Multi-focal EBV-mucocutaneous ulcer heralding late-onset T-cell immunodeficiency in a woman with lupus erythematosus

Abstract

Epstein Barr virus (EBV)-positive mucocutaneous ulcer (MCU) is a new clinicopathologic entity with a self-limited indolent course, and responds well to conservative management [1]. These are invariably localized (60% in oropharyngeal area) and may occur in patients with senile or iatrogenic immunosuppression. Lesions typically regress with reduction in immunosuppression, but may recur. Prognosis is always favorable. We report a unique case of multifocal EBV-related MCU as the first manifestation of an unsuspected T-cell immunodeficiency. A 45-year-old woman had been treated with azathioprine and steroids for lupus nephritis and encephalitis from age 20. Her medications were stopped for 10 years. She presented with mycobacterium avium intracellulare (MAI) lymphadenopathy of groin and was treated with ethambutol, clarithromycin and rifampicin. Six months later, she suffered from left facial palsy, molluscum contagiosum (Fig. 1a) and a gum lesion (Fig. 1b). Positron emission tomography (PET) scanning showed uptake in left ear, lung, and gum (SUVmax 1.5–5.0) (Fig. 1c). A biopsy (Fig. 1d, e) showed a dense lymphoid infiltrate positive for CD20 (L26), CD30 (BerH2), and EBER. This was compatible with EBV-related mucocutaneous lymphoproliferation [1]. Antibodies to human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV-1) and autoimmune markers were negative, but her CD4 (76 L/lL, normal 354–1,526) and CD8 counts (71 L/lL, normal 318–1,458) were severely depressed, with normal B and NK cell numbers. Cytogenetic study showed mosiac 46, XX, delXq27 [5]/46, XX [59]. In view of likely persistent low T-cell counts, disseminated lesions, and functional deficit, she was treated with rituximab (375 mg/ m 9 8) [2] with a complete metabolic response and partial facial nerve recovery. The CD4 and CD8 counts remained depressed at 2 years and she refused further genetic tests or family studies. We report the first case of multifocal EBV-related MCU in an adult patient with multiple opportunistic infections due to cellular immune defect. In HIV patients, molluscum contagiosum and MAI infections occur when the CD4 count falls near 50 L/lL [3], and both are rare in acquired T-cell immunodeficiency cases. Late-onset T-cell immunodeficiency (10% of cases and up to age 64) is increasingly recognized [4]. Over 20% of late-onset immunodeficiencies had lymphoma and autoimmune manifestations [4]. Patients with genetic T-cell defects are genetically heterogeneous ([150 disorders described). Intriguingly, our case carries a mosaic chromosome X cytogenetic defect. Iatrogenic immunodeficiency is also possible, but her therapy had been stopped many years ago, and her SLE is likely secondary to her T-cell dysregulation [5]. Irrespective of the underlying predisposition, in patients with unexplained sequential opportunistic infections and malignancies, a full work-up for immunodeficiency is needed. W. Y. Au (&) Department of Medicine, UMU, 4/F, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong, Hong Kong e-mail: auwing@hotmail.com