Unilateral lower limb cellulitis-like edema as an atypical cutaneous manifestation of antisynthetase syndrome: a case report and targeted literature review.

BACKGROUND: Antisynthetase syndrome (ASyS) is a distinct subtype of idiopathic inflammatory myopathy (IIM), characterized by multisystem involvement, including the lungs, skin, skeletal muscles, and joints, as well as the presence of anti-aminoacyl-tRNA synthetase (ARS) antibodies. While 8% to 30% of patients present with classic dermatomyositis-like rashes, atypical skin involvement can also occur. Rarely, patients may develop cutaneous edema that mimics cellulitis, which is highly susceptible to misdiagnosis. CASE PRESENTATION: A 72-year-old woman presented with a 1-week history of erythema, swelling, and pain in the right lower limb. Physical examination showed marked edema with a peau d'orange appearance, local warmth, and tenderness. Given the detection of fungal hyphae on the right foot, cellulitis was initially suspected. However, the lesions did not improve after 5 days of cefuroxime sodium treatment, and she developed right gastrocnemius tenderness, markedly elevated muscle enzymes, and interstitial changes on chest computed tomography. Myositis antibody testing was positive for anti-melanoma differentiation-associated gene 5(anti-MDA5) and anti-histidyl-tRNA synthetase(anti-Jo-1) antibodies. Right gastrocnemius biopsy showed fiber-size variation and scattered endomysial inflammatory infiltration, without necrosis or perifascicular atrophy; immunohistochemistry showed focal/patchy major histocompatibility complex class I (MHC-I) expression and weak non-perifascicular sarcoplasmic myxovirus resistance protein A (MxA) positivity. Antisynthetase syndrome was diagnosed. Moderate-dose oral prednisone was added and cefuroxime sodium was discontinued. Eight days later, erythema, swelling, and myalgia improved, with marked decreases in muscle enzymes and hypersensitive C-reactive protein(hs-CRP). After discharge, mycophenolate mofetil(MMF) and nintedanib were added. Three months later, the skin lesions had completely resolved, creatine kinase, lactate dehydrogenase, high-sensitivity troponin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) nearly normalized; interstitial lung disease (ILD) improved, and pleural/pericardial effusions markedly decreased. DISCUSSION: Notably, this case highlights that ASyS may mimic infectious cellulitis and cause misdiagnosis. Inflammatory myopathy should be considered when atypical skin lesions are accompanied by elevated muscle enzymes and ILD.