Severe Fatal Mucormycosis in a Patient with Chronic Lymphocytic Leukaemia Treated with Zanubrutinib: A Case Report and Review of the Literature.

Severe mucormycosis is a fatal disease rarely complicating chronic lymphoproliferative disorders. We present a fulminant and fatal case of a 74-year-old Caucasian woman suffering from CLL treated with second-generation BTK inhibitor zanubrutinib. After a first septic episode a month prior, originating from the lung with later systemic involvement by an unidentified agent and treated with large-spectrum antibiotics and fluconazonle, a slow-onset enlarging tender warm and erythematous nodular swollen cutaneous lesion appeared in her lower limbs and spread subsequently to her upper limbs, progressing towards central ulceration with a necrotic core. Suspecting a mycotic dissemination from an unknown agent, a skin punch biopsy was performed, and intraconazole was started. Due to spread of the skin lesions, the patient was hospitalized and intravenous liposomal ampthotericin B was started. Histopathology showed an atypical sporangium-rich mycotic angioinvasion of the small vessels. Only the increase of BDG and GM could corroborate the hypothesis of mycotic infection. However, long-term CLL, immunosuppressive therapies, neutropenia, and prior use of azoles and other antimycotic agents were risk factors for mucormycosis; BTK inhibitor could also be added as another novel risk factor. Despite all therapeutic efforts, the patient died. Post-mortem molecular exams confirmed the diagnosis of disseminated mucormycosis.