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Figure 1.
PRISMA Study Flowchart
PRISMA Study Flowchart

CENTRAL indicates Cochrane Central Register of Controlled Trials; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses.

Figure 2.
Risk of Bias Among Included Studies
Risk of Bias Among Included Studies

The Newcastle-Ottawa Scale was used to access the risk of bias. A green dot denotes low risk of bias; yellow, unclear risk of bias.

Figure 3.
Forest Plots of the Association of Hidradenitis Suppurativa (HS) With Crohn Disease and Ulcerative Colitis
Forest Plots of the Association of Hidradenitis Suppurativa (HS) With Crohn Disease and Ulcerative Colitis

Data were pooled separately by study design using random-effects model; the inverse variance (IV) technique was used for pooling of measures of effects. OR indicates odds ratio; SE, standard error.

Table 1.  
Characteristics of Included Case-Control and Cross-sectional Studies
Characteristics of Included Case-Control and Cross-sectional Studies
1.
Zouboulis  CC, Desai  N, Emtestam  L,  et al.  European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.  J Eur Acad Dermatol Venereol. 2015;29(4):619-644. doi:10.1111/jdv.12966PubMedGoogle ScholarCrossref
2.
Kelly  G, Hughes  R, McGarry  T,  et al.  Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa.  Br J Dermatol. 2015;173(6):1431-1439. doi:10.1111/bjd.14075PubMedGoogle ScholarCrossref
3.
Micheletti  RG.  Hidradenitis suppurativa: current views on epidemiology, pathogenesis, and pathophysiology.  Semin Cutan Med Surg. 2014;33(3)(suppl):S48-S50. doi:10.12788/j.sder.0091PubMedGoogle ScholarCrossref
4.
Guet-Revillet  H, Coignard-Biehler  H, Jais  J-P,  et al.  Bacterial pathogens associated with hidradenitis suppurativa, France.  Emerg Infect Dis. 2014;20(12):1990-1998. doi:10.3201/eid2012.140064PubMedGoogle ScholarCrossref
5.
van der Zee  HH, Horvath  B, Jemec  GBE, Prens  EP.  The association between hidradenitis suppurativa and Crohn’s disease: in search of the missing pathogenic link.  J Invest Dermatol. 2016;136(9):1747-1748. doi:10.1016/j.jid.2016.05.102PubMedGoogle ScholarCrossref
6.
Ellinghaus  D, Bethune  J, Petersen  BS, Franke  A.  The genetics of Crohn’s disease and ulcerative colitis: status quo and beyond.  Scand J Gastroenterol. 2015;50(1):13-23. doi:10.3109/00365521.2014.990507PubMedGoogle ScholarCrossref
7.
Baumgart  DC, Sandborn  WJ.  Inflammatory bowel disease: clinical aspects and established and evolving therapies.  Lancet. 2007;369(9573):1641-1657. doi:10.1016/S0140-6736(07)60751-XPubMedGoogle ScholarCrossref
8.
Rioux  JD, Xavier  RJ, Taylor  KD,  et al.  Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis.  Nat Genet. 2007;39(5):596-604. doi:10.1038/ng2032PubMedGoogle ScholarCrossref
9.
Sartor  RB, Wu  GD.  Roles for intestinal bacteria, viruses, and fungi in pathogenesis of inflammatory bowel diseases and therapeutic approaches.  Gastroenterology. 2017;152(2):327-339.e4.Google ScholarCrossref
10.
Kamal  N, Cohen  BL, Buche  S, Delaporte  E, Colombel  JF.  Features of patients with Crohn’s disease and hidradenitis suppurativa.  Clin Gastroenterol Hepatol. 2016;14(1):71-79. doi:10.1016/j.cgh.2015.04.180PubMedGoogle ScholarCrossref
11.
Alikhan  A, Lynch  PJ, Eisen  DB.  Hidradenitis suppurativa: a comprehensive review.  J Am Acad Dermatol. 2009;60(4):539-561. doi:10.1016/j.jaad.2008.11.911PubMedGoogle ScholarCrossref
12.
Jemec  GB.  Clinical practice: hidradenitis suppurativa.  N Engl J Med. 2012;366(2):158-164. doi:10.1056/NEJMcp1014163PubMedGoogle ScholarCrossref
13.
Richette  P, Molto  A, Viguier  M,  et al.  Hidradenitis suppurativa associated with spondyloarthritis: results from a multicenter national prospective study.  J Rheumatol. 2014;41(3):490-494. doi:10.3899/jrheum.130977PubMedGoogle ScholarCrossref
14.
Gionchetti  P, Calabrese  C, Rizzello  F.  Inflammatory bowel diseases and spondyloarthropathies.  J Rheumatol Suppl. 2015;93:21-23. doi:10.3899/jrheum.150628PubMedGoogle ScholarCrossref
15.
Matusiak  L, Bieniek  A, Szepietowski  JC.  Increased serum tumour necrosis factor-α in hidradenitis suppurativa patients: is there a basis for treatment with anti–tumour necrosis factor-α agents?  Acta Derm Venereol. 2009;89(6):601-603. doi:10.2340/00015555-0749PubMedGoogle ScholarCrossref
16.
Torres  J, Boyapati  RK, Kennedy  NA, Louis  E, Colombel  J-F, Satsangi  J.  Systematic review of effects of withdrawal of immunomodulators or biologic agents from patients with inflammatory bowel disease.  Gastroenterology. 2015;149(7):1716-1730. doi:10.1053/j.gastro.2015.08.055PubMedGoogle ScholarCrossref
17.
Ingram  JR, Woo  PN, Chua  SL,  et al.  Interventions for hidradenitis suppurativa.  Cochrane Database Syst Rev. 2015;(10):CD010081.PubMedGoogle Scholar
18.
Nazary  M, van der Zee  HH, Prens  EP, Folkerts  G, Boer  J.  Pathogenesis and pharmacotherapy of hidradenitis suppurativa.  Eur J Pharmacol. 2011;672(1-3):1-8. doi:10.1016/j.ejphar.2011.08.047PubMedGoogle ScholarCrossref
19.
Rosenfeld  G, Bressler  B.  The truth about cigarette smoking and the risk of inflammatory bowel disease.  Am J Gastroenterol. 2012;107(9):1407-1408. doi:10.1038/ajg.2012.190PubMedGoogle ScholarCrossref
20.
Sartorius  K, Emtestam  L, Jemec  GB, Lapins  J.  Objective scoring of hidradenitis suppurativa reflecting the role of tobacco smoking and obesity.  Br J Dermatol. 2009;161(4):831-839. doi:10.1111/j.1365-2133.2009.09198.xPubMedGoogle ScholarCrossref
21.
Miller  IM, McAndrew  RJ, Hamzavi  I.  Prevalence, risk factors, and comorbidities of hidradenitis suppurativa.  Dermatol Clin. 2016;34(1):7-16. doi:10.1016/j.det.2015.08.002PubMedGoogle ScholarCrossref
22.
van der Zee  HH, van der Woude  CJ, Florencia  EF, Prens  EP.  Hidradenitis suppurativa and inflammatory bowel disease: are they associated? results of a pilot study.  Br J Dermatol. 2010;162(1):195-197. doi:10.1111/j.1365-2133.2009.09430.xPubMedGoogle ScholarCrossref
23.
van der Zee  HH, de Winter  K, van der Woude  CJ, Prens  EP.  The prevalence of hidradenitis suppurativa in 1093 patients with inflammatory bowel disease.  Br J Dermatol. 2014;171(3):673-675. doi:10.1111/bjd.13002PubMedGoogle ScholarCrossref
24.
Yadav  S, Singh  S, Edakkanambeth Varayil  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(1):65-70. doi:10.1016/j.cgh.2015.04.173PubMedGoogle ScholarCrossref
25.
Deckers  IE, Benhadou  F, Koldijk  MJ,  et al.  Inflammatory bowel disease is associated with hidradenitis suppurativa: results from a multicenter cross-sectional study.  J Am Acad Dermatol. 2017;76(1):49-53. doi:10.1016/j.jaad.2016.08.031PubMedGoogle ScholarCrossref
26.
Lee  JH, Kwon  HS, Jung  HM, Kim  GM, Bae  JM.  Prevalence and comorbidities associated with hidradenitis suppurativa in Korea: a nationwide population-based study.  J Eur Acad Dermatol Venereol. 2018;32(10):1784-1790. doi:10.1111/jdv.15071PubMedGoogle ScholarCrossref
27.
Shalom  G, Freud  T, Ben Yakov  G,  et al.  Hidradenitis suppurativa and Inflammatory bowel disease: a cross-sectional study of 3,207 patients.  J Invest Dermatol. 2016;136(8):1716-1718. doi:10.1016/j.jid.2016.04.003PubMedGoogle ScholarCrossref
28.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement.  PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097PubMedGoogle ScholarCrossref
29.
Wells  G, Shea BJ, O’Connell D, Robertson J. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed August 8, 2018.
30.
Treadwell  JR, Tregear  SJ, Reston  JT, Turkelson  CM.  A system for rating the stability and strength of medical evidence.  BMC Med Res Methodol. 2006;6:52. doi:10.1186/1471-2288-6-52PubMedGoogle ScholarCrossref
31.
Higgins  JPT, Green  S, eds. Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. http://handbook-5-1.cochrane.org. Published March 2011. Accessed July 10, 2018.
32.
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(7):814-818.PubMedGoogle ScholarCrossref
33.
Cices  A, Ibler  E, Majewski  S,  et al.  Hidradenitis suppurativa association at the time of, or subsequent to, diagnosis of inflammatory bowel disease in a large US patient population.  J Eur Acad Dermatol Venereol. 2017;31(7):e311-e312. doi:10.1111/jdv.14097PubMedGoogle ScholarCrossref
34.
Egeberg  A, Jemec  GBE, Kimball  AB,  et al.  Prevalence and risk of inflammatory bowel disease in patients with hidradenitis suppurativa.  J Invest Dermatol. 2017;137(5):1060-1064. doi:10.1016/j.jid.2016.11.040PubMedGoogle ScholarCrossref
35.
Ingram  JR, Jenkins-Jones  S, Knipe  DW, Morgan  CLI, Cannings-John  R, Piguet  V.  Population-based Clinical Practice Research Datalink study using algorithm modelling to identify the true burden of hidradenitis suppurativa.  Br J Dermatol. 2018;178(4):917-924. doi:10.1111/bjd.16101PubMedGoogle ScholarCrossref
36.
Tiri  H, Jokelainen  J, Timonen  M, Tasanen  K, Huilaja  L.  Somatic and psychiatric comorbidities in hidradenitis suppurativa of childhood and adolescence.  J Am Acad Dermatol. 2018;79(3):514-519. doi:10.1016/j.jaad.2018.02.067Google ScholarCrossref
37.
Panaccione  R, Aletaha  D, Davis  M, Johnson  S, Skup  M, Garg  V.  The risk of developing subsequent immune mediated inflammatory diseases: a retrospective matched cohort study.  J Crohn Colitis. 2017;11:S437-S438. doi:10.1093/ecco-jcc/jjx002.822Google ScholarCrossref
38.
Janse  IC, Koldijk  MJ, Spekhorst  LM,  et al.  Identification of clinical and genetic parameters associated with hidradenitis suppurativa in inflammatory bowel disease.  Inflamm Bowel Dis. 2016;22(1):106-113. doi:10.1097/MIB.0000000000000579PubMedGoogle ScholarCrossref
39.
Fimmel  S, Zouboulis  CC.  Comorbidities of hidradenitis suppurativa (acne inversa).  Dermatoendocrinol. 2010;2(1):9-16. doi:10.4161/derm.2.1.12490PubMedGoogle ScholarCrossref
40.
Abraham  C, Cho  JH.  Inflammatory bowel disease.  N Engl J Med. 2009;361(21):2066-2078. doi:10.1056/NEJMra0804647PubMedGoogle ScholarCrossref
41.
Duerr  RH, Taylor  KD, Brant  SR,  et al.  A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.  Science. 2006;314(5804):1461-1463. doi:10.1126/science.1135245PubMedGoogle ScholarCrossref
42.
Schlapbach  C, Hänni  T, Yawalkar  N, Hunger  RE.  Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa.  J Am Acad Dermatol. 2011;65(4):790-798. doi:10.1016/j.jaad.2010.07.010PubMedGoogle ScholarCrossref
43.
Yang  Y, Owyang  C, Wu  GD.  East meets West: the increasing incidence of inflammatory bowel disease in Asia as a paradigm for environmental effects on the pathogenesis of immune-mediated disease.  Gastroenterology. 2016;151(6):e1-e5. doi:10.1053/j.gastro.2016.10.034PubMedGoogle ScholarCrossref
44.
Rakoff-Nahoum  S, Paglino  J, Eslami-Varzaneh  F, Edberg  S, Medzhitov  R.  Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.  Cell. 2004;118(2):229-241. doi:10.1016/j.cell.2004.07.002PubMedGoogle ScholarCrossref
45.
Thrash  B, Patel  M, Shah  KR, Boland  CR, Menter  A.  Cutaneous manifestations of gastrointestinal disease: part II.  J Am Acad Dermatol. 2013;68(2):211.e1-211.e33.Google ScholarCrossref
46.
Lai  Y, Di Nardo  A, Nakatsuji  T,  et al.  Commensal bacteria regulate toll-like receptor 3–dependent inflammation after skin injury.  Nat Med. 2009;15(12):1377-1382. doi:10.1038/nm.2062PubMedGoogle ScholarCrossref
47.
Nikoopour  E, Singh  B.  Reciprocity in microbiome and immune system interactions and its implications in disease and health.  Inflamm Allergy Drug Targets. 2014;13(2):94-104. doi:10.2174/1871528113666140330201056PubMedGoogle ScholarCrossref
48.
Ring  HC, Thorsen  J, Saunte  DM,  et al.  The follicular skin microbiome in patients with hidradenitis suppurativa and healthy controls.  JAMA Dermatol. 2017;153(9):897-905. doi:10.1001/jamadermatol.2017.0904PubMedGoogle ScholarCrossref
49.
Hansen  J, Gulati  A, Sartor  RB.  The role of mucosal immunity and host genetics in defining intestinal commensal bacteria.  Curr Opin Gastroenterol. 2010;26(6):564-571. doi:10.1097/MOG.0b013e32833f1195PubMedGoogle ScholarCrossref
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O’Neill  CA, Monteleone  G, McLaughlin  JT, Paus  R.  The gut-skin axis in health and disease: a paradigm with therapeutic implications.  Bioessays. 2016;38(11):1167-1176. doi:10.1002/bies.201600008PubMedGoogle ScholarCrossref
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Original Investigation
July 10, 2019

Association of Hidradenitis Suppurativa With Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan , Taiwan
  • 2Department of Dermatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • 3College of Medicine, Chang Gung University, Taoyuan, Taiwan
JAMA Dermatol. 2019;155(9):1022-1027. doi:10.1001/jamadermatol.2019.0891
Key Points

Question  Is hidradenitis suppurativa associated with inflammatory bowel disease?

Findings  This systematic review and meta-analysis included 5 case-control studies, 2 cross-sectional studies, and 1 cohort study with a total of 93 601 unique participants with hidradenitis suppurativa who had 2.12-fold increased odds for Crohn disease and 1.51-fold increased odds for ulcerative colitis. One cohort study found a 5.6-fold increased risk of inflammatory bowel disease in patients with hidradenitis suppurativa.

Meaning  Gastrointestinal tract symptoms, such as recurrent abdominal pain and chronic diarrhea, should not be overlooked in patients with hidradenitis suppurativa, and consultation with gastroenterologists should be sought.

Abstract

Importance  Hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) are inflammatory diseases that share common genetic susceptibility and immunologic features. However, the link between HS and IBD has been largely unclear.

Objective  To conduct a meta-analysis to investigate the association between HS and IBD.

Data Sources  A search of the MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases yielded 397 relevant studies from inception to June 10, 2018. Two additional studies were supplied by one of the investigators.

Study Selection  Case-control, cross-sectional, or cohort studies that examined the odds or risk of IBD in patients with HS were included. No geographic or language limitations were imposed.

Data Extraction and Synthesis  The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The Newcastle-Ottawa Scale was used to assess the risk of bias of included studies. Crohn disease and ulcerative colitis were analyzed separately, and a random-effects model meta-analysis was conducted.

Main Outcomes and Measures  The odds ratios (ORs) and hazard ratios (HRs) of IBD, Crohn disease, and ulcerative colitis in association with HS.

Results  Five case-control studies, 2 cross-sectional studies, and 1 cohort study with a total of 93 601 unique participants were included. The meta-analysis of case-control and cross-sectional studies showed significant associations of HS with Crohn disease (pooled OR, 2.12; 95% CI, 1.46-3.08) and ulcerative colitis (pooled OR, 1.51; 95% CI, 1.25-1.82). Two case-control studies found significant association of HS with IBD (ORs, 2.16 [95% CI, 1.40-3.34] and 10.00 [95% CI, 1.94-51.50]). One cohort study found an increased risk of IBD in patients with HS (HR, 5.6; 95% CI not reported; P < .002).

Conclusions and Relevance  The evidence to date supports an association of HS with IBD. These results suggest that consultation with gastroenterologists should be sought when patients with HS present with recurrent abdominal pain, chronic diarrhea, bloody stool, and body weight loss.

Introduction

Hidradenitis suppurativa (HS) or acne inversa is defined as “a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland–bearing areas of the body, most commonly the axillary, inguinal, and anogenital regions” (Dessau definition).1(p619) The etiology is largely unclear, but dysregulated inflammatory response of cytokines, follicular occlusion, obstruction and dilatation of the pilosebaceous unit, and altered microbiota may be involved in the pathogenesis of HS.2-5

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestinal tract. Inflammatory bowel disease consists of 2 predominant types: Crohn disease (CD) and ulcerative colitis (UC).6 Accumulating evidence indicates that genetic susceptibility to dysregulated inflammatory reaction and altered microbiota may play crucial roles in the pathogenesis of IBD.7-9

Hidradenitis suppurativa shares common clinical manifestations, genetic susceptibility, and immunologic features with IBD.5,10 Both diseases have similar clinical manifestations in the skin and gut, characterized by sterile abscesses in the perineal and inguinal areas, scarring, and sinus tract formation.1,7,11,12 Hidradenitis suppurativa and IBD have been associated with an increased prevalence of spondyloarthropathy, and both diseases respond well to tumor necrosis factor inhibitors.1,13-17 Moreover, smoking and obesity are known common risk factors for HS and IBD.18-21

Although some studies have suggested a link between HS and IBD,22-25 data on the association remain inconsistent and unclear. For example, one recent study26 failed to find a significant association between HS and CD, whereas another study27 did not detect a significant increase of UC in patients with HS. In this study, we aimed to systematically examine the evidence of an association of HS with IBD.

Methods
Eligibility Criteria and Evidence Search

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline,28 we conducted a meta-analysis of observational studies on the association of HS with IBD. The types of eligible studies included case-control, cross-sectional, and cohort studies.

The MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases were searched for relevant studies from the respective inception of these databases to June 10, 2018. We did not impose any language or geographic restrictions. Our search strategy is listed in the eTable in the Supplement.

Selection of Studies

Studies that met the following inclusion criteria were included: (1) observational studies examining the association of HS with IBD, including cross-sectional, case-control, or cohort studies; (2) human study participants; and (3) a case group consisting of patients with HS and a control group composed of people without HS. Both authors independently selected relevant studies by scanning the titles and abstracts of search results. The full text of potential studies was obtained and examined for eligibility. Disagreement was resolved by discussion.

Data Extraction and Risk of Bias Assessment

We extracted the following data from the included studies: study design, first author, year of publication, country, and risk estimates, including odds ratios (ORs) and hazard ratios (HRs) with corresponding 95% CIs on the association of HS with IBD. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies.29

Statistical Analysis

We used Review Manager software, version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration), to conduct meta-analyses when at least 3 studies provided usable data for 1 outcome.30 We calculated a pooled OR with 95% CI for case-control and cross-sectional studies and a pooled HR with 95% CI for cohort studies. The I2 statistic was calculated for examining statistical heterogeneity across the included studies. An I2 of greater than 50% was considered substantial heterogeneity.31 The random-effects model was chosen for meta-analyses because clinical heterogeneity was anticipated.

Results
Characteristics of Included Studies

The PRISMA study flow diagram is shown in Figure 1. After removing duplicates, 397 records were identified by our search. Two additional relevant studies were provided by 1 author (C.-C.C.).26,32 We excluded 375 citations after scanning the titles and abstracts. After examination of the full text, we included 5 case-control studies,26,33-36 2 cross-sectional studies,27,32 and 1 cohort study37 with a total of 93 601 unique study participants. One study was conducted in Asia,26 and the other 7 were conducted in the West.27,32-37 The characteristics of the included case-control studies are shown in Table 1.

Risk of Bias of Included Studies

The risk of bias among included case-control and cohort studies is summarized in Figure 2. No studies were rated with a high risk of bias in any item. As to the adequacy of case definition, 5 studies26,32-34,36 were rated with an unclear risk of bias because only codes from the International Classification of Diseases, Eighth Revision, and Ninth Revision, and Tenth Revision were used for identification of cases. Five case-control and cross-sectional studies26,33-36 and 1 cohort study37 were rated with an unclear risk of bias in the comparability of cases and controls or cohorts because the analyses controlled for age and sex but not body mass index and smoking. As to ascertainment of exposure, 6 case-control and cross-sectional studies26,32-36 and 1 cohort study37 were rated with an unclear risk of bias because only International Classification of Diseases codes were used.

Association of HS With IBD

Five studies with a combined 91 917 study participants, including 2 cross-sectional studies27,32 and 3 case-control studies,26,34,35 provided data on the association of HS with CD. Substantial statistical heterogeneity was found across these studies (I2 = 92%). As illustrated in Figure 3A, the meta-analysis illustrated a significantly increased odds of CD in patients with HS (pooled OR, 2.12; 95% CI, 1.46-3.08).

Four studies with a combined 39 497 study participants, including 1 cross-sectional study27 and 3 case-control studies,26,34,35 provided data on the association of HS with UC. We found no substantial statistical heterogeneity across these studies (I2 = 28%). As demonstrated in Figure 3B, the meta-analysis showed a significantly increased odds of UC in patients with HS (pooled OR, 1.51; 95% CI, 1.25-1.82).

Two case-control studies33,36 with a combined 1642 study participants provided data on the association of HS with IBD and found significantly increased odds of IBD in subjects with HS (ORs, 2.16 [95% CI, 1.40-3.34] and 10.00 (95% CI, 1.94-51.50]). One cohort study37 with 14 136 study participants found an increased risk of IBD in patients with HS (HR, 5.6; 95% CI not reported; P < .002).

Discussion

To the best of our knowledge, this study is the first meta-analysis to illustrate a significant association of HS with IBD. The evidence from case-control studies indicates that patients with HS had 2.12-fold odds of CD and 1.51-fold odds of UC when compared with controls. Meanwhile, the evidence from 1 cohort study37 reveals that patients with HS had a 5.6-fold HR of IBD when compared with controls.

Hidradenitis suppurativa and IBD share many characteristics, including clinical manifestations, genetic susceptibility, and immunologic features. There are several explanations of the link between HS and IBD. First, genetic susceptibility loci shared by HS and IBD have been found. Certain genes, for example SULT1B1 (OMIM 608436) and SULT1E1 (OMIM 600043), have been associated with HS as well as IBD.5,38,39 Second, emerging studies have shown that HS and IBD are diseases of immune dysregulation. Cytokine abnormalities, such as elevation of interleukin 1 (IL-1), IL-6, IL-17, IL-23, and tumor necrosis factor, are involved in HS and IBD.40-42 Third, altered microbiota with dysregulated immune responses may play an important role in HS and IBD.5,43 Microbiota affect the immunologic and physiologic homeostasis of the epithelia of skin and mucosa of gut by activation of toll-like receptors to recognize pathogens and repair damage.44-46 However, a variety of environmental factors can alter microbial balance with a resultant decrease in microbial diversity.7 Such alterations of microbiota may cause immune dysregulation and susceptibility to diseases, including HS and IBD.47 Altered microbiota have been found in the lesional and nonlesional skin of patients with HS when compared with healthy control individuals.48 Increasing evidence shows that altered intestinal microbiota may be involved in the pathogenesis of IBD, with decreases in specific Firmicutes species and a concomitant increase in Bacteroidetes species and facultative anaerobes such as Enterobacteriaceae.49 The alterations of microbiota may lead to systemic immune impairment. Such a close interplay between alterations of microbiota, cytokines, and dermatoses has been proposed as the gut-skin axis theory.50

We detected high statistical heterogeneity for the association of HS with CD (I2 = 92%) (Figure 3A). However, no significant statistical heterogeneity was present when we excluded 3 studies26,34,35 that did not control for body mass index and smoking habit (I2 = 47%; P = .17). Therefore, uncontrolled confounding may account for the high statistical heterogeneity detected in Figure 3A.

Limitations

This study has some limitations. First, no studies examined the association between different severity of HS and IBD. Second, most of the included studies were from Western countries (United States and Europe),27,32-37 with only 1 from Asia.26 More studies are warranted to confirm whether HS is associated with IBD in Asian or other racial/ethnic groups.

Conclusions

The evidence to date supports an association of HS with IBD. Patients with HS should be informed about the increased risk of IBD. Consultation with gastroenterologists should be sought when patients with HS present with recurrent abdominal pain, chronic diarrhea, bloody stool, and body weight loss.

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Article Information

Accepted for Publication: March 22, 2019.

Corresponding Author: Ching-Chi Chi, MD, MMS, DPhil, Department of Dermatology, Chang Gung Memorial Hospital, Linkou, 5, Fuxing St, Guishan District, Taoyuan 33305, Taiwan (chingchi@cgmh.org.tw).

Published Online: July 10, 2019. doi:10.1001/jamadermatol.2019.0891

Author Contributions: Dr Chi had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Chi.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Chen.

Critical revision of the manuscript for important intellectual content: Both authors.

Statistical analysis: Both authors.

Administrative, technical, or material support: Both authors.

Supervision: Chi.

Conflict of Interest Disclosures: None reported.

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