Dapsone-Induced Polyserositis Through Innate Immune Activation: A First Case Report

Abstract

Innate immune re-activation presenting as serositis in post liver transplant. We present a case of a 66-year-old female with NASH cirrhosis and Orthotopic Liver Transplant (OLT). One month after OLT, she was admitted for volume overload with pleural effusion and ascites which was managed medically. During follow up as outpatient, she continued to have low grade fever, and fatigue along with worsening abdominal distension and leg swelling. Six months after her OLT, she was admitted for severe anemia (hemoglobin=6.2 gm/dl) and acute on chronic kidney injury (serum creatinine=2.8 mg/dl) with persisting leukopenia. She had signs of congestive heart failure and clinically evident ascites. Chest X-ray showed possible pericardial effusion and echocardiogram showed cardiac tamponade. She underwent pericardiocentesis and fluid was negative for infection or tumor cells. She continued to have re-accumulation of hemorrhagic pericardial effusion requiring catheter placement. Her peritoneal fluid revealed a SAAG < 1.1 which ruled out portal hypertension. An extensive infectious workup was negative for bacterial, viral and fungal causes (Table 1). Malignancy was ruled out by negative fluid cytology. She had negative ANA, rheumatoid factor, ANCA, and dsDNA in serum but low IgG and C3 with an increased IgG in the peritoneal and pericardial fluid (Table 2). She had raised IL2 soluble receptor and TNF alpha indicating a cytokine release from immune reactivation suggestive of an immune-mediated polyserositis, likely from dapsone. She received IVIG for 4 days, as an immunomodulatory agent with improvement in serum creatinine and hemoglobin at discharge. She was started on prednisone which was tapered off over 6 weeks. She did not have any recurrence of serositis after discontinuation of dapsone favoring our final diagnosis. We know of cytokine storm and immune activation occurs as a result of immunosuppression in post liver transplant situation. Our patient had a sudden onset of immune reactivation with raised IL2 soluble receptor and also raised TNF alpha with low IgG. Severe forms of immune reactivation like Hemophagocytic Lymphohistiocytosis (HLH) have also been reported in post liver transplant. This is due to an imbalance where there is a uncontrolled macrophage activation with reduced CD8 function. This immune reactivation was reduced by the IVIG and withdrawing possible inciting agent which was dapsone in this case.Table: Table. Infectious Workup in Patient with Orthotopic Liver Transplant Presenting with PolyserositisTable: Table. Immunoligical workup in patient with Orthotopic Liver Transplant presenting with PolyserositisFigure: Pericardial effusion noted on echocardiogram.