Bridget E Shields1,2, Ludmila Perelygina3, Sara Samimi4, Paul Haun4, Thomas Leung4, Emily Abernathy3, Min-Hsin Chen3, LiJuan Hao3, Joseph Icenogle3, Beth Drolet1, Barbara Wilson5, Joshua S Bryer4, Ross England6, Emily Blumberg6, Karolyn A Wanat5,7, Kathleen Sullivan8,9, Misha Rosenbach4. 1. Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison. 2. Assistant Section Editor, JAMA Dermatology. 3. Centers for Disease Control and Prevention, Division of Viral Diseases, Atlanta, Georgia. 4. Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia. 5. Department of Dermatology, Medical College of Wisconsin, Milwaukee. 6. Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia. 7. Section Editor, JAMA Dermatology. 8. Division of Allergy and Immunology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 9. Division of Allergy and Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia.
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 PARTICIPANTS: A 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 MEASURES: Identification and genotyping of a novel immunodeficiency-related 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 RELEVANCE: The 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.
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 PARTICIPANTS: A 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 MEASURES: Identification and genotyping of a novel immunodeficiency-related 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 RELEVANCE: The 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.
Authors: Ludmila Perelygina; Raeesa Faisthalab; Emily Abernathy; Min-Hsin Chen; LiJuan Hao; Lionel Bercovitch; Diana K Bayer; Lenora M Noroski; Michael T Lam; Maria Pia Cicalese; Waleed Al-Herz; Arti Nanda; Joud Hajjar; Koen Vanden Driessche; Shari Schroven; Julie Leysen; Misha Rosenbach; Philipp Peters; Johannes Raedler; Michael H Albert; Roshini S Abraham; Hemalatha G Rangarjan; David Buchbinder; Lisa Kobrynski; Anne Pham-Huy; Julie Dhossche; Charlotte Cunningham Rundles; Anna K Meyer; Amy Theos; T Prescott Atkinson; Amy Musiek; Mehdi Adeli; Ute Derichs; Christoph Walz; Renate Krüger; Horst von Bernuth; Christoph Klein; Joseph Icenogle; Fabian Hauck; Kathleen E Sullivan Journal: Front Immunol Date: 2021-12-20 Impact factor: 7.561