Depression and Anxiety in Adults With Hidradenitis Suppurativa: A Systematic Review and Meta-analysis

Key Points

Question  What are the prevalence rates of and odds for depression and anxiety in adults with hidradenitis suppurativa?

Findings  This systematic review and meta-analysis of 10 studies comprising 40 307 participants with hidradenitis suppurativa found a prevalence of depression of 16.9% and a prevalence of anxiety of 4.9%. The odds ratio for depression among people with hidradenitis suppurativa was 1.84.

Meaning  Depression and anxiety are common comorbidities in people with hidradenitis suppurativa; efforts toward recognition, prevention, and management of those psychiatric comorbidities are warranted.

Importance  Previous studies suggest that depression and anxiety are common in patients with hidradenitis suppurativa (HS), more so than other dermatological conditions. Yet, to the authors’ knowledge, no previous systematic review or meta-analysis has estimated the prevalence or odds ratio (OR) for those psychiatric comorbidities in this population.

Objective  To assess the prevalence and odds for depression and anxiety in patients with HS.

Data Sources  From July 25 to September 30, 2018, observational studies investigating the prevalence and odds for depression and anxiety in adults with HS were systematically searched without language restriction from the inception of each database to July 25, 2018, in PubMed/MEDLINE, Embase, and PsycINFO databases. Searches used various configurations of the terms hidradenitis suppurativa; acne inversa; depressive disorder; depression; anxiety; anxiety disorders; phobia, social; suicide; and suicide, attempted. In addition, the reference lists of included references were screened manually.

Study Selection  Two investigators independently screened references that measured prevalence rates and odds for depressive and anxiety symptoms in patients with HS. Of 136 unique references, 10 ultimately met inclusion criteria.

Data Extraction and Synthesis  Relevant data were extracted from eligible references. Authors were contacted to provide further information when necessary. Methodological quality of included studies was assessed through a modified version of the Newcastle-Ottawa Scale. Random-effects models were used to synthesize available evidence.

Main Outcomes and Measures  Prevalence rates and ORs for depression and anxiety in adults with HS were the primary outcome measures. Heterogeneity across studies was assessed with the I² statistic. Sources of heterogeneity were explored through subgroup and meta-regression analyses.

Results  Ten studies comprising 40 307 participants with HS met inclusion criteria. The overall prevalence of depression was 16.9% (95% CI, 9.9%-27.2%). Heterogeneity was large. In the subgroup of studies that considered a clinical criteria–based diagnosis of depression, the prevalence of depression was 11.9% (95% CI, 4.9%-26.2%), compared with 26.8% (95% CI, 20.4%-34.5%) in studies that used a screening instrument. The methodological quality of included studies moderated those findings. The OR for depression in individuals with HS compared with individuals without HS was 1.84 (95% CI, 1.57-2.15). The prevalence of anxiety was 4.9% (95% CI, 1.7%-13.2%); there were insufficient data to determine an odds ratio for anxiety in persons with HS because 2 studies included a comparison group.

Conclusions and Relevance  This systematic review and meta-analysis indicates that depression and anxiety are common comorbid conditions in patients with HS. Results suggest that the development of strategies to recognize and treat those psychiatric comorbidities in patients with HS is warranted.

Hidradenitis suppurativa (HS) is a chronic recurrent inflammatory skin disease with a characteristic clinical presentation of painful and suppurating lesions in apocrine-gland bearing intertriginous regions.¹ The prevalence of HS varies between 0.05% to 4.00% depending on the methodology used to estimate the prevalence and the population studied.² Hidradenitis suppurativa commonly affects young populations with a female to male ratio of 3:1. It is associated with significant disability,^3-5 impaired quality of life,^5-7 sexual dysfunction,⁸ and disturbed body image.⁹ Furthermore, patient perspectives of living with HS convey physical, psychological, social, and emotional distress.⁴

Several studies^10-15 have assessed the prevalence of psychiatric comorbidities in patients with HS. Some studies have indicated an increased prevalence of depression^10,16,17 and anxiety^10,11 and an increased risk of suicide in people with HS compared with their healthy peers.^11,15 However, studies have used different methodological designs and have included samples from different settings (eg, clinical vs population-based samples). Therefore, the exact magnitude of the prevalence and odds of depression and anxiety in patients with HS is unclear.

Hidradenitis suppurativa is damaging to patient psychosocial well-being and daily activities with an added burden of stigma and shame when HS involves intimate body areas.^18,19 It is important to have a proper understanding of the magnitude of the burden of depression and anxiety among individuals with HS to determine whether targeted interventions for these psychiatric disorders in this population are warranted.

In the current systematic review and meta-analysis, we set out to examine the prevalence and odds for depression and anxiety in adults with HS. In addition, we aimed to explore potential sources of heterogeneity across studies.

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline²⁰ and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline (eAppendix in the Supplement).²¹ The literature search, title screening, abstract screening, final decision on eligibility after full-text review, methodological quality appraisal of included studies, and data extraction were independently performed by 2 investigators (M.O.M. and A.F.C.).

From July 15, 2018, to September 30, 2018, we conducted a systematic search of the PubMed/MEDLINE, Embase, and PsycINFO electronic databases from inception to July 25, 2018. We used various forms and combinations of the search terms hidradenitis suppurativa; acne inversa; depressive disorder; depression; anxiety; anxiety disorders; phobia, social; suicide; and suicide, attempted. The search strings that were used are available in the eAppendix in the Supplement. This search strategy was augmented through hand searching the reference lists of included references.

Inclusion and exclusion criteria were specified before the literature search was initiated. No restrictions were made as to publication date or language. Observational studies of any design were considered for inclusion. We included studies in which participants with HS were diagnosed by a physician. In addition, studies had to provide either the prevalence or the association (when a reference comparison group was available) of depression or anxiety. Specifically, we included studies that provided either Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5)²² or International Classification of Diseases, Tenth Revision (ICD-10)²³ diagnoses of a depressive disorder or an anxiety disorder. In addition, we included studies in which a validated screening tool with a cutoff score indicated the possible occurrence of depression or anxiety as well as studies that used validated algorithms to detect the possible presence of those mental health conditions. There were no limitations regarding the comparison group in studies that assessed the odds for depression and anxiety in adults with HS. When more than 1 comparison group was provided, we prioritized a healthy control group. Studies that enrolled pediatric patients (ie, with participants aged <18 years) were excluded.

We extracted data regarding the prevalence or odds of depression and anxiety from eligible studies. When ORs were not provided, we calculated this metric based on raw data provided by the included studies. In addition, the following variables were also extracted when available: (1) sample size; (2) mean age; (3) sex (% female); (4) measure of severity for HS; (5) method used to assess depression or anxiety (ie, structured diagnostic interview or coded diagnosis given by clinician or screening tool or validated algorithm); (6) study design; and (7) setting (eg, outpatient services or population-based sample). Both crude and adjusted association metrics with 95% CIs were extracted from included studies. When a study did not provide extractable information, the corresponding author was contacted in at least 2 different occasions over a period of 2 weeks to obtain the relevant primary epidemiologic data.

The Newcastle-Ottawa Scale (NOS) was used to rate the methodological quality of included studies. Because the NOS was primarily designed to assess the methodological quality of case-control or cohort studies, we used an adapted version to rate the methodological quality of cross-sectional studies.^24,25 Higher scores in the NOS indicate better methodological quality.²⁵

The prevalence rates or unadjusted ORs and 95% CIs obtained or calculated from included studies were synthesized by random-effects models when at least 3 independent datasets were available for each prevalence or association measure. Heterogeneity across studies was measured with the I² statistic; values greater than 50% are indicative of greater heterogeneity.²⁶ When at least 10 studies were available, we estimated the likelihood of publication bias using the Egger asymmetry test.^27,28 We used the following assumptions to assess the existence of small-study effect, an indication of publication bias: (1) the effect size of the largest study is more conservative than the effect size of the meta-analysis and (2) P < .10 in the Egger test.²⁹ The trim-and-fill procedure was used to estimate the effect size when publication bias was noted.³⁰

We explored potential sources of heterogeneity across studies using either subgroup (when at least 3 independent datasets were available per subgroup) or unrestricted maximum likelihood random-effects meta-regression analyses. The method used to assess depression and anxiety and the study setting were considered in subgroup analyses. Meta-regression analyses were conducted only when there were data from more than 5 independent datasets. For meta-regression analyses, we considered the following variables: (1) mean age; (2) percentage of female participants; (3) severity of HS as determined by physician; and (4) methodological quality (ie, NOS score). In addition, sensitivity analyses in which 1 study was excluded from analysis at a time were conducted for studies that assessed the odds for depression in adults with HS.

The statistical significance level for effect size estimates was set at a 2-tailed α of.05. All statistical analyses were conducted in Comprehensive Meta-Analysis Software version 3 (Biostat).

Our literature search and study selection process are depicted in Figure 1. The initial search of databases retrieved 137 references. After 1 duplicate record was removed, 136 references were screened on the basis of title, abstract, or both to determine potential eligibility. Ten unique references met inclusion criteria.^{10-12,14,16,17,31-34} No additional references were identified from the bibliographies of included articles.

Ten studies assessed the prevalence of depression in patients with HS (Table 1 and Figure 2A). The median (interquartile range [IQR]) modified NOS score of those studies was 4.5 (3.0-7.0). The overall prevalence of depression was 16.9% (95% CI, 9.9%-27.2%). There was no evidence of publication bias (Egger test, P = .22; eFigure 1 in the Supplement). Heterogeneity was great (I² = 99.4%). In subgroup analysis, the prevalence was 11.9% (95% CI, 4.9%-26.2%; κ = 4; I² = 99.7%) in studies that considered a clinical criteria–based diagnosis of depression; whereas in studies that used a screening instrument, the prevalence of probable depression as determined by the instrument was 26.8% (95% CI, 20.4%-34.5%; κ = 5; I² = 73.8%). The prevalence of depression was 25.9% (95% CI, 22.7%-29.4%; κ = 7; I² = 61.9%) among outpatients with HS. The methodological quality of included studies did not appear to moderate the prevalence of depression in HS (coefficient of variation = 0.06; z = 0.34; κ = 10; P = .73). In addition, the percentage of female patients (coefficient of variation = 0.00; z = 0.16; κ = 8; P = .87) and mean age (coefficient of variation = –0.20; z = –1.89; κ = 8; P = .06) did not moderate the prevalence of depression in HS. The pooled OR for depression was 1.84 (95% CI, 1.57-2.15; κ = 5) in studies that included a comparison group (Table 2 and Figure 2B). In sensitivity analyses where 1 study was excluded from analysis at a time, the OR for depression in HS remained significant (eFigure 2 in the Supplement).

Four studies measured the prevalence of anxiety in patients with HS (Table 1 and Figure 3). The median (IQR) modified NOS score of included studies was 6.6 (5.5-7.7). The prevalence of anxiety was 4.9% (95% CI, 1.7%-13.2%). Heterogeneity across studies was high (I² = 99.1%). Of the 4 studies, 2 included a comparison group (Table 2). The unadjusted ORs for those studies were 1.6 and 2.3, whereas the ORs of both studies were 1.7 after multivariable adjustment for potential confounding variables.

To our knowledge, this is the first systematic review and meta-analysis to assess the prevalence and relative odds for depression and anxiety in adults with HS. Our results indicate that both comorbidities are common among adults with HS, although fewer studies assessed anxiety in this population, and hence evidence remains preliminary. In addition, the prevalence of depression was higher among patients with HS compared with the respective comparison groups of included studies. Two studies compared the prevalence of anxiety in patients with HS to healthy controls,^10,11 and thus a meta-analysis could not be conducted.

Our results highlight that efforts toward the recognition and management of depression among patients with HS are warranted. Furthermore, the consequences of depression and anxiety on HS-related outcomes have recently received more attention. For example, those psychological distress symptoms may be independently associated with health-related quality of life in patients with HS.^6,34 In addition, impaired body image in patients with HS was associated with symptoms of both depression and anxiety in a previous study, suggesting that the association between depression and the manifestations of HS may not be independent.⁹ Therefore, clinical correlates of depression and anxiety among people with HS as well as the interaction of those psychiatric comorbidities with HS merit further investigation. Our exploratory meta-regression analysis did not provide evidence that sex and age moderate the prevalence of depression among adults with HS. However, this is a topic that merits further investigation.

Although our findings indicate that depression and anxiety may be common among people with HS, whether there is a causal relationship in those associations remains to be proved. For example, obesity and related metabolic disturbances are common in both HS³⁵ and depression,³⁶ and may thus at least partly explain the associations herein reported. On the other hand, common pathophysiological mechanisms may underpin these associations. For instance, peripheral immune activation may contribute to the development of depression in a meaningful subset of patients.^37,38 Accordingly, it has been recently hypothesized that peripheral inflammation may contribute to the frequent occurrence of depressive symptoms in patients with inflammatory skin diseases including HS.¹⁸ Future prospective studies are thus needed to determine whether there is a causal relationship between these disorders.

Some limitations of the current systematic review and meta-analysis merit discussion. First, to our knowledge, no study has assessed the presence of depression or anxiety among people with HS through validated structured diagnostic interviews, which are the criterion standard for the assessment of those disorders. Our subgroup analysis suggests that the prevalence of depression was greater in studies that used screening instruments (ie, 26.8%) compared with those that considered a clinical criteria–based diagnosis of depression (ie, 11.9%). Thus, the prevalence of depression and anxiety could have been overestimated to a certain extent, owing to differences in the methods used to assess those mental health conditions across studies. Second, the methodological quality of included studies varied. Third, although we observed greater odds for depression among adults with HS, comparison groups have varied across studies. In addition, the largest population-based study conducted to date found that notwithstanding the odds for depression were higher in adults with HS, those differences disappeared after adjustment for potential confounding variables.¹¹ It should also be noted that only 2 of the included studies^10,11 provided adjusted association metrics for depression in adults with HS; hence, further large-scale studies considering potential confounding variables are warranted to confirm our findings. Finally, heterogeneity across studies was great. Owing to the relatively few studies available, we could only explore potential sources of heterogeneity in studies that assessed the prevalence of depression in people with HS.

This systematic review and meta-analysis indicates that depression and anxiety are common in patients with HS, although the evidence base for anxiety was more limited than that for depression. In addition, although our results suggest that the odds of depression could be greater in adults with HS, substantial limitations in the available literature diminish the certainty of those findings. Therefore, research efforts should be directed to further elucidate potential moderators as well as those associations that may indicate a causal relationship. In addition, efforts should be directed to recognizing and treating those psychiatric comorbidities in patients with HS to improve health outcomes. Finally, strategies for the management of depression and anxiety in adults with HS are relevant research directions opened by the current work.

Accepted for Publication: March 15, 2019.

Corresponding Author: Andre F. Carvalho, MD, Centre for Addiction and Mental Health (CAMH), 33 Russell St, Tower Bldg, T314, Toronto, ON, M5S 2S1, Canada (andre.carvalho@camh.ca).

Published Online: June 5, 2019. doi:10.1001/jamadermatol.2019.0759

Author Contributions: Drs Machado and Carvalho had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Machado, Kurdyak, Lin, Firth, Alavi, Piguet, Carvalho.

Acquisition, analysis, or interpretation of data: Machado, Stergiopoulos, Maes, Wang, Shyu, Koyanagi, Solmi, Alavi, Piguet, Carvalho.

Drafting of the manuscript: Machado, Wang, Solmi, Alavi, Carvalho.

Critical revision of the manuscript for important intellectual content: Machado, Stergiopoulos, Maes, Kurdyak, Lin, Shyu, Firth, Koyanagi, Solmi, Alavi, Piguet, Carvalho.

Statistical analysis: Machado, Wang, Shyu, Koyanagi, Carvalho.

Obtained funding: Stergiopoulos, Wang, Shyu.

Administrative, technical, or material support: Kurdyak, Wang, Firth.

Supervision: Lin, Solmi, Piguet, Carvalho.

Conflict of Interest Disclosures: Dr Firth is supported by a Blackmores Institute Fellowship. Dr Alavi reported receiving honoraria from AbbVie for serving on an advisory board, as a consultant, on a speakers’ bureau, and as a clinical trials investigator; honoraria from Galderma for serving on an advisory board, as a consultant, and as a clinical trials investigator; honoraria from LEO Pharma for serving on an advisory board, as a consultant, and as a clinical trials investigator; honoraria from Janssen for serving on an advisory board, as a consultant, and as a clinical trials investigator; and honoraria from Novartis for serving on an advisory board, as a consultant, and as a clinical trials investigator. Dr. Piguet reported receiving grants and personal fees from AbbVie during the conduct of the study and receiving educational grants in his role as Department Division Director, Dermatology, at the University of Toronto from AbbVie, Celgene, Janssen, Naos, Lilly, Sanofi, Valeant, receiving nonfinancial support from La Roche-Posay and serving as an advisor for AbbVie. No other disclosures were reported.