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Open Access 01-12-2021 | Primary Immunodeficiency | Case Report

Leukocytoclastic vasculitis in patients with IL12B or IL12RB1 deficiency: case report and review of the literature

Authors: Niusha Sharifinejad, Seyed Alireza Mahdaviani, Mahnaz Jamee, Zahra Daneshmandi, Afshin Moniri, Majid Marjani, Payam Tabarsi, Parisa Farnia, Mahsa Rekabi, Mazdak Fallahi, Seyedeh Atefeh Hashemimoghaddam, Masoumeh Mohkam, Jacinta Bustamante, Jean-Laurent Casanova, Davood Mansouri, Ali Akbar Velayati

Published in: Pediatric Rheumatology | Issue 1/2021

Abstract

Background

Mendelian susceptibility to mycobacterial disease (MSMD) is an inborn error of immunity, resulting in susceptibility to weakly virulent mycobacteria and other intramacrophagic pathogens. Rheumatologic manifestations and vasculitis are considered rare manifestations in MSMD patients.

Case presentation

In this study, we reported a 20-year-old female who was presented with recurrent lymphadenitis following bacillus Calmette-Guérin (BCG) vaccination and a history of recurrent disseminated rash diagnosed as leukocytoclastic vasculitis (LCV). A slight reduction in lymphocyte subsets including CD4+, CD19+, and CD 16 + 56 T-cell count, as well as an elevation in immunoglobulins level (IgG, IgA, IgM, IgE), were observed in the patient. Whole exome sequencing revealed a homozygous Indel-frameshift mutation, c.527_528delCT (p. S176Cfs*12), at the exon 5 of the IL12B gene. She experienced symptom resolution after treatment with anti-mycobacterial agents and subcutaneous IFN-γ. We conducted a manual literature search for MSMD patients reported with vasculitis in PubMed, Web of Science, and Scopus databases. A total of 18 MSMD patients were found to be affected by a variety of vasculitis phenotypes mainly including LCV and Henoch-Schönlein purpura (HSP) with often skin involvement. Patients were all involved with vasculitis at the median age of 6.8 (2.6–7.7) years, nearly 6.1 years after the initial presentations. Sixteen patients (88.9%) had IL12RB1 defects and concurrent Salmonella infection was reported in 15 (88.2%) patients.

Conclusion

The lack of IL-12 and IL-23 signaling/activity/function and salmonella infection may be triggering factors for the development of leukocytoclastic vasculitis. IL12B or IL12RB1 deficiency and salmonellosis should be considered in MSMD patients with vasculitis.

Altare F, Durandy A, Lammas D, Emile JF, Lamhamedi S, Le Deist F, et al. Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science. 1998;280(5368):1432–5. https://doi.org/10.1126/science.280.5368.1432.CrossRefPubMed

Rosain J, Kong XF, Martinez-Barricarte R, Oleaga-Quintas C, Ramirez-Alejo N, Markle J, et al. Mendelian susceptibility to mycobacterial disease: 2014-2018 update. Immunol Cell Biol. 2019;97(4):360–7. https://doi.org/10.1111/imcb.12210.CrossRefPubMed

Jindal AK, Suri D, Guleria S, Rawat A, Garg S, Bal A, et al. Recurrent Salmonella typhi infection and autoimmunity in a young boy with complete IL-12 receptor β1 deficiency. J Clin Immunol. 2019;39(4):358–62. https://doi.org/10.1007/s10875-019-00637-0.CrossRefPubMed

Sanal O, Turul T, De Boer T, Van de Vosse E, Yalcin I, Tezcan I, et al. Presentation of interleukin-12/−23 receptor beta1 deficiency with various clinical symptoms of Salmonella infections. J Clin Immunol. 2006;26(1):1–6. https://doi.org/10.1007/s10875-006-7830-3.CrossRefPubMed

Bustamante J. Mendelian susceptibility to mycobacterial disease: recent discoveries. Hum Genet. 2020;139(6-7):993–1000. https://doi.org/10.1007/s00439-020-02120-y.CrossRefPubMedPubMedCentral

Yang R, Mele F, Worley L, Langlais D, Rosain J, Benhsaien I, et al. Human T-bet Governs Innate and Innate-like Adaptive IFN-γ Immunity against Mycobacteria. Cell. 2020;183:1826–1847.e1831.CrossRef

Le Voyer T, Neehus A-L, Yang R, Ogishi M, Rosain J, Alroqi F, et al. Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease. Proc Natl Acad Sci. 2021;118(15):e2102804118. https://doi.org/10.1073/pnas.2102804118.CrossRefPubMed

Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983;158(3):670–89. https://doi.org/10.1084/jem.158.3.670.CrossRefPubMed

Chen KR, Carlson JA. Clinical approach to cutaneous vasculitis. Am J Clin Dermatol. 2008;9(2):71–92. https://doi.org/10.2165/00128071-200809020-00001.CrossRefPubMed

10.

Filiz S, Kocacik Uygun DF, Verhard EM, Van Dissel JT, Uygun V, Bassorgun C, et al. Cutaneous leukocytoclastic vasculitis due to Salmonella enteritidis in a child with interleukin-12 receptor beta-1 deficiency. 2014;31:236–40.

11.

Rosain J, Oleaga-Quintas C, Deswarte C, Verdin H, Marot S, Syridou G, et al. A variety of Alu-mediated copy number variations can underlie IL-12Rβ1 deficiency. J Clin Immunol. 2018;38(5):617–27. https://doi.org/10.1007/s10875-018-0527-6.CrossRefPubMedPubMedCentral

12.

Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002;168(11):5699–708. https://doi.org/10.4049/jimmunol.168.11.5699.CrossRefPubMed

13.

de Beaucoudrey L, Puel A, Filipe-Santos O, Cobat A, Ghandil P, Chrabieh M, et al. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells. J Exp Med. 2008;205(7):1543–50. https://doi.org/10.1084/jem.20080321.CrossRefPubMedPubMedCentral

14.

Powell MD, Read KA, Sreekumar BK, Jones DM, Oestreich KJ. IL-12 signaling drives the differentiation and function of a TH1-derived TFH1-like cell population. Sci Rep. 2019;9(1):13991. https://doi.org/10.1038/s41598-019-50614-1.CrossRefPubMedPubMedCentral

15.

Mizuno Y, Takada H, Nomura A, Jin CH, Hattori H, Ihara K, et al. Th1 and Th1-inducing cytokines in Salmonella infection. Clin Exp Immunol. 2003;131(1):111–7. https://doi.org/10.1046/j.1365-2249.2003.02060.x.CrossRefPubMedPubMedCentral

16.

Abolhassani H, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, Yazdani R, et al. National consensus on diagnosis and management guidelines for primary immunodeficiency. Immunol Genet J. 2019;2:1–21.

17.

Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) registry working definitions for the clinical diagnosis of inborn errors of immunity. J Allergy Clin Immunol Pract. 2019;7(6):1763–70. https://doi.org/10.1016/j.jaip.2019.02.004.CrossRefPubMed

18.

Fang M, Abolhassani H, Lim CK, Zhang J, Hammarstrom L. Next generation sequencing data analysis in primary immunodeficiency disorders - future directions. J Clin Immunol. 2016;36(Suppl 1):68–75. https://doi.org/10.1007/s10875-016-0260-y.CrossRefPubMed

19.

Mahdaviani SA, Mansouri D, Jamee M, Zaki-Dizaji M, Aghdam KR, Mortaz E, et al. Mendelian susceptibility to mycobacterial disease (MSMD): clinical and genetic features of 32 Iranian patients. J Clin Immunol. 2020;40(6):872–82. https://doi.org/10.1007/s10875-020-00813-7.CrossRefPubMed

20.

Sanal O, Turul T, De Boer T, Van De Vosse E, Yalcin I, Tezcan I, et al. Presentation of interleukin-12/−23 receptor β1 deficiency with various clinical symptoms of salmonella infections. 2006;26:1–6.

21.

Kutukculer N, Genel F, Aksu G, Karapinar B, Ozturk C, Cavusoglu C, et al. Cutaneous leukocytoclastic vasculitis in a child with interleukin-12 receptor beta-1 deficiency. J Pediatr. 2006;148(3):407–9. https://doi.org/10.1016/j.jpeds.2005.10.003.CrossRefPubMed

22.

de Beaucoudrey L, Samarina A, Bustamante J, Cobat A, Boisson-Dupuis S, Feinberg J, et al. Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries. Medicine (Baltimore). 2010;89(6):381–402. https://doi.org/10.1097/MD.0b013e3181fdd832.CrossRef

23.

Khamassi I, Ben Ali M, Ben Mustapha I, Barbouche MR, Bejaoui M, Bouyahia O, et al. Salmonella enteriditis inducing cutaneous leucocytoclasic vasculitis: an unusual complication in a patient with an interleukine- 12 receptor beta-1 deficiency. Tunis Med. 2015;93(5):328–9.PubMed

24.

Mandola A, Broides A, Nahum A. Salmonella typhi infection causing prolonged chronic illness and cutaneous leucocytoclastic vasculitis in a patient with IL 12 receptor β-1 deficiency. LymphoSign Journal. 2016. https://doi.org/10.14785/lymphosign-2016-0013.

25.

Louvain de Souza T, de Souza Campos Fernandes RC, Azevedo da Silva J, Gomes Alves Júnior V, Gomes Coelho A, Souza Faria AC, et al. Microbial Disease Spectrum Linked to a Novel IL-12Rβ1 N-Terminal Signal Peptide Stop-Gain Homozygous Mutation with Paradoxical Receptor Cell-Surface Expression. Front Microbiol. 2017;8:616–6.CrossRef

26.

Doğruel D, Gündeşlioğlu Ö, Yılmaz M, Alabaz D, Altıntaş DU, Kocabaş E. Clinical findings and genetic analysis of the patients with IL-12Rβ1 deficiency from Southeast Turkey. Turk J Pediatr. 2019;61(2):174–9. https://doi.org/10.24953/turkjped.2019.02.004.CrossRefPubMed

27.

Sarrafzadeh SA, Nourizadeh M, Mahloojirad M, Fazlollahi MR, Shokouhi Shoormasti R, Badalzadeh M, et al. Molecular, immunological, and clinical features of 16 Iranian patients with Mendelian susceptibility to mycobacterial disease. J Clin Immunol. 2019;39(3):287–97. https://doi.org/10.1007/s10875-019-0593-4.CrossRefPubMed

28.

Kozlova A, Zinovieva N, Bustamante J, Boisson-Dupuis S, Casanova JL, Shcherbina A. P03-025 – differential diagnosis of autoimmune disorders. Pediatr Rheumatol. 2013;11(S1):A223. https://doi.org/10.1186/1546-0096-11-S1-A223.CrossRef

29.

Döffinger R, Jouanguy E, Dupuis S, Fondanèche MC, Stephan JL, Emile JF, et al. Partial interferon-gamma receptor signaling chain deficiency in a patient with bacille Calmette-Guérin and mycobacterium abscessus infection. J Infect Dis. 2000;181(1):379–84. https://doi.org/10.1086/315197.CrossRefPubMed

30.

Glosli H, Stray-Pedersen A, Brun AC, Holtmon LW, Tønjum T, Chapgier A, et al. Infections due to various atypical mycobacteria in a Norwegian multiplex family with dominant interferon-gamma receptor deficiency. Clin Infect Dis. 2008;46(3):e23–7. https://doi.org/10.1086/525855.CrossRefPubMed

31.

Somer T, Finegold SM. Vasculitides associated with infections, immunization, and antimicrobial drugs. Clin Infect Dis. 1995;20(4):1010–36. https://doi.org/10.1093/clinids/20.4.1010.CrossRefPubMed

32.

Touma Z, Haddad A, Gladman DD, Uleryk EM, Urowitz MB. Skin nontuberculous mycobacterial infection in systemic lupus erythematosus: an unusual skin infection mimicking lupus vasculitis. Semin Arthritis Rheum. 2013;42(5):498–506. https://doi.org/10.1016/j.semarthrit.2012.08.002.CrossRefPubMed

33.

Walsh TL, Baca V, Stalling SS, Natalie AA, Veldkamp PJ. Mycobacterium avium-intracellulare pulmonary infection complicated by cutaneous leukocytoclastic vasculitis in a woman with anorexia nervosa. Infection. 2014;42(3):559–63. https://doi.org/10.1007/s15010-013-0574-0.CrossRefPubMed

34.

Martinez Valenzuela L, Bordignon Draibe J, Fulladosa Oliveras X, Bestard Matamoros O, Cruzado Garrit JM, Torras Ambrós J. T-lymphocyte in ANCA-associated vasculitis: what do we know? A pathophysiological and therapeutic approach. Clin Kidney J. 2019;12(4):503–11. https://doi.org/10.1093/ckj/sfz029.CrossRefPubMedPubMedCentral

Title: Leukocytoclastic vasculitis in patients with IL12B or IL12RB1 deficiency: case report and review of the literature
Authors: Niusha Sharifinejad
Seyed Alireza Mahdaviani
Mahnaz Jamee
Zahra Daneshmandi
Afshin Moniri
Majid Marjani
Payam Tabarsi
Parisa Farnia
Mahsa Rekabi
Mazdak Fallahi
Seyedeh Atefeh Hashemimoghaddam
Masoumeh Mohkam
Jacinta Bustamante
Jean-Laurent Casanova
Davood Mansouri
Ali Akbar Velayati
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Primary Immunodeficiency
Vasculitis
Vasculitis
Leukocytoclastic Vasculitis
Leukocytoclastic Vasculitis
Published in: Pediatric Rheumatology / Issue 1/2021
Electronic ISSN: 1546-0096
DOI: https://doi.org/10.1186/s12969-021-00623-0

At a glance: The STEP trials

Springer Medicine

Leukocytoclastic vasculitis in patients with IL12B or IL12RB1 deficiency: case report and review of the literature

Abstract

Background

Case presentation

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Case presentation

Conclusion

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