Anti-MDA5-Positive Dermatomyositis Presenting as Fever of Unknown Origin

Abstract

Dermatomyositis is a chronic systemic autoimmune disease characterized by inflammatory infiltrates in the skin and muscle. The wide variability in clinical and serologic presentation poses a diagnostic challenge for the internist. Appreciation of the clinical variants of dermatomyositis allows for expedient diagnosis and avoidance of diagnostic error. We illustrate these challenges with the case of a 51-year-old VietnameseAmerican man who initially presented with fever of unknown origin in the absence of overt skin and muscle manifestations. The diagnosis of dermatomyositis was not evident on several clinical encounters due to the absence of these hallmark symptoms. We review the variable clinical manifestations of a subtype of dermatomyositis associated with an autoantibody against melanoma differentiation-associated protein 5 (anti-MDA5) and suggest consideration of dermatomyositis as a diagnosis in patients presenting with systemic illness and markedly elevated ferritin, even in the absence of elevated muscle enzymes and classic autoantibodies. CASE PRESENTATIONA 51-year-old Vietnamese-American male industrial engineer was admitted to the medical ward for evaluation of fever of unknown origin (FUO). He reported 3 weeks of fever, fatigue, generalized weakness, and dyspnea. His past medical history included a remote 10-pack-year history of cigarette smoking and latent tuberculosis treated with 9 months of isoniazid treatment, completed 5 years prior. He had moved from Vietnam to the United States 30 years earlier and denied any recent travel, sick contacts, or insect bites. Physical examination revealed a fatigued man, with a temperature of 38.1°C, pulse of 108 beats/minute, respiratory rate of 28 breaths/minute, and room air oxygen saturation of 96 %. Oropharyngeal, neurologic, pulmonary, cardiac, musculoskeletal, and skin evaluation were otherwise normal.A complete blood count (CBC) revealed anemia (hemoglobin 12.3 g/dL, hematocrit 38.5 %). White blood cell counts, platelet counts, and the basic metabolic panel were normal. Erythrocyte sedimentation rate (ESR) was 97 mm/hr and C-reactive protein (CRP) was 5.7 mg/dL. Muscle enzymes, sent to evaluate his weakness in the setting of elevated inflammatory markers, showed normal creatine kinase (CK) at 44 units/liter and mildly elevated aldolase to 9.4 U/L (normal: < 7.7 U/L). Blood, urine, and sputum cultures had no growth. Chest x-ray (CXR) demonstrated low lung volumes with increased reticular markings, small bilateral pleural effusions, and bibasilar opacities. During the hospitalization, he continued to have intermittent fevers as high as 39.1°C, generalized weakness, and dyspnea. Additionally, he developed bibasilar crackles on pulmonary exam and flat, diffuse, slightly hyperpigmented patches on his arms and chest that faded over several days. Extensive workup for infectious, inflammatory, and malignant causes of fever was unrevealing, including negative viral hepatitis serologies, human immunodeficiency virus antibody, anti-nuclear antibody (ANA), and anti-...

Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America

“…The anti-MDA5 autoantibody JIIM phenotype was also associated with a high frequency of constitutional symptoms (weight loss, fever and adenopathy), as previously reported [15,16,31]. Fever has been described in 25-67% of anti-MDA5 JDM and DM patients, and furthermore, as a single presenting symptom in the absence of cutaneous or muscular manifestations of DM [32].…”

Diagnostic value of FDG-PET/CT in fever of unknown origin

“…Dermatomyositis is a rare cause of FUO in the literature that was found in our study. Lee et al [ 26 ] have reported a similar case presenting as FUO. They concluded that certain subtypes of dermatomyositis can present with atypical presentations as FUO.…”

Clinical Features of Anti-Synthetase Syndrome Associated with Prognosis in Patients with Dermatomyositis and Polymyositis

“…The anti-Jo-1 antibody (anti-histidyl-tRNA synthetase), which is also classified as a myositis specific autoantibody, is the first antibody that was identified among various anti-ARS antibodies in ASA; anti-ARS antibodies are reported be detected in 20–40% of patients with IIM [ 23 , 24 ]. In the current study, 67 (77.9%) patients were tested for the anti-Jo-1 antibody, and 29.9% of the patients showed anti-Jo-1 positivity, which is in line with previous estimates [ 25 ].…”