Refractory Chronic Penicilliosis in a Patient Under Prolonged Immunosuppression: A Case Report

A 58-year-old woman with myasthenia gravis on chronic high-dose prednisone and a history of azathioprine, mycophenolate, and cyclophosphamide had multiple hospitalizations for myasthenic crises and opportunistic diseases such as cytomegalovirus uveitis and oroesophageal candidiasis. In 2024, she developed a cutaneous condition on the left upper limb, with extensive necrotic crusts and subcutaneous nodules with surrounding hyperemia. On 11/22/2024, biopsy of the lesions showed Penicillium spp. in culture, establishing chronic penicilliosis. She started liposomal amphotericin B followed by itraconazole, with unsatisfactory clinical response, requiring adjustment to voriconazole with serum level monitoring until reaching an adequate therapeutic dose. Invasive Penicillium spp. infections are rare in immunodeficient patients but are associated with high morbidity and mortality. Treatment guidelines for Talaromyces (Penicillium) marneffei, the best-studied pathogenic species in the genus, recommend induction with amphotericin B and maintenance with itraconazole, reserving voriconazole for refractory cases. Studies in HIV-positive patients show efficacy above 95% with this regimen; however, other species have a worse prognosis, lower cure rates, and greater need for combination therapy. In this case, persistence of infection despite antifungal management reinforces the chronic and refractory nature of penicilliosis in the setting of sustained immunosuppression. After attempts to taper prednisone, she developed a myasthenic crisis requiring noninvasive ventilation in intensive care. Prolonged antifungal therapy follows international recommendations, but immunologic stabilization is essential for definitive control. This case illustrates the complexity of treating rare mycoses in non-HIV immunosuppressed patients, requiring mycological surveillance, precise pathogen identification, and a multidisciplinary approach. Limited clinical response underscores the need for integrated strategies using second-line antifungals, immunomodulation, and ongoing clinical support. Penicilliosis is an emerging opportunistic infection, of low prevalence and difficult to control, with clinical presentations often underestimated and adverse outcomes, especially in contexts of immune fragility.