Rheumatoid arthritis complicated with immunodeficiency-associated lymphoproliferative disorders during treatment with adalimumab

Abstract

A 71-year-old woman was diagnosed with rheumatoid arthritis in 2002. Treatment was started with methotrexate and she was switched to adalimumab in 2006. In May 2008, she started complaining of swelling of the left axilla and the left elbow lymph nodes, and adalimumab was discontinued in December. Her lymphadenopathy did not resolve and she was admitted to hospital with fever in May 2009. Subsequent laboratory examinations showed that serum alkaline phosphatase, gamma-glutamyl transpeptidase, C-reactive protein, and soluble interleukin-2 receptor levels were 3,078 IU/l, 510 IU/l, 20 mg/dl, and 7,290 U/ml, respectively. Gallium scintigraphy showed high-intensity areas in the above-mentioned lymph nodes. She suddenly progressed to jaundice and died of pulmonary edema on the 25th day of hospitalization. Autopsy indicated large atypical cells with a distorted nucleus that had multiplied in the above-mentioned lymph nodes. On immunohistochemical staining these cells showed positive staining for CD15, CD30, PAX-5, Epstein-Barr virus (EBV) early small RNA (EBER), and LMP-1. Reactivation of EBV was diagnosed via EBV antibodies and an EBV DNA determination. We considered that she had developed EBV-associated lymphoproliferative disorders due to immunodeficiency caused by adalimumab administration. Reactivation of EBV associated with adalimumab and the relationship of this reactivation to malignant lymphoma have been rarely reported.