Case Presentation: A 6-week-old female presented to the emergency room with one day of fever associated with emesis, decreased urine output and fussiness. Initial evaluation included a normal urinalysis, no leukocytosis, mild thrombocytopenia and a mildly elevated procalcitonin. Ultrasound of the pylorus was normal. She was admitted for evaluation of sepsis and started on empiric antibiotics. On admission, she was noted to have had poor weight gain since birth, having gained only 12 grams per day. Exam was notable for a small infant with mild hepatomegaly. She continued to spike intermittent fevers, yet she remained well-appearing and hemodynamically stable. Given the hepatomegaly, a hepatic profile was obtained showing an AST of 1451 units/L, ALT of 597 units/L, total bilirubin of 2.7 mg/dL (direct 2.0 mg/dL) and an elevated GGT of 482 units/L. Hepatology was consulted with subsequent ultrasound showing an enlarged liver and spleen but no other anatomic abnormalities. Coagulopathy was also noted with an INR of 1.94, which did not improve after administration of Vitamin K.. Fibrinogen level was undetectable, and repeat CBC showed interval development of pancytopenia. This constellation of findings raised concern for hemophagocytic lymphohistiocytosis (HLH). Oncology and Infectious Disease were consulted. Viral testing, including HIV, was negative with the exception of a positive HHV-6 serum PCR. Ferritin and soluble IL-2 receptor were each markedly elevated. Triglycerides were normal. Testing for primary HLH resulted negative. Final diagnosis of disseminated histoplasmosis was established with a positive urine antigen test. Maternal testing for histoplasmosis infection was negative, suggesting infection from exposure to a large inoculum of fungus.

Discussion: Disseminated histoplasmosis is uncommon in pediatrics, especially in immunocompetent patients, although infants are at higher risk for invasive disease. Infection can often present with non-specific signs, such as fever and weight loss. Although the disease can have an indolent course, laboratory evaluation can be quite striking and have overlap with serious inflammatory conditions, such as HLH. One study estimates up to a 50% mortality rate for affected infants. Treatment is two weeks of Amphotericin B followed by three months of itraconazole.

Conclusions: Neonatal fever is a common problem for pediatric hospitalists. Attention should be given to history or exam findings that stand out, such as poor weight gain and hepatomegaly, as in this case. Although rare, histoplasmosis can be a cause of significant liver injury and severe inflammation in infants living in endemic regions. Prompt recognition is necessary due to the associated mortality risk. Diagnosis should also involve consideration of vertical transmission from maternal infection, as well as further evaluation of a possible immunodeficiency.