Chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis exacerbation in a patient with systemic lupus erythematosus

Abstract

Chronic active Epstein-Barr virus infection (CAEBV) is characterized by chronic infectious mononucleosis-like symptoms. We report a very rare case with autoimmune hepatitis (AIH) complicated by CAEBV. A 50-year-old woman with systemic lupus erythematosus (SLE) complicated by AIH began to suffer from acute respiratory failure and her clinical symptoms improved rapidly in response to steroid treatment. However, during the gradual tapering of the steroid dose, a steady increase of the serum hepatobiliary enzyme levels subsequently was observed and the patient began to have continuous fever. Moreover, upper gastrointestinal endoscopy revealed multiple intractable gastric ulcers. When EBER-ISH was performed on liver biopsy and gastric mucosal biopsy specimens, EBER-positive lymphocytes were observed. When peripheral blood was examined, 2.1 × 10(6) copies/µg of EBV-DNA were observed in the CD4-positive T cells, confirming the diagnosis of CAEBV. A cooling therapy was started by steroid and cyclosporine. Thereafter, despite the start of CHOP therapy, she developed a malignant lymphoma (PTCL-NOS) and died of hepatic failure. When treatment-resistant AIH patients are encountered, not only AIH exacerbation but also CAEBV should be considered in the differential diagnosis.

Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity

“…In particular, among autoimmune diseases, the development of systemic lupus erythematosus (SLE) has been correlated with EBV re-activation (as well as with several other causative infections) [76][77][78][79][80][81][82]. SLE is an autoimmune chronic inflammatory disease, usually characterized by injury to the skin, joints, kidneys, nervous system, and mucous membranes.…”

Autoimmune hepatitis: current challenges and future prospects

“…Although there is a report of AIH being induced in a patient with preexisting CAEBV and successfully treated with a corticosteroid,31 CAEBV is generally a life-threatening progressive disease if adequate management is neglected. In some cases of CAEBV, the clinical, laboratory, and histological features are quite similar to those of AIH, but the prognosis is extremely poor 32,33. CAEBV should be included in the differential diagnosis of patients who do not respond sufficiently to immunosuppressive therapy.…”

How compelling are the data for Epstein–Barr virus being a trigger for systemic lupus and other autoimmune diseases?

“…Numerous studies confirmed higher frequencies and elevated titres of EBV-directed antibodies, against lytic cycle antigens, in SLE patients compared to healthy controls (HCs), indicating frequent EBV reactivations (reviewed in [11,18] The decreased control of EBV in SLE patients was also lately demonstrated by the presence of EBV DNA detected by PCR in serum from SLE patients [26], and by several case reports. A 50-year-old woman diagnosed with SLE (and concurrent autoimmune hepatitis) developed chronic active EBV infection with EBER-positive lymphocytes found in both liver and gastric mucosal biopsies and in high concentrations in the CD4+ T-cells in the blood [27]. Similarly, an 86-year-old woman with SLE developed a rare form of EBVpositive plasmablastic lymphoma in the colon [28].…”