User login
A number of conditions can mimic myositis, but clues that can point to the correct diagnosis are often present in cases involving the mimics, according to Lisa Christopher-Stine, MD.
For example, elevated levels of certain muscle enzymes are an important source of diagnostic information, Dr. Christopher-Stine, director of the Johns Hopkins Myositis Center, Baltimore, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Isolated elevations in aldolase can be seen in connective tissue–associated interstitial lung disease or in patients with fascial edema, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), and creatine kinase (CK) levels can also be helpful, she explained.
The latter can also be elevated in the absence of muscle disease, for example, in healthy individuals following exercise. CK peaks at 24 hours after exercise before returning to baseline by 72 hours. In an experimental setting, a threefold increase in CK levels has been seen at 8-24 hours after exercise, Dr. Christopher-Stine said.
“HyperCKemia”
Trauma from causes such as intramuscular injection, electromyography (EMG), major surgery, or biopsy can also lead to increased CK levels. Motor neuron disease can also cause such increases. In one study, 75% of patients with amyotrophic lateral sclerosis had a mean twofold increase in CK levels, she said.
Asymptomatic CK elevations may also represent presymptomatic myopathies, type 1 or 2 macro-CK, manual labor occupations, or they may be idiopathic.
Race can play a role in CK levels as well. Black people tend to have higher CK levels than white people, she said, noting that one study of more than 10,000 adults showed that black race was strongly associated with CK, and that body composition largely explained differences in CK by age, but not by race/ethnicity (Medicine. Aug 2016;95[33]:e4344).
“So elevated CK may not herald any discernible illness,” she said.
Dr. Christopher-Stine described a case involving an otherwise healthy 30-year-old man with a CK level of 695 IU/L that was found incidentally. He had a desk job, no recent travel, and denied weakness, myalgias, joint pain, dysphagia, shortness of breath, and fevers. In this case, the elevated CK was felt to be secondary to his African American race given that other causes were ruled out.
Another case involved a 72-year-old man with left-arm pain. A cardiac event was ruled out, and CK was found to be about 4,500 IU/L. He reported “flare-ups” of diffuse swelling of the hands and feet. X-rays showed concerning signs of erosions. His transaminases and electromyogram were normal; he reported no weakness or myalgia; and an MRI showed no muscle edema. He was diagnosed with macro-CK, which refers to CK with an increased molecular weight. A clue to this diagnosis is a normal liver function test. In some cases, muscle/brain CK levels (CK-MB) are elevated and higher than total CK, she noted.
She presented an algorithm for the diagnostic work-up of patients presenting with elevated CK of unclear significance. Her recommended approach involves repeat CK assessment and a closer look at family history, medication, drug/toxin history, examination for weakness and neurologic abnormalities, and additional lab assessments in those whose levels remain elevated. In those in whom a diagnosis is not identified, the algorithm calls for observation every 3 months – including physical examination and labs – in asymptomatic patients with levels at less than five times the upper limit of normal, and further evaluation, including EMG with nerve-conduction velocity testing, muscle biopsy, and MRI in those with (or who later develop) marked elevation greater than five times the upper limit of normal and/or symptoms.
Patient assessment
The physical examination should involve localization and quantification of weakness, and assessment for fever, rash, atrophy/wasting/scooping of forearms, fasciculations, cranial nerve involvement, Raynaud’s phenomenon, nailfold capillary changes, arthritis, calcinosis, “mechanic’s hands,” signs of other autoimmune diseases, and lung crackles. Initial laboratory testing should include HIV and hepatitis B and C testing; measurement of CK, AST, ALT, aldolase, thyroid-stimulating hormone, and magnesium levels; a comprehensive metabolic panel and complete blood count; and measurement of erythrocyte sedimentation rate and C-reactive protein.
“Weakness may be secondary to a neuropathy, myopathy, or a problem at the neuropathic junction. Many causes of weakness can be readily identified by careful history taking, focused physical examination, and directed laboratory evaluation,” she said.
Features pointing toward a diagnosis of myositis include characteristic rashes, gradual symptom onset, proximal limb and truncal weakness, other connective tissue disease features such as Raynaud’s and arthritis, and the presence of lung disease, including interstitial lung disease or unexplained infiltrates, she said.
Features pointing away from a diagnosis of myositis include a family history of a similar illness, weakness that is associated with eating or fasting, neurologic signs, cranial nerve involvement, fasciculations, severe muscle cramping, early atrophy, and creatine phosphokinase levels that are either less than 2 times or more than 100 times the upper limit of normal.
Among the conditions to consider in the presence of the features that point away from a myositis diagnosis are muscular dystrophies, metabolic myopathies, and toxic (drug-induced) myopathies, to name a few, Dr. Christopher-Stine said.
She described a number of other cases to illustrate the need for – and to help develop – a differential diagnosis in patients presenting with apparent myositis.
Muscular dystrophies
A 38-year-old woman with limited scleroderma and anti-PM/Scl autoantibodies developed proximal weakness over 9 months and was eventually unable to walk up a flight of stairs. She had heliotrope rash and Gottron’s sign, her serum CK was 723 IU/L, and EMG showed an irritable myopathy.
Muscle biopsy showed inflammation, and she was treated with prednisone, but this led to worsening weakness. She complained of prominent fatigue and double vision at the end of the day, and these symptoms did not improve with steroids.
Anti-AChR and anti-MuSK antibodies were negative, but she had a decrement on repetitive nerve stimulation testing.
She was treated with pyridostigmine and experienced near-complete resolution of her proximal weakness and double vision. A chest CT scan showed thymic hyperplasia; thymectomy was recommended.
In another case, a 19-year-old woman who complained of leg pain after exercise was found to have intact strength but asymmetric calf hypertrophy. Her CK level was 5,000 IU/L, and she was referred to rule out acute myositis.
A quadriceps biopsy was performed and showed abnormal dystrophin immunostaining but no inflammation. A molecular genetic analysis showed deletions in Xp21 and she was diagnosed as a manifesting carrier of Duchenne muscular dystrophy. It was recommended that she be evaluated for cardiomyopathy and receive genetic counseling.
A number of other cases presented by Dr. Christopher-Stine highlighted other muscular dystrophies that can mimic myositis, such as:
- Myotonic dystrophies. These are more often type 2 than type 1. Myotonia may be subtle, cataracts are seen early in all patients, and cardiac arrhythmias are common.
- Limb girdle muscular dystrophy type 2 B (dysferlinopathy). In the legs, this often affects the gastrocnemius muscle, and this will be visible on MRI. In the arms, it most often affects the biceps, sparing the deltoids. CKs are typically very high.
- Facioscapulohumeral muscular dystrophy (FSHD). This involves facial weakness, especially obicularis oris, in 95% of cases, as well as scapular weakness and winging, inflammation on muscle biopsy in 75% of cases, and typically is endomysial or perivascular.
Metabolic myopathies
Among metabolic myopathies that can mimic myositis are disorders of carbohydrate metabolism such as McArdle’s disease, 6-phosphofructokinase deficiency, and Pompe’s disease (adult acid maltase deficiency); disorders of lipid metabolism such as carnitine deficiency and carnitine palmitoyltransferase 2 (CPT2) deficiency; and disorders of purine metabolism, such as myoadenylate deaminase deficiency.
A 27-year-old patient who complained of weakness with activity was referred for possible myositis and was found to have a CK of 3,650 IU/L that never normalized. Physical examination showed intact strength and no muscle atrophy or fasciculations, and an enzyme stain for myophosphorylase showed a normal staining pattern and complete absence of the enzyme on quadricep biopsy. A 22-year-old man with similar symptoms plus recent onset of brown/black urine after physical activity had CK of 110,000 IU/L when symptomatic, and also underwent biopsy after being referred for possible myopathy. Both patients were ultimately diagnosed with CPT2 deficiency, which is associated with risk of rhabdomyolysis triggered by prolonged exercise, diets low in carbohydrates and high in fat, or by fasting.
Myalgias are common, and CK levels are normal or only mildly elevated between episodes in CPT2 deficiency, Dr. Christopher-Stine noted.
Toxic myopathies
Drug-induced myopathies are among the most common etiologies of myopathy and can range from mild myalgia to massive rhabdomyolysis. They can cause mild to severe weakness and may be chronic. The mechanism of toxic injury is direct via myotoxins such as ethyl alcohol, glucocorticoids, lipid-lowering drugs, cocaine, antimalarial drugs, antipsychotic drugs, colchicine, and Ipecac syrup.
One case described by Dr. Christopher-Stine involved “statin myopathy.”
A 55-year-old man on atorvastatin complained of myalgias and brown urine, but had no definitive weakness. He had intact strength and diffuse myalgias that weren’t reproducible. His CK was 45,000 IU/L.
Statin myopathy, as seen in this patient, is usually self-limited and is not associated with autoimmunity or with anti-HMGCR autoantibody positivity.
The mechanism is unknown, but statin myopathy has an incidence of 1.2 per 10,000 patient-years. Myalgias, myositis, rhabdomyolysis, and asymptomatic hyperCKemia are commonly seen. This is in contrast to the immune-mediated necrotizing myelitis that can be secondary to statins and is responsive to immunosuppression, she noted.
Other myositis mimics
In addition to these common myositis mimics, certain other neurologic diseases (such as ALS and cervical myelopathy), endocrinopathies (such as hypothyroidism), and infections (like toxoplasmosis) can also be mistaken for myositis, Dr. Christopher-Stine said, noting that cases illustrating these mimics underscore the need for careful consideration of possible alternate diagnoses.
“While most noninflammatory myopathies are self-limited or have no therapies available, knowing the diagnosis can be helpful for genetic counseling of the patient and family, for mitigating risk factors, and for precluding the use of unwarranted immunosuppressive agents,” she said.
Dr. Christopher-Stine reported having intellectual property interest in a novel Inova Diagnostics autoantibody assay detection for anti-HMGCR. She was also the safety officer for the JBT-101 Trial sponsored by Corbus and funded by the National Institutes of Health.
A number of conditions can mimic myositis, but clues that can point to the correct diagnosis are often present in cases involving the mimics, according to Lisa Christopher-Stine, MD.
For example, elevated levels of certain muscle enzymes are an important source of diagnostic information, Dr. Christopher-Stine, director of the Johns Hopkins Myositis Center, Baltimore, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Isolated elevations in aldolase can be seen in connective tissue–associated interstitial lung disease or in patients with fascial edema, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), and creatine kinase (CK) levels can also be helpful, she explained.
The latter can also be elevated in the absence of muscle disease, for example, in healthy individuals following exercise. CK peaks at 24 hours after exercise before returning to baseline by 72 hours. In an experimental setting, a threefold increase in CK levels has been seen at 8-24 hours after exercise, Dr. Christopher-Stine said.
“HyperCKemia”
Trauma from causes such as intramuscular injection, electromyography (EMG), major surgery, or biopsy can also lead to increased CK levels. Motor neuron disease can also cause such increases. In one study, 75% of patients with amyotrophic lateral sclerosis had a mean twofold increase in CK levels, she said.
Asymptomatic CK elevations may also represent presymptomatic myopathies, type 1 or 2 macro-CK, manual labor occupations, or they may be idiopathic.
Race can play a role in CK levels as well. Black people tend to have higher CK levels than white people, she said, noting that one study of more than 10,000 adults showed that black race was strongly associated with CK, and that body composition largely explained differences in CK by age, but not by race/ethnicity (Medicine. Aug 2016;95[33]:e4344).
“So elevated CK may not herald any discernible illness,” she said.
Dr. Christopher-Stine described a case involving an otherwise healthy 30-year-old man with a CK level of 695 IU/L that was found incidentally. He had a desk job, no recent travel, and denied weakness, myalgias, joint pain, dysphagia, shortness of breath, and fevers. In this case, the elevated CK was felt to be secondary to his African American race given that other causes were ruled out.
Another case involved a 72-year-old man with left-arm pain. A cardiac event was ruled out, and CK was found to be about 4,500 IU/L. He reported “flare-ups” of diffuse swelling of the hands and feet. X-rays showed concerning signs of erosions. His transaminases and electromyogram were normal; he reported no weakness or myalgia; and an MRI showed no muscle edema. He was diagnosed with macro-CK, which refers to CK with an increased molecular weight. A clue to this diagnosis is a normal liver function test. In some cases, muscle/brain CK levels (CK-MB) are elevated and higher than total CK, she noted.
She presented an algorithm for the diagnostic work-up of patients presenting with elevated CK of unclear significance. Her recommended approach involves repeat CK assessment and a closer look at family history, medication, drug/toxin history, examination for weakness and neurologic abnormalities, and additional lab assessments in those whose levels remain elevated. In those in whom a diagnosis is not identified, the algorithm calls for observation every 3 months – including physical examination and labs – in asymptomatic patients with levels at less than five times the upper limit of normal, and further evaluation, including EMG with nerve-conduction velocity testing, muscle biopsy, and MRI in those with (or who later develop) marked elevation greater than five times the upper limit of normal and/or symptoms.
Patient assessment
The physical examination should involve localization and quantification of weakness, and assessment for fever, rash, atrophy/wasting/scooping of forearms, fasciculations, cranial nerve involvement, Raynaud’s phenomenon, nailfold capillary changes, arthritis, calcinosis, “mechanic’s hands,” signs of other autoimmune diseases, and lung crackles. Initial laboratory testing should include HIV and hepatitis B and C testing; measurement of CK, AST, ALT, aldolase, thyroid-stimulating hormone, and magnesium levels; a comprehensive metabolic panel and complete blood count; and measurement of erythrocyte sedimentation rate and C-reactive protein.
“Weakness may be secondary to a neuropathy, myopathy, or a problem at the neuropathic junction. Many causes of weakness can be readily identified by careful history taking, focused physical examination, and directed laboratory evaluation,” she said.
Features pointing toward a diagnosis of myositis include characteristic rashes, gradual symptom onset, proximal limb and truncal weakness, other connective tissue disease features such as Raynaud’s and arthritis, and the presence of lung disease, including interstitial lung disease or unexplained infiltrates, she said.
Features pointing away from a diagnosis of myositis include a family history of a similar illness, weakness that is associated with eating or fasting, neurologic signs, cranial nerve involvement, fasciculations, severe muscle cramping, early atrophy, and creatine phosphokinase levels that are either less than 2 times or more than 100 times the upper limit of normal.
Among the conditions to consider in the presence of the features that point away from a myositis diagnosis are muscular dystrophies, metabolic myopathies, and toxic (drug-induced) myopathies, to name a few, Dr. Christopher-Stine said.
She described a number of other cases to illustrate the need for – and to help develop – a differential diagnosis in patients presenting with apparent myositis.
Muscular dystrophies
A 38-year-old woman with limited scleroderma and anti-PM/Scl autoantibodies developed proximal weakness over 9 months and was eventually unable to walk up a flight of stairs. She had heliotrope rash and Gottron’s sign, her serum CK was 723 IU/L, and EMG showed an irritable myopathy.
Muscle biopsy showed inflammation, and she was treated with prednisone, but this led to worsening weakness. She complained of prominent fatigue and double vision at the end of the day, and these symptoms did not improve with steroids.
Anti-AChR and anti-MuSK antibodies were negative, but she had a decrement on repetitive nerve stimulation testing.
She was treated with pyridostigmine and experienced near-complete resolution of her proximal weakness and double vision. A chest CT scan showed thymic hyperplasia; thymectomy was recommended.
In another case, a 19-year-old woman who complained of leg pain after exercise was found to have intact strength but asymmetric calf hypertrophy. Her CK level was 5,000 IU/L, and she was referred to rule out acute myositis.
A quadriceps biopsy was performed and showed abnormal dystrophin immunostaining but no inflammation. A molecular genetic analysis showed deletions in Xp21 and she was diagnosed as a manifesting carrier of Duchenne muscular dystrophy. It was recommended that she be evaluated for cardiomyopathy and receive genetic counseling.
A number of other cases presented by Dr. Christopher-Stine highlighted other muscular dystrophies that can mimic myositis, such as:
- Myotonic dystrophies. These are more often type 2 than type 1. Myotonia may be subtle, cataracts are seen early in all patients, and cardiac arrhythmias are common.
- Limb girdle muscular dystrophy type 2 B (dysferlinopathy). In the legs, this often affects the gastrocnemius muscle, and this will be visible on MRI. In the arms, it most often affects the biceps, sparing the deltoids. CKs are typically very high.
- Facioscapulohumeral muscular dystrophy (FSHD). This involves facial weakness, especially obicularis oris, in 95% of cases, as well as scapular weakness and winging, inflammation on muscle biopsy in 75% of cases, and typically is endomysial or perivascular.
Metabolic myopathies
Among metabolic myopathies that can mimic myositis are disorders of carbohydrate metabolism such as McArdle’s disease, 6-phosphofructokinase deficiency, and Pompe’s disease (adult acid maltase deficiency); disorders of lipid metabolism such as carnitine deficiency and carnitine palmitoyltransferase 2 (CPT2) deficiency; and disorders of purine metabolism, such as myoadenylate deaminase deficiency.
A 27-year-old patient who complained of weakness with activity was referred for possible myositis and was found to have a CK of 3,650 IU/L that never normalized. Physical examination showed intact strength and no muscle atrophy or fasciculations, and an enzyme stain for myophosphorylase showed a normal staining pattern and complete absence of the enzyme on quadricep biopsy. A 22-year-old man with similar symptoms plus recent onset of brown/black urine after physical activity had CK of 110,000 IU/L when symptomatic, and also underwent biopsy after being referred for possible myopathy. Both patients were ultimately diagnosed with CPT2 deficiency, which is associated with risk of rhabdomyolysis triggered by prolonged exercise, diets low in carbohydrates and high in fat, or by fasting.
Myalgias are common, and CK levels are normal or only mildly elevated between episodes in CPT2 deficiency, Dr. Christopher-Stine noted.
Toxic myopathies
Drug-induced myopathies are among the most common etiologies of myopathy and can range from mild myalgia to massive rhabdomyolysis. They can cause mild to severe weakness and may be chronic. The mechanism of toxic injury is direct via myotoxins such as ethyl alcohol, glucocorticoids, lipid-lowering drugs, cocaine, antimalarial drugs, antipsychotic drugs, colchicine, and Ipecac syrup.
One case described by Dr. Christopher-Stine involved “statin myopathy.”
A 55-year-old man on atorvastatin complained of myalgias and brown urine, but had no definitive weakness. He had intact strength and diffuse myalgias that weren’t reproducible. His CK was 45,000 IU/L.
Statin myopathy, as seen in this patient, is usually self-limited and is not associated with autoimmunity or with anti-HMGCR autoantibody positivity.
The mechanism is unknown, but statin myopathy has an incidence of 1.2 per 10,000 patient-years. Myalgias, myositis, rhabdomyolysis, and asymptomatic hyperCKemia are commonly seen. This is in contrast to the immune-mediated necrotizing myelitis that can be secondary to statins and is responsive to immunosuppression, she noted.
Other myositis mimics
In addition to these common myositis mimics, certain other neurologic diseases (such as ALS and cervical myelopathy), endocrinopathies (such as hypothyroidism), and infections (like toxoplasmosis) can also be mistaken for myositis, Dr. Christopher-Stine said, noting that cases illustrating these mimics underscore the need for careful consideration of possible alternate diagnoses.
“While most noninflammatory myopathies are self-limited or have no therapies available, knowing the diagnosis can be helpful for genetic counseling of the patient and family, for mitigating risk factors, and for precluding the use of unwarranted immunosuppressive agents,” she said.
Dr. Christopher-Stine reported having intellectual property interest in a novel Inova Diagnostics autoantibody assay detection for anti-HMGCR. She was also the safety officer for the JBT-101 Trial sponsored by Corbus and funded by the National Institutes of Health.
A number of conditions can mimic myositis, but clues that can point to the correct diagnosis are often present in cases involving the mimics, according to Lisa Christopher-Stine, MD.
For example, elevated levels of certain muscle enzymes are an important source of diagnostic information, Dr. Christopher-Stine, director of the Johns Hopkins Myositis Center, Baltimore, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Isolated elevations in aldolase can be seen in connective tissue–associated interstitial lung disease or in patients with fascial edema, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH), and creatine kinase (CK) levels can also be helpful, she explained.
The latter can also be elevated in the absence of muscle disease, for example, in healthy individuals following exercise. CK peaks at 24 hours after exercise before returning to baseline by 72 hours. In an experimental setting, a threefold increase in CK levels has been seen at 8-24 hours after exercise, Dr. Christopher-Stine said.
“HyperCKemia”
Trauma from causes such as intramuscular injection, electromyography (EMG), major surgery, or biopsy can also lead to increased CK levels. Motor neuron disease can also cause such increases. In one study, 75% of patients with amyotrophic lateral sclerosis had a mean twofold increase in CK levels, she said.
Asymptomatic CK elevations may also represent presymptomatic myopathies, type 1 or 2 macro-CK, manual labor occupations, or they may be idiopathic.
Race can play a role in CK levels as well. Black people tend to have higher CK levels than white people, she said, noting that one study of more than 10,000 adults showed that black race was strongly associated with CK, and that body composition largely explained differences in CK by age, but not by race/ethnicity (Medicine. Aug 2016;95[33]:e4344).
“So elevated CK may not herald any discernible illness,” she said.
Dr. Christopher-Stine described a case involving an otherwise healthy 30-year-old man with a CK level of 695 IU/L that was found incidentally. He had a desk job, no recent travel, and denied weakness, myalgias, joint pain, dysphagia, shortness of breath, and fevers. In this case, the elevated CK was felt to be secondary to his African American race given that other causes were ruled out.
Another case involved a 72-year-old man with left-arm pain. A cardiac event was ruled out, and CK was found to be about 4,500 IU/L. He reported “flare-ups” of diffuse swelling of the hands and feet. X-rays showed concerning signs of erosions. His transaminases and electromyogram were normal; he reported no weakness or myalgia; and an MRI showed no muscle edema. He was diagnosed with macro-CK, which refers to CK with an increased molecular weight. A clue to this diagnosis is a normal liver function test. In some cases, muscle/brain CK levels (CK-MB) are elevated and higher than total CK, she noted.
She presented an algorithm for the diagnostic work-up of patients presenting with elevated CK of unclear significance. Her recommended approach involves repeat CK assessment and a closer look at family history, medication, drug/toxin history, examination for weakness and neurologic abnormalities, and additional lab assessments in those whose levels remain elevated. In those in whom a diagnosis is not identified, the algorithm calls for observation every 3 months – including physical examination and labs – in asymptomatic patients with levels at less than five times the upper limit of normal, and further evaluation, including EMG with nerve-conduction velocity testing, muscle biopsy, and MRI in those with (or who later develop) marked elevation greater than five times the upper limit of normal and/or symptoms.
Patient assessment
The physical examination should involve localization and quantification of weakness, and assessment for fever, rash, atrophy/wasting/scooping of forearms, fasciculations, cranial nerve involvement, Raynaud’s phenomenon, nailfold capillary changes, arthritis, calcinosis, “mechanic’s hands,” signs of other autoimmune diseases, and lung crackles. Initial laboratory testing should include HIV and hepatitis B and C testing; measurement of CK, AST, ALT, aldolase, thyroid-stimulating hormone, and magnesium levels; a comprehensive metabolic panel and complete blood count; and measurement of erythrocyte sedimentation rate and C-reactive protein.
“Weakness may be secondary to a neuropathy, myopathy, or a problem at the neuropathic junction. Many causes of weakness can be readily identified by careful history taking, focused physical examination, and directed laboratory evaluation,” she said.
Features pointing toward a diagnosis of myositis include characteristic rashes, gradual symptom onset, proximal limb and truncal weakness, other connective tissue disease features such as Raynaud’s and arthritis, and the presence of lung disease, including interstitial lung disease or unexplained infiltrates, she said.
Features pointing away from a diagnosis of myositis include a family history of a similar illness, weakness that is associated with eating or fasting, neurologic signs, cranial nerve involvement, fasciculations, severe muscle cramping, early atrophy, and creatine phosphokinase levels that are either less than 2 times or more than 100 times the upper limit of normal.
Among the conditions to consider in the presence of the features that point away from a myositis diagnosis are muscular dystrophies, metabolic myopathies, and toxic (drug-induced) myopathies, to name a few, Dr. Christopher-Stine said.
She described a number of other cases to illustrate the need for – and to help develop – a differential diagnosis in patients presenting with apparent myositis.
Muscular dystrophies
A 38-year-old woman with limited scleroderma and anti-PM/Scl autoantibodies developed proximal weakness over 9 months and was eventually unable to walk up a flight of stairs. She had heliotrope rash and Gottron’s sign, her serum CK was 723 IU/L, and EMG showed an irritable myopathy.
Muscle biopsy showed inflammation, and she was treated with prednisone, but this led to worsening weakness. She complained of prominent fatigue and double vision at the end of the day, and these symptoms did not improve with steroids.
Anti-AChR and anti-MuSK antibodies were negative, but she had a decrement on repetitive nerve stimulation testing.
She was treated with pyridostigmine and experienced near-complete resolution of her proximal weakness and double vision. A chest CT scan showed thymic hyperplasia; thymectomy was recommended.
In another case, a 19-year-old woman who complained of leg pain after exercise was found to have intact strength but asymmetric calf hypertrophy. Her CK level was 5,000 IU/L, and she was referred to rule out acute myositis.
A quadriceps biopsy was performed and showed abnormal dystrophin immunostaining but no inflammation. A molecular genetic analysis showed deletions in Xp21 and she was diagnosed as a manifesting carrier of Duchenne muscular dystrophy. It was recommended that she be evaluated for cardiomyopathy and receive genetic counseling.
A number of other cases presented by Dr. Christopher-Stine highlighted other muscular dystrophies that can mimic myositis, such as:
- Myotonic dystrophies. These are more often type 2 than type 1. Myotonia may be subtle, cataracts are seen early in all patients, and cardiac arrhythmias are common.
- Limb girdle muscular dystrophy type 2 B (dysferlinopathy). In the legs, this often affects the gastrocnemius muscle, and this will be visible on MRI. In the arms, it most often affects the biceps, sparing the deltoids. CKs are typically very high.
- Facioscapulohumeral muscular dystrophy (FSHD). This involves facial weakness, especially obicularis oris, in 95% of cases, as well as scapular weakness and winging, inflammation on muscle biopsy in 75% of cases, and typically is endomysial or perivascular.
Metabolic myopathies
Among metabolic myopathies that can mimic myositis are disorders of carbohydrate metabolism such as McArdle’s disease, 6-phosphofructokinase deficiency, and Pompe’s disease (adult acid maltase deficiency); disorders of lipid metabolism such as carnitine deficiency and carnitine palmitoyltransferase 2 (CPT2) deficiency; and disorders of purine metabolism, such as myoadenylate deaminase deficiency.
A 27-year-old patient who complained of weakness with activity was referred for possible myositis and was found to have a CK of 3,650 IU/L that never normalized. Physical examination showed intact strength and no muscle atrophy or fasciculations, and an enzyme stain for myophosphorylase showed a normal staining pattern and complete absence of the enzyme on quadricep biopsy. A 22-year-old man with similar symptoms plus recent onset of brown/black urine after physical activity had CK of 110,000 IU/L when symptomatic, and also underwent biopsy after being referred for possible myopathy. Both patients were ultimately diagnosed with CPT2 deficiency, which is associated with risk of rhabdomyolysis triggered by prolonged exercise, diets low in carbohydrates and high in fat, or by fasting.
Myalgias are common, and CK levels are normal or only mildly elevated between episodes in CPT2 deficiency, Dr. Christopher-Stine noted.
Toxic myopathies
Drug-induced myopathies are among the most common etiologies of myopathy and can range from mild myalgia to massive rhabdomyolysis. They can cause mild to severe weakness and may be chronic. The mechanism of toxic injury is direct via myotoxins such as ethyl alcohol, glucocorticoids, lipid-lowering drugs, cocaine, antimalarial drugs, antipsychotic drugs, colchicine, and Ipecac syrup.
One case described by Dr. Christopher-Stine involved “statin myopathy.”
A 55-year-old man on atorvastatin complained of myalgias and brown urine, but had no definitive weakness. He had intact strength and diffuse myalgias that weren’t reproducible. His CK was 45,000 IU/L.
Statin myopathy, as seen in this patient, is usually self-limited and is not associated with autoimmunity or with anti-HMGCR autoantibody positivity.
The mechanism is unknown, but statin myopathy has an incidence of 1.2 per 10,000 patient-years. Myalgias, myositis, rhabdomyolysis, and asymptomatic hyperCKemia are commonly seen. This is in contrast to the immune-mediated necrotizing myelitis that can be secondary to statins and is responsive to immunosuppression, she noted.
Other myositis mimics
In addition to these common myositis mimics, certain other neurologic diseases (such as ALS and cervical myelopathy), endocrinopathies (such as hypothyroidism), and infections (like toxoplasmosis) can also be mistaken for myositis, Dr. Christopher-Stine said, noting that cases illustrating these mimics underscore the need for careful consideration of possible alternate diagnoses.
“While most noninflammatory myopathies are self-limited or have no therapies available, knowing the diagnosis can be helpful for genetic counseling of the patient and family, for mitigating risk factors, and for precluding the use of unwarranted immunosuppressive agents,” she said.
Dr. Christopher-Stine reported having intellectual property interest in a novel Inova Diagnostics autoantibody assay detection for anti-HMGCR. She was also the safety officer for the JBT-101 Trial sponsored by Corbus and funded by the National Institutes of Health.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM