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Pyoderma Gangrenosum in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

  • Vanessa States
  • Stephen O’Brien
  • Jayesh P. Rai
  • Henry L. Roberts
  • Mason Paas
  • Kayla Feagins
  • Evangeline J. Pierce
  • Richard N. Baumgartner
  • Susan GalandiukEmail author
Original Article
  • 38 Downloads

Abstract

Background

Pyoderma gangrenosum (PG) is an uncommon but severe extra-intestinal manifestation (EIM) of inflammatory bowel disease (IBD). The incidence and risk factors for PG are disputed.

Aims

To assess the incidence of PG and identify factors associated with PG in IBD patients.

Methods

A search of electronic databases (Ovid and PubMed) was conducted between 1966 and 2019. Studies that calculated the incidence of PG in IBD patient cohorts were included. Patient demographics, IBD subtype, and EIM presence were recorded. A review of our institutional database of 1057 IBD patients was conducted. A multivariate regression model and meta-analysis were conducted to identify risk factors for PG. A random effects model was used to combine the data of included studies.

Results

Fourteen studies were included in addition to 1057 IBD patients and 26 PG cases from the Louisville cohort. In total, there were 379 cases of PG in the cumulative cohort of 61,695 IBD patients. The PG incidence in individual studies ranged from 0.4 to 2.6%. In the institutional cohort, ocular EIMs and a permanent stoma were significant risk factors for PG. In the meta-analysis, PG was associated with female gender (RR = 1.328, 95% CI 1.161–1.520), Crohn’s disease (RR = 1.193, 95% CI 1.001–1.422), erythema nodosum (RR = 9.281, 95% CI 6.081–14.164), and ocular EIM (RR = 4.55, 95% CI 3.04–6.81). There was study heterogeneity when assessing IBD subtype, ocular, and joint EIMs.

Conclusions

There are conflicting data on the incidence and risk factors for PG. This meta-analysis confirms an association between PG and female gender, Crohn’s disease, erythema nodosum, and ocular EIM that have been described in smaller studies.

Keywords

Pyoderma gangrenosum Inflammatory bowel disease Systematic review Meta-analysis Extra-intestinal manifestations 

Notes

Acknowledgments

The statistical methods for this paper were reviewed by Dr. Shesh Rai, Wendell Cherry Chair in Clinical Trial Research, Professor of Biostatistics, University of Louisville, Louisville, Kentucky, USA.

Author’s contribution

VS, SG helped in original study design; VS, SOB, HR, MP, KF helped in data collection ; JR, EP, RB, KF helped in data analysis; VS, SOB, SG helped in data interpretation; VS, SOB, HR, JR, KF helped in drafting of article; VS, SOB, MP helped in figures; SOB, MP, EP, KF, RB SG helped in revision of manuscript. All authors had access to all the data and approved final draft of manuscript.

Funding

This work was supported by the John W. Price and Barbara Thruston Atwood Price Trust and a grant from the Mary K. Oxley Foundation.

Compliance with Ethical Standards

Conflict of interest

EP is an employee and shareholder in Eli Lily & Company, Indianapolis, Indiana, USA. Eli Lily & Company had no role in this manuscript. This work was completed while she was a graduate student at University of Louisville. There are no other conflicts of interests.

Supplementary material

10620_2019_5999_MOESM1_ESM.tif (11.4 mb)
Supplementary Figure 1 PRISMA flow diagram of search process, inclusion, and exclusion criteria for studies investigating PG patient cohorts. (TIFF 11683 kb)
10620_2019_5999_MOESM2_ESM.tif (56 kb)
Supplementary Figure 2 Venn diagram representation of the distribution of PG among total Louisville patient cohort (TIFF 56 kb)
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Supplementary material 3 (DOCX 12 kb)
10620_2019_5999_MOESM4_ESM.docx (14 kb)
Supplementary material 4 (DOCX 13 kb)
10620_2019_5999_MOESM5_ESM.docx (13 kb)
Supplementary material 5 (DOCX 12 kb)
10620_2019_5999_MOESM6_ESM.docx (12 kb)
Supplementary material 6 (DOCX 12 kb)

References

  1. 1.
    Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2007;5:1424–1429.Google Scholar
  2. 2.
    Lakatos L, Pandur T, David G, et al. Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: results of a 25-year follow-up study. World J Gastroenterol. 2003;9:2300–2307.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Roberts H, Rai SN, Pan J, et al. Extraintestinal manifestations of inflammatory bowel disease and the influence of smoking. Digestion. 2014;90:122–129.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Ricart E, Panaccione R, Loftus EV Jr, et al. Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2004;10:207–214.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996;23:29–34.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Christodoulou DK, Katsanos KH, Kitsanou M, Stergiopoulou C, Hatzis J, Tsianos EV. Frequency of extraintestinal manifestations in patients with inflammatory bowel disease in Northwest Greece and review of the literature. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2002;34:781–786.Google Scholar
  7. 7.
    Garg A, Hundal J, Strunk A. Overall and subgroup prevalence of Crohn disease among patients with hidradenitis suppurativa: a population-based analysis in the United States. JAMA Dermatol. 2018;154:814–818.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76:377–390.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Huang BL, Chandra S, Shih DQ. Skin manifestations of inflammatory bowel disease. Front Physiol. 2012;3:13.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Kridin K, Cohen AD, Amber KT. Underlying systemic diseases in pyoderma gangrenosum: a systematic review and meta-analysis. Am J Clin Dermatol. 2018;19:479–487.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Tuffaha SH, Sarhane KA, Mundinger GS, et al. Pyoderma gangrenosum after breast surgery: diagnostic pearls and treatment recommendations based on a systematic literature review. Ann Plast Surg. 2016;77:e39–e44.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Xia FD, Liu K, Lockwood S, et al. Risk of developing pyoderma gangrenosum after procedures in patients with a known history of pyoderma gangrenosum—a retrospective analysis. J Am Acad Dermatol. 2018;78:e311.Google Scholar
  13. 13.
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Mahid SS, Hornung CA, Minor KS, Turina M, Galandiuk S. Systematic reviews and meta-analysis for the surgeon scientist. Br J Surg. 2006;93:1315–1324.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127:820–826.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System Survey Questionnaire. Accessed February 24, 2018; 2018.Google Scholar
  17. 17.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188.CrossRefGoogle Scholar
  18. 18.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ (Clin Res Ed). 2003;327:557–560.CrossRefGoogle Scholar
  19. 19.
    Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. Philadelphia: Lippincott Williams & Wilkins; 2008.Google Scholar
  20. 20.
    Polcz M, Gu J, Florin T. Pyoderma gangrenosum in inflammatory bowel disease: the experience at Mater Health Services’ Adult Hospital 1998–2009. J Crohn’s Colitis. 2011;5:148–151.CrossRefGoogle Scholar
  21. 21.
    Yuksel I, Basar O, Ataseven H, et al. Mucocutaneous manifestations in inflammatory bowel disease. Inflamm Bowel Dis. 2009;15:546–550.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Farhi D, Cosnes J, Zizi N, et al. Significance of erythema nodosum and pyoderma gangrenosum in inflammatory bowel diseases: a cohort study of 2402 patients. Medicine. 2008;87:281–293.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Moravvej H, Razavi GM, Farshchian M, Malekzadeh R. Cutaneous manifestations in 404 Iranian patients with inflammatory bowel disease: a retrospective study. Indian J Dermatol Venereol Leprol. 2008;74:607–610.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106:110–119.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Mebazaa A, Aounallah A, Naija N, et al. Dermatologic manifestations in inflammatory bowel disease in Tunisia. La Tunisie Med. 2012;90:252–257.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Isene R, Bernklev T, Hoie O, et al. Extraintestinal manifestations in Crohn’s disease and ulcerative colitis: results from a prospective, population-based European inception cohort. Scand J Gastroenterol. 2015;50:300–305.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Ampuero J, Rojas-Feria M, Castro-Fernandez M, Cano C, Romero-Gomez M. Predictive factors for erythema nodosum and pyoderma gangrenosum in inflammatory bowel disease. J Gastroenterol Hepatol. 2014;29:291–295.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Karmiris K, Avgerinos A, Tavernaraki A, et al. Prevalence and characteristics of extra-intestinal manifestations in a large cohort of Greek patients with inflammatory bowel disease. J Crohn’s Colitis. 2016;10:429–436.CrossRefGoogle Scholar
  29. 29.
    Cardoneanu A, Cijevschi Prelipcean C, Danciu M, et al. Looking beyond gut inflammation in inflammatory bowel disease. Rom J Morphol Embryol. 2018;59:1097–1105.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Roth N, Biedermann L, Fournier N, et al. Occurrence of skin manifestations in patients of the Swiss Inflammatory Bowel Disease Cohort Study. PLoS One. 2019;14:e0210436.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Halling ML, Kjeldsen J, Knudsen T, Nielsen J, Hansen LK. Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases. World J Gastroenterol. 2017;23:6137–6146.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Vide J, Osório F, Costa-Silva M, et al. Cutaneous morbidity among inflammatory bowel disease patients: a cohort study. J Crohns Colitis. 2018;12:442–451.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Freeman HJ. Erythema nodosum and pyoderma gangrenosum in 50 patients with Crohn’s disease. Can J Gastroenterol. 2005;19:603–606.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn’s disease and ulcerative colitis: a study of 700 patients. Medicine. 1976;55:401–412.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Veloso FT. Extraintestinal manifestations of inflammatory bowel disease: do they influence treatment and outcome? World J Gastroenterol. 2011;17:2702–2707.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Mir-Madjlessi SH, Taylor JS, Farmer RG. Clinical course and evolution of erythema nodosum and pyoderma gangrenosum in chronic ulcerative colitis: a study of 42 patients. Am J Gastroenterol. 1985;80:615–620.PubMedPubMedCentralGoogle Scholar
  37. 37.
    McElnea E, Stephenson K, Fulcher T. Pyoderma gangrenosum affecting the eye, orbit, and adnexa. A review. Orbit (Amsterdam, Netherlands).. 2018;37:26–31.Google Scholar
  38. 38.
    Gupta AS, Ortega-Loayza AG. Ocular pyoderma gangrenosum: a systematic review. J Am Acad Dermatol. 2017;76:512–518.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001;96:1116–1122.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Menachem Y, Gotsman I. Clinical manifestations of pyoderma gangrenosum associated with inflammatory bowel disease. Israel Med Assoc J IMAJ. 2004;6:88–90.Google Scholar
  41. 41.
    Trost LB, McDonnell JK. Important cutaneous manifestations of inflammatory bowel disease. Postgrad Med J. 2005;81:580–585.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Lyon CC, Smith AJ, Griffiths CE, Beck MH. The spectrum of skin disorders in abdominal stoma patients. Br J Dermatol. 2000;143:1248–1260.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Wu XR, Mukewar S, Kiran RP, Remzi FH, Hammel J, Shen B. Risk factors for peristomal pyoderma gangrenosum complicating inflammatory bowel disease. J Crohn’s Colitis. 2013;7:e171–e177.CrossRefGoogle Scholar
  44. 44.
    Afifi L, Sanchez IM, Wallace MM, Braswell SF, Ortega-Loayza AG, Shinkai K. Diagnosis and management of peristomal pyoderma gangrenosum: A systematic review. J Am Acad Dermatol. 2018;78:e1191.CrossRefGoogle Scholar
  45. 45.
    Nguyen GC, Torres EA, Regueiro M, et al. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. 2006;101:1012–1023.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Ott C, Takses A, Obermeier F, Schnoy E, Muller M. Smoking increases the risk of extraintestinal manifestations in Crohn’s disease. World J Gastroenterol. 2014;20:12269–12276.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Manguso F, Sanges M, Staiano T, et al. Cigarette smoking and appendectomy are risk factors for extraintestinal manifestations in ulcerative colitis. Am J Gastroenterol. 2004;99:327–334.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Satsangi J, Grootscholten C, Holt H, Jewell DP. Clinical patterns of familial inflammatory bowel disease. Gut. 1996;38:738–741.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Maverakis E, Ma C, Shinkai K, et al. Diagnostic criteria of ulcerative pyoderma gangrenosum: a Delphi consensus of international experts. JAMA Dermatol. 2018;154:461–466.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Vanessa States
    • 1
  • Stephen O’Brien
    • 1
  • Jayesh P. Rai
    • 2
  • Henry L. Roberts
    • 1
  • Mason Paas
    • 1
  • Kayla Feagins
    • 1
  • Evangeline J. Pierce
    • 3
  • Richard N. Baumgartner
    • 4
  • Susan Galandiuk
    • 1
    Email author
  1. 1.Price Institute of Surgical Research, The Hiram C. Polk Jr., MD Department of SurgeryUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of CardiologyUniversity of LouisvilleLouisvilleUSA
  3. 3.Eli Lily and CompanyIndianapolisUSA
  4. 4.Department of EpidemiologyUniversity of LouisvilleLouisvilleUSA

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