An Atypical case of Hemophagocytic Lymphohistiocytosis possibly secondary to Systemic Lupus Erythematosus Flare in a Female Patient

Hemophagocytic Lymphohistiocytosis (HLH) is a rare autoimmune disease in which histiocytes and lymphocytes attack the body’s own resulting in severe fever, organ damage, and pancytopenia. Initial signs and symptoms of HLH can mimic common infections, malignancy, hepatitis, or encephalitis making it difficult to distinguish.

Case Presentation:

A 33-year-old female presented to the hospital for daily recurrent fevers ongoing for 2 weeks. Four weeks prior, patient underwent a dilatation and curettage procedure for a molar pregnancy. Patient endorses 5 kg unintentional weight loss, heavy night sweats, nausea, vomiting, and chills. She immigrated to the U.S. from Nepal three years prior.

Upon admission, her labs were significant for pancytopenia. Her physical exam was significant for bilateral axillary lymphadenopathy. She was subsequently started on broad-spectrum antibiotics due to concern for possible endometritis. All infectious workup was unremarkable. After 5 days of antibiotic treatment, she continued having cyclical fevers without resolution of symptoms.

CT imaging revealed bilateral lymphadenopathy that was concerning for possible malignancy. Her lymph node biopsy was significant for necrotizing granulomatous lymphadenitis (NGL). NGL is very nonspecific and includes a wide array of differentials from malignancy, infectious etiology, or autoimmune disease. Bone marrow biopsy was significant for pancytopenia and depleted iron stores While waiting for her biopsy results, autoimmune work up was initiated as patient reported diffuse joint stiffness, dry mouth, and a malar rash. Autoimmune work up was significant for elevated ANA titer and elevated IL2- receptor. However, C3, C4, RF, anti-ds DNA, anti-Smith, and CCP within normal limits. Initially, rheumatology believed this was not a lupus flare as C3 and C4 levels were normal. About 8 days after admission, the patient started experiencing right upper quadrant pain and labs revealed significant transaminitis and proteinuria. However, autoimmune hepatitis panel was negative. On day 15 of admission, the patient’s malar rash resolved and she was afebrile for 2 days. Due to her clinical improvement, Adult onset Still’s disease and Kikuchi’s lymphadenitis were high on the differential, which usually spontaneously resolve. However, on day 17 of admission, patient started to experience high grade fevers and became very hypotensive. Her labs showed worsening transaminitis, elevated triglycerides at 517, and elevated ferritin level above 40,000. Due to her worsening clinical condition, she was started on high dose steroids and hydroxychloroquine for HLH and possible acute lupus flare. After initiation of treatment, patient started to show signs of clinical improvement and labs were trending in the right direction.

The patient met 4/17 diagnostic criteria for lupus and 5/8 diagnostic criteria for HLH. However, it was hard to determine in HLH was primary, secondary to an acute lupus flare, or secondary to stress from a miscarriage. Although the patient met diagnostic criteria for lupus; normal complement levels make a lupus flare less likely. In HLH, bone marrow biopsy usually shows the presence of macrophages, but hers only showed pancytopenia and iron depletion. This case emphasizes that clinicians cannot always rely on typical diagnostic findings and sometimes must treat based on a risk-benefit analysis.