered using vacuum extraction. The newborn was immediately sent to the neonatal intensive care unit (NICU) with a suspected humerus fracture and poor respiration. Mechanical ventilation and treatment for hypoperfusion were initiated. She had persistently low Apgar scores, intracranial hemorrhaging, seizures, severe metabolic acidosis, and hypoxic ischemic encephalopathy. She has quadraparetic cerebral palsy with related disabilities.

PARENTS’ CLAIM The ObGyn and hospital were negligent in the treatment of the mother during labor and delivery, causing the child to be born with serious injuries.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4,250,000 Texas settlement was reached, including $75,000 for the parents, and the remainder placed into a trust for the child.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Premature infant has CP: $14.5M verdict
After learning that, 14 years earlier, a 36-year-old woman had undergone an emergency cesarean delivery at 32 weeks’ gestation, her health-care providers planned a cesarean delivery for the new pregnancy. The woman was admitted to the hospital in preterm labor. Three days later, she was discharged, but readmitted twice more over a 2-week period. At each admission, preterm labor was halted using medication and bed rest.

The patient’s water broke and she was admitted to the hospital at 25 weeks’ gestation, about a week after the previous admission. Shortly after admission, the patient asked about a cesarean delivery, but no action was taken. When her ObGyn arrived at the hospital 5 hours later, the patient asked for a cesarean delivery; the ObGyn said he wanted to wait to see how her labor was progressing. After 3 hours, the fetus showed signs of distress, and an emergency cesarean delivery was undertaken. The infant experienced a massive brain hemorrhage, resulting in cerebral palsy (CP). The child has cognitive delays, visual impairment, and additional problems; he will require lifelong care.

PARENTS’ CLAIM The ObGyn and hospital were negligent in discharging the woman from admission for preterm labor. Cesarean delivery should have been performed much earlier due to nonreassuring fetal heart tones. Severe variable decelerations caused cerebral blood flow fluctuations that led to the hemorrhage.

DEFENDANTS’ DEFENSE The child’s prematurity and a severe placental infection led to the injuries. Nothing would have changed the outcome.

VERDICT A $14.5 million Ohio verdict was returned, including $1.5 million for the mother.

_______________

Costs returned afterverdict for the defense
A 65-year-old woman underwent a hysterectomy for treatment of uterine cancer performed by a gynecologic oncologist. Postoperatively, the patient developed an infection. A small-bowel injury was surgically repaired. The patient was hospitalized for 4 months for treatment of sepsis.

PARENTS’ CLAIM The physician was negligent for injuring the patient’s bowel and then failing to identify and repair the injury during surgery.

PHYSICIAN’S DEFENSE There was no negligence. The patient had significant adhesions from prior surgeries. The physician noted minor serosal tears of the bowel, several of which were repaired during surgery. He checked the length of the bowel for tears/perforations several times during the procedure, but found none. The patient had areas of weakness in her bowel, one of which broke down after surgery. The perforation was repaired in a timely manner.

VERDICT A Michigan defense verdict was returned. The physician was awarded $14,535 in costs.

_______________

Colon injury after cystectomy
A 21-year-old woman underwent laparoscopic ovarian cystectomy, performed by her gynecologist, and was discharged the next day. Eight days later, the patient went to the emergency department (ED) with pelvic pain. Testing revealed a perforated colon with peritonitis. She underwent repair by laparotomy, including bowel resection and colostomy, which was reversed several months later. She has not regained regular bowel function, cannot digest food that has not been finely sliced, and constantly uses laxatives.

PARENTS’ CLAIM The colon injury occurred during cystectomy because the gynecologist was negligent in failing to maintain proper anatomical landmarks. The injury should have been recognized at the time of surgery by injecting saline solution into the colon. She had not been informed of the risk of colon injury.

DEFENDANTS’ DEFENSE Colon injury is a known complication of cystectomy. The injury could have occurred after surgery due to a minor nick of the colon that was undetectable during surgery. Proper informed consent was acquired.

VERDICT A $340,000 New York settlement was reached.

_______________

Mother hemorrhages, dies after delivery: $1M settlement
A 19-year-old woman presented at full term to a community hospital. After several hours of labor, an emergency cesarean delivery was performed due to arrested descent.

Fifteen minutes after delivery, the mother exhibited moderate bleeding with decreasing blood pressure and tachycardia. The post-anesthesia care unit nurse assessed the patient’s uterus as “boggy,” and alerted the ObGyn, who immediately reacted by expressing clots from the uterus. He noted that the fundus was firm. He ordered intravenous (IV) oxytocin, but the patient continued to hemorrhage. Fifteen minutes later, the patient’s vital signs worsened. The ObGyn ordered blood products, uterotonics, and an additional IV line for fluid resuscitation. He began to massage the fundus and expressed clots.

When the patient did not stabilize, she was returned to the OR. After attempting to stop the bleeding with O’Leary stitches, the ObGyn performed a hysterectomy. Six hours after surgery, and after transfusion of a total of 12 units of blood, the woman coded multiple times. She died 14 hours after delivery. Cause of death was disseminated intravascular coagulopathy caused by an atonic uterus.

ESTATE’S CLAIM The ObGyn failed to recognize the extent of the postpartum hemorrhage and should have acted more aggressively with resuscitation. He should have returned her to the OR earlier. The ObGyn was negligent in waiting 45 minutes for cross-matched blood rather than using universal donor O-negative blood that was readily available.

PHYSICIAN’S DEFENSE The ObGyn denied negligence and maintained that he had acted properly. He returned the patient to the OR within 90 minutes of first learning of the hemorrhage.

VERDICT A $1 million Virginia settlement was reached.

_______________

Infant born with broken arms, collarbone, facial bones
A 23-year-old woman had gestational diabetes. She is 5’9” tall and weighed 300 lb while pregnant. She went to the hospital in labor.

During delivery, shoulder dystocia was encountered. The ObGyn performed a variety of techniques, including the McRobert’s maneuver. Forceps were eventually used for delivery.

Both of the newborn’s arms were broken, and she had a broken collarbone and facial fractures. The mother also suffered significant vaginal lacerations and required an episiotomy. She continues to complain of bladder and bowel problems.

PARENTS’ CLAIM A vaginal delivery should not have been attempted due to the mother’s gestational diabetes and the risk of having a macrosomic baby. A cesarean delivery should have been performed. The ObGyn did not use the proper techniques when delivering the child after shoulder dystocia was encountered.

PHYSICIAN’S DEFENSE The ObGyn denied negligence. He claimed that the baby recovered well from her injuries. The mother underwent surgery and now has excellent bladder and bowel control.

VERDICT A confidential Louisiana settlement was reached with the hospital before trial. A defense verdict was returned for the ObGyn.

_______________

Protein found in urine at 39 weeks’ gestation: mother and child die
At 39 weeks' gestation, a woman saw her ObGyn for a prenatal visit. During the examination, the ObGyn found high levels of protein in the woman’s urine, an accumulation of fluid in her ankles, and the highest blood pressure (BP) reading of the woman’s pregnancy. However, because the BP reading was lower than that required to diagnose preeclampsia, the ObGyn sent the patient home and scheduled the next prenatal visit for the following week. The woman and her unborn child died 5 days later.

ESTATE’S CLAIM The ObGyn was negligent in failing to order a urine study and more closely monitor the mother’s symptoms when signs of preeclampsia were evident at 39 weeks’ gestation. Delivery of the child would have resolved the problem and saved both lives.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $3 million Illinois settlement was reached.

_______________

Baby dies from group B strep
A 16-year-old woman planned delivery at a local hospital. Her ObGyn’s practice regularly sends the hospital its patients’ prenatal records, starting at 25 weeks’ gestation. At 33 weeks, the ObGyn took a vaginal culture to test for group B Streptococcus (GBS) bacteria. The laboratory reported positive GBS results to a computer in the ObGyn’s office, but the results were not entered into the patient’s chart.

The mother went to the ED in labor a week later; she was evaluated and discharged. Several days later, she returned to the ED, but was again discharged. She returned the next day, now in gestational week 36. An on-call ObGyn admitted her. A labor and delivery nurse claimed that the ObGyn’s office reported that the mother was GBS negative, so the nurse placed a negative sign in the prenatal record in the chart. When the patient’s ObGyn arrived at the hospital, he noticed the negative sign in the chart.

At birth, the baby’s Apgar scores were 7 at 1 minute and 7 at 5 minutes. She appeared limp and was grunting. A pediatrician diagnosed transient respiratory problems related to prematurity. The baby continued to deteriorate; antibiotics were ordered 7 hours after birth. After the child was transported to another facility, she died. The cause of death was GBS sepsis and pneumonia.

PARENTS’ CLAIM The ObGyn was negligent in failing to properly and timely note the positive GBS test result in the mother’s chart. The ObGyn’s office staff was negligent in miscommunicating the GBS status to the nurse.

DEFENDANTS’ DEFENSE The ObGyn usually noted laboratory results at the next prenatal visit, but the mother gave birth before that occurred. The on-call ObGyn failed to give antibiotics when the mother presented in preterm labor with unknown GBS status. The hospital did not have a protocol that required the on-call ObGyn to prescribe prophylactic antibiotics in this context. The nurse was negligent for failing to verify the oral telephone report of GBS-negative status with a written or faxed laboratory report.

The ObGyn surmised that the infection had occurred in utero, not during birth; antibiotics would not have changed the outcome.

VERDICT The parents settled with the hospital for a confidential amount. An Arizona defense verdict was returned for the ObGyn. 

_______________

Child has quadraparetic CP after oxytocin-augmented delivery
A pregnant woman was hospitalized for 23-hour observation with blood work and obstetric ultrasonography. The admitting nurse noted that the patient was having mild contractions and that fetal heart tones were 130 bpm with moderate variability. The mother’s cervix was dilated to 2.5 cm, 70% effaced, at –1 station, with intact and bulging membranes and normal maternal vital signs. The ObGyn ordered intravenous ampicillin and sent the mother to labor and delivery. He prescribed oxytocin (6 mU/min), but, after its initiation, oxytocin was discontinued for almost 2 hours. When the mother had five contractions in 10 minutes, oxytocin was restarted at 8 mU/min. The oxytocin dosage was later increased to 10 mU/min, and then to 12 mU/min.

When shoulder dystocia was encountered, various maneuvers were performed. The baby was delivered using vacuum extraction. The newborn was immediately sent to the neonatal intensive care unit (NICU) with a suspected humerus fracture and poor respiration. Mechanical ventilation and treatment for hypoperfusion were initiated. She had persistently low Apgar scores, intracranial hemorrhaging, seizures, severe metabolic acidosis, and hypoxic ischemic encephalopathy. She has quadraparetic cerebral palsy with related disabilities.

PARENTS’ CLAIM The ObGyn and hospital were negligent in the treatment of the mother during labor and delivery, causing the child to be born with serious injuries.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4,250,000 Texas settlement was reached, including $75,000 for the parents, and the remainder placed into a trust for the child.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Premature infant has CP: $14.5M verdict
After learning that, 14 years earlier, a 36-year-old woman had undergone an emergency cesarean delivery at 32 weeks’ gestation, her health-care providers planned a cesarean delivery for the new pregnancy. The woman was admitted to the hospital in preterm labor. Three days later, she was discharged, but readmitted twice more over a 2-week period. At each admission, preterm labor was halted using medication and bed rest.

The patient’s water broke and she was admitted to the hospital at 25 weeks’ gestation, about a week after the previous admission. Shortly after admission, the patient asked about a cesarean delivery, but no action was taken. When her ObGyn arrived at the hospital 5 hours later, the patient asked for a cesarean delivery; the ObGyn said he wanted to wait to see how her labor was progressing. After 3 hours, the fetus showed signs of distress, and an emergency cesarean delivery was undertaken. The infant experienced a massive brain hemorrhage, resulting in cerebral palsy (CP). The child has cognitive delays, visual impairment, and additional problems; he will require lifelong care.

PARENTS’ CLAIM The ObGyn and hospital were negligent in discharging the woman from admission for preterm labor. Cesarean delivery should have been performed much earlier due to nonreassuring fetal heart tones. Severe variable decelerations caused cerebral blood flow fluctuations that led to the hemorrhage.

DEFENDANTS’ DEFENSE The child’s prematurity and a severe placental infection led to the injuries. Nothing would have changed the outcome.

VERDICT A $14.5 million Ohio verdict was returned, including $1.5 million for the mother.

_______________

Costs returned afterverdict for the defense
A 65-year-old woman underwent a hysterectomy for treatment of uterine cancer performed by a gynecologic oncologist. Postoperatively, the patient developed an infection. A small-bowel injury was surgically repaired. The patient was hospitalized for 4 months for treatment of sepsis.

PARENTS’ CLAIM The physician was negligent for injuring the patient’s bowel and then failing to identify and repair the injury during surgery.

PHYSICIAN’S DEFENSE There was no negligence. The patient had significant adhesions from prior surgeries. The physician noted minor serosal tears of the bowel, several of which were repaired during surgery. He checked the length of the bowel for tears/perforations several times during the procedure, but found none. The patient had areas of weakness in her bowel, one of which broke down after surgery. The perforation was repaired in a timely manner.

VERDICT A Michigan defense verdict was returned. The physician was awarded $14,535 in costs.

_______________

Colon injury after cystectomy
A 21-year-old woman underwent laparoscopic ovarian cystectomy, performed by her gynecologist, and was discharged the next day. Eight days later, the patient went to the emergency department (ED) with pelvic pain. Testing revealed a perforated colon with peritonitis. She underwent repair by laparotomy, including bowel resection and colostomy, which was reversed several months later. She has not regained regular bowel function, cannot digest food that has not been finely sliced, and constantly uses laxatives.

PARENTS’ CLAIM The colon injury occurred during cystectomy because the gynecologist was negligent in failing to maintain proper anatomical landmarks. The injury should have been recognized at the time of surgery by injecting saline solution into the colon. She had not been informed of the risk of colon injury.

DEFENDANTS’ DEFENSE Colon injury is a known complication of cystectomy. The injury could have occurred after surgery due to a minor nick of the colon that was undetectable during surgery. Proper informed consent was acquired.

VERDICT A $340,000 New York settlement was reached.

_______________

Mother hemorrhages, dies after delivery: $1M settlement
A 19-year-old woman presented at full term to a community hospital. After several hours of labor, an emergency cesarean delivery was performed due to arrested descent.

Fifteen minutes after delivery, the mother exhibited moderate bleeding with decreasing blood pressure and tachycardia. The post-anesthesia care unit nurse assessed the patient’s uterus as “boggy,” and alerted the ObGyn, who immediately reacted by expressing clots from the uterus. He noted that the fundus was firm. He ordered intravenous (IV) oxytocin, but the patient continued to hemorrhage. Fifteen minutes later, the patient’s vital signs worsened. The ObGyn ordered blood products, uterotonics, and an additional IV line for fluid resuscitation. He began to massage the fundus and expressed clots.

When the patient did not stabilize, she was returned to the OR. After attempting to stop the bleeding with O’Leary stitches, the ObGyn performed a hysterectomy. Six hours after surgery, and after transfusion of a total of 12 units of blood, the woman coded multiple times. She died 14 hours after delivery. Cause of death was disseminated intravascular coagulopathy caused by an atonic uterus.

ESTATE’S CLAIM The ObGyn failed to recognize the extent of the postpartum hemorrhage and should have acted more aggressively with resuscitation. He should have returned her to the OR earlier. The ObGyn was negligent in waiting 45 minutes for cross-matched blood rather than using universal donor O-negative blood that was readily available.

PHYSICIAN’S DEFENSE The ObGyn denied negligence and maintained that he had acted properly. He returned the patient to the OR within 90 minutes of first learning of the hemorrhage.

VERDICT A $1 million Virginia settlement was reached.

_______________

Infant born with broken arms, collarbone, facial bones
A 23-year-old woman had gestational diabetes. She is 5’9” tall and weighed 300 lb while pregnant. She went to the hospital in labor.

During delivery, shoulder dystocia was encountered. The ObGyn performed a variety of techniques, including the McRobert’s maneuver. Forceps were eventually used for delivery.

Both of the newborn’s arms were broken, and she had a broken collarbone and facial fractures. The mother also suffered significant vaginal lacerations and required an episiotomy. She continues to complain of bladder and bowel problems.

PARENTS’ CLAIM A vaginal delivery should not have been attempted due to the mother’s gestational diabetes and the risk of having a macrosomic baby. A cesarean delivery should have been performed. The ObGyn did not use the proper techniques when delivering the child after shoulder dystocia was encountered.

PHYSICIAN’S DEFENSE The ObGyn denied negligence. He claimed that the baby recovered well from her injuries. The mother underwent surgery and now has excellent bladder and bowel control.

VERDICT A confidential Louisiana settlement was reached with the hospital before trial. A defense verdict was returned for the ObGyn.

_______________

Protein found in urine at 39 weeks’ gestation: mother and child die
At 39 weeks' gestation, a woman saw her ObGyn for a prenatal visit. During the examination, the ObGyn found high levels of protein in the woman’s urine, an accumulation of fluid in her ankles, and the highest blood pressure (BP) reading of the woman’s pregnancy. However, because the BP reading was lower than that required to diagnose preeclampsia, the ObGyn sent the patient home and scheduled the next prenatal visit for the following week. The woman and her unborn child died 5 days later.

ESTATE’S CLAIM The ObGyn was negligent in failing to order a urine study and more closely monitor the mother’s symptoms when signs of preeclampsia were evident at 39 weeks’ gestation. Delivery of the child would have resolved the problem and saved both lives.

PHYSICIAN’S DEFENSE The case was settled during the trial.

VERDICT A $3 million Illinois settlement was reached.

_______________

Baby dies from group B strep
A 16-year-old woman planned delivery at a local hospital. Her ObGyn’s practice regularly sends the hospital its patients’ prenatal records, starting at 25 weeks’ gestation. At 33 weeks, the ObGyn took a vaginal culture to test for group B Streptococcus (GBS) bacteria. The laboratory reported positive GBS results to a computer in the ObGyn’s office, but the results were not entered into the patient’s chart.

The mother went to the ED in labor a week later; she was evaluated and discharged. Several days later, she returned to the ED, but was again discharged. She returned the next day, now in gestational week 36. An on-call ObGyn admitted her. A labor and delivery nurse claimed that the ObGyn’s office reported that the mother was GBS negative, so the nurse placed a negative sign in the prenatal record in the chart. When the patient’s ObGyn arrived at the hospital, he noticed the negative sign in the chart.

At birth, the baby’s Apgar scores were 7 at 1 minute and 7 at 5 minutes. She appeared limp and was grunting. A pediatrician diagnosed transient respiratory problems related to prematurity. The baby continued to deteriorate; antibiotics were ordered 7 hours after birth. After the child was transported to another facility, she died. The cause of death was GBS sepsis and pneumonia.

PARENTS’ CLAIM The ObGyn was negligent in failing to properly and timely note the positive GBS test result in the mother’s chart. The ObGyn’s office staff was negligent in miscommunicating the GBS status to the nurse.

DEFENDANTS’ DEFENSE The ObGyn usually noted laboratory results at the next prenatal visit, but the mother gave birth before that occurred. The on-call ObGyn failed to give antibiotics when the mother presented in preterm labor with unknown GBS status. The hospital did not have a protocol that required the on-call ObGyn to prescribe prophylactic antibiotics in this context. The nurse was negligent for failing to verify the oral telephone report of GBS-negative status with a written or faxed laboratory report.

The ObGyn surmised that the infection had occurred in utero, not during birth; antibiotics would not have changed the outcome.

VERDICT The parents settled with the hospital for a confidential amount. An Arizona defense verdict was returned for the ObGyn. 

_______________

Child has quadraparetic CP after oxytocin-augmented delivery
A pregnant woman was hospitalized for 23-hour observation with blood work and obstetric ultrasonography. The admitting nurse noted that the patient was having mild contractions and that fetal heart tones were 130 bpm with moderate variability. The mother’s cervix was dilated to 2.5 cm, 70% effaced, at –1 station, with intact and bulging membranes and normal maternal vital signs. The ObGyn ordered intravenous ampicillin and sent the mother to labor and delivery. He prescribed oxytocin (6 mU/min), but, after its initiation, oxytocin was discontinued for almost 2 hours. When the mother had five contractions in 10 minutes, oxytocin was restarted at 8 mU/min. The oxytocin dosage was later increased to 10 mU/min, and then to 12 mU/min.

When shoulder dystocia was encountered, various maneuvers were performed. The baby was delivered using vacuum extraction. The newborn was immediately sent to the neonatal intensive care unit (NICU) with a suspected humerus fracture and poor respiration. Mechanical ventilation and treatment for hypoperfusion were initiated. She had persistently low Apgar scores, intracranial hemorrhaging, seizures, severe metabolic acidosis, and hypoxic ischemic encephalopathy. She has quadraparetic cerebral palsy with related disabilities.

PARENTS’ CLAIM The ObGyn and hospital were negligent in the treatment of the mother during labor and delivery, causing the child to be born with serious injuries.

DEFENDANTS’ DEFENSE The case was settled during the trial.

VERDICT A $4,250,000 Texas settlement was reached, including $75,000 for the parents, and the remainder placed into a trust for the child.  

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

The European Medicines Agency (EMA) has granted orphan status to Atir, a product consisting of T-cell-depleted donor immune cells, for the treatment of acute myeloid leukemia (AML).

The EMA and the US Food and Drug Administration previously granted Atir orphan status for the prevention of acute graft-vs-host-disease (GVHD) following hematopoietic stem cell transplant (HSCT).

The EMA’s orphan designation provides incentives to support drug development. This includes fee reductions and a 10-year period of market exclusivity in the European Union after product approval.

About Atir

Atir consists of donor immune cells from which the alloreactive T-cells that would otherwise attack the patient’s body have been selectively eliminated.

The product is produced using a molecule known as TH9402 to selectively remove those T cells from the donor graft, while preserving other immune cells. To activate patient-reactive T cells, the graft is mixed (ex vivo) with patient cells.

Then, TH9402 is added. As this phototoxic compound selectively accumulates in activated T cells, the cells can be eliminated by exposing the cell mixture to light of a specific wavelength. The resulting Atir product can be frozen and stored and is infused into the patient in a scheduled procedure.

Trial data

Researchers said Atir proved safe and effective in a phase 1/2 study in which high-risk leukemia patients with very poor prognosis were treated with escalating doses of Atir after a haploidentical HSCT.

The overall survival of 19 patients who received an optimal dose of Atir was 78% at 1 year and 67% at 5 years, rates that compare favorably to outcomes of HSCTs from fully matched donors. The data also suggest that immune cells responsible for the graft-vs-leukemia effect are retained in Atir.

Five-year follow-up data show that none of the 19 patients developed acute grade 3/4 GVHD, compared to an incidence of 30% in matched unrelated HSCTs. In the 9 patients who received an optimal dose of Atir, there was no transplant-related mortality.

Researchers are currently testing Atir in a phase 2 study of patients with AML, acute lymphoblastic leukemia, and myelodysplastic syndrome, to corroborate and extend the safety and efficacy results from the phase 1/2 study. Data from this trial are expected in the second half of 2014.

Atir is under development by Kiadis Pharma. For more information, visit the company’s website.

The European Medicines Agency (EMA) has granted orphan status to Atir, a product consisting of T-cell-depleted donor immune cells, for the treatment of acute myeloid leukemia (AML).

The EMA and the US Food and Drug Administration previously granted Atir orphan status for the prevention of acute graft-vs-host-disease (GVHD) following hematopoietic stem cell transplant (HSCT).

The EMA’s orphan designation provides incentives to support drug development. This includes fee reductions and a 10-year period of market exclusivity in the European Union after product approval.

About Atir

Atir consists of donor immune cells from which the alloreactive T-cells that would otherwise attack the patient’s body have been selectively eliminated.

The product is produced using a molecule known as TH9402 to selectively remove those T cells from the donor graft, while preserving other immune cells. To activate patient-reactive T cells, the graft is mixed (ex vivo) with patient cells.

Then, TH9402 is added. As this phototoxic compound selectively accumulates in activated T cells, the cells can be eliminated by exposing the cell mixture to light of a specific wavelength. The resulting Atir product can be frozen and stored and is infused into the patient in a scheduled procedure.

Trial data

Researchers said Atir proved safe and effective in a phase 1/2 study in which high-risk leukemia patients with very poor prognosis were treated with escalating doses of Atir after a haploidentical HSCT.

The overall survival of 19 patients who received an optimal dose of Atir was 78% at 1 year and 67% at 5 years, rates that compare favorably to outcomes of HSCTs from fully matched donors. The data also suggest that immune cells responsible for the graft-vs-leukemia effect are retained in Atir.

Five-year follow-up data show that none of the 19 patients developed acute grade 3/4 GVHD, compared to an incidence of 30% in matched unrelated HSCTs. In the 9 patients who received an optimal dose of Atir, there was no transplant-related mortality.

Researchers are currently testing Atir in a phase 2 study of patients with AML, acute lymphoblastic leukemia, and myelodysplastic syndrome, to corroborate and extend the safety and efficacy results from the phase 1/2 study. Data from this trial are expected in the second half of 2014.

Atir is under development by Kiadis Pharma. For more information, visit the company’s website.

The European Medicines Agency (EMA) has granted orphan status to Atir, a product consisting of T-cell-depleted donor immune cells, for the treatment of acute myeloid leukemia (AML).

The EMA and the US Food and Drug Administration previously granted Atir orphan status for the prevention of acute graft-vs-host-disease (GVHD) following hematopoietic stem cell transplant (HSCT).

The EMA’s orphan designation provides incentives to support drug development. This includes fee reductions and a 10-year period of market exclusivity in the European Union after product approval.

About Atir

Atir consists of donor immune cells from which the alloreactive T-cells that would otherwise attack the patient’s body have been selectively eliminated.

The product is produced using a molecule known as TH9402 to selectively remove those T cells from the donor graft, while preserving other immune cells. To activate patient-reactive T cells, the graft is mixed (ex vivo) with patient cells.

Then, TH9402 is added. As this phototoxic compound selectively accumulates in activated T cells, the cells can be eliminated by exposing the cell mixture to light of a specific wavelength. The resulting Atir product can be frozen and stored and is infused into the patient in a scheduled procedure.

Trial data

Researchers said Atir proved safe and effective in a phase 1/2 study in which high-risk leukemia patients with very poor prognosis were treated with escalating doses of Atir after a haploidentical HSCT.

The overall survival of 19 patients who received an optimal dose of Atir was 78% at 1 year and 67% at 5 years, rates that compare favorably to outcomes of HSCTs from fully matched donors. The data also suggest that immune cells responsible for the graft-vs-leukemia effect are retained in Atir.

Five-year follow-up data show that none of the 19 patients developed acute grade 3/4 GVHD, compared to an incidence of 30% in matched unrelated HSCTs. In the 9 patients who received an optimal dose of Atir, there was no transplant-related mortality.

Researchers are currently testing Atir in a phase 2 study of patients with AML, acute lymphoblastic leukemia, and myelodysplastic syndrome, to corroborate and extend the safety and efficacy results from the phase 1/2 study. Data from this trial are expected in the second half of 2014.

Atir is under development by Kiadis Pharma. For more information, visit the company’s website.

Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.

Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.

Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.

Series Editor: Arthur T. Skarin, MD, FACP, FCCP

Each year approximately 228,000 Americans will be diagnosed with lung cancer, and 159,000 will die of this disease. An estimated 85% of lung cancer cases are non–small cell lung cancer (NSCLC), more than 50% of NSCLC is comprised of adenocarcinoma, the median age at diagnosis is 71 years, and 25% of patients with this diagnosis present with stage III disease. In 2010 the seventh edition of the American Joint Committee on Cancer (AJCC) TNM staging system for lung cancer was released, and several changes were made which affect the patient population designated as having stage III disease.

To read the full article in PDF:

Click here

Series Editor: Arthur T. Skarin, MD, FACP, FCCP

Each year approximately 228,000 Americans will be diagnosed with lung cancer, and 159,000 will die of this disease. An estimated 85% of lung cancer cases are non–small cell lung cancer (NSCLC), more than 50% of NSCLC is comprised of adenocarcinoma, the median age at diagnosis is 71 years, and 25% of patients with this diagnosis present with stage III disease. In 2010 the seventh edition of the American Joint Committee on Cancer (AJCC) TNM staging system for lung cancer was released, and several changes were made which affect the patient population designated as having stage III disease.

To read the full article in PDF:

Click here

Series Editor: Arthur T. Skarin, MD, FACP, FCCP

Each year approximately 228,000 Americans will be diagnosed with lung cancer, and 159,000 will die of this disease. An estimated 85% of lung cancer cases are non–small cell lung cancer (NSCLC), more than 50% of NSCLC is comprised of adenocarcinoma, the median age at diagnosis is 71 years, and 25% of patients with this diagnosis present with stage III disease. In 2010 the seventh edition of the American Joint Committee on Cancer (AJCC) TNM staging system for lung cancer was released, and several changes were made which affect the patient population designated as having stage III disease.

To read the full article in PDF:

Click here