Faculty Collaboration Database

Association of Persistent Rubella Virus With Idiopathic Skin Granulomas in Clinically Immunocompetent Adults. JAMA Dermatol 2022 Jun 01;158(6):626-633

Date

03/27/2022

Pubmed ID

35338705

Pubmed Central ID

PMC8957700

DOI

10.1001/jamadermatol.2022.0828

Scopus ID

2-s2.0-85127719644 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

IMPORTANCE: Vaccine-derived and wild-type rubella virus (RuV) has been identified within granulomas in patients with inborn errors of immunity, but has not been described in granulomas of healthy adults.

OBJECTIVE: To determine the association between RuV and atypical granulomatous inflammation in immune-competent adults.

DESIGN, SETTING, AND PARTICIPANTS: This case series, conducted in US academic dermatology clinics from January 2019 to January 2021, investigated the presence of RuV in skin specimens using RuV immunofluorescent staining of paraffin-embedded tissue sections, real-time reverse-transcription polymerase chain reaction, whole-genome sequencing with phylogenetic analyses, and cell culture by the US Centers for Disease Control and Prevention. Rubella immunoglobulin G, immunoglobulin M enzyme-linked immunoassay, and viral neutralization assays were performed for the sera of immunocompetent individuals with treatment refractory cutaneous granulomas and histopathology demonstrating atypical palisaded and necrotizing granulomas. Clinical immune evaluation was performed.

MAIN OUTCOMES AND MEASURES: Identification, genotyping, and culture of vaccine-derived and wild-type RuV within granulomatous dermatitis of otherwise clinically immune competent adults.

RESULTS: Of the 4 total immunocompetent participants, 3 (75%) were women, and the mean (range) age was 61.5 (49.0-73.0) years. The RuV capsid protein was detected by immunohistochemistry in cutaneous granulomas. The presence of RuV RNA was confirmed by real-time reverse-transcription polymerase chain reaction in fresh-frozen skin biopsies and whole-genome sequencing. Phylogenetic analysis of the RuV sequences showed vaccine-derived RuV in 3 cases and wild-type RuV in 1. Live RuV was recovered from the affected skin in 2 participants. Immunology workup results demonstrated no primary immune deficiencies.

CONCLUSIONS AND RELEVANCE: The case series study results suggest that RuV (vaccine derived and wild type) can persist for years in cutaneous granulomas in clinically immunocompetent adults and is associated with atypical (palisaded and necrotizing type) chronic cutaneous granulomas. These findings represent a potential paradigm shift in the evaluation, workup, and management of atypical granulomatous dermatitis and raises questions regarding the potential transmissibility of persistent live RuV.

Author List

Wanat KA, Perelygina L, Chen MH, Hao L, Abernathy E, Bender NR, Shields BE, Wilson BD, Crosby D, Routes J, Samimi SS, Haun PL, Sokumbi O, Icenogle JP, Sullivan KE, Rosenbach M, Drolet BA

Authors

Karolyn A. Wanat MD Vice Chair, Professor in the Dermatology department at Medical College of Wisconsin
Barbara D. Wilson MD Professor in the Dermatology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Connective Tissue Diseases
Dermatitis
Female
Granuloma
Humans
Immunocompetence
Male
Middle Aged
Phylogeny
Rubella
Rubella virus
United States