Case Presentation: A 27-year-old incarcerated female with no past medical history presented with abdominal pain and fevers. Initial workup demonstrated neutropenia, anemia, and thrombocytopenia as well as an elevated ferritin level of 2000mg/dL. Abdominal imaging revealed hepatomegaly and diffuse adenopathy concerning for a lymphoproliferative disorder. A comprehensive workup revealed a positive EBV PCR, positive HSV on BAL, negative bone marrow and lymph node biopsies, and a positive autoimmune evaluation with hypocomplementemia and positive antibodies, and eventually a renal biopsy was consistent with lupus nephritis class IV and V. Her condition rapidly deteriorated and included multi-organ failure requiring mechanical ventilation and hemodialysis. Repeat labs at that time demonstrated a ferritin of >40,000ng/mL, elevated transaminases and bilirubin, and a suppressed fibrinogen. Given her clinical presentation of fevers, markedly elevated ferritin, and liver dysfunction in the setting of two acute infections and newly diagnosed lupus, she was clinically diagnosed with HLH and started on etoposide while treating her underlying conditions with improvement.
Discussion: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome characterized by marked dysregulation of the immune system. Although rare in adults, it is associated with infections, autoimmune diseases, and malignancy. Here, we present a complicated case of HLH in the setting of systemic lupus erythematosus (SLE) and coinfection with EBV and HSV. The prevalence of HLH alone in the adult population has not been reported due its rarity. While the exact etiology can be difficult to determine, clinicians must be thorough and systematic in their approach to doing so as treatment of the driving condition is paramount. The prevalence of HLH in conjunction with SLE is estimated at 0.9-4.6%, and far less when also present in the setting of acute EBV and HSV. Our determination that EBV and HSV were contributing factors to the development of HLH are supported by the worsening of her condition and rapid rise in ferritin despite proper treatment for acute SLE.
Conclusions: HLH is a clinical diagnosis which should be considered when several of the diagnostic criteria are present, however the diagnosis can be difficult in the setting of SLE which has some clinical overlap. Like in our patient, ferritin greater than 500 mg/dL is considered the most important marker that differentiates HLH from SLE and has a high sensitivity and 100% specificity. This unusual presentation of HLH in the setting of both lupus and active viral infections illustrates how imperative it is that clinicians maintain a high suspicion for HLH. Due to the clinical overlap, HLH can often be missed and has a high mortality rate of 40% despite appropriate treatment.