A Unique Case of Cryptococcus and Histoplasmosis Co-infection in an HIV-negative Male on Chronic Steroid Therapy

Abstract

Introduction Histoplasmosis and cryptococcosis are systemic fungal diseases frequently encountered in immunocompromised hosts, particularly in patients with HIV with low CD4 counts. However, co-infection with histoplasmosis and cryptococcosis is an uncommon clinical scenario.Considering that patients having these co-infections are mostly immunocompromised individuals, an overlooked diagnosis will inevitably delay care and worsen prognosis. Here we present a case of an elderly, HIV-negative gentleman who was diagnosed with a synchronous pulmonary cryptococcosis and histoplasmosis. Case report A 71-year-old gentleman with Myasthenia gravis (MG) and type 2 diabetes mellitus was evaluated for chest pain with dyspnea. He was afebrile with bibasilar crackles on physical examination. He had a white cell count of 11,300mm3 with 95% neutrophilic predominance. Creatinine was 1.0 mg/dl. A CT chest angiogram showed multifocal infiltrates in all lung lobes. Patient tested negative for HIV. Broadspectrum antibiotics including vancomycin, piperacillin-tazobactam, and ciprofloxacin were started. His treatment regimen for MG included prednisone 20 mg daily, mycophenolate 1000 mg twice daily and intravenous immunoglobulins (IVIG) every 4 weeks, along with pyridostigmine. Bronchoscopy was performed to rule out atypical infections. Urinary streptococcal, histoplasmosis and legionella antigens were ordered. Viral respiratory PCR testing, bacterial, fungal and acid-fast bacilli (AFB) cultures were performed on the bronchoalveolar lavage (BAL). He was discharged home after completion of antibiotic therapy. He was re-admitted within a week with acute hypoxemic respiratory failure. Repeat CT chest angiogram showed diffuse nodular infiltrates with worsening despite recent antimicrobial therapy. Results from recent BAL returned positive for histoplasma antigen; silver stain was positive for budding yeast, subsequently identified as Cryptococcus. Urine histoplasma antigen returned positive as well. Infectious disease team was consulted. Intravenous liposomal amphotericin B was started for disseminated histoplasmosis with pulmonary manifestation. Serum cryptococcal antigen was positive. Cerebrospinal fluid (CSF) cryptococcal antigen and cultures remained negative. Amphotericin was continued for 1 week until acute kidney injury occurred with doubling of creatinine to 2.1 mg/dl. Patient was transitioned to fluconazole.Discussion: Literature review from 1940 to date on PubMed and Medline, revealed only 11 prior reported cases of cryptococcosis-histoplasmosis co-infection.All but three of these were associated with HIV with low CD4 counts.1 Of cases not associated with HIV, one patient was diabetic; second was diabetic on steroids for autoimmune thrombocytopenia; no risk factors were identified in the third case. Both infections are acquired via inhalation. An intact immune system usually controls the infection.2 For Cryptococcus, about 40% infected individuals develop pulmonary symptoms; in less than 1% cases, there is dissemination to meninges, bones, joints, skin or soft tissues3 with meningoencephalitis being the most common extra-thoracic manifestation. Histoplasmosis is usually asymptomatic in immunocompetent patients; however, in cases of immunodeficiency, 95% patients develop symptomatic infection.4 All medicine practitioners frequently manage patients with immunocompromised states: chronic steroid therapy for multiple disease states such as rheumatoid arthritis, elderly, solid organ transplant recipients or patients with hematological malignancies as well as HIV. Co-infections are rare; diagnosis of one fungal disease may result in inadequate evaluation and failure to diagnose the other. Management in such complicated situations may require specialty referrals. Hence, it is important to report these cases for the knowledge of all general practitioners.