A Unique Case of Granulomatosis with Polyangiitis Presenting with Proximal Muscle Weakness

Abstract Granulomatosis with polyangiitis (GPA) is a subtype of ANCA-associated vasculitis that can have a heterogeneous clinical presentation. Although classically involving the respiratory tract and kidneys, GPA can rarely present with predominant skeletal muscle involvement. This is unique given that skeletal muscle involvement has predominantly been associated with eosinophilic GPA and microscopic polyangiitis in the literature. Here, we detail a patient who presented with acute, progressive bilateral proximal lower extremity weakness and thigh pain, along with weight loss and transiently elevated creatine kinase and aldolase. The clinical course was complicated by temporally distinct focal cerebral infarctions, alongside findings of rhinosinusitis and multiple pulmonary nodules. Serology was positive for PR3-ANCA antibodies, and magnetic resonance angiography of the brain utilising black blood sequence confirmed central nervous system (CNS) vasculitis. Crucially, targeted biopsies of the right vastus lateralis and lung nodule demonstrated fibrinoid necrosis and necrotizing granulomatous inflammation, respectively. Together, this histopathological evidence strongly suggests the proximal myopathy and CNS infarction as the result of profound, systemic microvascular ischaemia. This case highlights that GPA may initially manifest as muscle weakness. Recognising this atypical presentation is crucial to ensure timely initiation of treatment to reduce disease-associated morbidity and mortality.