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Association of autoimmune blistering disease, and specifically, pemphigus vulgaris, with cardiovascular disease and its risk factors: a systematic review and meta-analysis

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Abstract

Previous studies have found conflicting results about the association of autoimmune blistering disease (AIBD) with cardiovascular disease (CVD) risk. The objective of the study was to systematically review the relationship of AIBD, including pemphigus vulgaris (PV), and its treatment with CVD and CVD risk factors. MEDLINE, EMBASE, Cochrane, LILACS, SCOPUS, and Web of Science were searched. We included all studies of CVD and CVD risk factors in AIBD patients. Two reviewers performed title and/or abstract review and data extraction. Pooled random-effects meta-analysis was performed. Forty papers met inclusion criteria. AIBD was associated with higher odds of diabetes (DM) (odds ratio [95% confidence interval]: 1.809 [1.258–2.601]), hypertension (HTN) (1.393 [1.088–1.784]), dyslipidemia (2.177 [1.163–4.073]) and heart failure (1.919 [1.603–2.298]), but was not associated with obesity, stroke, angina, heart attack, or arrhythmia. The pooled random-effects prevalence for treatment-related adverse events (AEs) in AIBD was 13.7% for DM, 10.7% for HTN, and 17.1% for CVD. Sensitivity analysis of high-quality studies revealed similar results. AIBD patients have increased CVD risk factors and heart failure. Systemic corticosteroid treatment results in CVD-related AEs in AIBD. Increased CVD screening and prevention strategies are warranted in AIBD.

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Abbreviations

AE:

Adverse event

AIBD:

Autoimmune blistering disease

CI:

Confidence interval

CVD:

Cardiovascular disease

DM:

Diabetes mellitus

HF:

Heart failure

HTN:

Hypertension

NOS:

Newcastle–Ottawa Scale

OR:

Odds ratio

PF:

Pemphigus foliaceous

PV:

Pemphigus vulgaris

TRAE:

Treatment-related adverse event

References

  1. Sticherling M, Erfurt-Berge C (2012) Autoimmune blistering diseases of the skin. Autoimmun Rev 11(3):226–230

    Article  CAS  PubMed  Google Scholar 

  2. Kluger N, Pankakoski A, Panelius J (2020) Depression and anxiety in patients with bullous pemphigoid: impact and management challenges. Clin Cosmet Investig Dermatol 13:73–76

    Article  PubMed  Google Scholar 

  3. Kalinska-Bienias A, Piotrowski T, Kowalczyk E et al (2019) Actigraphy-measured nocturnal wrist movements and assessment of sleep quality in patients with bullous pemphigoid: a pilot case-control study. Clin Exp Dermatol 44(7):759–765

    Article  CAS  PubMed  Google Scholar 

  4. Kulczycka-Siennicka L, Cynkier A, Waszczykowska E, Wozniacka A, Zebrowska A (2017) The role of intereukin-31 in pathogenesis of itch and its intensity in a course of bullous pemphigoid and dermatitis herpetiformis. Biomed Res Int 2017:5965492

    Article  PubMed  PubMed Central  Google Scholar 

  5. Pedroni MN, Hirotsu C, Porro AM, Tufik S, Andersen ML (2017) The role of sleep in pemphigus: a review of mechanisms and perspectives. Arch Dermatol Res 309(8):659–664

    Article  PubMed  Google Scholar 

  6. Kouris A, Platsidaki E, Christodoulou C et al (2016) Quality of life, depression, anxiety and loneliness in patients with bullous pemphigoid. A case control study. An Bras Dermatol 91(5):601–603

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wohl Y, Mashiah J, Kutz A, Hadj-Rabia S, Cohen AD (2015) Pemphigus and depression comorbidity: a case control study. Eur J Dermatol 25(6):602–605

    Article  CAS  PubMed  Google Scholar 

  8. Hsu DY, Brieva J, Nardone B, West D, Silverberg JI (2017) Association of pemphigus and systemic corticosteroid use with comorbid health disorders: a case-control study. Dermatol Online J. https://doi.org/10.5070/D32312037664

    Article  PubMed  Google Scholar 

  9. Hsu DY, Brieva J, Sinha AA, Langan SM, Silverberg JI (2016) Comorbidities and inpatient mortality for pemphigus in the United States. Br Dermatol 174(6):1290–1298

    Article  Google Scholar 

  10. Ren Z, Hsu DY, Silverberg NB, Silverberg JI (2017) The inpatient burden of autoimmune blistering disease in us children: analysis of nationwide inpatient sample data. Am J Clin Dermatol 18(2):287–297

    Article  PubMed  Google Scholar 

  11. Ambiel MV, Roselino AM (2014) Prevalence of metabolic syndrome and its components in a Brazilian sample of pemphigus patients. An Bras Dermatol 89(5):752–756

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wohl Y, Dreiher J, Cohen AD (2009) Pemphigus and dyslipidaemia: a case-control study. Br J Dermatol 161(6):1418–1420

    Article  CAS  PubMed  Google Scholar 

  13. Martin LK, Werth V, Villanueva E, Segall J, Murrell DF (2009) Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev 1:Cd006263

    Google Scholar 

  14. Rees K, Hartley L, Day C, Flowers N, Clarke A, Stranges S (2013) Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 1:Cd009671

    Google Scholar 

  15. Akarsu S, Özbağçivan Ö, Dolaş N, Aktan Ş (2017) Possible triggering factors and comorbidities in newly diagnosed autoimmune bullous diseases. Turk J Med Sci 47(3):832–840

    Article  CAS  PubMed  Google Scholar 

  16. Baican A, Chiorean R, Leucuta DC et al (2015) Prediction of survival for patients with pemphigus vulgaris and pemphigus foliaceus: a retrospective cohort study. Orphanet J Rare Dis. https://doi.org/10.1186/s13023-015-0263-4

    Article  PubMed  PubMed Central  Google Scholar 

  17. Belgnaoui FZ, Senouci K, Chraibi H et al (2007) Predisposition to infection in patients with pemphigus retrospective study of 141 cases. Presse Medicale 36(11 I):1563–1569

    Article  PubMed  Google Scholar 

  18. Gupta VK, Kelbel TE, Nguyen D et al (2011) A globally available internet-based patient survey of pemphigus vulgaris: epidemiology and disease characteristics. Dermatol Clin 29(3):393–404

    Article  CAS  PubMed  Google Scholar 

  19. Heelan K, Mahar AL, Walsh S, Shear NH (2015) Pemphigus and associated comorbidities: a cross-sectional study. Clin Exp Dermatol 40(6):593–599

    Article  CAS  PubMed  Google Scholar 

  20. Jain R, Kumar B (2003) Immediate and delayed complications of dexamethasone cyclophosphamide pulse (DCP) therapy. J Dermatol 30(10):713–718

    Article  CAS  PubMed  Google Scholar 

  21. Jelti L, Cordel N, Gillibert A et al (2019) Incidence and mortality of pemphigus in France. J Investig Dermatol 139(2):469–473

    Article  CAS  PubMed  Google Scholar 

  22. Karabay EA, Cerman AA, Altunay IK (2018) Evaluation of comorbidities in patients with autoimmune bullous diseases: a retrospective study. Med Bulletin of Sisli Etfal Hospital 52(4):302–306

    Google Scholar 

  23. Kridin K, Zelber-Sagi S, Bergman R (2018) Risk factors for lethal outcome in patients with pemphigus: a retrospective cohort study. Eur J Dermatol 28(1):26–37

    PubMed  Google Scholar 

  24. Kwa MC, Silverberg JI (2017) Association between inflammatory skin disease and cardiovascular and cerebrovascular co-morbidities in us adults: analysis of nationwide inpatient sample data. Am J Clin Dermatol 18(6):813–823

    Article  PubMed  Google Scholar 

  25. Leshem YA, Gdalevich M, Ziv M, David M, Hodak E, Mimouni D (2014) Opportunistic infections in patients with pemphigus. J Am Acad Dermatol 71(2):284–292

    Article  PubMed  Google Scholar 

  26. Mahajan VK, Sharma NL, Sharma RC, Garg G (2005) Twelve-year clinico-therapeutic experience in pemphigus: a retrospective study of 54 cases. Int J Dermatol 44(10):821–827

    Article  PubMed  Google Scholar 

  27. Michailidou EZ, Belazi MA, Markopoulos AK, Tsatsos MI, Mourellou ON, Antoniades DZ (2007) Epidemiologic survey of pemphigus vulgaris with oral manifestations in northern Greece: retrospective study of 129 patients. Int J Dermatol 46(4):356–361

    Article  PubMed  Google Scholar 

  28. Patsatsi A, Lamprou F, Kokolios M et al (2017) Spectrum of autoimmune bullous diseases in Northern Greece. A 4-year retrospective study and review of the literature. Acta Dermatovenerol Croat 25(3):195–201

    PubMed  Google Scholar 

  29. Shafi M, Khatri ML, Mashina M, Ben-Ghazeil M (1994) Pemphigus: a clinical study of 109 cases from Tripoli, Libya. Indian J Dermatol Venereol Leprol 60(3):140–143

    Google Scholar 

  30. Uzun S, Durdu M, Akman A et al (2006) Pemphigus in the mediterranean region of Turkey: a study of 148 cases. Int J Dermatol 45(5):523–528

    Article  PubMed  Google Scholar 

  31. Darjani A, Nickhah N, Hedayati Emami MH et al (2017) Assessment of the prevalence and risk factors associated with glucocorticoid-induced diabetes mellitus in pemphigus vulgaris patients. Acta Med Iran 55(6):375–380

    PubMed  Google Scholar 

  32. Alsaleh QA, Nanda A, Al-Baghli NM, Dvorak R (1999) Pemphigus in Kuwait. Int J Dermatol 38(5):351–356

    Article  CAS  PubMed  Google Scholar 

  33. Amal S, Hocar O, Zidane W, Laissaoui K, Squalli DH (2005) Epidemiologie study of pemphigus in Marrakech: 134 cases. Ann Dermatol Venereol 132(12):1008–1009

    Article  CAS  PubMed  Google Scholar 

  34. Benchikhi H, Ghafour S, Disky A, Janati K, Bichra L, Lakhdar H (2006) Pemphigus: treatment and outcome in 122 cases [3]. Ann Dermatol Venereol 133(12):1012–1014

    Article  CAS  PubMed  Google Scholar 

  35. Bhatia K, Kataria R, Sharma R (2015) Management of pemphigus vulgaris by dexamethasone cyclophosphamide pulse therapy: a SAIMS experience. J Am Acad Dermato 72(5):AB121

    Article  Google Scholar 

  36. Chams-Davatchi C, Valikhani M, Daneshpazhooh M et al (2005) Pemphigus: analysis of 1209 cases. Int J Dermatol 44(6):470–476

    Article  PubMed  Google Scholar 

  37. Chmurova N, Svecova D (2009) Pemphigus vulgaris: a 11-year review. Bratisl Med J 110(8):500–503

    CAS  Google Scholar 

  38. Coronel-Pérez IM, Rodríguez-Rey EM, Pérez-Bernal AM, Camacho FM (2009) Epidemiology of pemphigus in hospital universitario virgen macarena, seville, spain, 2005–2006. Actas dermo-sifiliograficas 100(2):121–125

    Article  PubMed  Google Scholar 

  39. Corven CB, Carvalho P, Prost C et al (2003) Treatment of pemphigus vulgaris by azathioprine and low doses of prednisone (Lever scheme). Annales de Dermat et de Venereol 130(1 I):13–15

    Google Scholar 

  40. Dǎnescu AS, Bâldea I, Leucuţa DC et al (2018) Immunological markers as predictors of developing steroid-induced diabetes mellitus in pemphigus vulgaris patients. Medicine (United States) 97(17):e0463

    Google Scholar 

  41. Fernandes NC, Perez M (2001) Treatment of pemphigus vulgaris and pemphigus foliaceus: experience with 71 patients over a 20 year period. Rev Inst Med Trop Sao Paulo 43(1):33–36

    Article  CAS  PubMed  Google Scholar 

  42. Joly P, Maho-Vaillant M, Prost-Squarcioni C et al (2017) First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 389(10083):2031–2040

    Article  CAS  PubMed  Google Scholar 

  43. Khamidov SA, Stoyanov BG, Kilichev RM, Valikhanov UA, Kurbanov OD, Tereshko TA (1992) On the clinical picture, therapy, and follow-up of patients with true pemphigus-vulgaris, living in hot climatic conditioNS. Vestnik Dermatii I Venerolii 9:42–45

    Google Scholar 

  44. Kim BD, Kim SC (2005) Clinical study of Korean patients with pemphigus. Korean J Dermatol 43(8):1077–1084

    Google Scholar 

  45. Konstantinov D (1980) Side effects in patients with pemphigus vulgaris treated with corticosteroids. Acta Dermatovenerol Iugosl 7(1):43–46

    Google Scholar 

  46. Krain LS (1974) Pemphigus epidemiologic and survival characteristics of 59 patients, 1955–1973. Arch Dermat 110(6):862–865

    Article  CAS  Google Scholar 

  47. Valikhani M, Niko MK, Tork AN (2007) Risk factors and frequency of steroid - induced diabetes in pemphigus vulgaris patients during 1 year study. Iran J Diabetes Lipid Disord 6(3):97–103 (+E136)

    Google Scholar 

  48. Yu KJ, Yang LJ, Kuan YZ, Ho HC, Hong HS (2007) Pemphigus - clinical analysis of 129 cases. Dermatol Sin 25(2):95–102

    Google Scholar 

  49. da Cunha SF, dos Santos VM, Monteiro JP et al (2003) Serum lipids of pemphigus foliaceus patients on long-term glucocorticoid therapy. Rev Soc Bras Med Trop 36(1):1–4

    Article  PubMed  Google Scholar 

  50. Miller IM, Ellervik C, Yazdanyar S, Jemec GB (2013) Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. J Am Acad Dermatol 69(6):1014–1024

    Article  PubMed  Google Scholar 

  51. Tzellos T, Zouboulis CC, Gulliver W, Cohen AD, Wolkenstein P, Jemec GB (2015) Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies. Br J Dermatol 173(5):1142–1155

    Article  CAS  PubMed  Google Scholar 

  52. Zhang A, Silverberg JI (2015) Association of atopic dermatitis with being overweight and obese: a systematic review and metaanalysis. J Am Acad Dermatol 72(4):606-616.e604

    Article  PubMed  Google Scholar 

  53. Davidovici BB, Sattar N, Jörg PC et al (2010) Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. J Investig Dermatol 130(7):1785–1796

    Article  CAS  PubMed  Google Scholar 

  54. Vassileva S, Drenovska K, Manuelyan K (2014) Autoimmune blistering dermatoses as systemic diseases. Clin Dermatol 32(3):364–375

    Article  PubMed  Google Scholar 

  55. Xue J, Su W, Chen Z, Ke Y, Du X, Zhou Q (2014) Overexpression of interleukin-23 and interleukin-17 in the lesion of pemphigus vulgaris: a preliminary study. Mediators Inflamm 2014:463928

    Article  PubMed  PubMed Central  Google Scholar 

  56. Lee SH, Hong WJ, Kim SC (2017) Analysis of serum cytokine profile in pemphigus. Ann Dermatol 29(4):438–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. D’Auria L, Bonifati C, Mussi A et al (1997) Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity. Eur Cytokine Netw 8(4):383–387

    CAS  PubMed  Google Scholar 

  58. Alecu M, Alecu S, Coman G, Gălăţescu E, Ursaciuc C (1999) ICAM-1, ELAM-1, TNF-alpha and IL-6 in serum and blister liquid of pemphigus vulgaris patients. Roum Arch Microbiol Immunol 58(2):121–130

    CAS  PubMed  Google Scholar 

  59. Raychaudhuri SP, Gross J (2000) Psoriasis risk factors: role of lifestyle practices. Cutis 66(5):348–352

    CAS  PubMed  Google Scholar 

  60. Silverberg JI, Song J, Pinto D et al (2016) Atopic dermatitis is associated with less physical activity in US adults. J Investig Dermatol 136(8):1714–1716

    Article  CAS  PubMed  Google Scholar 

  61. Strom MA, Silverberg JI (2016) Associations of physical activity and sedentary behavior with atopic disease in united states children. J Pediatr 174:247-253.e243

    Article  PubMed  Google Scholar 

  62. Silverberg JI, Kantor RW, Dalal P et al (2018) A comprehensive conceptual model of the experience of chronic itch in adults. Am J Clin Dermatol 19(5):759–769

    Article  PubMed  PubMed Central  Google Scholar 

  63. Silverberg JI, Lei D, Yousaf M et al (2020) Association of itch triggers with atopic dermatitis severity and course in adults. Annals Allergy, Asthma Immunol: Off Publ Am Coll Allergy, Asthma, Immunol 125:552-559.e2

    Article  Google Scholar 

  64. Chams-Davatchi C, Esmaili N, Daneshpazhooh M et al (2007) Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol 57(4):622–628

    Article  PubMed  Google Scholar 

  65. Ahmed AR, Spigelman Z, Cavacini LA, Posner MR (2006) Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med 355(17):1772–1779

    Article  CAS  PubMed  Google Scholar 

  66. Sukanjanapong S, Thongtan D, Kanokrungsee S, Suchonwanit P, Chanprapaph K (2020) A comparison of azathioprine and mycophenolate mofetil as adjuvant drugs in patients with pemphigus: a retrospective cohort study. Dermatology and therapy 10(1):179–189

    Article  PubMed  Google Scholar 

  67. Zheng J, Liu N, Wang Y, Chen F, Ding Y (2020) Pemphigus vulgaris with psoriasis vulgaris successfully treated with methotrexate and low-dose methylprednisolone. Dermatol Ther 33(1):e13165

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. The University of Illinois at Chicago, Chicago, IL, USA

    Alex M. Rokni

  2. NYU Langone Hospital - Long Island, Mineola, NY, USA

    Marissa Ayasse

  3. AMITA Health Saint Joseph Hospital Chicago, Chicago, IL, USA

    Adnan Ahmed

  4. Departments of Medicine and Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Lauren Guggina

  5. Department of Dermatology, State University of New York Downstate Medical Center, Brooklyn, NY, USA

    Robert W. Kantor

  6. Department of Dermatology, the George Washington University School of Medicine and Health Sciences, 2150 Pennsylvania Avenue NW Suite 2B-425, Washington, DC, 20037, USA

    Jonathan I. Silverberg

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  1. Alex M. Rokni
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  4. Lauren Guggina
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Contributions

JI Silverberg had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: JIS. Acquisition of data: AAA, KW. Analysis and interpretation of data: AM, RA, JI Silverberg. Drafting of the manuscript: RA, AM, AA. Critical revision of manuscript for important intellectual content: JI Silverberg. Statistical analysis: RA, AM. Administrative technical or material support: none. Study supervision: none.

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Rokni, A.M., Ayasse, M., Ahmed, A. et al. Association of autoimmune blistering disease, and specifically, pemphigus vulgaris, with cardiovascular disease and its risk factors: a systematic review and meta-analysis. Arch Dermatol Res 315, 207–213 (2023). https://doi.org/10.1007/s00403-022-02346-y

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