Case Presentation:
A 52 year old Haitian woman was admitted for right leg cellulitis with a hyperpigmented lesion and recurrent fever for the last 3 weeks after failed oral antibiotic treatment. During the first few weeks of hospitalization, she received multiple intravenous broad spectrum antibiotics without improving her fever or cellulitis. She further developed altered mental status, pancytopenia, renal failure, respiratory failure, severe acidosis and required intubation, mechanical ventilation, and hemodialysis. She was evaluated by multiple specialty physicians including infectious disease, hematology, dermatology, gastroenterology, nephrology and rhueumatology. She underwent an extensive work up including various imaging studies, blood tests, lumbar puncture, bone marrow biopsy, renal biopsy, skin biopsy and tests including fungal, tuberculosis, and bacterial infections. All results were negative. HLH with multi‐organ failure was suspected when she had recurrent fever, hepatospleenomegaly, increased ferritin, triglyceride levels and low fibrinogen levels in spite of the available treatment. EBV and cytomegalovirus titers were ordered. PCR results for EBV were positive with 1 million copies. The HLH‐94 protocol was followed. She then received intravenous immunoglobulin, steroids, etoposide, and rituximab. Her clinical condition including mental status and skin lesions improved. She no longer required mechanical ventilation and hemodialysis. Her liver plus renal functions normalized with decreased EBV PCR copies (1 million to 300), ferritin levels (54376 to 2918 ng/mL), and triglyceride levels (264 to 118 mg/dL).Genetic testing results were sent to a specialized center to confirm primary versus secondary HLH.
Discussion:
HLH is a condition in which T cells, natural killer cells, and macrophages are aberrantly activated, resulting in hypercytokinemia, cellular damage and multi‐organ failure. It is characterized by prolonged fever, hepatospleenomegaly, cytopenia, coagulopathy, hypertriglyceridemia, and erythrophagocytosis in the bone marrow. In this patient, diagnosis was delayed as it resembled like sever sepsis. However, she improved with treatment but developed necrotizing pneumonia, febrile neutropenia. She died after 5 weeks and 3 days of chemotherapy due to septic shock and ST elevation myocardial infarction.
Conclusions:
HLH is an aggressive and life‐threatening syndrome of excessive immune activation causing multi‐organ failure. Prompt initiation of treatment is essential for the survival of affected patients. In 20% of cases, bone marrow biopsy is negative. Often the greatest barrier to a successful outcome is a delay in diagnosis, which is difficult because of the rarity of this syndrome, the variable clinical presentation, and the lack of specificity of the clinical and laboratory findings.