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A Practical Guide for Primary Care Providers on Timely Diagnosis and Comprehensive Care Strategies for Hidradenitis Suppurativa

Open AccessPublished:October 13, 2022DOI:https://doi.org/10.1016/j.amjmed.2022.09.025

      Abstract

      Hidradenitis suppurativa is a chronic, progressive inflammatory disease of the skin with many systemic implications. Hidradenitis suppurativa is frequently underdiagnosed or misdiagnosed, particularly because of heterogeneity in presentation and low disease recognition. Patients can see multiple types of health care providers, including primary care providers, along their journey to an accurate diagnosis. This review provides a comprehensive overview of the clinical presentation, associated comorbidities, and life impact associated with hidradenitis suppurativa. Disease features described here can facilitate earlier identification of hidradenitis suppurativa, differentiation from common mimickers, and timely referrals for multidisciplinary management when needed. Engagement of the medical community will also support comprehensive care strategies necessary in hidradenitis suppurativa.

      Keywords

      Clinical Significance
      • Hidradenitis suppurativa is a progressive inflammatory skin disease that is often underdiagnosed or misdiagnosed because of poor recognition in the medical community.
      • Increased awareness of the clinical presentation, associated comorbidities, and quality of life impact can help address unmet needs for patients.
      • This practical guide provides detailed information that can support timely hidradenitis suppurativa diagnosis and care strategies by primary care providers.

      Statement of Literature Search

      This review is based on previously published studies and does not contain novel data. This narrative review included publications identified from a series of PubMed searches from June 2021 through January 2022. A general internet search for relevant resources on hidradenitis suppurativa was also conducted to include useful resources for providers and patients to access. References detailing information on the hidradenitis suppurativa population, clinical presentation, diagnosis, common comorbidities and screenings, impact on patient quality of life and mental health, understanding of hidradenitis suppurativa pathogenesis, therapeutic options, and management were included. Based on the authors’ judgement, publications determined to be irrelevant were excluded from consideration. Any relevant references cited within the publications discussed in this review and articles known by the authors were also considered.

      Introduction to Hidradenitis Suppurativa

      Hidradenitis suppurativa is a chronic, progressive, and potentially debilitating inflammatory skin disease characterized by painful nodules, abscesses, draining tunnels, and disfiguring scars.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.
      Prevalence ranges from 0.1% to 2.0% in the United States and Europe,
      • Jemec GB
      • Kimball AB
      Hidradenitis suppurativa: epidemiology and scope of the problem.
      • Vazquez BG
      • Alikhan A
      • Weaver AL
      • Wetter DA
      • Davis MD
      Incidence of hidradenitis suppurativa and associated factors: a population-based study of Olmsted County, Minnesota.
      • Garg A
      • Kirby JS
      • Lavian J
      • Lin G
      • Strunk A
      Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States.
      and the incidence in the United States is approximately 11.4 cases per 100,000 population.
      • Garg A
      • Lavian J
      • Lin G
      • Strunk A
      • Alloo A
      Incidence of hidradenitis suppurativa in the United States: a sex- and age-adjusted population analysis.
      ,
      • Naik HB
      • Paul M
      • Cohen SR
      • Alavi A
      • Suarez-Farinas M
      • Lowes MA
      Distribution of self-reported hidradenitis suppurativa age at onset.
      Standardized prevalence is highest among patients aged 18 to 40 years.
      • Garg A
      • Kirby JS
      • Lavian J
      • Lin G
      • Strunk A
      Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States.
      ,
      • Naik HB
      • Paul M
      • Cohen SR
      • Alavi A
      • Suarez-Farinas M
      • Lowes MA
      Distribution of self-reported hidradenitis suppurativa age at onset.
      ,
      • Revuz JE
      • Canoui-Poitrine F
      • Wolkenstein P
      • et al.
      Prevalence and factors associated with hidradenitis suppurativa: results from two case-control studies.
      Hidradenitis suppurativa onset most commonly occurs in early adulthood, and onset prior to adrenarche is rare.
      • Garg A
      • Wertenteil S
      • Baltz R
      • Strunk A
      • Finelt N
      Prevalence estimates for hidradenitis suppurativa among children and adolescents in the United States: a gender- and age-adjusted population analysis.
      Additionally, hidradenitis suppurativa has a bimodal distribution and is also known to occur in midlife.
      • Naik HB
      • Paul M
      • Cohen SR
      • Alavi A
      • Suarez-Farinas M
      • Lowes MA
      Distribution of self-reported hidradenitis suppurativa age at onset.
      Hidradenitis suppurativa predominantly affects women,
      • Garg A
      • Kirby JS
      • Lavian J
      • Lin G
      • Strunk A
      Sex- and age-adjusted population analysis of prevalence estimates for hidradenitis suppurativa in the United States.
      ,
      • Phan K
      • Charlton O
      • Smith SD
      Global prevalence of hidradenitis suppurativa and geographical variation—systematic review and meta-analysis.
      and Black Americans are disproportionately affected compared with the general population.
      • Sachdeva M
      • Shah M
      • Alavi A
      Race-specific prevalence of hidradenitis suppurativa.
      ,
      • Vlassova N
      • Kuhn D
      • Okoye GA
      Hidradenitis suppurativa disproportionately affects African Americans: a single-center retrospective analysis.
      Pain, drainage, and odor are among the most burdensome symptoms for patients with hidradenitis suppurativa. In a prospective multinational survey, approximately 60% of patients reported recent hidradenitis suppurativa-related pain as “moderate or higher,” while nearly 5% described recent pain to be “the worst possible.”
      • Garg A
      • Neuren E
      • Cha D
      • et al.
      Evaluating patients' unmet needs in hidradenitis suppurativa: results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project.
      Additionally, malodorous drainage frequently requires management. The negative impact of hidradenitis suppurativa on quality of life due to the physical, psychosocial, and comorbid burden of the disease is substantial.
      • Kimball AB
      • Crowley JJ
      • Papp K
      • et al.
      Baseline patient-reported outcomes from UNITE: an observational, international, multicentre registry to evaluate hidradenitis suppurativa in clinical practice.
      ,
      • Mac Mahon J
      • Kirthi S
      • Byrne N
      • O'Grady C
      • Tobin AM
      An update on health-related quality of life and patient-reported outcomes in hidradenitis suppurativa.
      In part, because of poor recognition of hidradenitis suppurativa within the medical community, the average time from onset of symptoms to diagnosis is approximately 10 years.
      • Garg A
      • Neuren E
      • Cha D
      • et al.
      Evaluating patients' unmet needs in hidradenitis suppurativa: results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project.
      During this period, patients may experience disease progression that can lead to disfigurement and disability. Additionally, patients often experience fragmented care for flare management at acute and ambulatory care facilities with a variety of providers.
      • Desai N
      • Shah P
      High burden of hospital resource utilization in patients with hidradenitis suppurativa in England: a retrospective cohort study using hospital episode statistics.
      • Khalsa A
      • Liu G
      • Kirby JS
      Increased utilization of emergency department and inpatient care by patients with hidradenitis suppurativa.
      • Kirby JS
      • Miller JJ
      • Adams DR
      • Leslie D
      Health care utilization patterns and costs for patients with hidradenitis suppurativa.
      There is an opportunity for primary care and specialty providers to support timely recognition of hidradenitis suppurativa and screening and management for the numerous comorbid conditions associated with the disease.
      • Garg A
      • Malviya N
      • Strunk A
      • et al.
      Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations.
      ,
      • Reddy S
      • Strunk A
      • Garg A
      Comparative overall comorbidity burden among patients with hidradenitis suppurativa.
      We provide a comprehensive review of the clinical manifestations, associated comorbidities, and life impact of hidradenitis suppurativa to facilitate early recognition and diagnosis of hidradenitis suppurativa and insights into pathogenesis and therapeutic options.

      Recognizing the Clinical Presentation of Hidradenitis Suppurativa

      In the absence of a diagnostic biomarker, hidradenitis suppurativa remains a clinical diagnosis defined by 3 major diagnostic criteria: 1) presence of inflammatory nodules, abscesses, and tunnels (fistula or sinus) on the skin; 2) involvement of typical anatomic sites—axillae, inframammary and intermammary folds, inguinal creases, perineal region, and buttocks; and 3) recurrence and chronicity (Figure, A).
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.
      ,
      • Ingram JR
      The epidemiology of hidradenitis suppurativa.
      ,
      • Zouboulis CC
      • Desai N
      • Emtestam L
      • et al.
      European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.
      Inflamed nodules and abscesses are often erythematous and tender, with abscesses showing warmth and fluctuance.
      • Zouboulis CC
      • Desai N
      • Emtestam L
      • et al.
      European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.
      Tunnels may open to the skin surface and form coalescing and interconnecting tracts within the dermis.
      • Frew JW
      • Lowes MA
      • Goldfarb N
      • et al.
      Global harmonization of morphological definitions in hidradenitis suppurativa for a proposed glossary.
      Drainage of malodorous material containing cellular debris, microbes, and pus may be seen.
      • Huang CM
      • Kirchhof MG
      Hidradenitis suppurativa from a patient perspective including symptoms and self-treatment.
      Culture of lesions or drainage commonly reveals polymicrobial content or normal skin flora. Hidradenitis suppurativa is an inflammatory disease, and the potential role of the skin microbiome on the surface or in the dermis of the skin is not yet well established.
      • Naik HB
      • Jo JH
      • Paul M
      • Kong HH
      Skin microbiota perturbations are distinct and disease severity-dependent in hidradenitis suppurativa.
      Some antibiotic strategies have utility in the management of hidradenitis suppurativa; however, it is not yet clear whether their effectiveness relates to their anti-inflammatory or antimicrobial properties.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.
      Typical hidradenitis suppurativa lesions may be solitary or multiple, and the chronicity of the disease results in significant scarring and disfigurement (Figure, A).
      • Frew JW
      • Lowes MA
      • Goldfarb N
      • et al.
      Global harmonization of morphological definitions in hidradenitis suppurativa for a proposed glossary.
      ,
      • Kokolakis G
      • Wolk K
      • Schneider-Burrus S
      • et al.
      Delayed diagnosis of hidradenitis suppurativa and its effect on patients and healthcare system.
      Hidradenitis suppurativa is frequently misdiagnosed as cutaneous abscess, inflamed epidermal cyst, furunculosis, cellulitis, and occasionally, necrotizing fasciitis;
      • Kokolakis G
      • Wolk K
      • Schneider-Burrus S
      • et al.
      Delayed diagnosis of hidradenitis suppurativa and its effect on patients and healthcare system.
      ,
      • Freeman AF
      • Domingo DL
      • Holland SM
      Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations.
      however, recurrent episodes of lesions favoring folds of the body help to distinguish hidradenitis suppurativa from these other entities.
      Figure
      Figure(A) Clinical features of hidradenitis suppurativa lesions and (B) a schematic of the pathogenesis of hidradenitis suppurativa.
      IFN = interferon; IL = interleukin; TGFβ = transforming growth factor β; Th = T helper; TNF = tumor necrosis factor.

      Common Comorbidities in Hidradenitis Suppurativa

      The chronic inflammatory state observed in hidradenitis suppurativa is associated with upregulation of tissue and circulating cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, IL-6, and IL-17, among others. Inflammatory cytokine upregulation has been hypothesized as a pathogenic link to several associated comorbid conditions.
      • Garg A
      • Malviya N
      • Strunk A
      • et al.
      Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations.
      A cross-sectional analysis of electronic health record data for patients with hidradenitis suppurativa and matched controls found that patients with hidradenitis suppurativa had significantly higher overall comorbidity burden.
      • Reddy S
      • Strunk A
      • Garg A
      Comparative overall comorbidity burden among patients with hidradenitis suppurativa.
      Hidradenitis suppurativa has also been associated with an adjusted increase in all-cause mortality risk of 14% compared with healthy controls.
      • Reddy S
      • Strunk A
      • Garg A
      All-cause mortality among patients with hidradenitis suppurativa: a population-based cohort study in the United States.
      In addition to recognizing the disease early in its course, primary and specialty physicians have a critical role in the interdisciplinary management of patients with hidradenitis suppurativa who require comprehensive comorbidity screening and mitigation strategies.
      Comorbid conditions associated with hidradenitis suppurativa include endocrine
      • Garg A
      • Neuren E
      • Strunk A.
      Hidradenitis suppurativa is associated with polycystic ovary syndrome: a population-based analysis in the United States.
      ,
      • Shlyankevich J
      • Chen AJ
      • Kim GE
      • Kimball AB
      Hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chart-verified case-control analysis.
      and metabolic-related conditions,
      • Shlyankevich J
      • Chen AJ
      • Kim GE
      • Kimball AB
      Hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chart-verified case-control analysis.
      • Gold DA
      • Reeder VJ
      • Mahan MG
      • Hamzavi IH
      The prevalence of metabolic syndrome in patients with hidradenitis suppurativa.
      • Sabat R
      • Chanwangpong A
      • Schneider-Burrus S
      • et al.
      Increased prevalence of metabolic syndrome in patients with acne inversa.
      • Bui TL
      • Silva-Hirschberg C
      • Torres J
      • Armstrong AW
      Hidradenitis suppurativa and diabetes mellitus: a systematic review and meta-analysis.
      • Garg A
      • Birabaharan M
      • Strunk A
      Prevalence of type 2 diabetes mellitus among patients with hidradenitis suppurativa in the United States.
      • Kimball AB
      • Sundaram M
      • Gauthier G
      • et al.
      The comorbidity burden of hidradenitis suppurativa in the United States: a claims data analysis.
      • Miller IM
      • Ellervik C
      • Vinding GR
      • et al.
      Association of metabolic syndrome and hidradenitis suppurativa.
      • Tzellos T
      • Zouboulis CC
      • Gulliver W
      • Cohen AD
      • Wolkenstein P
      • Jemec GB
      Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.
      cardiovascular disease,
      • Egeberg A
      • Gislason GH
      • Hansen PR
      Risk of major adverse cardiovascular events and all-cause mortality in patients with hidradenitis suppurativa.
      ,
      • Reddy S
      • Strunk A
      • Jemec GBE
      • Garg A
      Incidence of myocardial infarction and cerebrovascular accident in patients with hidradenitis suppurativa.
      obstetric risks,
      • Fitzpatrick L
      • Hsiao J
      • Tannenbaum R
      • Strunk A
      • Garg A
      Adverse pregnancy and maternal outcomes in women with hidradenitis suppurativa.
      gastrointestinal disorders,
      • Egeberg A
      • Jemec GBE
      • Kimball AB
      • et al.
      Prevalence and risk of inflammatory bowel disease in patients with hidradenitis suppurativa.
      ,
      • 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.
      musculoskeletal diseases,
      • Fauconier M
      • Reguiai Z
      • Barbe C
      • et al.
      Association between hidradenitis suppurativa and spondyloarthritis.
      ,
      • Lee JH
      • Kwon HS
      • Jung HM
      • Kim GM
      • Bae JM
      Prevalence and comorbidities associated with hidradenitis suppurativa in Korea: a nationwide population-based study.
      and—perhaps most importantly—mental health disorders
      • Garg A
      • Malviya N
      • Strunk A
      • et al.
      Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations.
      ,
      • Machado MO
      • Stergiopoulos V
      • Maes M
      • et al.
      Depression and anxiety in adults with hidradenitis suppurativa: a systematic review and meta-analysis.
      • Onderdijk AJ
      • van der Zee HH
      • Esmann S
      • et al.
      Depression in patients with hidradenitis suppurativa.
      • Shavit E
      • Dreiher J
      • Freud T
      • Halevy S
      • Vinker S
      • Cohen AD
      Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa.
      • Theut Riis P
      • Pedersen OB
      • Sigsgaard V
      • et al.
      Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study.
      • Thorlacius L
      • Cohen AD
      • Gislason GH
      • Jemec GBE
      • Egeberg A
      Increased suicide risk in patients with hidradenitis suppurativa.
      • Slyper M
      • Strunk A
      • Garg A
      Incidence of sexual dysfunction among patients with hidradenitis suppurativa: a population-based retrospective analysis.
      as well as other comorbidities (Table 1).
      • Tzellos T
      • Zouboulis CC
      • Gulliver W
      • Cohen AD
      • Wolkenstein P
      • Jemec GB
      Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.
      ,
      • Garg A
      • Papagermanos V
      • Midura M
      • Strunk A
      Incidence of hidradenitis suppurativa among tobacco smokers: a population-based retrospective analysis in the U.S.A.
      • Garg A
      • Papagermanos V
      • Midura M
      • Strunk A
      • Merson J
      Opioid, alcohol, and cannabis misuse among patients with hidradenitis suppurativa: a population-based analysis in the United States.
      • Reddy S
      • Orenstein LAV
      • Strunk A
      • Garg A
      Incidence of long-term opioid use among opioid-naive patients with hidradenitis suppurativa in the United States.
      • Schrader AM
      • Deckers IE
      • van der Zee HH
      • Boer J
      • Prens EP
      Hidradenitis suppurativa: a retrospective study of 846 Dutch patients to identify factors associated with disease severity.
      • Wright S
      • Strunk A
      • Garg A
      Trends in body mass index before and after diagnosis of hidradenitis suppurativa.
      A comprehensive comorbidity screening strategy for patients with hidradenitis suppurativa is critical to achieving and maintaining overall health. Primary care providers have an important role in managing and coordinating care for the treatment of these conditions to help manage and improve hidradenitis suppurativa disease burden.
      Table 1Common Comorbidities Associated with Hidradenitis Suppurativa
      Comorbid ConditionIncreased Prevalence or Odds Among Patients with Hidradenitis Suppurativa
      Polycystic ovary syndrome
      • A large cross-sectional analysis reported a prevalence rate of up to 9.0% for polycystic ovary syndrome in women with hidradenitis suppurativa compared with 2.9% in controls
        • Garg A
        • Neuren E
        • Strunk A.
        Hidradenitis suppurativa is associated with polycystic ovary syndrome: a population-based analysis in the United States.
      • A retrospective case-control study of US patient data estimated that the increased OR in a multivariate analysis of polycystic ovary syndrome in women with hidradenitis suppurativa is 13.7 times (95% CI, 4.00-47.3) higher than that in control individuals
        • Shlyankevich J
        • Chen AJ
        • Kim GE
        • Kimball AB
        Hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chart-verified case-control analysis.
      Metabolic syndrome and related conditions
      • A case-controlled study found that patients with hidradenitis suppurativa have a greater risk of metabolic syndrome, with an OR of 4.46 compared with control participants
        • Sabat R
        • Chanwangpong A
        • Schneider-Burrus S
        • et al.
        Increased prevalence of metabolic syndrome in patients with acne inversa.
      • Retrospective studies have estimated a prevalence of metabolic syndrome as high as approximately 50% in hidradenitis suppurativa
        • Gold DA
        • Reeder VJ
        • Mahan MG
        • Hamzavi IH
        The prevalence of metabolic syndrome in patients with hidradenitis suppurativa.
       Dyslipidemia
      • Higher prevalence of dyslipidemia was found in patients with mild and severe hidradenitis suppurativa compared with control individuals (28.8% vs 17.2% and 30.7% vs 18.7%, respectively) in a retrospective cohort analysis of US patient claims data
        • Kimball AB
        • Sundaram M
        • Gauthier G
        • et al.
        The comorbidity burden of hidradenitis suppurativa in the United States: a claims data analysis.
      • A retrospective case-control study of US patient data reported an increased OR (95% CI) for experiencing dyslipidemia among patients with hidradenitis suppurativa (4.06 [2.54-6.48]) compared with control individuals
        • Shlyankevich J
        • Chen AJ
        • Kim GE
        • Kimball AB
        Hidradenitis suppurativa is a systemic disease with substantial comorbidity burden: a chart-verified case-control analysis.
      • A large meta-analysis demonstrated an increased OR (95% CI) of 1.67 (1.14-2.47) and 2.48 (1.49-4.16) for hypertriglyceridemia and low high-density lipoprotein, respectively, among patients with hidradenitis suppurativa compared with controls
        • Tzellos T
        • Zouboulis CC
        • Gulliver W
        • Cohen AD
        • Wolkenstein P
        • Jemec GB
        Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.
       Diabetes mellitus
      • An increased prevalence rate of up to 24.8% for diabetes mellitus has also been observed among patients with hidradenitis suppurativa
        • Garg A
        • Birabaharan M
        • Strunk A
        Prevalence of type 2 diabetes mellitus among patients with hidradenitis suppurativa in the United States.
      • Meta-analyses have estimated a 1.5- to 2.8-fold higher risk of diabetes mellitus in these patients compared with controls
        • Bui TL
        • Silva-Hirschberg C
        • Torres J
        • Armstrong AW
        Hidradenitis suppurativa and diabetes mellitus: a systematic review and meta-analysis.
        ,
        • Miller IM
        • Ellervik C
        • Vinding GR
        • et al.
        Association of metabolic syndrome and hidradenitis suppurativa.
       Obesity
      • Patients with hidradenitis suppurativa were found to be 3.5 times more likely to be obese than control individuals in a meta-analysis
        • Tzellos T
        • Zouboulis CC
        • Gulliver W
        • Cohen AD
        • Wolkenstein P
        • Jemec GB
        Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.
      • Increased smoking (in pack-years) and higher BMI have been associated with greater disease severity in a cohort study of patients in Denmark
        • Schrader AM
        • Deckers IE
        • van der Zee HH
        • Boer J
        • Prens EP
        Hidradenitis suppurativa: a retrospective study of 846 Dutch patients to identify factors associated with disease severity.
      • A retrospective study cohort study of patients with hidradenitis suppurativa reported that BMI was significantly higher in patients with hidradenitis suppurativa than in matched controls
        • Wright S
        • Strunk A
        • Garg A
        Trends in body mass index before and after diagnosis of hidradenitis suppurativa.
      • This difference was more pronounced in women than in men and in patients diagnosed prior to 40 years of age compared with those diagnosed after 40 years of age
        • Wright S
        • Strunk A
        • Garg A
        Trends in body mass index before and after diagnosis of hidradenitis suppurativa.
      Cardiovascular events
      • In a cohort study that included population-based registry data for patients with hidradenitis suppurativa, incidence risk of major adverse cardiac events and cardiovascular-related death was 1.5 and 1.6 times higher, respectively, in these patients vs a control population
        • Egeberg A
        • Gislason GH
        • Hansen PR
        Risk of major adverse cardiovascular events and all-cause mortality in patients with hidradenitis suppurativa.
      • A retrospective cohort analysis of EHR data for patients with hidradenitis suppurativa reported an increased risk (HR [95% CI]) of myocardial infarction (1.21 [1.12-1.32]; P < .001), cerebrovascular accident (1.22 [1.14-1.31]; P < .001), and major adverse cardiac event (1.23 [1.17-1.30]; P < .001) compared with controls
        • Reddy S
        • Strunk A
        • Jemec GBE
        • Garg A
        Incidence of myocardial infarction and cerebrovascular accident in patients with hidradenitis suppurativa.
      Obstetrics risks
      • A retrospective cohort analysis of pregnancy and maternal outcomes for women with hidradenitis suppurativa showed that hidradenitis suppurativa was associated (OR [95% CI]) with spontaneous abortion (1.20 [1.04-1.38]), gestational diabetes (1.26 [1.07-1.48]), and cesarean birth (1.09 [1.004-1.17])
        • Fitzpatrick L
        • Hsiao J
        • Tannenbaum R
        • Strunk A
        • Garg A
        Adverse pregnancy and maternal outcomes in women with hidradenitis suppurativa.
      Inflammatory bowel disease, including ulcerative colitis and Crohn disease
      • A large cohort study of Danish individuals in national registries found that patients with hidradenitis suppurativa had an increased OR (95% CI) for Crohn disease and ulcerative colitis of 2.04 (1.59-2.62) and 1.75 (1.44-2.13), respectively, compared with the general population
        • Egeberg A
        • Jemec GBE
        • Kimball AB
        • et al.
        Prevalence and risk of inflammatory bowel disease in patients with hidradenitis suppurativa.
      • In a cross-sectional analysis of EHR data for patients with hidradenitis suppurativa, the prevalence of Crohn disease was significantly higher in patients with hidradenitis suppurativa than in those without hidradenitis suppurativa (2.0% vs 0.6%; P < .001), and patients with hidradenitis suppurativa had an increased adjusted OR (95% CI) of 3.05 times (2.87-3.25) for Crohn disease
        • 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.
      Arthropathies
      • Two cohort studies also determined increased odds of spondyloarthritis of 1.5 to 9.4 times that in patients with hidradenitis suppurativa
        • Fauconier M
        • Reguiai Z
        • Barbe C
        • et al.
        Association between hidradenitis suppurativa and spondyloarthritis.
        ,
        • Lee JH
        • Kwon HS
        • Jung HM
        • Kim GM
        • Bae JM
        Prevalence and comorbidities associated with hidradenitis suppurativa in Korea: a nationwide population-based study.
      Psychological distress and related conditions
      • The prevalence rates of depression and generalized anxiety disorder in patients with hidradenitis suppurativa are as high as 26% and 5%, respectively
        • Machado MO
        • Stergiopoulos V
        • Maes M
        • et al.
        Depression and anxiety in adults with hidradenitis suppurativa: a systematic review and meta-analysis.
      • Large retrospective cohort studies have reported an increased risk of developing both depression and generalized anxiety disorder, as well as increased suicidality, in patients with hidradenitis suppurativa compared with control populations
        • Machado MO
        • Stergiopoulos V
        • Maes M
        • et al.
        Depression and anxiety in adults with hidradenitis suppurativa: a systematic review and meta-analysis.
        • Onderdijk AJ
        • van der Zee HH
        • Esmann S
        • et al.
        Depression in patients with hidradenitis suppurativa.
        • Shavit E
        • Dreiher J
        • Freud T
        • Halevy S
        • Vinker S
        • Cohen AD
        Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa.
        • Theut Riis P
        • Pedersen OB
        • Sigsgaard V
        • et al.
        Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study.
        • Thorlacius L
        • Cohen AD
        • Gislason GH
        • Jemec GBE
        • Egeberg A
        Increased suicide risk in patients with hidradenitis suppurativa.
       Sexual dysfunction
      • The increased incidence (OR [95% CI]) of sexual dysfunction (1.38 [1.28-1.48]; P < .001) in patients with hidradenitis suppurativa compared with those without hidradenitis suppurativa was reported in an adjusted retrospective analysis of patient EHR data. The 5-year cumulative incidence of sexual dysfunction was found to be 1.7% for patients with hidradenitis suppurativa vs 1.5% for controls
        • Slyper M
        • Strunk A
        • Garg A
        Incidence of sexual dysfunction among patients with hidradenitis suppurativa: a population-based retrospective analysis.
      • A higher incidence of sexual dysfunction was also found in patients with hidradenitis suppurativa with depressive disorder and generalized anxiety disorder vs those without each disorder
      • Depression and anxiety disorders were significant effect modifiers of the relationship between hidradenitis suppurativa and sexual dysfunction
        • Slyper M
        • Strunk A
        • Garg A
        Incidence of sexual dysfunction among patients with hidradenitis suppurativa: a population-based retrospective analysis.
      Modifiable risk factors
       Substance use disorders
      • A cross-sectional analysis of EHRs for patients with hidradenitis suppurativa found that 47.9%, 32.7%, and 29.7% of patients experienced substance use disorders related to alcohol, opioids, and cannabis, respectively
        • Garg A
        • Papagermanos V
        • Midura M
        • Strunk A
        • Merson J
        Opioid, alcohol, and cannabis misuse among patients with hidradenitis suppurativa: a population-based analysis in the United States.
      • A retrospective cohort study of patients with hidradenitis suppurativa reported that patients had 1.53 times greater odds of new long-term opioid use compared with controls
        • Reddy S
        • Orenstein LAV
        • Strunk A
        • Garg A
        Incidence of long-term opioid use among opioid-naive patients with hidradenitis suppurativa in the United States.
       Tobacco smoking
      • An increased risk of 90% for experiencing a new hidradenitis suppurativa diagnosis among smokers compared with nonsmokers in the United States was estimated in a retrospective cohort study
        • Garg A
        • Papagermanos V
        • Midura M
        • Strunk A
        Incidence of hidradenitis suppurativa among tobacco smokers: a population-based retrospective analysis in the U.S.A.
      • One retrospective cohort analysis found that the adjusted OR (95% CI) for developing hidradenitis suppurativa was 1.90 (1.84-1.96) among tobacco smokers compared with nonsmokers
        • Garg A
        • Papagermanos V
        • Midura M
        • Strunk A
        Incidence of hidradenitis suppurativa among tobacco smokers: a population-based retrospective analysis in the U.S.A.
      • A systematic review reported a significant association (OR [95%CI]) between patients with hidradenitis suppurativa and current smoking (4.34 [2.48-7.60]) and obesity (3.45 [2.20-5.38]) compared with control populations
        • Tzellos T
        • Zouboulis CC
        • Gulliver W
        • Cohen AD
        • Wolkenstein P
        • Jemec GB
        Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.
      BMI = body mass index; CI = confidence interval; EHR = electronic health record; HR = hazard ratio; OR = odds ratio.

      The Psychological Burden Experienced with Hidradenitis Suppurativa

      Hidradenitis suppurativa symptoms—including pain, itch, drainage, and odor—often interfere with daily functions.
      • Kaaz K
      • Szepietowski JC
      • Matusiak L
      Influence of itch and pain on sleep quality in patients with hidradenitis suppurativa.
      • Matusiak L
      • Szczech J
      • Kaaz K
      • Lelonek E
      • Szepietowski JC
      Clinical characteristics of pruritus and pain in patients with hidradenitis suppurativa.
      • Riis PT
      • Vinding GR
      • Ring HC
      • Jemec GB
      Disutility in patients with hidradenitis suppurativa: a cross-sectional study using EuroQoL-5D.
      • Vossen A
      • Schoenmakers A
      • van Straalen KR
      • Prens EP
      • van der Zee HH
      Assessing pruritus in hidradenitis suppurativa: a cross-sectional study.
      Patients also experience significant social stigma
      • Kirby JS
      • Leiphart P
      Standing up together to the shame and stigma associated with hidradenitis suppurativa.
      ,
      • Koumaki D
      • Efthymiou O
      • Bozi E
      • Katoulis AC
      Perspectives on perceived stigma and self-stigma in patients with hidradenitis suppurativa.
      and negative body image
      • Schneider-Burrus S
      • Jost A
      • Peters EMJ
      • Witte-Haendel E
      • Sterry W
      • Sabat R
      Association of hidradenitis suppurativa with body image.
      due to affected body areas, malodor, disfigurement, and associated obesity and tobacco smoking. The substantial emotional and psychological impact of hidradenitis suppurativa
      • Kimball AB
      • Crowley JJ
      • Papp K
      • et al.
      Baseline patient-reported outcomes from UNITE: an observational, international, multicentre registry to evaluate hidradenitis suppurativa in clinical practice.
      has also been associated with low self-esteem and poor body image, which can negatively impact social and intimate relationships.
      • Alavi A
      • Farzanfar D
      • Rogalska T
      • Lowes MA
      • Chavoshi S
      Quality of life and sexual health in patients with hidradenitis suppurativa.
      ,
      • Janse IC
      • Deckers IE
      • van der Maten AD
      • et al.
      Sexual health and quality of life are impaired in hidradenitis suppurativa: a multicentre cross-sectional study.
      The adjusted odds of depression and suicide among patients with hidradenitis suppurativa compared with those without hidradenitis suppurativa are 1.3 to 4.8 times
      • Shavit E
      • Dreiher J
      • Freud T
      • Halevy S
      • Vinker S
      • Cohen AD
      Psychiatric comorbidities in 3207 patients with hidradenitis suppurativa.
      ,
      • Theut Riis P
      • Pedersen OB
      • Sigsgaard V
      • et al.
      Prevalence of patients with self-reported hidradenitis suppurativa in a cohort of Danish blood donors: a cross-sectional study.
      ,
      • Huilaja L
      • Tiri H
      • Jokelainen J
      • Timonen M
      • Tasanen K
      Patients with hidradenitis suppurativa have a high psychiatric disease burden: a Finnish nationwide registry study.
      ,
      • 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.
      and 2.4 to 2.8 times
      • Thorlacius L
      • Cohen AD
      • Gislason GH
      • Jemec GBE
      • Egeberg A
      Increased suicide risk in patients with hidradenitis suppurativa.
      ,
      • Tiri H
      • Huilaja L
      • Jokelainen J
      • Timonen M
      • Tasanen K
      Women with hidradenitis suppurativa have an elevated risk of suicide.
      higher, respectively. Additionally, anxiety is more common in those with hidradenitis suppurativa.
      • Machado MO
      • Stergiopoulos V
      • Maes M
      • et al.
      Depression and anxiety in adults with hidradenitis suppurativa: a systematic review and meta-analysis.
      ,
      • Tiri H
      • Huilaja L
      • Jokelainen J
      • Timonen M
      • Tasanen K
      Women with hidradenitis suppurativa have an elevated risk of suicide.
      Furthermore, the ongoing cost and challenges to access of care and increased health care resource utilization related to managing mental health disorders impose a significant financial burden on patients.
      • Marvel J
      • Vlahiotis A
      • Sainski-Nguyen A
      • Willson T
      • Kimball A
      Disease burden and cost of hidradenitis suppurativa: a retrospective examination of US administrative claims data.
      ,
      • Patel KR
      • Rastogi S
      • Singam V
      • Lee HH
      • Amin AZ
      • Silverberg JI
      Association between hidradenitis suppurativa and hospitalization for psychiatric disorders: a cross-sectional analysis of the National Inpatient Sample.
      Taken together, a thorough understanding of the key clinical features of hidradenitis suppurativa, the psychological impact, and frequent comorbidities will facilitate an identification of hidradenitis suppurativa.

      Current Understanding of the Pathogenesis of Hidradenitis Suppurativa

      The pathogenic mechanisms of hidradenitis suppurativa are not well understood; however, genetics, microbes, immune dysregulation, and hormonal fluctuations are thought to play important roles in its pathophysiology (Figure, B).
      Retrospective cohort studies have reported that up to 40% of patients have a family history of hidradenitis suppurativa, which has also been associated with earlier disease onset.
      • Schrader AM
      • Deckers IE
      • van der Zee HH
      • Boer J
      • Prens EP
      Hidradenitis suppurativa: a retrospective study of 846 Dutch patients to identify factors associated with disease severity.
      ,
      • von der Werth JM
      • Williams HC
      The natural history of hidradenitis suppurativa.
      Mutations in the γ-secretase complex have been identified in patients with hidradenitis suppurativa and are associated with a severe, widespread clinical phenotype.
      • Pink AE
      • Simpson MA
      • Desai N
      • Trembath RC
      • Barker JNW
      gamma-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis.
      Preclinical studies have suggested that loss-of-function mutations in γ-secretase genes may lead to initiation of follicular hyperkeratosis and cyst formation similar to hidradenitis suppurativa.
      • Pink AE
      • Simpson MA
      • Desai N
      • Trembath RC
      • Barker JNW
      gamma-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis.
      Mutations in genes important in innate immune function have been implicated in hidradenitis suppurativa. Patients with pyogenic arthritis, pyoderma gangrenosum, and acne syndrome can have a hidradenitis suppurativa-like phenotype, and these patients have autosomal dominant mutations in PSTPIP1. Mutations in MEFV, the gene that encodes pyrin and is implicated in familial Mediterranean fever, has also been implicated in hidradenitis suppurativa. These data suggest a potential role for innate immune dysfunction in hidradenitis suppurativa pathogenesis.
      • Vossen A
      • van der Zee HH
      • Prens EP
      Hidradenitis suppurativa: a systematic review integrating inflammatory pathways into a cohesive pathogenic model.
      Follicular occlusion due to hyperproliferation of keratinocytes is believed to be the initiating event in hidradenitis suppurativa.
      • Hotz C
      • Boniotto M
      • Guguin A
      • et al.
      Intrinsic defect in keratinocyte function leads to inflammation in hidradenitis suppurativa.
      ,
      • Prens E
      • Deckers I
      Pathophysiology of hidradenitis suppurativa: an update.
      Subsequent follicle rupture leads to the seeding of microbes and keratinocyte debris from the hair follicle into the surrounding dermis. A subsequent inflammatory response is triggered and results in the recruitment of inflammatory cells, including neutrophils and lymphocytes, leading to the development of inflammatory lesions.
      • Napolitano M
      • Megna M
      • Timoshchuk EA
      • et al.
      Hidradenitis suppurativa: from pathogenesis to diagnosis and treatment.
      This response sustains the chronic inflammation seen with hidradenitis suppurativa.
      • Naik HB
      • Jo JH
      • Paul M
      • Kong HH
      Skin microbiota perturbations are distinct and disease severity-dependent in hidradenitis suppurativa.
      ,
      • Marasca C
      • Tranchini P
      • Marino V
      • et al.
      The pharmacology of antibiotic therapy in hidradenitis suppurativa.
      ,
      • Scala E
      • Cacciapuoti S
      • Garzorz-Stark N
      • et al.
      Hidradenitis suppurativa: where we are and where we are going.
      Elevated levels of circulating complement factors are proposed drivers of neutrophil recruitment and activation that cause subsequent enzyme release in hidradenitis suppurativa lesions.
      • Kanni T
      • Zenker O
      • Habel M
      • Riedemann N
      • Giamarellos-Bourboulis EJ
      Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?.
      Aberrant inflammatory signaling is also thought to increase levels of pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-23, IL-12, and IL-17,
      • Del Duca E
      • Morelli P
      • Bennardo L
      • Di Raimondo C
      • Nisticò SP
      Cytokine pathways and investigational target therapies in hidradenitis suppurativa.
      ,
      • van der Zee HH
      • de Ruiter L
      • van den Broecke DG
      • Dik WA
      • Laman JD
      • Prens EP
      Elevated levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-alpha and IL-1beta.
      which have been observed in lesional skin and serum in patients with hidradenitis suppurativa.
      • Witte-Handel E
      • Wolk K
      • Tsaousi A
      • et al.
      The IL-1 pathway is hyperactive in hidradenitis suppurativa and contributes to skin infiltration and destruction.
      • Kelly G
      • Hughes R
      • McGarry T
      • et al.
      Dysregulated cytokine expression in lesional and nonlesional skin in hidradenitis suppurativa.
      • Schlapbach C
      • Hanni T
      • Yawalkar N
      • Hunger RE
      Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa.
      • Thomi R
      • Cazzaniga S
      • Seyed Jafari SM
      • Schlapbach C
      • Hunger RE
      Association of hidradenitis suppurativa with T helper 1/T helper 17 phenotypes: a semantic map analysis.
      The post-adrenarche and premenopausal onset, association with polycystic ovary syndrome, and perimenstrual and peripartum disease flares suggest that hormone dysregulation may be an underlying factor in the pathogenesis of hidradenitis suppurativa.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.
      ,
      • Garg A
      • Neuren E
      • Strunk A.
      Hidradenitis suppurativa is associated with polycystic ovary syndrome: a population-based analysis in the United States.
      ,
      • Riis PT
      • Ring HC
      • Themstrup L
      • Jemec GB
      The role of androgens and estrogens in hidradenitis suppurativa – a systematic review.
      While the direct role of sex hormones is not well understood in hidradenitis suppurativa, there is evidence to suggest that patients may experience benefit from anti-androgen therapies.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.
      Deepening understanding of hidradenitis suppurativa biology will facilitate identification of disease targets that may ultimately lead to development of effective novel therapeutics.

      Therapeutic Options and Disease Management

      A multifaceted approach to care should include medical and surgical management as well as screening for and managing associated comorbidities. Given the heterogeneity in response to treatments and potential for disease progression, early referral to dermatology should be considered for patients with suspected hidradenitis suppurativa.
      Medical treatments for hidradenitis suppurativa are described in Table 2. First-line treatments in early-stage hidradenitis suppurativa include topical and systemic antibiotics.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.
      Topical management of early hidradenitis suppurativa includes antiseptic cleansers, including benzoyl peroxide wash, and antibiotics, although evidence supporting their efficacy is limited.
      • Zouboulis CC
      • Desai N
      • Emtestam L
      • et al.
      European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.
      ,
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.
      ,
      • Alavi A
      • Kirsner RS
      Local wound care and topical management of hidradenitis suppurativa.
      Oral tetracyclines, most commonly doxycycline, as first-line systemic antibiotics for mild disease may improve symptoms via anti-inflammatory activity. Combination oral antibiotic regimens have also shown efficacy.
      • Delage M
      • Jais JP
      • Lam T
      • et al.
      Rifampin-moxifloxacin-metronidazole combination therapy for severe Hurley Stage 1 hidradenitis suppurativa: prospective short-term trial and one-year follow-up in 28 consecutive patients [online ahead of print].
      ,
      • Join-Lambert O
      • Coignard H
      • Jais JP
      • et al.
      Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa.
      Therapeutic strategies for antibiotic regimens should consider the potential benefit with the risk of resistance to optimize treatment duration and frequency. While the role of androgens in hidradenitis suppurativa is unclear, anti-androgen treatments have been observed to improve symptoms.
      • Khandalavala BN
      • Do MV
      Finasteride in hidradenitis suppurativa: a "male" therapy for a predominantly "female" disease.
      • Kraft JN
      • Searles GE
      Hidradenitis suppurativa in 64 female patients: retrospective study comparing oral antibiotics and antiandrogen therapy.
      • Verdolini R
      • Clayton N
      • Smith A
      • Alwash N
      • Mannello B
      Metformin for the treatment of hidradenitis suppurativa: a little help along the way.
      In women with hidradenitis suppurativa, spironolactone 100-200 mg daily is generally well tolerated and may be as effective as antibiotic strategies.
      Table 2Treatment Options Available for Hidradenitis Suppurativa
      Available First-Line Treatments That Can Be Administered Prior to Dermatologist Visits
      Topical therapiesClindamycin 1% solution/gel QD-BID

      Washes: zinc pyrithione, chlorhexidine, benzoyl peroxide

      Triamcinolone (intralesional) 40 mg/mL in up to 3 lesions
      Systemic antibioticsDoxycycline 100 mg BID

      Rifampin 300 mg BID and clindamycin 300 mg BID

      Rifampin 300 mg BID plus moxifloxacin 400 mg QD and metronidazole 500 mg TID
      Hormonal therapiesCombination contraceptives

      Spironolactone 100-150 mg QD (or divided BID)

      Metformin 500 mg QD to BID

      Finasteride 1.25-5 mg QD
      Treatment considerations after diagnostic confirmation by a dermatologist
       RetinoidsIsotretinoin

      Acitretin

      Alitretinoin
       Systemic immunomodulatory therapiesCyclosporine

      Systemic steroids
       BiologicsTNF-α inhibitors: adalimumab,
      Adalimumab is the only Food and Drug Administration-approved treatment for hidradenitis suppurativa.
      golimumab, infliximab

      IL-17 inhibitors: secukinumab

      IL-1 inhibitors: anakinra, canakinumab

      IL-12/23 inhibitors: ustekinumab
       Surgical proceduresIncision and drainage

      Cryosurgery

      Unroofing/deroofing

      Lesional or wide excision
      Additional opportunities for PCPs for comprehensive disease management
       Patient educationInform patients of the following:
      • Chronic nature of disease
      • To adhere with dermatologist recommendationsActively manage specialists collaborating on patient care that include:
      • Dermatology provider
      • Pain management or palliative care specialist
      • Plastic surgeon
      • Mental health provider
      • Rheumatologist
      • Gynecologist or urologist
      BID = twice daily; IL = interleukin; PCP = primary care provider; QD = daily; TID = 3 times a day; TNF = tumor necrosis factor.
      low asterisk Adalimumab is the only Food and Drug Administration-approved treatment for hidradenitis suppurativa.
      A paradigm shift in treatment strategy may be needed to focus on early referral to dermatologists (Table 3) and earlier use of biologics that appropriately address the underlying inflammation associated with hidradenitis suppurativa (Table 2). The application of biologics in hidradenitis suppurativa is an evolving area of research. However, the Food and Drug Administration-approved human monoclonal antibody against TNF-α, adalimumab, is approved for use in moderate to severe hidradenitis suppurativa.

      Humira (adalimumab). Package insert. North Chicago, Ill: AbbVie, Inc.

      Two parallel placebo-controlled phase 3 clinical trials (PIONEER 1 and 2) evaluated adalimumab in adult patients with moderate to severe hidradenitis suppurativa. The primary efficacy outcome of 50% reduction in counts of abscesses and nodules was achieved by significantly more participants who received adalimumab in PIONEER 1 (41.8% vs 26.0%) and PIONEER 2 (58.9% vs 27.6%) than by those who received placebo. Significantly greater improvements in lesion counts, pain, and modified Sartorius score for disease activity were observed in patients who received adalimumab vs placebo.
      • Kimball AB
      • Okun MM
      • Williams DA
      • et al.
      Two phase 3 trials of adalimumab for hidradenitis suppurativa.
      Furthermore, in an open-label extension follow-up study, sustained improvements in hidradenitis suppurativa clinical response, lesion counts, skin pain, and Dermatology Life Quality Index score were maintained through week 168 with continuous weekly dosing with adalimumab.
      • Zouboulis CC
      • Okun MM
      • Prens EP
      • et al.
      Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of a phase 3 open-label extension study.
      Although limited studies are available, some have demonstrated the efficacy of infliximab,
      • Casseres RG
      • Prussick L
      • Zancanaro P
      • et al.
      Secukinumab in the treatment of moderate to severe hidradenitis suppurativa: results of an open-label trial.
      ,
      • Prussick L
      • Rothstein B
      • Joshipura D
      • et al.
      Open-label, investigator-initiated, single-site exploratory trial evaluating secukinumab, an anti-interleukin-17A monoclonal antibody, for patients with moderate-to-severe hidradenitis suppurativa.
      ustekinumab,
      • Blok JL
      • Li K
      • Brodmerkel C
      • Horvatovich P
      • Jonkman MF
      • Horvath B
      Ustekinumab in hidradenitis suppurativa: clinical results and a search for potential biomarkers in serum.
      ,
      • Sharon VR
      • Garcia MS
      • Bagheri S
      • et al.
      Management of recalcitrant hidradenitis suppurativa with ustekinumab.
      anakinra,
      • Leslie KS
      • Tripathi SV
      • Nguyen TV
      • Pauli M
      • Rosenblum MD
      An open-label study of anakinra for the treatment of moderate to severe hidradenitis suppurativa.
      ,
      • Tzanetakou V
      • Kanni T
      • Giatrakou S
      • et al.
      Safety and efficacy of anakinra in severe hidradenitis suppurativa: a randomized clinical trial.
      bimekizumab,
      • Glatt S
      • Jemec GBE
      • Forman S
      • et al.
      Efficacy and safety of bimekizumab in moderate to severe hidradenitis suppurativa: a phase 2, double-blind, placebo-controlled randomized clinical trial.
      and secukinumab
      • Casseres RG
      • Prussick L
      • Zancanaro P
      • et al.
      Secukinumab in the treatment of moderate to severe hidradenitis suppurativa: results of an open-label trial.
      for the treatment of patients with hidradenitis suppurativa. Biologic therapy centered on inhibition of inflammatory cytokines is a therapeutic option for patients with moderate and severe hidradenitis suppurativa. Improved disease management may be achieved with aggressive systemic therapies coupled with appropriate management of comorbidities.
      Table 3Resources for Hidradenitis Suppurativa Awareness and Education
      Hidradenitis Suppurativa FoundationHidradenitis Suppurativa Foundation includes information and resources for both patients and providers about education, management, and events for hidradenitis suppurativa

      Available online: https://www.hs-foundation.org/

      Including a hidradenitis suppurativa clinic finder: https://www.hs-foundation.org/hs-specialty-clinics
      Hidradenitis Suppurativa Source: Hidradenitis Suppurativa Clinical ResourceAbbVie has compiled an online portal that includes support and resources for both patients and providers to increase hidradenitis suppurativa awareness and education, including patient handouts and conversation guides

      Available online: https://www.hsdiseasesource.com/resources
      Hope for Hidradenitis SuppurativaHope for Hidradenitis Suppurativa—a volunteer-based patient and provider nonprofit organization to support and advocate for patients with hidradenitis suppurativa—provides hidradenitis suppurativa resources, such as support group information, patient care information, research, and news

      Available online: https://hopeforhs.org/
      Hidradenitis Suppurativa ConnectHidradenitis Suppurativa Connect provides resources for providers (dermatologists and general clinicians) and patients (adult and pediatric), including mental health support, community connections and events, and clinical trial recruitment information

      Available online: https://www.hsconnect.org/
      American Academy of Dermatology (AAD)The AAD has compiled a collection of hidradenitis suppurativa information to increase education and awareness of this disease for providers and patients, including symptoms, causes, treatments, self-care, mechanisms for coping with depression, and dietary changes that may impact hidradenitis suppurativa

      Available online: https://www.aad.org/public/diseases/a-z/hidradenitis-suppurativa-overview
      Surgical interventions have an important role in the management of hidradenitis suppurativa. Deroofing is an ambulatory procedure that can eliminate draining tunnels that open to the surface of the skin.
      • Saylor DK
      • Brownstone ND
      • Naik HB
      Office-based surgical intervention for hidradenitis suppurativa (HS): a focused review for dermatologists.
      Wide local excision is used to remove more extensive inflamed and scarred areas of skin.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.
      It is important to optimize medical therapy to reduce the inflammatory burden prior to surgical interventions and to emphasize that surgical interventions are not curative or protective against hidradenitis suppurativa.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management.
      A thorough consideration of appropriate therapeutic options and awareness of the potential to shift or combine therapeutic strategies to optimize disease management can facilitate comprehensive patient care.

      Comprehensive Patient Care Strategies

      Screening and referral when needed for comorbid conditions, including endocrine
      Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
      Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.
      and metabolic disorders, cardiovascular disorders,
      • Virani SS
      • Alonso A
      • Benjamin EJ
      • et al.
      Heart Disease and Stroke Statistics–2020 update: a report from the American Heart Association.
      obstetric risks,
      • Fitzpatrick L
      • Hsiao J
      • Tannenbaum R
      • Strunk A
      • Garg A
      Adverse pregnancy and maternal outcomes in women with hidradenitis suppurativa.
      gastrointestinal and musculoskeletal disorders, substance misuse,
      • Bush K
      • Kivlahan DR
      • McDonell MB
      • Fihn SD
      • Bradley KA
      The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test.
      ,
      • Enamandram M
      • Rathmell JP
      • Kimball AB
      Chronic pain management in dermatology: pharmacotherapy and therapeutic monitoring with opioid analgesia.
      mental health disorders,
      • Mitchell AJ
      • Coyne JC
      Do ultra-short screening instruments accurately detect depression in primary care? A pooled analysis and meta-analysis of 22 studies.
      • Spitzer RL
      • Kroenke K
      • Williams JB
      • Lowe B
      A brief measure for assessing generalized anxiety disorder: the GAD-7.
      • Uebelacker LA
      • German NM
      • Gaudiano BA
      • Miller IW
      Patient health questionnaire depression scale as a suicide screening instrument in depressed primary care patients: a cross-sectional study.
      and pain
      • Krajewski PK
      • Matusiak L
      • von Stebut E
      • et al.
      Pain in hidradenitis suppurativa: a cross-sectional study of 1,795 patients.
      ,
      • Montero-Vilchez T
      • Diaz-Calvillo P
      • Rodriguez-Pozo JA
      • et al.
      The burden of hidradenitis suppurativa signs and symptoms in quality of life: systematic review and meta-analysis.
      can help patients manage their overall health (Table 4). Mental health disorders are some of the most frequent comorbidities of hidradenitis suppurativa. The Patient Health Questionnaire 2
      • Kroenke K
      • Spitzer RL
      • Williams JB
      The Patient Health Questionnaire-2: validity of a two-item depression screener.
      is a quick screening tool for depression,
      • Garg A
      • Malviya N
      • Strunk A
      • et al.
      Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations.
      ,
      • Levis B
      • Sun Y
      • He C
      • et al.
      Accuracy of the PHQ-2 alone and in combination with the PHQ-9 for screening to detect major depression: systematic review and meta-analysis.
      which, if positive, can be followed up with the more comprehensive 9-item Patient Health Questionnaire.
      • Kroenke K
      • Spitzer RL
      • Williams JB
      The PHQ-9: validity of a brief depression severity measure.
      Limited data support smoking cessation and weight reduction as strategies for hidradenitis suppurativa management.
      • Kromann CB
      • Deckers IE
      • Esmann S
      • Boer J
      • Prens EP
      • Jemec GB
      Risk factors, clinical course and long-term prognosis in hidradenitis suppurativa: a cross-sectional study.
      ,
      • Kromann CB
      • Ibler KS
      • Kristiansen VB
      • Jemec GB
      The influence of body weight on the prevalence and severity of hidradenitis suppurativa.
      However, given the associations between hidradenitis suppurativa and smoking and obesity, it is important to counsel patients on the benefits of risk factor modifications to improve overall health outcomes.
      Table 4Recommended Screening Methods for Comorbidities Associated with Hidradenitis Suppurativa
      Comorbid ConditionScreening Method
      Metabolic syndrome and related conditions (eg, glucose dysregulation, hypertension, dyslipidemia, and obesity)
      • Assess for abnormality in ≥3 of the following: blood pressure levels, fasted triglyceride levels, fasted HDL levels, fasted blood glucose levels, waist circumference measurement
      • Evaluate for dyslipidemia based on fasted lipid panel results
       Obesity
      • Calculate body mass index with patient height and weight
      • Monitor changes
       Diabetes mellitus
      • Measure glycosylated hemoglobin or fasted blood glucose levels
       Polycystic ovary syndrome
      • Order basic screening laboratory tests, such as measurement of testosterone, LH, and FSH levels
      • Determine whether patient meets Rotterdam criteria for polycystic ovary syndrome of ≥2 of the following: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries on transvaginal ultrasonography examination
      Cardiovascular disease and related conditions
      • Conduct general cardiovascular disease assessments, including anthropometric and waist circumference measurements, blood pressure levels, fasting lipid and blood glucose levels, tobacco use, physical activity, and diet
      • Assess hypertension based on blood pressure measurements
      Inflammatory bowel disease
      • Screen for abdominal pain experienced ≥3 times weekly for ≥4 weeks
      • Screen for bloody stools and diarrhea (>3 bowel movements daily for 7 consecutive days)
      Spondyloarthritis
      • Screen for joint pain or stiffness that is worse first thing in the morning or after a period of inactivity, but gets better throughout the day
      Depression/depressive symptoms
      • Initiate assessment by administering the Patient Health Questionnaire-2
      • Follow-up with the Patient Health Questionnaire-9 if the Patient Health Questionnaire-2 result is positive
      Generalized anxiety disorder
      • Administer the Generalized Anxiety Disorder 7-item scale
      Suicidality/self-harm
      • Utilize item 9 of the Patient Health Questionnaire-9 to assess self-harm
      • Screen for history of suicide attempts and any current plans to self-harm
      Pain
      • Use self-administered patient-reported measures of pain, such as the Brief Pain Inventory short form, numerical rating intensity scale, or pain visual analog scale
      • Inquire about pain history, duration, and frequency; pain medication use; and lost workdays
      Substance use disorder
      • Assess for alcohol abuse with the Alcohol Use Disorders Identification Test-C questionnaire
      • Assess for opioid abuse with the Opioid Risk Tool
      FSH = follicle-stimulating hormone; HDL = high-density lipoproteins; LH = luteinizing hormone.
      Pain related to disease flares has a major impact on quality of life for patients with hidradenitis suppurativa.
      • Krajewski PK
      • Matusiak L
      • von Stebut E
      • et al.
      Pain in hidradenitis suppurativa: a cross-sectional study of 1,795 patients.
      ,
      • Montero-Vilchez T
      • Diaz-Calvillo P
      • Rodriguez-Pozo JA
      • et al.
      The burden of hidradenitis suppurativa signs and symptoms in quality of life: systematic review and meta-analysis.
      Identification and management of acute and chronic pain related to hidradenitis suppurativa can aid in the establishment of an optimal treatment plan.
      • Garcovich S
      • Muratori S
      • Moltrasio C
      • et al.
      Prevalence of neuropathic pain and related characteristics in hidradenitis suppurativa: a cross-sectional study.
      • Horvath B
      • Janse IC
      • Sibbald GR
      Pain management in patients with hidradenitis suppurativa.
      • Savage KT
      • Singh V
      • Patel ZS
      • et al.
      Pain management in hidradenitis suppurativa and a proposed treatment algorithm.
      Acute pain is primarily thought to be neuropathic and typically presents as sharp, burning, stinging, or shooting pain. Acute pain can be experienced with hidradenitis suppurativa inflammatory lesions and frequently requires medical intervention.
      • Horvath B
      • Janse IC
      • Sibbald GR
      Pain management in patients with hidradenitis suppurativa.
      Chronic pain is primarily thought to be nociceptive, may be experienced with advanced hidradenitis suppurativa, and is described as gnawing, aching, or tender, and is triggered by mechanical stress.
      • Savage KT
      • Singh V
      • Patel ZS
      • et al.
      Pain management in hidradenitis suppurativa and a proposed treatment algorithm.
      Topical analgesics, acetaminophen, and nonsteroidal anti-inflammatory medications can be used to treat acute pain in patients with hidradenitis suppurativa. The use of opioids may be necessary for some patients but should be used with caution due to the potential for addiction, misuse, and dependence.
      • Alikhan A
      • Sayed C
      • Alavi A
      • et al.
      North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.
      ,
      • Enamandram M
      • Rathmell JP
      • Kimball AB
      Chronic pain management in dermatology: pharmacotherapy and therapeutic monitoring with opioid analgesia.
      Psychological comorbidities that affect perception and tolerance of pain should be considered as part of the optimal pain management strategy for each patient. Ultimately, referral to a pain management or palliative care specialist may be necessary.
      Resources are available to support awareness in and education of patients with hidradenitis suppurativa related to disease course, disease impact, and opportunities to engage behaviors that may support overall health (Table 3). Patients will also benefit from understanding the inflammatory nature of the disease and the potential for immunomodulating therapies to control disease symptoms.

      Conclusion

      Several opportunities to improve care and outcomes for patients with hidradenitis suppurativa are available. Timely disease recognition and management are essential to controlling symptoms, mitigating disease progression, and improving quality of life for patients with hidradenitis suppurativa. Comprehensive care strategies coordinated among medical and surgical disciplines are necessary to improve the overall health of patients with hidradenitis suppurativa.

      Acknowledgments

      Medical writing support was provided by Charli Dominguez, PhD, CMPP, of Health Interactions, Inc, Chicago, IL, and was funded by Novartis Pharmaceuticals Corporation. This manuscript was developed in accordance with Good Publication Practice (GPP3) guidelines. Authors had full control of the content and made the final decision on all aspects of this publication.

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