Granulomatous Dermatitis Associated With Rubella Virus Infection in an Adult With Immunodeficiency

Abstract

IMPORTANCE Immunodeficiency-related, vaccine-derived rubella virus (RuV) as an antigenic trigger of cutaneous and visceral granulomas is a rare, recently described phenomenon in children and young adults treated with immunosuppressant agents.OBJECTIVE To perform a comprehensive clinical, histologic, immunologic, molecular, and genomic evaluation to elucidate the potential cause of an adult patient's atypical cutaneous granulomas. DESIGN, SETTING, AND PARTICIPANTSA prospective evaluation of skin biopsies, nasopharyngeal swabs, and serum samples submitted to the Centers for Disease Control and Prevention was conducted to assess for RuV using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and viral genomic sequencing. The samples were obtained from a man in his 70s with extensive cutaneous granulomas mimicking both cutaneous sarcoidosis (clinically) and CD8 + granulomatous cutaneous T-cell lymphoma (histopathologically). The study was conducted from September 2019 to February 2021. MAIN OUTCOMES AND MEASURESIdentification and genotyping of a novel immunodeficiencyrelated RuV-associated granulomatous dermatitis.RESULTS Immunohistochemistry for RuV capsid protein and RT-PCR testing for RuV RNA revealed RuV in 4 discrete skin biopsies from different body sites. In addition, RuV RNA was detected in the patient's nasopharyngeal swabs by RT-PCR. The full viral genome was sequenced from the patient's skin biopsy (RVs/Philadelphia.PA.USA/46.19/GR, GenBank Accession #MT249313). The patient was ultimately diagnosed with a novel RuV-associated granulomatous dermatitis. CONCLUSIONS AND RELEVANCEThe findings of this study suggest that clinicians and pathologists may consider RuV-associated granulomatous dermatitis during evaluation of a patient because it might have implications for the diagnosis of cutaneous sarcoidosis, with RuV serving as a potential antigenic trigger, and for the diagnosis of granulomatous cutaneous T-cell lymphoma, with histopathologic features that may prompt an evaluation for immunodeficiency and/or RuV.

Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity

“…This report is one of the few to describe therapeutic efforts to treat granulomas in IEI patients, which have not been standardized and were limited to small case series ( 18 , 21 , 23 , 37 ). Unfortunately, the lack of an animal model for RuV persistent infections is impeding thorough investigations of antiviral strategies.…”

“…Patients with IEI develop rubella-associated granulomas from weeks to decades after MMR vaccination ( 18 ). The recent report of a patient with common variable immunodeficiency (CVID) with wild type RuV associated granulomas presenting in his 70s provides the first evidence that, in addition to vaccine virus strain, wild type RuV strains are also capable of long-term asymptomatic persistence and clinical re-emergence as symptomatic granulomas decades later ( 21 ). The cellular or tissue reservoir for latent iVDRV and wild type RuV, the mechanism of virus persistence, and the cause of virus-associated lesions in different organs is presently unknown.…”

Association of Persistent Rubella Virus With Idiopathic Skin Granulomas in Clinically Immunocompetent Adults

“…This cluster of viruses, from different patients each with persistent RuV infection and with evidence of initial infection for 2 of them between the late 1950s and early 1970s in the US, is associated with a previously undescribed lineage of RuVs. 7,11 The points of initial RuV infections were estimated based on phylogenetic sequencing and similarity of those sequences to known viruses in circulation at different points. Most all virologic surveillance for RuVs has been performed after 1980.…”

A case of wild‐type rubella‐associated cutaneous granuloma in ataxia telangiectasia

“…6 Another recent reported case of wild-type rubella in cutaneous granuloma in an elderly patient with common variable immunodeficiency, demonstrates that it is not vaccine strain-specific. 7 To our knowledge, this is the first reported case of wild-type rubellaassociated granuloma in an immunodeficient patient born and immunized in the era since rubella vaccination has been available.…”