Rubella Virus-Associated Cutaneous Granulomatous Disease: a Unique Complication in Immune-Deficient Patients, Not Limited to DNA Repair Disorders

David Buchbinder, Fabian Hauck, Michael H. Albert, Anita Rack, Shahrzad Bakhtiar, Anna Shcherbina, Elena Deripapa, Kathleen E. Sullivan, Ludmila Perelygina, Marc Eloit, Bénédicte Neven, Philippe Pérot, Despina Moshous, Félipe Suarez, Christine Bodemer, Francisco A. Bonilla, Louise E. Vaz, Alfons L. Krol, Christoph Klein, Mikko SeppanenDiane J. Nugent, Jasjit Singh, Hans D. Ochs

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3–18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2–152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalJournal of Clinical Immunology
Volume39
Issue number1
DOIs
StatePublished - Jan 15 2019

Keywords

  • Artemis deficiency
  • DNA ligase 4 deficiency
  • Nijmegen breakage syndrome
  • ataxia telangiectasia
  • chronic rubella infection resulting in cutaneous granuloma formation
  • combined immunodeficiency

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Buchbinder, D., Hauck, F., Albert, M. H., Rack, A., Bakhtiar, S., Shcherbina, A., Deripapa, E., Sullivan, K. E., Perelygina, L., Eloit, M., Neven, B., Pérot, P., Moshous, D., Suarez, F., Bodemer, C., Bonilla, F. A., Vaz, L. E., Krol, A. L., Klein, C., ... Ochs, H. D. (2019). Rubella Virus-Associated Cutaneous Granulomatous Disease: a Unique Complication in Immune-Deficient Patients, Not Limited to DNA Repair Disorders. Journal of Clinical Immunology, 39(1), 81-89. https://doi.org/10.1007/s10875-018-0581-0