Misleading Hepatitis B Serology Following Intravenous Immunoglobulin Treatment for Pemphigus Vulgaris

A man in his 50s with Pemphigus Vulgaris presented to the Dermatology outpatient department of a tertiary hospital. He had a two-year history of progressive mucocutaneous lesions. His medical background consisted of type two diabetes mellitus, hypertension, and hyperlipidaemia. On examination he had widespread flaccid bullae and numerous oral and genital mucosal ulcerations. His Pemphigus Vulgaris remained active despite current treatment consisting of four doses of monthly intravenous immunoglobulin (IVIG), oral prednisolone, and potent topical corticosteroids. A decision was made to proceed with intravenous rituximab. Blood tests including a full pre-immunosuppression screen were completed as this had not been done prior to commencing IVIG. Screening for hepatitis B includes three serological tests—surface antigen (HBsAg), core antibody (anti-HBc) and surface antibody (anti-HBs) which determine infection, exposure and immunity (through vaccination or past infection) respectively [1]. Of note, hepatitis B core antibody and surface antibody were positive in keeping with past, cleared infection. The patient was unaware of any history of past hepatitis B infection, had no risk factors for acquisition, and previous serology had been negative. Prior to rituximab treatment it is essential to clarify hepatitis B status. Patients with serologic evidence of past hepatitis B infection are at moderate risk of hepatitis B reactivation if they receive anti-CD20 therapy and may require preventative antiviral therapy [1]. Due to the inconsistent hepatitis B results, serology was repeated at two separate laboratories 2.5 weeks and 3 weeks post IVIG. Repeat serology demonstrated negative hepatitis B core antibody and positive hepatitis B surface antibody, consistent with prior hepatitis B immunisation but no evidence of past infection. After consultation with Gastroenterology, the initial serology was deemed a false positive likely in the setting of recent IVIG treatment. A false positive anti-HBc result irrespective of IVIG is possible, however this is uncommon with the specificity of modern anti-HBc tests reported to be between 99% and 100% [2]. There are several documented cases of false positive hepatitis B serology in the context of IVIG administration [3, 4]. IVIG is derived from pooled plasma of multiple donors and reflects the serological status of the donor population, some of whom may have had prior exposure to hepatitis B virus. Passive transfer of antibodies can lead to temporary spurious results on infectious screening [5]. Other documented cases include false positive syphilis, toxoplasma, and cytomegalovirus serology in the setting of IVIG [3, 6]. Pruessman et al. conducted a retrospective cohort study of 17 patients with no prior hepatitis B infection and found that 12 patients had positive hepatitis B core antibodies 4 weeks after commencing IVIG [5]. These false positives typically decline as a function of immunoglobulin half-life [6]. This is demonstrated in our case where core antibody reactivity resolved within 3 weeks. We wish to highlight this case of IVIG causing false positive hepatitis B serology given treatment with IVIG is becoming more common in patients with autoimmune skin diseases. Misinterpretation may lead to unnecessary investigations or prescription of preventative antiviral therapy. Where possible, hepatitis screening should be completed prior to IVIG therapy to prevent diagnostic confusion. The authors have nothing to report. AI Statement: There was no use of AI in the formation of this letter. Patient consent was obtained for publication. The authors declare no conflicts of interest. The authors have nothing to report.