Hidradenitis Suppurativa and Concurrent Psoriasis: Comparison of Epidemiology, Comorbidity Profiles, and Risk Factors

Hidradenitis suppurativa (HS) is a chronic, progressive, highly inflammatory, painful, and destructive follicular skin disorder. HS manifests in nodules which can progress to abscesses, sinus tracts, and fistulae [1]. Inflammatory lesions mainly affect the inverse body areas, including axillae, the inguinal and anogenital region, and inframammary areas in women [2, 3]. Women are more frequently affected than men, with a ratio of 3:1 [4, 5]. Due to variations in clinical appearance, treatment response, and involved specialties, accurate diagnosis can be complex and is often delayed [6].

Conflicting opinions exist regarding the epidemiology of HS, with an estimated prevalence ranging from 0.03% to 4% worldwide [7, 8]. The average prevalence has been reported as 0.8% in the UK [9], 1% in France, 0.7% in Australia [10], and 0.1% in the USA [11]. Scarce data on global incidences of HS are available; a study from the UK reported an annual incidence of physician-diagnosed cases from 1996 to 2013 as 0.028% [9]; however, in the USA, an overall incidence of 0.011% was reported between 2015 and 2016 [11].

In comparison with other chronic cutaneous diseases such as psoriasis (PsO), expenses for HS disease management are dominated by high-cost settings, e.g., inpatient and emergency department care, including surgical interventions [12]. In addition to the severe impact on a patient’s quality of life (QoL), HS impairs the patient’s ability to work, subsequently affecting annual income, resulting in both unmet medical and socioeconomic needs [13, 14].

To provide optimal health care to HS patients and to quantify the societal burden of this disease, it is essential to understand the demography and epidemiology of HS, frequently associated comorbidities, and risk factors. Analysis of the comorbidity profile and risk are important to understand and dissect the systemic aspects of the disease and can help to optimize clinical care.

Smoking has been attributed to HS development and has been identified as a decisive risk factor, with the incidence of HS doubled amongst smokers compared with nonsmokers [5, 15, 16]. HS is often accompanied by severe comorbidities, including metabolic syndrome and Crohn’s disease (CD) [6, 17]. In addition, patients with HS have a higher prevalence of depression, anxiety, and suicidal ideation, demonstrating the impact of HS on psychosocial wellbeing and QoL [18, 19].

HS and PsO have overlapping immunopathogenic pathways as well as patterns of inflammation-related comorbidity [20]. Data on co-occurrence of both pathologies are however scarce. Type 1 and 3 cytokines such as TNF-α, Interferon-γ, IL-1-α/β, IL-6, IL-8, and IL-17 are upregulated, indicating that the Th1/Th17 axis is activated and may drive inflammation in both diseases [21, 22].

A large-scale population study in Israel reported a greater prevalence of HS in PsO patients than in the general population. HS and PsO coexistence was associated with an increased prevalence of obesity and smoking [23]. A Danish monocentric analysis of patients with HS and PsO consistently observed a threefold increased risk of HS patients for concomitant PsO [24]; other studies suggest more severe comorbidities in concomitant HS and PsO [25].

The present study is conducted to assess the demography and epidemiology of HS patients, PsO patients, and HS patients with concurrent PsO in the German population. In addition, comorbidity profiles are assessed, and a risk analysis is conducted for metabolic, cardiovascular, psychiatric, and immunological comorbidities.

This study describes the demography and epidemiology of HS, PsO, and HS-PsO. Here, we show that most HS patients were between the ages of 30 and 60 years. In studies from both the UK and the USA, HS prevalence peaked in patients around 40 years, similar to this German population [11, 28]. The age distribution of PsO validated a previous study of the German population, in which a large proportion of the population were over 50 years [29]. Consistent with recent reports, HS-PsO patients had a similar age distribution to HS patients, with the majority between 30 and 60 years [23]. In contrast to the sex bias reported by smaller case–control studies, the sex ratio in the cohorts diagnosed with HS, PsO, and HS-PsO in the present study was balanced (Supplementary Table 1) [4, 5].

Interestingly, the percentage of patients with HS with or without PsO declined after the sixth decade of life. Although previously described in epidemiological studies, the immunological reasons for this are not well understood. However, women regularly report the onset of HS disease with menarche, flare up according to the menstrual cycle, and resolution of disease in later life following menopause, supporting the idea of hormonal influence in HS [28, 30].

The prevalence and incidence of HS in this study were relatively low (68.1 cases per 100,000 and 10.1 cases per 100,000 per year, respectively) compared with figures reported worldwide. The prevalence and incidence of HS varies greatly depending on study design, population size, and determination of diagnosis. HICs data and electronic health records in large populations have yielded prevalences of 0.1% [11] (100 cases per 100,000) and 0.05% [31] (50 cases per 100,000), respectively, whereas smaller self-reported studies using questionnaires observed values of 4% [32] (4000 cases per 100,000) and 2.1% [33] (2100 cases per 100,000), respectively. Differences in reported prevalence can be related to a higher misdiagnosis of HS in clinical routine and, therefore, underreporting in SHI. Nevertheless, the observed incidence of HS in this study was in line with other larger studies [34]. The prevalence of PsO, 2% (1962.9 cases per 100,000), in our study was consistent with others, validating this study population [35, 36]. Although the prevalence and incidence of HS-PsO were generally low, these figures account for 6.3% and 1.9% of the HS population, respectively. Most HS patients were diagnosed in a hospital, whereas PsO patients were generally diagnosed in private practices, suggesting that the observed cases of HS may be low due to a lack of identification of disease/delayed diagnosis. The bias of delayed diagnosis was determined to be on average 1.6 years for PsO but 7.2 years for HS [37]. The main reasons for delayed diagnosis of HS are a lack of knowledge as well as the heterogeneous phenotype and unspecific early signs of the disease [38].

Consistent with previous reports, HS patients showed a higher prevalence and increased risk for the development of cardiovascular and metabolic comorbidities compared with the control population (Fig. 2a) [39, 40]. This was also true, albeit to a smaller extent, for PsO patients (Fig. 2b). Intriguingly, in the HS population, the cardiovascular risk was primarily determined by smoking status (Fig. 2a versus Supplementary Fig. 1A). Interestingly, matching for nicotine dependence reduced the risk of myocardial infarction in HS patients almost to the level of the control population. In the PsO population, the risk of developing these comorbidities was both generally lower and less modulated by smoking status (Fig. 2b versus Supplementary Fig. 2B). This indicates that the increased risk of cardiovascular events in HS patients is largely attributed to smoking and not to HS-related processes, e.g., systemic inflammatory processes caused by HS [41, 42]. This is of high relevance for clinical practice since the prevalence of smoking is exceptionally high among HS patients. In this analysis, almost half of the HS population were nicotine dependent compared with 16.2% of PsO patients and 11.7% of the overall population. Smoking cessation does not only improve treatment outcomes in HS but also strongly reduces the elevated cardiovascular risk in these patients [43].

HS-PsO patients suffer with more psychological and rheumatological comorbidities compared with HS or PsO alone patients. Although it is well reported that HS and PsO patients have a reduced QoL and higher prevalence of depression, there are limited data on the effect of HS-PsO on psychological comorbidities [23, 25, 44, 45]. Consistently, Patel et al. described a higher proportion of HS-PsO patients with depression compared with HS or PsO alone [25]. The current study is the first to describe the increased frequency of rheumatological comorbidities in a HS-PsO population. Here, we observed a fourfold increase in the frequency of inflammatory spondyloarthropathies in HS-PsO compared with HS alone. This increase may resemble the pathomechanistic influence of PsO, with studies demonstrating that the risk of PsA is constant over time following a diagnosis of PsO, with a 1% mean annual incidence of PsA in PsO patients [46, 47].

The key strength of HIC analyses is the very large sample size of hospitalized as well as outpatient-treated continuously insured patients in Germany. This allows for analysis of the epidemiology of PsO and HS coprevalence. However, mild to moderate HS forms are commonly misdiagnosed, especially at the beginning of the disease course; thus, HIC data may rather underestimate the prevalence of HS [48]. This may be also impacted by the fact that HS was not exclusively diagnosed by dermatologists, e.g., in case of HS diagnosis in the hospital. Prevalence of HS calculated from other German SHI data showed similar incidence and prevalence and estimated the rate of potential misdiagnosis of HS at 34.7% [49]. The analyzed HIC data do not allow assessment of the influence of ethnicity, the patient’s profession, educational level, subtypes of HS, laboratory data, or the duration or severity of both diseases on the prevalence of different comorbidities. Coding inconsistencies as well as ICD-10 (L73.2) coding error by misdiagnosis (mainly of HS) might further contribute to lower numbers in HIC analysis. Correct diagnosing is, however, more reliable compared with patient-completed questionnaires, which is noteworthy with phenotypically complex diseases such as HS. HS was mostly diagnosed in a hospital setting, with only one-fifth of patients diagnosed by dermatologists. This may result in an overrepresentation of patients with high disease severity within our population. Analyses of comorbidity frequency and risk were performed independently of disease severity, not visible in HIC data, therefore not allowing for a correlation of comorbidity profile/risk and disease activity. Although this analysis was conducted using a HICs dataset restricted to Germany, its findings may be valuable in other countries with a similar demographic structure, especially within Europe.

In summary, patients with chronic inflammatory skin diseases such as PsO and HS have an increased occurrence of comorbidity. Interestingly, the prevalence of concomitant psychiatric and cardiovascular diseases is even more increased upon co-occurrence of PsO and HS (HS-PsO cohort). The elevated cardiovascular risk of HS patients can, however, be largely attributed to smoking.