Unusual Case of Granulomatosis with Polyangiitis Complicated with Hormographilella aspergillata Skin Infection

Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated small-vessel vasculitis that predominantly affects the respiratory tract and kidneys, while cutaneous manifestations occur less frequently. Opportunistic fungal infections complicating GPA are uncommon, particularly involving rare filamentous basidiomycetes. We describe a 32-year-old male with a prolonged history of crusting rhinitis, tinnitus, and progressive nodular and ulcerative skin lesions on the trunk and extremities, accompanied by fever and lower limb edema. Laboratory evaluation revealed elevated inflammatory markers and positive c-ANCA (anti-PR3). Histopathology demonstrated granulomatous inflammation consistent with GPA. The clinical course was complicated by a secondary cutaneous infection caused by Hormographiella aspergillata, isolated from a skin lesion. Initial antifungal therapy with itraconazole was ineffective; subsequent treatment with voriconazole resulted in resolution of the fungal infection. The patient was then successfully treated with systemic immunosuppressive therapy, achieving long-term remission. To our knowledge, this is the first reported case of GPA complicated by a cutaneous infection with H. aspergillata. This case highlights the diagnostic challenges of GPA with atypical skin manifestations and underscores the importance of microbiological evaluation of skin lesions prior to initiating aggressive immunosuppressive therapy. KEYWORDS: granulomatosis with polyangiitis; ANCA-associated vasculitis; Hormographiella aspergillata; opportunistic fungal infection Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis, is a necrotizing granulomatous vasculitis affecting small to medium-sized blood vessels and belonging to the group of ANCA-associated vasculitides (AAV) (1). The disease is characterized by granulomatous inflammation, necrotizing vasculitis, and the presence of antineutrophil cytoplasmic antibodies, most commonly proteinase-3 ANCA (PR3-ANCA) (2). GPA may involve virtually any organ system, with predominant involvement of the upper and lower respiratory tract and kidneys (3). Cutaneous manifestations are reported in approximately 30-50% of patients and are usually associated with systemic disease activity (4). Opportunistic infections may complicate the course of GPA, particularly in the context of delayed diagnosis or immunosuppressive therapy. Infections caused by rare filamentous fungi such as Hormographiella (H) aspergillata are exceptionally rare and have predominantly been reported in immunocompromised patients with hematological malignancies (5, 6). A 32-year-old male was admitted with multiple painful ulcerations and nodules on the trunk and extremities, accompanied by high fever and marked bilateral lower limb edema. Four months before admission, nodular lesions on the left auricle and right nipple regressed spontaneously after purulent discharge. Six weeks prior to referral, painless nodules on the back and right upper arm were surgically incised and treated with antibiotics, followed by clinical deterioration with fever, progressive ulcerations, and painful swelling of the feet and ankles (figures 1a and !b). The patient had a two-year history of nasal obstruction, crusting rhinitis, and intermittent right-sided tinnitus. Rhinoscopy revealed mucosal thickening and septal perforation with crusts and synechiae. Dermatological examination showed deep ulcerations with yellow-brown crusts on the back, right upper arm, and left cheek (figures 1a and 1b). Laboratory evaluation demonstrated elevated inflammatory markers (ESR 76 mm/h, CRP 47.4 mg/L), hypoalbuminemia, and positive c-ANCA (anti-PR3). Initial microbiological cultures were sterile. Histopathology revealed granulomatous panniculitis with abscess formation. Fungal culture isolated H. aspergillata. Itraconazole therapy was ineffective; subsequent voriconazole treatment led to complete resolution of the cutaneous infection. Due to persistent systemic inflammation and c-ANCA positivity, the patient was treated with high-dose glucocorticoids and cyclophosphamide, which gradually led to completely remission of skin lesions (figure 2). Renal involvement developed during treatment, manifested as proteinuria. Long-term immunosuppressive therapy resulted in sustained remission with mild residual renal impairment. GPA is a rare multisystem autoimmune disease with heterogeneous clinical presentation, often leading to delayed diagnosis. Cutaneous involvement may be the initial manifestation and includes purpura, nodules, necrosis, and ulcerations, reflecting underlying vasculitis and granulomatous processes (2). In our patient, prominent skin lesions preceded the diagnosis by several months and contributed to diagnostic uncertainty. Opportunistic infections are a recognized complication in GPA, particularly following immunosuppression; however, fungal infections caused by filamentous basidiomycetes are exceedingly rare (5, 6). Hormographiella aspergillata, the anamorphic form of Coprinopsis cinerea, is an environmental fungus that has been implicated almost exclusively in invasive infections in patients with hematological malignancies, with reported mortality rates up to 70% (5, 6). To our knowledge, no previous case of GPA complicated by cutaneous infection with H. aspergillata has been reported. The present case underscores the importance of thorough microbiological evaluation of atypical or non-healing skin lesions in patients with suspected systemic vasculitis, particularly before initiation of intensive immunosuppressive therapy. Failure to recognize opportunistic infections may lead to significant morbidity and mortality. This case emphasizes the crucial role of dermatologists in the early recognition of systemic vasculitis presenting with skin manifestations. Comprehensive clinical, histological, and microbiological assessment is essential to establish the correct diagnosis and to identify rare infectious complications. Multidisciplinary management and careful monitoring are necessary to achieve long-term remission and to minimize treatment-related complications.