Portal de Periódicos da CAPES

Hidradenitis Suppurativa and Inflammatory Bowel Disease: A Cross-Sectional Study of 3,207 Patients

2016; Elsevier BV; Volume: 136; Issue: 8 Linguagem: Inglês

10.1016/j.jid.2016.04.003

1523-1747

Guy Shalom, Tamar Freud, Gil Ben Yakov, Raed Khoury, Jacob Dreiher, Daniel Vardy, Doron Comaneshter, Arnon D. Cohen,

Microscopic Colitis

Crohn’s disease (CD) and ulcerative colitis (UC), both subtypes of inflammatory bowel disease (IBD), were observed to be risk factors for hidradenitis suppurativa (HS), yet the risk for IBD in HS patients has been poorly defined. The purpose of our study, therefore, was to evaluate the association between HS and IBD, both CD and UC, based on the comprehensive population-based database of Clalit Health Services (CHS). CHS is the largest health maintenance organization in Israel, serving a population of more than 4,300,000 enrollees. CHS’s database is a comprehensive computerized database with continuous real-time input from pharmaceutical, medical, and administrative operating systems. Our study was designed as a cross-sectional study with an age- and sex-matched control subjects. The group of HS patients consisted of patients with at least one documented HS diagnosis in their medical records between the years 1998 and 2013, registered by a CHS dermatologist in a primary care center. The control group consisted of age- and sex-matched subjects without HS. Group matching, rather than individual matching, was used. The extracted information from the chronic disease register included age, sex, ethnicity, smoking status of the subject, obesity, and presence of IBD: UC, CD, or indeterminate colitis diagnoses. In the present study, the included IBD diagnoses were made by a CHS gastroenterologist in line with the European evidence-based consensus on the diagnosis of UC and CD (Stange et al., 2006Stange E.F. Travis S.P. Vermeire S. Beglinger C. Kupcinkas L. Geboes K. et al.European evidence based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis.Gut. 2006; 5: i1-i15Crossref Scopus (499) Google Scholar, Stange et al., 2008Stange E.F. Travis S.P. Vermeire S. Reinisch W. Geboes K. Barakauskiene A. et al.European evidence-based consensus on the diagnosis and management of ulcerative colitis: definitions and diagnosis.J Crohns Colitis. 2008; 2: 1-23Abstract Full Text Full Text PDF PubMed Scopus (442) Google Scholar). All files of IBD patients were manually reviewed by a dermatologist (GS, RK) to confirm HS diagnoses based on dermatologist clinic visits, health care services use, pharmacy claims, and/or surgical procedures. IBD diagnoses were manually validated as well; in cases of uncertain diagnoses, files were re-evaluated by a gastroenterologist (GBY), and the appropriate diagnoses were made. Statistical analysis was performed using the SPSS package, version 20 (SPSS Inc., Chicago, IL). Demographic data at baseline were compared between the study groups. The association between HS and CD or UC was tested in a univariate analysis and logistic regression model, adjusting for age, sex, ethnicity, obesity, and smoking status of the subject. A P-value of less than 0.05 was considered statistically significant. The study was approved by the institutional review board of Meir Medical Center, Kfar Saba, Israel. The study included 3,207 HS patients diagnosed by a dermatologist in primary care centers and 6,412 age- and sex-matched control subjects without HS. HS patients were mostly female, and most (74.3%) were younger than 50 years. HS was significantly associated with CD (odds ratio = 2.03, 95% confidence interval = 1.14–3.62, P = .01) but not with UC (odds ratio = 1.82, 95% confidence interval = 0.81–4.05, P = .15), compared with control subjects, both in the univariate and the adjusted multivariate analyses (Table 1).Table 1The association between HS and investigated comorbidities by univariate analysis and the association between each categorical variable and IBDHS Patients N (%), N = 3,207Controls N (%), N = 6,412OR95% CIP-ValueUnivariate analysis Crohn’s disease26 (0.8)23 (0.4)2.271.29–3.980.004 Ulcerative colitis12 (0.4)13 (0.2)1.850.84–4.050.138Ulcerative ColitisCrohn’s DiseaseOR95% CIP-ValueOR95% CIP-ValueMultivariate analysis1ORs are adjusted with ethnicity, obesity, age, sex, and smoking status of the subjects. HS1.820.81–4.050.1502.031.14–3.620.010 Arab ethnicity0.800.27–2.380.2400.430.16–1.260.130 Female (vs. male)1.350.61–2.960.9501.230.68–2.220.460 Smokers, ever (vs nonsmokers)0.910.42–1.980.9801.360.76–2.420.310 Obesity (vs no obesity)0.970.38–2.420.7101.290.67–2.530.360 Age (per year)1.031.01–1.050.2901.010.98–1.030.430Abbreviations: CI, confidence interval; HS, hidradenitis suppurativa; OR, odds ratio.1 ORs are adjusted with ethnicity, obesity, age, sex, and smoking status of the subjects. Open table in a new tab Abbreviations: CI, confidence interval; HS, hidradenitis suppurativa; OR, odds ratio. Our observation is consistent with recent population-based studies (Kohorst et al., 2015Kohorst J.J. Kimball A.B. Davis M.D. Systemic associations of hidradenitis suppurativa.J Am Acad Dermatol. 2015; 73: S27-S35Abstract Full Text Full Text PDF PubMed Scopus (98) Google Scholar, van der Zee et al., 2014van der Zee H.H. de Winter K. van der Woude C.J. Prens E.P. The prevalence of hidradenitis suppurativa in 1093 patients with inflammatory bowel disease.Br J Dermatol. 2014; 171: 673-675Crossref PubMed Scopus (61) Google Scholar, Yadav et al., 2016Yadav S. Singh S. Edakkanambeth Varayil J. Harmsen W.S. Zinsmeister A.R. Tremaine W.J. et al.Hidradenitis suppurativa in patients with inflammatory bowel disease: a population-based cohort study in Olmsted County, Minnesota.Clin Gastroenterol Hepatol. 2016; 14: 65-70Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar), yet it adds essential data because it strengthens the notion in previous reports that the association between HS and IBD is stronger for CD than for UC. Additionally, our study is population based and therefore overcomes a potential selection bias of tertiary center-based investigations (Berksonian bias). Higher risk for HS in IBD patients was first noticed in the 1990s (Ostlere et al., 1991Ostlere L.S. Langtry J.A. Mortimer P.S. Staughton R.C. Hidradenitis suppurativa in Crohn’s disease.Br J Dermatol. 1991; 125: 384-386Crossref PubMed Scopus (70) Google Scholar), and this was followed by numerous consistent individual case reports. Treatment with tumor necrosis factor-α inhibitors for IBD attained relief in HS symptoms in IBD patients with concomitant HS (Martínez et al., 2001Martínez F. Nos P. Benlloch S. Ponce J. Hidradenitis suppurativa and Crohn’s disease: response to treatment with infliximab.Inflamm Bowel Dis. 2001; 7: 323-326Crossref PubMed Scopus (153) Google Scholar). These observations led to great progress in the management of HS and suggest common denominators in the pathogenesis of both HS and IBD. In van der Zee et al., 2010van der Zee H.H. van der Woude C.J. Florencia E.F. Prens E.P. Hidradenitis suppurativa and inflammatory bowel disease: are they associated? Results of a pilot study.Br J Dermatol. 2010; 162: 195-197Crossref PubMed Scopus (121) Google Scholar estimated the prevalence of HS at 16% in a cohort of 158 patients with IBD, with higher prevalence for CD than UC. In a follow-up study, based on a self-reported questionnaire, the authors observed 23% prevalence of HS in patients with IBD, again with a preference to CD over UC (van der Zee et al., 2014van der Zee H.H. de Winter K. van der Woude C.J. Prens E.P. The prevalence of hidradenitis suppurativa in 1093 patients with inflammatory bowel disease.Br J Dermatol. 2014; 171: 673-675Crossref PubMed Scopus (61) Google Scholar). In a population-based study from Minnesota (Yadav et al., 2016Yadav S. Singh S. Edakkanambeth Varayil J. Harmsen W.S. Zinsmeister A.R. Tremaine W.J. et al.Hidradenitis suppurativa in patients with inflammatory bowel disease: a population-based cohort study in Olmsted County, Minnesota.Clin Gastroenterol Hepatol. 2016; 14: 65-70Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar), the HS point prevalence was 1.2% in 679 IBD patients. The authors estimated the relative risk of HS in IBD to be approximately nine times higher compared with the general population, with higher risk for CD than for UC. Our study supports a stronger association between HS and CD (compared with UC). This stronger association may be partly due to misdiagnosis of metastatic CD (genital or extragenital) as HS. However, if this stronger association does truly exist for HS and CD, it can give a new lead in understanding the pathogenesis of both CD and HS. Although our study has some strong points, it also has several limitations. First, underestimation of HS frequency is possible. Second, a causal link between HS and IBD could not be assessed. As in any cross-sectional study, we could not determine the temporal relationship between the diagnoses of IBD and HS. We cannot definitely ascertain whether HS appeared first and led to the diagnosis of IBD or vice versa. Patients with IBD are more likely to have sought care from dermatologists compared with control subjects; therefore, detection bias still remains a possible limitation of our study. Although cases of HS and concomitant IBD were manually validated by dermatologists (GS, RK), misdiagnosis of metastatic CD as HS remains possible. This potential error can alternatively explain the slight differences between our study and the study from Minnesota and thus may represent another weakness of our study. In spite of these limitations, the present study shows important data regarding the association between HS and IBD. In conclusion, we observed an association between HS and CD but not UC. This pattern can further enlighten the pathogenesis of both CD and HS. Early detection and treatment of CD in patients with HS may prevent late complications. Therefore, clinicians should consider whether HS patients may have undiagnosed IBD, especially CD, and suggest an appropriate screening and treatment. ADC served as an advisor, investigator, or speaker for Abbvie, BI Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa. The authors state no conflict of interest. The present study was funded by an independent research grant from Abbvie, Inc. The company was not involved in any part of the study or writing. The Association between Hidradenitis Suppurativa and Crohn’s Disease: in Search of the Missing Pathogenic LinkJournal of Investigative DermatologyVol. 136Issue 9PreviewHidradenitis suppurativa is a chronic, autoinflammatory skin disease. Shalom et al. demonstrate in a large cross-sectional study an association between Crohn’s disease and hidradenitis suppurativa, but not with ulcerative colitis. This association supports the hypothesis that a similar pathogenic mechanism contributes to both diseases, providing new possibilities for functional studies and therapy development. Full-Text PDF Open Archive