Background Haemophagocytic Lymphohistiocytosis (HLH) is an aggressive, life-threatening syndrome of increased immune activation.1 HLH secondary to underlying systemic lupus erythematosus (SLE) is described as acute lupus haemophagocytic syndrome (ALHS).2 ALHS presenting with negative ANA is uncommon. We describe a case of ALHS with diagnostic difficulty, presenting with negative ANA.
Materials and methods We present an unusual case of a 57 year old female hospitalised with on and off fever, episodes of confusion and alopecia for 03 months.
Results Investigations showed a pancytopenia (haemoglobin 6.0 g/dl, WBC 1,690/mm3, platelets 102,000/mm3). ESR was 76 mm/hour. CRP was 02 mg/L. Septic screen was negative except for a positive sputum culture for coliforms. Chest x-ray was normal. Direct Coombs test was positive. The fever persisted despite treatment with IV antibiotics. ANA and Ds-DNA were negative. Bone marrow revealed features of primary or secondary haemophagocytosis. Serum ferritin (>1650 ng/dl) and triglycerides were elevated. Diagnosis of HLH probably due to an evolving autoimmune disorder was made and the patient was treated with steroids. The patient dramatically improved and was discharged on oral steroids.
After 06 months, she experienced frothy urine, ankle swelling and readmitted. Evaluation revealed proteinuria with active sediment in urine. ANA and Ds DNA were positive. Complement C3 and C4 were reduced. Renal biopsy revealed Class IV G lupus nephritis with immunofluorescence pattern consistent with SLE. The dose of steroids were increased and she was started on mycophenolate mofetil. The patient improved.
Conclusion This case showcases an uncommon presentation of ALHS with initial negative ANA probably due to its cytokine mediated pathogenesis. This is the first such reported case in South Asia to our knowledge. Interestingly, according to the ACR criteria and its 1997 update, this patient does not fulfil the criteria for SLE diagnosis for the initial hospitalisation. But according to the 2012 SLICC revised ACR SLE criteria, the patient fulfils the criteria for SLE even in the first hospitalisation which was subsequently proven without doubt with renal biopsy findings. This case confirms the increased sensitivity of SLICC criteria over ACR criteria in diagnosis of SLE.
References 1. Rahal AK, Fernandez J, Dakhil C. Undiagnosed Systemic Lupus Erythematosus Presenting as Hemophagocytic Lymphohistiocytosis. Case Rep Rheumatol. 2015;2015:748713.
2. Wong KF, Hui PK, Chan JK, Chan YW, Ha SY. The acute lupus hemophagocytic syndrome. Ann Intern Med. 1991;114(5):387–90.