A Diagnostic Dilemma of a Case of Granulomatosis With Polyangiitis (GPA) Presenting With Thrombotic Vasculopathy

Granulomatosis with polyangiitis (GPA) is a rare disease with a prevalence of about three in 100,000 persons in the United States. GPA is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis affecting predominantly small-sized vessels. It can present with localized or systemic symptoms with multiple organ involvement, thus making diagnosis challenging. Common skin lesions in GPA are palpable purpura, petechiae, ulcers, and livedo reticularis. These lesions usually have underlying vasculitis with or without granuloma on histology findings. To date, there have been no previous reports about thrombotic vasculopathy in GPA before. We present a case of a 25-year-old female who presented with intermittent joint pain for weeks, purpuric rash, and mild hemoptysis for a few days. A review of systems was notable for a 15-pound weight loss in one year. Physical examination was significant for a purpuric rash on the left elbow and toe, and left knee swelling and erythema. Presenting laboratory results were notable for anemia, indirect hyperbilirubinemia, mildly elevated D-dimers, and microscopic hematuria. Chest radiograph revealed confluent airspace disease. Extensive infectious workup was negative. A skin biopsy of her left toe revealed dermal intravascular thrombi without evidence of vasculitis. The thrombotic vasculopathy did not favor vasculitis but raised concern for a hypercoagulable state. However, extensive hematologic workup was negative. Bronchoscopy findings were consistent with diffuse alveolar hemorrhage. Later, cytoplasmic ANCA (c-ANCA) and anti-proteinase 3 (PR3) antibody titers were positive. Her diagnosis was unclear since both skin biopsy and bronchoscopy were nonspecific and inconsistent with her positive antibody results. The patient eventually underwent a kidney biopsy, which showed pauci-immune necrotizing and crescentic glomerulonephritis. Finally, a diagnosis of granulomatosis with polyangiitis was made based on the kidney biopsy and positive c-ANCA. The patient was treated with steroids and IV rituximab and discharged home with outpatient rheumatology follow-up. Due to multiple signs and symptoms including thrombotic vasculopathy, there was a diagnostic dilemma requiring a multidisciplinary approach. This case highlights the importance of pattern recognition for the diagnostic framework of rare disease entities and the multidisciplinary collaborative efforts required to reach the final diagnosis.