A Cytokine Storm in Fungal Infection: Disseminated Histoplasmosis-Induced Hemophagocytic Lymphohistiocytosis in a Kidney Transplant Recipient

Introduction: Hemophagocytic lympho-histiocytosis (HLH) is a rare clinical condition. HLH is characterized by dysregulated immune activity resulting in malignant inflammation and multiorgan failure. HLH presents as two distinct entities. Primary HLH is an autosomal recessive disorder presenting in childhood. Secondary HLH is triggered by immune insults such as infections or autoimmune disorders. HLH, as a rare complication after kidney, liver, and hematopoietic stem cell transplants, has been described in the literature. We present a case of HLH in a patient with 2nd deceased donor kidney transplant (DDKT) triggered by disseminated histoplasmosis (DH). Case Description: A 27-year-old African American female with end-stage kidney disease (ESKD) due to Lupus nephritis who received her second renal transplant presented with fevers and headaches for one week. Before admission, she had multiple ED visits for intermittent fevers, abdominal pain, and weakness and was treated empirically with IV antibiotics followed by oral Keflex with no benefit. On admission, given elevated temperature, cytopenia, elevated ferritin and triglycerides, low fibrinogen, and elevated soluble IL2 receptor (see attached lab trends below), a provisional diagnosis of HLH was made based on 2004 diagnostic criteria. The patient was started on itraconazole and anakinra. On the 9th day of admission, she was noted to have gaze deviation, and a CT scan of the brain showed a subarachnoid hemorrhage with cerebral edema. Neurosurgery was consulted and an EVD was placed. Despite all supportive efforts and interventions, the patient continued to deteriorate and expired on the 10th day of admission. Discussion: HLH is a rare disease and should be suspected in patients with fever, cytopenia, and ferritin > 500 µg/L. A high index of suspicion is warranted in the clinical context of immunosuppression and unrelenting fevers. Secondary HLH has a very poor prognosis and an extremely high fatality rate. Early diagnosis with multidisciplinary care involving infectious disease and hematology services can potentially lead to improved outcomes.