Rubella Vaccine Persistence Within Cutaneous Granulomas in Common Variable Immunodeficiency Disorder

Abstract

Common variable immunodeficiency disorder is a primary immunodeficiency disorder characterized by reduced levels of serum immunoglobulins and impaired antibody response. This condition may be associated with development of noninfectious granulomatous dermatitis of the skin which may be disfiguring and destructive. There are no published guidelines for the treatment of cutaneous granulomas in this patient population. In recent studies, rubella virus–positive cells in granulomas were localized to M2 macrophages which have an important role in wound healing and the secretion of immunoregulatory cytokines. We present a case of treatment-refractory, disfiguring common variable immunodeficiency disorder–associated granulomatous dermatitis. Immunofluorescence microscopy of the biopsy specimen confirmed the presence of rubella vaccine capsid proteins in M2 macrophages within the granuloma, a newly recognized phenomenon in this patient population. This knowledge may serve to identify future therapeutic targets or preventative strategies for granulomatous dermatitis in patients with primary immunodeficiency disorder.

Rubella vaccine–induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity

“…Rubella-associated granulomas are a known complication in IEIs (10)(11)(12)(28)(29)(30)(31)(32). In a series of 66 patients, 17 suffered from AT, 16 from atypical SCID, 25 from various forms of combined immunodeficiencies, 6 patients from CVID and 2 patients from Xlinked agammaglobulinemia (13).…”

Rubella virus‐associated necrotizing granulomatous inflammation with extensive eyelid, ocular, and orbital involvement

“…RuV has been isolated from skin biopsies through several assays including viral cell culture, PCR, and immunohistochemical analysis 1–3,6,7,14 . RuV failed to grow from viral cell culture in our patient, and this has also been observed in two of four immunocompetent adults with RuV in cutaneous granulomas 7 .…”

“…The standard MMR vaccine includes attenuated rubella viral strain RA27/3. While this vaccine is contraindicated in children with severe antibody or T‐cell deficiencies, or other innate immune disorders, there are several reports of the identification of a primary immunodeficiency in patients who develop cutaneous granulomas following MMR vaccination 3,4 . The RA27/3 vaccine strain has been shown to persist for limited periods in immunologically competent individuals 10 .…”

“…Granulomatous dermatitis associated with rubella virus (RuV) is rare, and most commonly seen in children with primary immunodeficiencies, largely DNA repair disorders affecting T cells 1–4 . Skin lesions are most commonly found on the face and limbs 1–3 . When facial involvement has been reported, the lesions were reported to involve the cheeks and nose 1,2 .…”

What Works When Treating Granulomatous Disease in Genetically Undefined CVID? A Systematic Review

“…Human Herpes virus-8 and Toxoplasma gondii are reported in relation to granuloma formation in CVID (9,10). More recently, Rubella positive M2 macrophages were identified in granulomas in a patient with CVID that received a Rubella vaccine during childhood (11). However, reports are limited or could not be reproduced and further research is required to better understand the pathogenesis of granulomatous disease in CVID.…”