Case Presentation: A 21-year-old man with well-controlled ulcerative colitis (UC) on mesalamine and chronic vaping presented with rapidly progressive ischemia of all digits. Symptoms began after an upper-respiratory illness followed by abdominal pain and hematochezia. Evaluation revealed normal platelets, elevated inflammatory markers, preserved renal function with mild proteinuria and microscopic hematuria, increased reticulocyte count, rising LDH, and low haptoglobin. Endoscopy showed normal colonic mucosa without active, chronic, or microscopic colitis. Serologies showed c-ANCA positivity, and chest CT revealed bilateral ground-glass opacities, prompting evaluation for ANCA-associated vasculitis.Skin biopsy demonstrated epidermal necrosis, dermal fibrosis, and small-vessel thrombotic occlusions without leukocytoclastic vasculitis. Schistocytes subsequently developed. ADAMTS13 activity, C3, and C4 were normal. Evaluation identified glucose-6-phosphate dehydrogenase (G6PD) deficiency, and respiratory PCR confirmed enterovirus/rhinovirus infection. Cytokine profiling showed elevated IL-6 and IFN-γ. Renal biopsy confirmed acute thrombotic microangiopathy (TMA). Despite treatment with high-dose corticosteroids, oral and topical vasodilators, and botulinum toxin injections, digital ischemia progressed to dry gangrene, ultimately requiring upper-digit and bilateral Lisfranc amputations.
Discussion: Acquired atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening complement-mediated TMA that can be triggered by viral infections through uncontrolled alternative-pathway activation and cytokine-driven endothelial injury. Enterovirus is a recognized trigger of acquired aHUS, and concurrent rhinovirus infection may synergistically enhance endothelial vulnerability. In this young athlete, G6PD deficiency and vaping-related oxidative stress likely increased endothelial susceptibility, while UC served as an additional complement-amplifying condition. These factors supported a diagnosis of viral-triggered aHUS resulting in severe microvascular thrombosis and tissue necrosis. Confounding c-ANCA positivity, notable urine sediment, abnormal chest CT, and delayed appearance of schistocytes mimicked ANCA-associated vasculitis and contributed to diagnostic uncertainty. Preserved renal function and normal platelets do not exclude complement-mediated TMA, particularly in evolving or partially treated disease.
Conclusions: This case represents the first reported instance of enterovirus/rhinovirus–triggered aHUS in a patient with UC, G6PD deficiency, and chronic vaping. Vasculitis mimicry despite positive serologies and overlapping features underscores the importance of early recognition of viral-triggered complement activation. Prompt identification may allow for timely escalation to complement-directed therapies, potentially altering outcomes in similarly refractory cases.
.png)
.png)