Population-based mortality in hidradenitis suppurativa: A systematic review

To the Editor: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by painful nodules affecting hair follicles.1Zouboulis C.C. Desai N. Emtestam L. et al.European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.J Eur Acad Dermatol Venereol. 2015; 29: 619-644https://doi.org/10.1111/jdv.12966Crossref PubMed Scopus (808) Google Scholar It is associated with multiple comorbidities including pyschologic illness and metabolic syndromes, which may increase organ-related mortality risk.1Zouboulis C.C. Desai N. Emtestam L. et al.European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.J Eur Acad Dermatol Venereol. 2015; 29: 619-644https://doi.org/10.1111/jdv.12966Crossref PubMed Scopus (808) Google Scholar We hypothesized that patients with HS would demonstrate higher mortality. However, studies on the direct relationship between HS and mortality are limited and report conflicting results. Our study aimed to address this gap through a systematic review and meta-analysis. The study protocol was preregistered on International Prospective Register of Systematic Reviews (CRD42023442455) a priori and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE, Embase, and Cochrane Databases from database inception to August 2023, without restrictions. The search strategy, refined by a Librarian, included main search terms: (1) Hidradenitis suppurativa (2) Mortality, (3) Population-based studies. Two independent authors conducted screening, full-text review, and data extraction (using a standardized tool). Using random-effects meta-analyses, we calculated the pooled incidence rate ratio (IRR) for mortality and assessed heterogeneity using the I2 statistic. Publication bias was assessed by visually inspecting a funnel plot, and the methodological quality of the studies was evaluated using the Newcastle-Ottawa scale. Analyses were performed using Stata (StataCorp. 2019). Of 22 identified records, 5 were included in the systematic review (52,336 patients with HS and 1,011,277 controls) and 3 in the meta-analysis (Supplementary 1 and 2, available via Mendeley at https://doi.org/10.17632/rbndbf39mx.2).2Reddy S. Strunk A. Garg A. All-cause mortality among patients with hidradenitis suppurativa: a population-based cohort study in the United States.J Am Acad Dermatol. 2019; 10: 937-942https://doi.org/10.1016/j.jaad.2019.06.016Abstract Full Text Full Text PDF Scopus (20) Google Scholar, 3Lee S. Lee J.Y. Han J.H. et al.All-Cause and Cause-Specific Mortality Risks among Patients with Hidradenitis Suppurativa: A Korean Nationwide Population-Based Cohort Study.J Invest Dermatol. 2023; 143: 944-953.e8https://doi.org/10.1016/j.jid.2022.11.019Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar, 4Egeberg A. Gislason G.H. Hansen P.R. Risk of major adverse cardiovascular events and all-cause mortality in patients with hidradenitis suppurativa.JAMA Dermatol. 2016; 152: 429-434https://doi.org/10.1001/jamadermatol.2015.6264Crossref PubMed Scopus (184) Google Scholar Random-effects meta-analysis revealed a nonsignificant pooled association between the IRR of mortality in patients with HS (IRR = 1.00 [0.94, 1.07], I2 = 86.7%) (Supplementary 3, available via Mendeley at https://doi.org/10.17632/rbndbf39mx.2). Inspection of funnel plot did not reveal significant evidence of publication bias (Egger regression: 0.83) (Supplementary 4, available via Mendeley at https://doi.org/10.17632/rbndbf39mx.2). Patients with HS and concurrent comorbidities were associated with an increased risk of mortality compared to control patients with these same comorbidities alone, after adjusting for confounders (Supplementary 5, available via Mendeley at https://doi.org/10.17632/rbndbf39mx.2). Cardiovascular-specific mortality, including cardiovascular-related death (IRR, 1.95; 1.42-2.67 and hazard ratio [HR], 1.20; 0.97-1.48), myocardial infarction (IRR, 1.57; 1.14-2.17, HR, 1.33; 1.04-1.68, HR, 0.99; 0.61-1.61), and stroke (IRR, 1.33; 1.01-1.76, HR, 0.82; 0.59-1.14, HR, 1.56; 0.86-2.80) were all increased in patients with HS compared to controls (Supplementary 5, available via Mendeley at https://doi.org/10.17632/rbndbf39mx.2). Our systematic review also showed significantly increased mortality in patients with HS with psychiatric disease (HR, 1.45; 1.10-1.91), chronic kidney disease (HR, 2.00; 1.06-3.75), and urogenital disease (HR, 1.80; 1.08-3.00). Diseases of chronic inflammation such as psoriasis and HS have been linked to accelerated atherosclerosis, cardiovascular risk factors, and increased mortality.2Reddy S. Strunk A. Garg A. All-cause mortality among patients with hidradenitis suppurativa: a population-based cohort study in the United States.J Am Acad Dermatol. 2019; 10: 937-942https://doi.org/10.1016/j.jaad.2019.06.016Abstract Full Text Full Text PDF Scopus (20) Google Scholar,5Sorriento D. Iaccarino G. Inflammation and cardiovascular diseases: the most recent findings.Int J Mol Sci. 2019; 20: 3879https://doi.org/10.3390/ijms20163879Crossref PubMed Scopus (82) Google Scholar However, patients with HS with noncardiovascular comorbidities such as kidney disease and psychiatric disease also had higher mortality risk. HS's association with mortality and specific comorbidities is likely multifactorial. Our study found that HS was not significantly associated with overall mortality (IRR = 1.00 [0.94, 1.07], I2 = 86.7%). However, patients with HS and specific coexisting comorbidities had an increased mortality risk. Understanding the interplay between HS and these comorbidities, and studying the potential impact of treatment of these comorbidities will be essential for optimal assessment, triage, and treatment of patients with HS. None disclosed.