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The relationship between pemphigus and systemic lupus erythematosus: a cross-sectional study, systematic review, and meta-analysis

  • Khalaf KridinEmail author
  • Rimma Laufer-Britva
  • Mouhammad Kridin
  • Doron Comaneshter
  • Erez Batat
  • Arnon D. Cohen
Original Article
  • 18 Downloads

Abstract

The coexistence of pemphigus and systemic lupus erythematosus (SLE) had been reported anecdotally. Anti-desmoglein (Dsg)1 and anti-Dsg3 antibodies were detected concomitantly with antinuclear autoantibodies among blood donors. The aim of the current study was to study the association between pemphigus and SLE in Israeli patients and to synthesize existing data on this association in the current literature. The current study included two sections. Initially, a cross-sectional study was performed to compare pemphigus patients with age-, sex-, and ethnicity-matched control subjects regarding the prevalence of SLE using a real-life large-scale computerized database. Next, a systematic review and meta-analysis of similar observational studies in Medline, Embase, and Web of Science (1823–2017) was conducted. As for the cross-sectional study, a total of 1985 patients with pemphigus and 9874 controls were included in the study. The prevalence of SLE was slightly higher among patients with pemphigus as compared to controls (OR, 1.85; 95% CI, 0.89–3.82). In a sensitivity analysis that included patients who received pemphigus-related treatments, the association between pemphigus and SLE had been substantiated and was statistically significant (OR, 2.10; 95% CI, 1.00–4.48). In the meta-analysis section, three eligible studies, comprising 10,389 pemphigus patients met the eligibility criteria. The overall pooled multivariate OR was 2.50 (95% CI 1.54–4.07, I2 = 44.19%, P = 0.167) across all studies. In conclusion, the meta-analysis provides epidemiologic evidence that these B cell-driven diseases are significantly associated. Further research is required to elucidate the molecular mechanism underlying this association.

Keywords

Pemphigus SLE Systemic lupus erythematosus Lupus Association Meta-analysis Systematic review 

Notes

Compliance with ethical standards

Conflict of interests

Prof. Arnon Cohen received research grants from Janssen, Novartis, AbbVie, Janssen, and Sanofi. Prof. Arnon Cohen served as a consultant, advisor, or speaker to AbbVie, Amgen, Boehringer Ingelheim, Dexcel pharma, Janssen, Kamedis, Lilly, Neopharm, Novartis, Perrigo, Pfizer, Rafa, Samsung Bioepis, Sanofi, Sirbal, and Taro. No funding was gained for the research.

Supplementary material

12026_2019_9065_MOESM1_ESM.docx (16 kb)
Supplementary Table 1 Literature search strategy for each one the databases examined (DOCX 16 kb)
12026_2019_9065_MOESM2_ESM.docx (17 kb)
Supplementary Figure 1 Funnel plot for all the included studies. (DOCX 16 kb)

References

  1. 1.
    Malik M, Ahmed AR. Concurrence of systemic lupus erythematosus and pemphigus: coincidence or correlation? Dermatology. 2007;214:231–9.CrossRefGoogle Scholar
  2. 2.
    Parameswaran A, Attwood K, Sato R, Seiffert-Sinha K, Sinha AA. Identification of a new disease cluster of pemphigus vulgaris with autoimmune thyroid disease, rheumatoid arthritis and type I diabetes. Br J Dermatol. 2015;172:729–38.CrossRefGoogle Scholar
  3. 3.
    Chiu Y-W, Chen Y-D, Hua T-C, Wu C-H, Liu H-N, Chang Y-T. Comorbid autoimmune diseases in patients with pemphigus: a nationwide case-control study in Taiwan. Eur J Dermatol. 2017;27:375–81.PubMedGoogle Scholar
  4. 4.
    Hsu DY, Brieva J, Sinha AA, Langan SM, Silverberg JI. Comorbidities and inpatient mortality for pemphigus in the U.S.A. Br J Dermatol. 2016;174:1290–8.CrossRefGoogle Scholar
  5. 5.
    Muro Y. Antinuclear antibodies. Autoimmunity. 2005;38:3–9.CrossRefGoogle Scholar
  6. 6.
    Prüßmann J, Prüßmann W, Recke A, Rentzsch K, Juhl D, Henschler R, et al. Co-occurrence of autoantibodies in healthy blood donors. Exp Dermatol. 2014;23:519–21.CrossRefGoogle Scholar
  7. 7.
    Sezin T, Vorobyev A, Sadik CD, Zillikens D, Gupta Y, Ludwig RJ. Gene expression analysis reveals novel shared gene signatures and candidate molecular mechanisms between pemphigus and systemic lupus erythematosus in CD4+ T cells. Front Immunol. 2018;8:1992.CrossRefGoogle Scholar
  8. 8.
    Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Ulcerative colitis associated with pemphigus: a population-based large-scale study. Scand J Gastroenterol. 2017;52(12):1360–4.  https://doi.org/10.1080/00365521.2017.1380839.
  9. 9.
    Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Is there an association between pemphigus and hepatitis viruses? A population-based large-scale study. Immunol Res. 2017;65:1083–8.CrossRefGoogle Scholar
  10. 10.
    Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Association between pemphigus and neurologic diseases. JAMA Dermatol. 2018;154:281–5.CrossRefGoogle Scholar
  11. 11.
    Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.CrossRefGoogle Scholar
  12. 12.
    Somers EC, Thomas SL, Smeeth L, Hall AJ. Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiology. 2006;17:202–17.CrossRefGoogle Scholar
  13. 13.
    Szyper-Kravitz M, Marai I, Shoenfeld Y. Coexistence of thyroid autoimmunity with other autoimmune diseases: friend or foe? Additional aspects on the mosaic of autoimmunity. Autoimmunity. 2005;38:247–55.CrossRefGoogle Scholar
  14. 14.
    Davidson A, Diamond B. Autoimmune diseases. New Engl J Med. 2001;345:340–50.CrossRefGoogle Scholar
  15. 15.
    Leshem YA, Katzenelson V, Yosipovitch G, David M, Mimouni D. Autoimmune diseases in patients with pemphigus and their first-degree relatives. Int J Dermatol. 2011;50:827–31.CrossRefGoogle Scholar
  16. 16.
    Kridin K, Zelber-Sagi S, Comaneshter D, Cohen AD. Ulcerative colitis associated with pemphigus: a population-based large-scale study. Scand J Gastroenterol. 2017;52:1360–4.CrossRefGoogle Scholar
  17. 17.
    McDonagh JE, Isenberg DA. Development of additional autoimmune diseases in a population of patients with systemic lupus erythematosus. Ann Rheum Dis BMJ Publishing Group. 2000;59:230–2.CrossRefGoogle Scholar
  18. 18.
    Ghandi N, Kamyab K, Attar SNG, Ghiasi M, Daneshpazhooh M, Karbakhsh M, et al. Antinuclear antibody in patients with pemphigus vulgaris: a case-control study. Br J Dermatol. 2012;167:107.Google Scholar
  19. 19.
    Blondin DA, Zhang ZH, Shideler KK, Hou HY, Fritzler MJ, Mydlarski PR. Prvalence of non-organ-specific autoantibodies in patients with pemphigus vulgaris. J Cutan Med Surg. 2009;13:82–7.CrossRefGoogle Scholar
  20. 20.
    Amber KT, Valdebran M, Grando SA. Non-desmoglein antibodies in patients with pemphigus vulgaris. Front Immunol. 2018;9:1190.  https://doi.org/10.3389/fimmu.2018.01190. eCollection 2018.
  21. 21.
    Ippolito A, Wallace DJ, Gladman D, Fortin PR, Urowitz M, Werth V, et al. Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity. Lupus. 2011;20:250–5.CrossRefGoogle Scholar
  22. 22.
    Chan LS, Vanderlugt CJ, Hashimoto T, Nishikawa T, Zone JJ, Black MM, et al. Epitope spreading: lessons from autoimmune skin diseases. J Invest Dermatol. 1998;110:103–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of DermatologyRambam Health Care CampusHaifaIsrael
  2. 2.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Department of Quality Measurements and Research, Chief Physician’s OfficeClalit Health ServicesTel AvivIsrael
  4. 4.Siaal Research Center for Family Medicine and Primary Care, Faculty of Health SciencesBen-Gurion University of the NegevBeer-ShevaIsrael

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