Cumulative life course impairment: Evidence for hidradenitis suppurativa.

MDT – conception and design, data acquisition, analysis and interpretation, drafting and revision; RSG and CS – conception and design, data acquisition, drafting; MLP and ABK – conception and design, revision, final approval of the manuscript.

Not applicable.

This study does not require IRB approval.

None.

To identify the studies evaluating the risk and protective factors that affect the life course of patients with HS, we searched PubMed, EMBASE and Cochrane Library between January 2023 to February 2024, with the following keywords and related MeSH terms: “hidradenitis suppurativa”, “HS”, “acne inversa” AND “employment”, “career”, “work”, “productivity”, “salary”, “disability”, “social life”, “presenteeism”, “absenteeism”, “employment”, “productivity”, “education”, “sexual health”, “relationship”, “marriage”, “quality of life”, “pregnancy”, “infertility” and “quality of life” “anxiety”, “depression”, “mental health”, “suicide”, “schizophrenia”, “protective”, “surgery” and “bipolar”. Two authors independently reviewed the articles to make sure they were relevant to the subject. Conference abstracts and meeting presentations were also included. 2064 records were identified. A total of 1990 articles, including those published in languages other than English, duplicates and articles deemed irrelevant, were excluded from the review. A total of, 74 articles were included (Figure  1 ). Demographic information, design, sample size, data quality and outcomes were recorded from the studies. The authors summarized the findings in tables, which include the following: Author/year of publication, study type/sample size, country of study, key evidence and quality assessment (see Tables  1 , 2 , 3 , 4 , 5 ). Each study underwent quality assessment independently by two authors. The quality assessment utilized the Newcastle‐Ottawa Scale (NOS) for cross‐sectional studies, which allows for a maximum of 2 points for the Aim, 8 points for Selection, 2 points for Comparability and 4 points for Outcome. For case–controls and cohorts studies, the assessment included a maximum of 4 points for Selection, 2 points for Comparability and 3 points for Outcome (see Table  S1 ). PRISMA diagram of literature review. Employment, disability and education (14 articles). Abbreviations: SES, socioeconomic status; TWPI, total work productivity impairment; WAI, work ability index; WPAI, work productivity and activity impairment. Studies outside of the cross‐sectional, cohort and case–control designs were excluded from quality assessment to ensure methodological consistency and reliability in evaluating observational data.

The cross‐sectional studies ( n  = 45) were categorized as focusing on employment, disability and education 11 ; relationships 16 ; mental health 10 ; quality of life (8, including 2 studies overlapping content with relationship) and protective factors. 2 The average Newcastle ‐Ottawa Scale quality assessments for the cross‐sectional studies were 1.7/2 for clearly stated aim, 5.9/8 for subject selection, 1.6/2 for comparability and 3/4 for outcome assessments. Some of the papers about relationships had somewhat lower scores. The cohort studies ( n  = 14) were categorized as focusing on employment, disability and education, 2 relationships, 7 mental health 2 quality of life (1 common study with employment, disability and education) and protective factors. 3 The average Newcastle‐Ottawa Scale quality assessments were 3.7/4 for subject selection, 1.5/2 for comparability and 2.6/3 for outcome assessments. The case–control studies ( n  = 4) were categorized as focusing on relationships, 1 and mental health. 3 The average Newcastle‐Ottawa Scale quality assessments were 3.3/4 for subject selection, 1.8/2 for comparability and 2/3 for outcome assessments. We identified 14 studies related to the effect of HS on a patient's work life and education (Table  1 ) Patients with HS experience higher rates of missed work, decreased productivity, lower salaries and fewer promotions compared to unaffected individuals. Unemployment rates for HS patients are consistently higher than those of the general population. HS impacts the work ability index (WAI‐23), school attendance, absenteeism (percentage of work missed), presenteeism (productivity loss at work) and total work productivity impairment (TWPI). Additionally, studies show a significant link between Hurley stage and the number of workdays affected by HS. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 The unemployed HS population had a significantly higher DLQI (Dermatology life quality index) scores than the employed group in a study by Theut Riis et al. 19 Van Straalen et al.'s data are also consistent with these findings. They also noted that pain, DLQI and EuroQol–5 Dimensions scores were significantly associated with presenteeism and at‐work productivity loss in multivariate regression models. Unemployed patients with HS had significantly more inguinal/gluteal HS, increased HS severity, higher pain scores, the presence of fibromyalgia and higher depression and anxiety scores. 20 Patients with HS who participated in Kearney et al.'s study reported receiving more education than their parents. Despite this, they have experienced a decline in their social status, with higher unemployment rates and reliance on illness benefits as a result of a disease. The onset of the disease tends to occur during the peak years of education. The study concluded that the disease does not affect education, but accumulating health issues during working years may limit HS patients' opportunities. 21 Delay in diagnosis, severe disease, pain and decreased quality life scores have been associated with work productivity. 22 , 23 , 24 , 25 As per Kokolakis et al., patients with a longer delay in HS diagnosis more frequently reported both the inability to work and the number of days being work disabled than those that had a shorter delay in diagnosis. 26 Tzellos et al. reported that HS affects salary, income growth, work retention and promotion. Patients with HS were found to have a smaller income growth and lower annual income than the general population. They also have a higher risk of leaving the workforce and more total absence days. A calculated loss of gross value of around €12.6 billion results from the effect of HS on patients and their ability to work in Germany. 15 Higher individual annual total indirect costs (disability and medically related absenteeism costs) were detected in patients with HS compared to the general population ($2925 vs. $1483) in the United States. 11 Consistent with these findings, patients with HS have a higher degree of work impairment and lower socioeconomic status (SES) compared to psoriasis patients. 27 , 28 Twenty‐six studies addressed the negative impact HS can have on patients' sexual health, fertility and relationships (Table  2 ). Relationships (26 articles). Abbreviations: ASEX, Arizona sexual experience scale; DLOQ, dermatology life quality index; ED, erectile dysfunction; SD sexual dysfunction; FDLQI, family dermatology life quality index; FKKS SSEX, Frankfurt self‐concept scale for sexuality; FSFI, female sexual function index; IIEF, International index of erectile function; IIEF‐5, International index of erectile dysfunction; QoL, Quality of Life; SD, sexual dysfunction; STEEP, skin‐tissue‐sparing excision with electrosurgical peeling. Studies outside of the cross‐sectional, cohort and case–control designs were excluded from quality assessment to ensure methodological consistency and reliability in evaluating observational data. Cuenca‐Barrales et al. extensively studied sexual health in patients with HS in Spain. Their data showed that HS affects patients' perception of their sexual health. Patients with HS feared rejection or reaction from a sexual partner more than the non‐HS population. Common reasons for fear of rejection included insecurity and physical appearance, which occurred more with younger patients in the absence of stable relationships and an increase in the number of scarred areas. Even patients in stable relationships stated that HS negatively impacted their relationships and reported that pain interfered with their sexual relationships. 29 Thompson et al. also reported HS affecting multiple aspects of patients' relationships. Patients were hesitant to discuss their condition with their significant others, citing communication barriers, fear of partners being bothered by boils, scars and malodorous drainage, or thinking their symptoms were a serious infection or sexually transmitted illness. 30 , 31 In addition to their perceptions of sexual health, HS has been associated with sexual dysfunction. Multiple studies observed patients with HS have a higher likelihood of sexual dysfunction and sexual distress compared to matched controls; females were generally affected more than males. 32 , 33 , 34 , 35 , 36 , 37 , 38 However, Slyper et al. showed that HS was significantly associated with sexual dysfunction (SD) among both men and women compared to patients of the same gender without HS, and this association did not differ significantly by sex. 33 Sexual dysfunction (SD) in patients with HS was shown to be related to educational status, disease activity, pain scale, absence of a stable relationship and unpleasant odour. Erectile dysfunction (ED) in patients with HS was related to age, lesions in the genital area and the number of active lesions. 35 Multiple studies showed that HS is significantly associated with SD in patients with mental disorders including depression and anxiety. The SD incidence was higher in those with HS and depression/anxiety compared to those without HS with these conditions. 33 , 39 Patients with HS also reported higher SD than other skin conditions (prurigo, blistering, psoriasis, urticaria or eczema). 39 Janse et al. confirmed diminished quality of life (QoL) and sexual health in patients with HS. Despite QoL impairment being linked to anogenital involvement, early onset of HS, and disease severity and activity, sexual health was not correlated with any of these factors. 38 Alavi et al. also confirmed that the SD contribution to QoL impairment is independent of genital lesions. 37 Prens et al. evaluated the Arizona Sexual Experiences Scale (ASEX), DLQI, and measures of activity and overall work impairment in patients with HS who underwent Skin‐Tissue‐sparing Excision with Electrosurgical Peeling (STEEP). They reported that surgery did not improve sexual experiences at 6 months post‐surgery. 34 Multiple studies evaluate the impact of HS on patients and their family members in terms of QoL and sexual function and the related risk factors, demonstrating that HS not only negatively affects the patients but also their family members. The Family Dermatology Life Quality Index (FDLQI) score of relatives is associated with the DLQI score of patients and their Hurley stage. Partners or spouses reported a higher FDLQI compared to parents. ED has a high prevalence among male partners, greater than the prevalence of SD in the female partners with HS. This prevalence is similar to that observed in men with HS. 36 , 40 , 41 , 42 HS has also been associated with infertility. Multiple studies showed a higher infertility rate in patients with HS, which is more significant in female patients. Some of them reported that they had had unsuccessful attempts to conceive for more than a year. Patients reported that HS interfered with their ability to conceive due to reduced sexual activity or the potential effects that HS medications have on fertility. Some believed that pregnancy necessitates discontinuation of all HS medications for safety reasons. Other common beliefs included the possibility of children inheriting HS or getting infected from HS during vaginal delivery. Additionally, those with HS affecting the vulva and groin were concerned that childbirth might be more challenging, while those who had HS affecting the breast were worried about difficulties with breastfeeding. 31 , 43 , 44 PCOS is also independently known to be one of the leading causes of infertility, and the prevalence of PCOS is higher in HS. 45 , 46 HS appears to also have a negative impact on pregnancy outcomes. Investigations are consistent with a lower risk of live birth and a higher risk of spontaneous abortion, preterm birth, preeclampsia, elective terminations, gestational hypertension/diabetes and delivering by caesarean section, as well as having a baby with congenital anomalies in pregnant patients with HS. 47 , 48 , 49 With one exception, Lyons et al. did not find an increased risk of poor pregnancy outcomes in patients with HS compared to the general population. 50 Studies have inconsistent results regarding flares or improvement of HS during pregnancy. 51 , 52 Prens et al. noted that an improvement was found earlier in pregnancy and worsened later in pregnancy. 53 Vossen et al. showed that the amelioration during pregnancy was more frequently reported by patients who had perimenstrual flares. 54 We found 20 studies assessing mental health in patients with HS (Table  3 ). Multiple studies have demonstrated that patients with HS have higher rates of depression and anxiety. 55 , 56 , 57 These patients also reported more loneliness, social isolation and lower self‐esteem compared to the general population. 58 Rymaszewska et al. also noted no difference in the prevalence of anxiety and depression between both genders with HS and observed a significant correlation between GAD and HS duration. 59 A meta‐analysis by Phan et al. found a significant association between HS and other mental disorders, including bipolar disorders, schizophrenia, personality disorders, suicidal behaviour and substance‐related disorders, in addition to depression and anxiety. 60 , 61 , 62 , 63 , 64 Patient with HS and psychiatric disorders were younger and had higher body mass index (BMI). 64 Tzur Bitan et al.'s data showed HS is independently and positively associated with bipolar disease, but the association was not statistically significant after controlling for body mass. 62 Paediatric patients with HS also experience increased prevalence of psychiatric conditions, specifically depression and anxiety. 65 , 66 , 67 Mental health (20 articles). Abbreviation: FoS, feelings of stigmatization. Studies outside of the cross‐sectional, cohort and case–control designs were excluded from quality assessment to ensure methodological consistency and reliability in evaluating observational data. Few studies have evaluated the prevalence of suicide among patients with HS; however, their findings are consistent with a strong correlation between HS and suicides or suicidal ideation. 68 The risk is mostly observed in patients with a history of psychiatric disorder and those who have undergone biologic treatments, which may indicate more severe disease. 69 HS has been associated with feelings of stigmatization which can affect social interactions and mental health. A strong relationship was found between HS severity and psychological distress and mental health disorder in patients with HS secondary to stigmatization. 70 , 71 When evaluating factors contributing to mental health, there were no racial differences in mental health outcomes in patients with HS. 72 Mental health disorders were more common in hospitalized patients with HS than those without, but HS was not associated with primary hospitalization for a mental health disorder overall. 73 Alya et al. evaluated DLQI, depression and employment status in chronic skin diseases, including atopic dermatitis, psoriasis and HS. They found significantly higher DLQI and depression scores as well as a lower percentage of employed participants among patients with HS compared to those with atopic dermatitis and psoriasis. 74 Eleven studies focused on QoL in patients with HS were included (Table  4 ). Quality of Life (11 articles). No significant difference in DLQI scoring based on Hurley classification (I: 11.7, II: 12.0, III: 14.4) The only statistically significant difference in DLQI scores by Hurley stage was between stages 0 and 3 ( p  < 0.05). Abbreviations: DLQI, dermatology life quality index; IHS4, International HS severity scoring system; NRS, number rating scale; PGA, physicians' global assessment. Studies outside of the cross‐sectional, cohort and case–control designs were excluded from quality assessment to ensure methodological consistency and reliability in evaluating observational data. DLQI is a frequently used patient‐reported scale with a maximum score of 30 that encompasses six domains, including symptoms and feelings, daily activities, leisure, work and school performance, personal relationships and treatment. Based on the DLQI, HS has an immense impact on patients' QoL. Multiple studies showed that the mean DLQI score for patients with HS is higher than that of the general population. Higher values of pain, pruritus, malodor and HS severity are associated with higher DLQI scores. Hurley III was found to have a significantly higher average DLQI compared to Hurley II and Hurley I. 17 , 37 , 40 , 58 , 70 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 A similar pattern was found for paediatric patients with HS. 80 However, Senthilnathan et al. found no difference in DLQI scoring based on the Hurley classification. 83 The DLQI scores are significantly higher in HS than in other chronic skin conditions, such as psoriasis. Even mild HS has a significant impact on QoL that is comparable to or exceeds that of moderate‐to‐severe atopic dermatitis and psoriasis. 28 , 76 , 83 , 84 As several of the above factors are negative influences on the CLCI model, there are also factors that have a positive impact on the CLCI (Table  5 ). Protecting HS Patients from CLCI (7 articles). United States Norway United States Denmark Abbreviations: DLQI, dermatology life quality index; HiSCR, Hidradenitis suppurativa clinical response; HRQOL, health‐related quality of life; HSQL, hidradenitis suppurativa quality of life; NRS, number rating scale; ROR, reporting odds ratios; SB, suicidal behaviours. Studies outside of the cross‐sectional, cohort and case–control designs were excluded from quality assessment to ensure methodological consistency and reliability in evaluating observational data. Efficacious long‐term management has been associated with improvement in patients' QoL. Standard medical interventions typically consist of antibiotics, hormonal therapies and biologics. Clinical trials showed that treatment with Adalimumab and Secukinumab in moderate‐to‐severe HS clinical trials resulted in improvement in DLQI, work productivity, activity impairment and HS‐pain because of treatment. 85 , 86 Treatment of HS with TNF‐alpha antagonists has been shown to reduce the risk of suicidal behaviours, further supporting that adequate treatment of the disease will help to improve the psychological diseases associated with HS. 87 Surgical intervention is frequently utilized to manage recurrent nodules and fistulas. Dick et al. data showed significant improvement in QoL and pain in patients with HS post Wide Local Excision (WLE). 88 Ravi et al. evaluated patients with HS status post‐surgical deroofing or local excision and demonstrated a high degree of satisfaction with surgery. Recovery was typically rapid, and most patients reported that postoperative pain was less severe than the pain experienced during flares. 89 , 90 A survey demonstrated that resilience moderates depression in patients with HS. 91 This may underscore the importance of patients learning resilience through therapy and training programs to decrease the impact of the disease on QoL. Providers should consider therapy and training programmes as an adjunctive option to medical management to help improve QoL. In one study, single and married patients with HS have improved QoL and reported higher social support than those who were formerly partnered (divorced, separated or widowed). 92 Providers should be aware of the social support situation and can potentially provide information on national HS organizations and resources.

The effect of HS extends to the workplace associated with increased absenteeism, decreased work productivity and lower salaries. HS, moreover, impacts a patient's quality of life, mental health, social and sexual relationships and pregnancies. Since HS is commonly present in young adulthood, these effects can alter the trajectory of a patient's life course. The current body of literature describing components of CLCI is not large but is generally well‐conducted generally. Further longitudinal data is needed to determine which patients and factors led to greater risk for CLCI. Moreover, delay in diagnosis and initiation of treatment has been associated with decreased responsiveness to treatments. 90 Earlier intervention and diagnosis can help symptom and disease management, potentially mitigating some of the disease's impact on the key life milestones in a patient's life and restore some of the patient's life potential. The recent S2k guideline for treatment of HS emphasizes that treatment decisions should take into account both objective disease severity measures and the individual subjective impact on patients. 93 The CLCI paradigm demonstrates the impact HS can have on multidimensional life course outcomes and reinforces the need for early identification and appropriate treatment.

Cumulative life course impairment (CLCI) is a holistic model that evaluates the impact of a disease and its associated factors on an individual's life course and major life‐changing decisions (MLCDs). Children, adolescents and young adults are particularly susceptible to disease impacts that influence their life course, as MLCDs are made during these formative years. 1 , 2 , 3 , 4 Young adult patients with chronic or life‐threatening diseases achieve fewer milestones in all course‐of‐life domains. 4 This CLCI paradigm has been applied to chronic conditions, such as paediatric malignancies, endometriosis, 5 and psoriasis 6 to analyse the disease impacts that could affect the life course trajectory of a patient, including effects on major life decisions and opportunities, such as relationships, career path, education and starting a family. 4 Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin condition with an estimated population prevalence of 0.4%, commonly affecting young adults and it has a predilection for females, affecting them about twice as frequently as males. 7 , 8 , 9 Patients with HS may experience debilitating pain and social stigmatization that can have lasting repercussions. 10 Here we review the evidence for multiple life course domains, including work impairment, educational attainment, sexual health, quality of life and we apply the CLCI framework to the impact of HS on a patient's life course.

Dr. Kimball is receiving honoraria or consulting with Abbvie, Alumis, Avalo, Boehringer Ingelheim, Eli Lilly, Evoimmune, Innovaderm, Janssen, Merck, Moonlake, Novartis, Pfizer, Priovant, Sanofi, Sonoma Bio, Target RWE, UCB, Union Therapeutics and Takeda. Dr. Kimball is on the board of directors of Almirall and the American Dermatologic Association. Dr. Kimball's institution receives grants from: Abbvie, Anapyts Bio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, Prometheus, Sanofi, Sonoma Bio, UCB. Dr. Porter is a consultant and/or investigator for Abbvie, Anapyts Bio, Aristea, Bristol Myers Squibb, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, Prometheus, Sanofi, Sonoma Bio, UCB, Regeneron, Bayer, Alumis, Avalo, Trifecta Clinical/WCG, Zurabio. Dr. Porter receives royalties from BIDMC Licensed HS training module. She is a member of the AAD Patient Safety Quality Committee, HS Foundation Research and Therapeutics Committee, and AAD DataDerm Committee. Dr. Gibson's fellowship was funded through the National Psoriasis Foundation. Dr. Doroudian Tehrani is an investigator for Abbvie, Eli Lilly, Incyte, Moonlake, Prometheus, Sanofi, Insmed, UCB and Bristol Myers Squibb. Corey Snyder has no conflicts of interest to disclose.

Data S1.