Case Presentation: A 39-year-old obese man with type 2 diabetes, dyslipidemia, and hypertension presented to the ED with intermittent abdominal pain, diarrhea, nausea, and emesis 2 weeks after an illness with sore throat. He denied fever, chills, shortness of breath, epistaxis, gum bleeding, or easy bruising. Medications included losartan-hydrochlorothiazide, metformin, and tirzepatide. Vital signs showed tachycardic (104 bpm) with a blood pressure of 98/66 mmHg. The physical exam was unremarkable. Labs revealed hemoglobin 11 g/dL, MCV 75.5 FL, platelet count 17 × 10^9/L, WBC 1.32 × 10^9/L, ANC 0.32 × 10^9/L, sodium 129 mmol/L, ALT 113 IU/L, and AST 321 IU/L. Additional workup revealed haptoglobin < 10 mg/dL, LDH 1469 U/L, reticulocyte count 94%, and a positive direct Coombs test, raising concern for autoimmune hemolytic anemia (AIHA). A CT of the abdomen/pelvis revealed hepatomegaly and splenomegaly without malignancy. Given the overall clinical picture, a bone marrow biopsy was performed, which showed hemophagocytosis. Ferritin level was elevated at 9852 ng/mL and soluble CD25 was 905 U/mL, further raising suspicion for hemophagocytic lymphohistiocytosis (HLH) since he met 5/8 criteria [5]. He was given platelet transfusions and empiric antibiotics. Workup for a secondary cause of HLH confirmed elevated adenovirus Ab titers (>1;64). Tests for hepatitis B, C, EBV, CMV, HSV, HHV-6, Bartonella, HIV, and ANA were negative. He was also diagnosed with Evans syndrome due to the triad of hemolytic anemia, immune thrombocytopenia (ITP), and neutropenia. He was treated with methylprednisolone and IVIG and later transitioned to high-dose oral prednisone taper at discharge. At his follow-up appointment with hematology, his blood counts had recovered.
Discussion: HLH is a rare, life-threatening hyperinflammatory syndrome characterized by uncontrolled immune activation, often triggered by viral illness or genetic predispositions [1]. Diagnosing HLH is challenging due to its nonspecific presentation and overlap with conditions like MAS-HLH, a subtype secondary to autoimmune disease [1]. Evans Syndrome is defined by two or more cytopenias, including AIHA and ITP, with or without immune neutropenia [3,4]. A review of the literature revealed only two prior cases of secondary HLH presenting as Evans Syndrome, highlighting possible overlapping features of these conditions [1, 2]. Recognizing the possibility of this overlap is essential for timely and appropriate management.
Conclusions: This case highlights the diagnostic challenge of differentiating between HLH and Evans syndrome and adds to the limited literature on this overlap. These patients are typically admitted by hospital medicine and understanding these complex hematologic disorders is crucial for timely and effective treatment.