Cryptococcal Meningitis Presenting as a Fever of Unknown Origin Following Immunosuppressive Therapy for Autoimmune Hepatitis

Abstract

Introduction: Cryptococcus neoformans (C.N) is an opportunistic pathogen causing chronic meningitis in immunocompromised patients. The diagnosis is often missed or delayed in these patients because of the non-specific clinical features, limited usefulness of available serological tests, and failure to isolate CN in blood cultures, positive in less than one third of patients. Case Report: A 20-year-old female with congenital arthrogryposis presented with ascites, lower extremity edema, jaundice, coagulopathy and an autoantibody profile of autoimmune hepatitis. Diagnostic liver biopsy was followed by asymptomatic temp. to 103 F and the patient admitted for observation. An extensive fever workup during a 10 ten hospitalization was negative. She was readmitted one week with lethargy, confusion, bradycardia and recurrent fever. Medications included:Prednisone 7.5 mg daily and Immuran 100 mg daily for treatment of autoimmune hepatitis. P.E. revealed a febrile somnolent cushingoid female without focal neurologic or abdominal findings. Labs revealed coagulopathy secondary to liver dysfunction. On the second day of hospitalization, blood cultures were notable for a fungal species. She rapidly developed severe headache, vomiting, disconjugate gaze and meningismus. A lumbar puncture showed increased ICP and India ink staining of the CSF and spinal fluid and blood cultures confirmed the diagnosis of Cryptococcal meningitis. The patient was treated with Amphotericin B and 5-Flucytosine. Multiple lumbar drainages were required to control increased ICP. She made a complete neurological recovery. Discussion: Patients on immunosuppressive therapy are at increased risk for cryptococcal diseases. Cirrhosis may be an additional predisposing factor by impairment of host defenses including complement deficiency, defects in neutrophil chemotaxis, and lymphocyte hyporesponsiveness. To our knowledge, the diagnosis of disseminated Cryptococcosis by blood cultures in a patient with Autoimmune Hepatitis has not been described previously. This case demonstrates that prolonged fever and therapy with corticosteroids and immunomodulators should raise concern for emerging disseminated Cryptococcal disease. The acute and atypical clinical manifestations in our patient indicate the importance of early consideration of this disease as clinical deterioration and death may be precipitous.