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Inflammatory myopathies can be classified into dermatomyositis; overlap myositis, including antisynthetase syndrome; immune-mediated necrotizing myopathy; inclusion body myositis; and polymyositis. Among the 5, polymyositis is the rarest.
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Dermatomyositis-associated antibodies include MJ(NXP2), TIF1gamma, SAE, Mi-2, MDA-5. Inclusion body myositis is associated with anti-NT5c1A antibodies.
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Cancer risk is increased in older MJ (NXP2) and TIF1 gamma–positive dermatomyositis patients. MDA-5-positive
Inflammatory Myopathies: Utility of Antibody Testing
Section snippets
Key points
Case clinical presentation 1
A 76-year-old woman with a medical history of invasive ductal carcinoma of the right breast 2 years ago that was treated with surgical resection and radiation therapy and was in remission who presented for evaluation of 2-week to 3-week history of gradually progressive lower extremity swelling and shortness of breath. She also had difficulty swallowing. Over the preceding week, she also experienced increasing weakness in her arms and legs, and she noticed an increase in her abdominal girth. Her
Diagnostic studies
Her laboratory studies showed an increase in serum creatinine level of 2.43 mg/dL from her baseline of 0.62 mg/dL, creatine kinase (CK) 6453 U/L, aldolase 78.0 U/L, sedimentation rate 73 mm/h, C-reactive protein 12.7 mg/dL, and thyroid-stimulating hormone 10.1 IU/L. Her antinuclear antibody (ANA), anti-SSA and SSB antibodies, rheumatoid factor (RF), anti–DS DNA antibody, anti-Jo1 antibody, and anticentromere antibody were normal. Her chest computed tomography (CT) with and without contrast
Treatment and definitive diagnosis
This patient’s history, examination, and diagnostic studies are compatible with DM. Because of her history of breast cancer, cancer antigen 19-9, alpha fetoprotein tumor marker, carcinoembryonic antigen, and a paraneoplastic antibody panel were obtained and were normal. Her PL-7, PL-12, EJ, OJ, signal recognition particle (SRP), Mi-2, TIF1 gamma, MJ/NXP-2, anti-PM/SCL, U2 snRNP, fibrillarin, anti–U1-RNP, anti–SAE, and Ku antibodies were negative. Her MDA-5 antibody titer was increased. Her
Discussion
DM is a subtype of idiopathic inflammatory myopathy in which proximal muscle weakness and cutaneous abnormalities are the most prominent clinical features.1 The clinical presentation of DM can be heterogeneous, and amyopathic DM is a recognized and well-defined subgroup of DM.2 Patients diagnosed with DM can have a variety of skin manifestations, varying degrees of muscle weakness, and other systemic disorders. Although the classic skin findings in DM include purplish periorbital edematous rash
Case clinical presentation 2
A 74-year-old woman presented to clinic for progressive weakness and swallowing difficulty for the last 2.5 months. Her past medical history was pertinent for chronic lymphocytic leukemia diagnosed more than 5 years ago, and she had been in remission for the last couple of years. Her family history was noncontributory.
She had normal cranial nerve examination and nasal speech. She was constantly drooling because of swallowing difficulty. She had weakness in neck flexors and proximal muscles in
Diagnostic studies
The CK level was increased at 845 U/L (normal, 12–191 U/L). ANA, Sjögren antibodies, RF, paraneoplastic panel, and serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) with immunofixation electrophoresis were normal. Her chest, abdomen, and pelvis CT as well as whole-body PET-CT were unremarkable. Her electrodiagnostic studies showed normal nerve conduction responses and the needle EMG revealed increased insertional activity, abnormal spontaneous activity in the form of
Treatment and definitive diagnosis
Perifascicular atrophy is defined as the presence of small fibers observed in the periphery of a muscle fiber fascicle. Some of these fibers result from fiber atrophy, whereas others are regenerating fibers. Perifascicular atrophy is not typically seen in any of the other choices listed.
In addition to perifascicular atrophy, other features seen in DM are collections of mostly perimysial/perivascular inflammatory cells (Fig. 2), cytochrome oxidase (COX)–negative fibers mostly located in the
Discussion
MJ (NXP2) DM is usually seen in juvenile patients, and calcinosis is observed frequently in MJ (NXP2)-positive patients. The incidence of calcinosis is reported to be higher in juvenile cases.10, 11, 12
The presence of MJ antibody may portend an increased risk for cancer and may prompt clinicians to search for a malignancy more aggressively. Cancer risk is increased in older patients, especially in individuals older than 39 years of age who harbor TIF1gamma and MJ (NXP2) antibodies.12,13 In
Case clinical presentation 3
A 48-year-old white woman presented to the neuromuscular outpatient clinic complaining of speech problems, swallowing difficulty, and arm and leg weakness for the last 2.5 years. She had slurred speech and could not pronounce the letters as smoothly as she could before the onset of her weakness. She denied having double vision, droopy eyelids, or shortness of breath. Her past medical history was notable for hypertension and migraine headaches. There was no family history of muscle disorders or
Diagnostic studies
The CK level was increased at 532 U/L (normal, 12–191 U/L). The rest of her laboratory studies, including complete blood count (CBC), comprehensive metabolic panel (CMP), ANA, RF, erythrocyte sedimentation rate, and C-reactive protein, were normal. Electrodiagnostic studies showed normal nerve conduction studies. Her needle EMG study showed increased insertional activity as well as abnormal spontaneous activity in the form of rare positive waves in quadriceps muscles and early recruitment in
Treatment and definitive diagnosis
This patient is presenting with facial, symmetric proximal, and asymmetric distal muscle weakness in the extremities and mildly increased CK level. There are several hereditary myopathies that can cause facial weakness, such as fascioscapulohumeral dystrophy (FSHD), congenital myopathies (CMs), myotonic dystrophy, and oculopharyngeal muscular dystrophy (OPMD). Facial weakness is not a feature. Even though the possibility of an underlying hereditary myopathy still exists, it is less likely given
Discussion
sIBM is the most common inflammatory myopathy after the fifth decade of life; it presents with asymmetrical weakness and has a predilection for finger flexor and quadriceps weakness. Dysphagia is one of the common early complaints (reported in one-third of patients), and patients are often referred to see ear, nose, and throat or gastrointestinal specialists before seeking further evaluation by a neurologist. The only antibody associated with sIBM is cytosolic 5′-nucleotidase 1A (NT5c1A)
Case clinical presentation 4
A 71-year-old Hispanic woman presented with weakness that has been present for the 1.5 years. The weakness began in her legs then spread to her arms followed by neck involvement over the next 6 months. She denied having speech problems. She had difficulty swallowing when her neck started to bend forward. She was not on statin therapy in the past. Her past medical history was pertinent for breast cancer that was in remission for the last few years. She did not have family members with similar
Diagnostic studies
The CBC; CMP; paraneoplastic panel; FSHD 1 and 2 genetic studies; chest, abdomen, and pelvis CT with contrast; and whole-body PET-CT were normal. The CK level was increased at 1134 U/L (normal, 12–191 U/L).
Electrodiagnostic studies showed mild to moderately increased spontaneous activity in both arms, proximal greater than distal and posterior neck muscles. There was mildly increased spontaneous activity in the proximal leg muscles. Short-duration and polyphasic motor unit potentials were
Treatment and definitive diagnosis
Contactin antibodies are associated with chronic inflammatory demyelinating polyneuropathies and can be seen in treatment-resistant cases. HMGCR antibodies are present in autoimmune necrotizing myopathy, which does not cause skin rash; however, in some cases, patients can have scapular winging on examination. LRP4 antibodies are found in myasthenia gravis and can present with head drop and acute respiratory failure. These patients do not have cutaneous lesions or scapular winging. NT5c1a is
Discussion
Overlap myositis is a subtype of idiopathic inflammatory myopathy and consists of myositis associated with antisynthetase syndrome (ASS) or myositis associated with clinical features of a connective tissue disorder such as systemic lupus erythematosus. This condition is the most common subtype of inflammatory myopathies and accounts for approximately 50% of all the cases.32 Antibodies associated with overlap myositis excluding the ASS antibodies are anti-Ku, anti-Pm-Scl, anti-Ro/Sjögren
Case clinical presentation 5
An 87-year-old man presented for evaluation of lower extremity weakness progressing over the prior 4 months. He was started on atorvastatin in November 2017 and, by March 2018, he began to have trouble walking. He could not walk as fast as he normally did and had to have help getting out of a vehicle because he was unable to stand up. He also had shortness of breath with exertion, and difficulty climbing the stairs, getting up from the floor, and getting in and out of the bathtub. Because of
Diagnostic studies
His laboratory studies showed CK level of 6397 U/L, aspartate aminotransferase 229 IU/L, alanine aminotransferase 190 IU/L, and C-reactive protein 7.4 mg/L. His ANA, RF, anti-DS DNA antibody, RNP antibody, anti-SSA and SSB antibodies, anti–Jo-1 antibody, anti–scleroderma-70 antibody, Smith antibody, and anti–centromere B antibodies were normal. His nerve conduction studies showed a median neuropathy across the wrist and his needle electromyography study showed fibrillation potentials and
Treatment and definitive diagnosis
A biceps muscle biopsy was performed that showed rare collections of perimysial perivascular inflammatory cells and many necrotic fibers and upregulation of MHC-1 compatible with a necrotizing myopathy. His Mi-2, Ku, PL-7, PL-2, EJ, and OJ antibodies were negative. His SRP antibody titer was increased. The patient was diagnosed with IMNM with SRP antibodies. His transthoracic echocardiogram showed a normal ejection fraction.
He was treated with a 5-day course of IVIg and 3-day course of
Discussion
IMNM is a subtype of idiopathic inflammatory myopathy defined pathologically by muscle fiber necrosis in the absence or scarcity of inflammatory cell infiltrate on the muscle biopsy.37 Muscle biopsies from patients who have anti-SRP antibody were the first to be identified as having this pathologic characteristic.38 Subsequently, muscle biopsies from patients who have HMGCR antibody were also described to have the same pathologic features.39 Approximately one-third of patients diagnosed with
Case clinical presentation 6
A 51-year-old woman with a history of Lyme disease confirmed by serologic testing and adequately treated with antibiotics presented for evaluation of a 10-year history of progressive weakness. She first noticed generalized weakness after being diagnosed with Lyme disease. She had trouble with certain activities, such as walking up the stairs, walking up an incline, and getting up from a deep chair. A few years after the onset of her muscular symptoms, her balance became more impaired and she
Diagnostic studies
Her laboratory testing showed borderline increased anti-DS DNA antibody level of 5 IU/mL and an increased anti-SSB antibody level. Her antineutrophil cytoplasmic antibodies, CK, C-reactive protein, sedimentation rate, anti–scleroderma-70 antibody, anti-SSA antibody, anti–centromere B antibody, Smith antibody, RNP antibody, anti-ds DNA antibody, and RF were normal. Her thyroid function studies were normal. Her electrophysiologic testing showed an essentially normal nerve conduction study and her
Treatment and definitive diagnosis
A biceps muscle biopsy was performed and showed scattered perimysial and perivascular inflammatory infiltrates. Her PL-12 antibody was positive. Her PL-7, Mi-2, Ku, EJ, OJ, SRP, and Jo-1 antibodies were negative. The patient was diagnosed with antisynthetase syndrome based on the findings on her antibody testing. CT chest without contrast was obtained that showed left more than right ground-glass opacification in both lower lobes, and her pulmonary function testing was normal.
She was started on
Discussion
Antisynthetase syndrome is a heterogeneous group of disorders with main clinical features consisting of myositis, ILD, Raynaud's phenomenon, arthritis, fever, and hyperkeratotic skin changes on the fingers, especially at the tips (known as mechanic’s hand).47 Antisynthetase syndrome is sometimes categorized as a subgroup of overlap myositis because of the association of myositis with other systemic autoimmune disorders. The unifying characteristic of this syndrome is the finding of
Disclosure
The authors have nothing to disclose.
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