Case Presentation: 19 month old female with a history of unspecified T- cell immunodeficiency presented with a 10 day history of cough, fatigue, and persistent fevers. The patient had just returned from Mexico and reportedly was diagnosed with influenza there. Previously the patient had been on Bactrim prophylaxis, but ran out of it while in Mexico and had not been on it for the past 6 months. On admission, patient was febrile, nontoxic but tired appearing with dry mucous membranes and diffuse crackles bilaterally and required oxygen via nasal cannula. Pertinent laboratory findings include pancytopenia (WBC 3.9 k/cmm, Hb 8.7 g/dL, platelet 54 k/cmm), transaminitis (AST 497 unit/L, ALT 321 unit/L), CRP 70 mg/L, and procalcitonin 1.01 ng/mL. Initial chest x-ray showed no findings of pneumonia, however when repeated 7 days later, it showed a patchy opacity at the right lung base. Abdominal US was negative. CT chest, abdomen, and pelvis was significant for a small right pleural effusion with patchy right middle lobe and lingular opacities with mild perihilar lymphadenopathy bilaterally. Extensive workup was undertaken including T spot, HIV, Fungitell, titers for CMV, EBV, Typhus, Brucella, Coccidiomycosis, Cryptococcus and Toxoplasmosis, CSF cell counts and culture, flow cytometry, bone marrow aspirate and bronchoalveolar lavage with routine cultures and PCR testing for HSV, CMV and Pneumocystis jerovecii pneumonia, all of which resulted as negative. Serum IgM and IgG Histoplasmosis and urine Histoplasma antigen resulted positive, after which the patient was started on Amphotericin B and Itraconazole.
Discussion: Disseminated Histoplasmosis is a rare occurrence in the pediatric population and is defined by uncontrolled growth of Histoplasma capsulatum in multiple organs. Immunosuppression increases the risk of disseminated disease. Among 83 reported cases of pediatric Histoplasmosis, primary immunodeficiency was a common underlying condition. Patients with disseminated Histoplasmosis present with nonspecific constitutional symptoms, making the disease difficult to identify and diagnose. Fever, weight loss, and cough were the most reported symptoms, and lymphadenopathy and hepatosplenomegaly were the most common physical exam findings. Histoplasmosis infections are commonly seen with pancytopenia. In an immunosuppressed child with persistent fevers, our initial differential diagnosis was broad, including tuberculosis, malignancy, hemophagocytic lymph histiocytosis, Pneumocystis jiroveci pneumonia, and other opportunistic fungal infections. An unremarkable physical examination should not exclude disseminated Histoplasmosis and should always be considered higher in the differential in a patient with a history of a primary immunodeficiency or travel to an endemic area, including central and eastern North America, Central and South America, Africa, Southeast Asia, and Australia.
Conclusions: Most Histoplasmosis infections are asymptomatic or self-limited, but some patients develop acute pulmonary infections or severe disseminated infection. Disseminated Histoplasmosis occurs in two forms, acute and chronic. Acute infection is mostly seen in infants and heavily immunocompromised patients. T cell immunity plays a major role in recovering from Histoplasmosis. Our patient’s age in addition to her history of T-cell immunodeficiency creates the perfect reservoir for disseminated Histoplasmosis.