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Resident PGY 1
Henry Ford Hospital
Introduction: Hemophagocytic lymphohistiocytosisis (HLH) is a rare and often fatal condition characterized by an overactive but ineffective response of the immune system. There have been several documented causes, which include genetic predisposition, malignancy, infection, autoimmune disease, and chronic immunosuppressive therapy.
Case Presentation: A 42 year-old woman with a two year history of ankylosing spondylitis, who was recently initiated on Infliximab, presented with abdominal pain, fevers, and jaundice. She had a temperature of 104F and a leukocytosis. She was suspected to have acute cholangitis and was initially treated with antibiotics, however, several imaging studies, including ultrasound, HIDA, and MRCP did not appreciate intra or extra hepatic duct dilatation, bile duct wall thickening, or cholelithiasis/choledocholithiasis. She remained febrile and had persistent elevation of her liver enzymes and bilirubin. Her clinical condition worsened, progressing to renal failure, cerebral edema and new onset seizures. Liver biopsy was obtained and demonstrated acute granulomatous hepatitis secondary to fungal organisms, morphologically consistent with histoplasmosis. Further history from the patient revealed that she had been maintaining a chicken coop in her backyard for the past several years. Due to her persistent fevers, cytopenia and a ferritin level of 20,308, the suspicion for HLH continued to grow. Bone marrow biopsy was performed which noted hemophagocytic cells, as well as fungal yeast forms, as seen with use of GMS stain. She met six of the eight diagnostic criteria for HLH based on the Histiocyte Society’s Guidelines (HLH-2004) - [Fever, bi-cytopenia, hypertriglyceridemia, elevated ferritin, elevated soluble IL-2 receptor, and hemophagocytosis on bone marrow biopsy]. It was believed that her HLH was secondary to disseminated histoplasmosis. She was started on liposomal Amphotericin B for treatment of disseminated histoplasmosis, as well as Etoposide and Dexamethasone for treatment of HLH. Her clinical condition improved, and within 3 weeks of initial diagnosis of HLH, she was ultimately discharged with continued treatment with Itraconazole, as well as a four week taper of Dexamethasone.
Discussion: This case illustrates a patient, who after initiation of treatment with an anti-TNF agent for ankylosing spondylitis, developed HLH due to disseminated infection with Histoplasma capsulatum. HLH is an under-recognized, severely aggressive syndrome with high mortality rates. It is typically provoked by disruptions in immune homeostasis, such as infection or immunosuppression. It is most commonly associated to viral infections, Histoplasma is more commonly associated with advanced HIV infection in high endemic areas. Prompt recognition and diagnosis of this disease is crucial to ensure timely treatment, however due to its rarity, and non-specific clinical presentation, this may be of great obstacle.
Kazem, Ahmed and Abreu-Lanfranco, Odaliz, "Chicken Coop-Induced Hemophagocytic Lymphohistiocytosis" (2020). Case Reports. 66.