P3C273: Spiraling out of Control: A Case of Histoplasmosis Induced Hemophagocytic Lymphohistiocytosis

Introduction: Histoplasmosis is a fungal infection that is endemic to Ohio and Mississippi River valleys, as well as several regions in Mexico. Although often asymptomatic, histoplasmosis can present with flu-like symptoms or develop into a severe, systemic infection. Infants, those 55 or older, and immunocompromised individuals are at greatest risk for severe infection and additional complications, such as hemophagocytic lymphohistocytosis (HLH).

Case Description: A 15-year-old male with trisomy 21 and hypothyroidism was recently found to be COVID-19 positive and treated for a secondary pneumonia with antibiotics and a five-day course of steroids. He was discharged home with outpatient follow-up. He now presents to the emergency department (ED) with four weeks of abdominal pain and two days of vomiting and fevers. The patient was alert, oriented, and in mild distress. His blood pressure was 69/34; other vitals were normal. He was started on antibiotics on admission to the pediatric intensive care unit for septic shock. His clinical status improved, but he was persistently febrile. On further history, the family had just returned from a 3-week trip to Mexico. It was also discovered that he was recently diagnosed with hidradenitis suppurativa and started on adalimumab. Given his immunosuppression, fungal testing was sent (Table 1). His clinical status started to decline as he became hypotensive and hypothermic, and amphotericin B was added to broad spectrum antibiotics. Histoplasmosis serum and urine antigen were positive, but he did not improve despite anti-fungal therapy. Lab work showed worsening thrombocytopenia and anemia and increasing ferritin and transaminases. Bone marrow biopsy results showed hemophagocytosis (Table 1). This biopsy, along with lab results, confirmed the diagnosis of HLH secondary to disseminated histoplasmosis infection. He was started on steroids and quickly improved, ultimately discharge home two weeks later when he transitioned to oral steroids.

Discussion: HLH is a potentially fatal, rare disorder characterized by uncontrolled immune response to an inciting factor. Genetic conditions and infections are major causes of HLH in children. However, malignancy and rheumatologic conditions, such as systemic juvenile idiopathic arthritis (sJIA), are additional inciting factors to consider. There are reported cases of HLH caused by histoplasmosis, primarily in immunocompromised patients with disseminated infections. Treatment includes steroids and a standardized chemotherapy regimen while also identifying the inciting cause. In severe cases such as multiple recurrent episodes or genetic risk factors a bone marrow transplant may be considered.

Conclusion: This case emphasizes the importance of a high index of suspicion for the diagnosis of HLH as it can mimic many conditions. Additionally, it highlights the importance of obtaining a through history and maintaining a broad differential, especially when a patient is reacting to treatment as expected.