LAUSR

A 75-year-old female with multiple myeloma on fourth line treatment with bortezomib, cyclophosphamide and dexamethasone (VCD), complained of headaches, confusion and fluctuating drowsiness over 2 weeks. Significant investigations showed: neutrophils 0 8 9 10/l, platelet count 109 9 10/l, C reactive protein (CRP) <1 mg/l (normal <5) and normal cerebral computed tomography (CT) and magnetic resonance imaging (MRI) scans. Cerebrospinal fluid (CSF) was acellular with a raised protein (2477 mg/l; normal 150–400), a negative Gram stain and no bacterial growth on culture. Subsequent tests showed a positive cryptococcal antigen (CrAg) test in CSF at 1/1280 and in serum at 1/640 dilution. CD4 and CD8 count was 0 141 9 10/l (0 404–1 612) and 0 789 9 10/l (0 220–1 129), respectively, and serology for human immunodeficiency virus (HIV) 1 and 2 was negative. The patient was treated with liposomal amphotericin plus flucytosine intravenously and then consolidated with high dose fluconazole. She initially improved but relapsed on fluconazole with recurrent confusion 10 weeks later. At this time an MRI scan showed marked parenchymal inflammation with bi-hemispheric white matter signal change (left). A bone marrow aspirate showed relapsed myeloma. After initial improvement on further liposomal amphotericin and flucytosine, she deteriorated and died. A 79-year-old male with immunoglobulin M myeloma on sixth line treatment with pomalidomide and dexamethasone was admitted with cough and fever. Significant investigations were: total nucleated cell count 4 1 9 10/l, neutrophils 0 8 9 10/l, platelet count 45 9 10/l, haemoglobin concentration 94 g/l, CRP 60 mg/l, paraprotein rising to 19 g/l, CD4 0 108 9 10/l, CD8 0 789 9 10/l, HIV 1 and 2 negative. The fever failed to settle on two lines of broad-spectrum antibiotics. On the fourth day the blood culture grew Cryptococcus neoformans with the typical ‘double membrane’ appearance on India ink staining and budding demonstrated (right). The peripheral blood film showed plasma cell leukaemia with 32% of nucleated cells being plasma cells. His fever responded to liposomal amphotericin B and flucytosine, followed subsequently with high dose fluconazole. Unfortunately, his myeloma was progressing and the patient died 5 weeks later. Human cryptococcal infection, usually with C. neoformans, is most commonly seen in HIV-positive individuals. Low CD4 counts are a risk factor. Cryptococcal infection is increasingly reported in HIV-negative patients on novel immunosuppressive treatments for cancer and connective tissue disorders and mortality is high. The organism usually enters through the lungs, spreads via the blood stream and seeds within the central nervous system causing a meningoencephalitis. In myeloma, CD4 cell counts fall with progression of the disease and successive therapies. Cryptococcal infection in myeloma has rarely been reported, but our cases highlight the increasing spectrum of atypical infections seen in late stage myeloma patients treated with novel immunosuppressive therapies and high dose corticosteroids. CT and MRI findings in cryptococcal infection are often non-specific, especially at presentation, and the key to diagnosis is to ‘consider it’ and request a CrAg test.