Unusual acute lupus hemophagocytic syndrome – a test of diagnostic criteria: a case report

BACKGROUND: Hemophagocytic lymphohistiocytosis is an aggressive life-threatening syndrome of excessive immune activation. Hemophagocytic lymphohistiocytosis due to systemic lupus erythematosus is described as acute lupus hemophagocytic syndrome. Acute lupus hemophagocytic syndrome presenting with negative antinuclear antibody is uncommon. CASE PRESENTATION: A 57-year-old Sri Lankan woman presented with intermittent fever, weight loss, episodic confusion, and alopecia for 3 months. Investigations showed pancytopenia. Her erythrocyte sedimentation rate was 76 mm/hour and C-reactive protein was 2 mg/l. Septic screen was negative except for a positive sputum culture for Gram-negative coliforms. Chest X-ray was normal. Direct antiglobulin test was positive. Fever persisted with clinical worsening despite treatment with intravenous antibiotics. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were negative. Bone marrow aspiration revealed features compatible with hemophagocytosis. Her serum ferritin and triglycerides were elevated. Diagnosis of hemophagocytic lymphohistiocytosis due to an evolving autoimmune disorder was made and she was treated with steroids. She showed a dramatic improvement and was discharged on oral steroids. After 6 months, while the steroids were being tapered she experienced oral ulcers, frothy urine, and ankle swelling and she was rehospitalized. Urine analysis revealed proteinuria with active sediment. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were positive. Complement C3 and C4 were reduced. A renal biopsy revealed class IV-G lupus nephritis with immunofluorescence pattern consistent with systemic lupus erythematosus. Steroid dose was increased and mycophenolate mofetil was commenced. She improved. CONCLUSIONS: This case showcases an uncommon presentation of acute lupus hemophagocytic syndrome with initial negative antinuclear antibody probably due to its cytokine-mediated pathogenesis. This is the first such reported case in South Asia to the best of our knowledge. According to the American College of Rheumatology criteria, our patient did not fulfill the criteria for systemic lupus erythematosus diagnosis for the initial hospitalization. But, according to the 2012 Systemic Lupus International Collaborating Clinics criteria, she did fulfill the criteria for systemic lupus erythematosus even in the first hospitalization which was subsequently proven with renal biopsy findings. This case confirms the increased sensitivity of Systemic Lupus International Collaborating Clinics criteria over American College of Rheumatology criteria in diagnosis of systemic lupus erythematosus.