Hospitalized hidradenitis suppurativa patients at a university clinic: a fifteen-year retrospective analysis of hospitalized patients with a focus on sex differences Dubravka Živanović1,2*, Marko Demenj1*, Miloš Nikolić1,2 ✉, Dušan Škiljević1,2, Mirjana Milinković Srećković1,2, Snežana Minić1,2, Neda Delić1, Svetlana Popadić1,2 1Dermatology and Venereology Clinic, University Clinical Center of Serbia, Belgrade, Serbia. 2Department of Dermatology and Venereology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 163 2024;33:163-169 doi: 10.15570/actaapa.2024.31 Introduction Hidradenitis suppurativa (HS) is a chronic follicular occlusive skin disorder characterized by recurrent abscesses, draining si- nuses, and scarring, with a multifactorial pathogenesis. HS may be considered a systemic disease due to the presence of accompa- nying systemic manifestations (1). The estimated prevalence of the disease is around 0.4% when combining western European and Scandinavian countries, the United States and Australia (2). Diagnosing HS mainly relies on clinical presentation, which consists of double or multi-ended comedones, painful nodules, abscesses, and sinus tracts with fre- quent scar formation. Localization of the lesions and chronicity are crucial for diagnosis (3, 4). For assessing the clinical sever- ity, the most widely used staging is the one proposed by Hurley, which categorizes patients into three groups based on the extent and severity of the clinical presentation (5). Along with the distress emerging from the pain and inflam- mation, many other factors can contribute: delay in diagnosis, a broad spectrum of comorbidities associated with HS, or social habits. One of the main contributing factors is the lack of stand- ardized treatment regimens for HS, and foremost often incom- plete response to these therapeutics, which is especially true when novel treatment options are unavailable. Although clinical characteristics of HS and associated diseases have been well studied, data from southeastern Europe are sparse. Therefore, this study investigates the degree to which these fac- tors are displayed in hospitalized patients diagnosed with HS in a 15-year retrospective study at a university clinic of dermatology and venereology. Methods Study population A retrospective, cross-sectional study was conducted, encom- passing hospitalized patients at a university clinic of dermatol- ogy and venereology from 2007 to 2022. The patients included in this study were hospitalized for the first time during this period, and HS was the main cause of hospital admission. Data regarding demographic characteristics, including smoking habits (current and previous), disease duration, clinical presentation, laboratory findings, concomitant diseases, and treatment regimens, were taken from the electronic national healthcare data system (Heli- ant), as well as from hard copies of hospital patient histories. Assessment of clinical features Disease severity was assessed using the Hurley classification sys- tem. To determine the localization of lesions, typically affected Abstract Introduction: Hidradenitis suppurativa (HS) is a chronic skin disease marked by recurrent abscesses, sinus tracts, and scarring, often accompanied by systemic symptoms. Diagnosed clinically, HS affects around 0.4% of people in western populations, but standardized treatment options are limited, leading to inconsistent outcomes. This study retrospectively analyzes 15 years of HS cases in southeastern Europe to better understand regional characteristics and treatment responses. Methods: This is a retrospective, cross-sectional study encompassing 103 HS patients hospitalized from 2007 to 2022 at a univer- sity dermatology and venereology clinic. Results: Women were younger than men at onset of HS (19 vs. 28 years old) and at first hospitalization (31 vs. 39 years old). Men were most often diagnosed as Hurley stage III at hospital admission (50.8%), whereas women predominantly had Hurley stage II (57.5%, p = 0.032). Trunk involvement was more prevalent in women (62.5% vs. 41.3%, p = 0.036) and the back of the neck in men (30.2% vs. 7.5%, p = 0.006). Obesity was the most commonly found concurrent disease (35.9%) overall, and a history of acne was the most frequent dermatological comorbidity (29.1%). HS patients had a fivefold increase in their chance of having psoriasis. The most com- monly employed systemic treatments were oral antibiotics: rifampicin with clindamycin (62.1%) followed by tetracyclines (42.7%). Conclusions: HS patients had a fivefold higher likelihood of having psoriasis. Female patients were less likely to experience severe disease presentations. Although metabolic syndrome and its components were relatively common, they showed no correlation with disease severity. Treatment approaches for HS varied notably between males and females. Keywords: hidradenitis suppurativa, inverse acne, psoriasis, retrospective study, single-center study Acta Dermatovenerologica Alpina, Pannonica et Adriatica Acta Dermatovenerol APA Received: 12 September 2024 | Returned for modification: 11 October 2024 | Accepted: 31 October 2024 ✉ Corresponding author: milos.nikolic@med.bg.ac.rs *Co-first authors, these two authors contributed equally to this article. 164 Acta Dermatovenerol APA | 2024;33:163-169D. Živanović et al. areas were divided into occipital and neck, axillary, trunk, gluteal, and genital and groin area. Patients were classified into non- overweight (BMI < 25 kg/m²) and overweight (BMI ≥ 25 kg/m²). We recorded the presence of concomitant systemic and/or skin diseases from the patients’ medical files. Available data on metabolic parameters were used to determine the presence of metabolic syndrome in the patients, as proposed by the International Diabetes Federation (IDF) classification system (6). The treatment regimens included the following: topical and/or systemic antibiotics, systemic retinoids, systemic corticosteroids, oral dapsone, biological therapy (secukinumab, ustekinumab, adalimumab), and surgery. Statistical analysis Statistical analyses were performed using SPSS® 27.0 (IBM, New York, USA); p < 0.050 was considered significant. Descrip- tive analyses were given as proportions, frequencies, and central tendency measures presented as mean ± standard deviation. The Mann–Whitney U or Kruskal–Wallis test was employed because the numerical data did not follow a normal distribution, whereas the chi-squared test or Fisher’s exact test was used for categorical data. Binary logistic regression analyses were employed to evalu- ate the predictive strength of clinical parameters on the severity of HS. The logistic regression model included variables that showed an association with HD severity (p < 0.100) in univariate analysis. Results Patients’ characteristics and differences between sexes Table 1 summarizes the sociodemographic and clinical data of all hospitalized patients and highlights the differences between men and women. In the given timeframe, out of 119 patients that were hospitalized for diagnostic and treatment purposes, 103 were in- cluded in this study (63 males and 40 females). Sixteen patients were excluded from further analyses because of insufficient clini- cal and laboratory data. The mean age of disease onset was 28.3 ± 12.6, and the mean age of first-time hospitalization was 37.7 ± 14.3 years. The age of disease onset ranged from 6 to 59 years. Only one patient was in the first decade (6 years old) at disease onset. The mean duration of the disease before hospitalization was 9.2 years. There was a statistically significant earlier age of women versus men for onset (19 vs. 28 years, p = 0.020) and age of first-time hos- pitalization (31 vs. 39 years, p = 0.004). The percentage of smokers among men was significantly higher than among women (92.1% vs. 60.0%, p < 0.001). Thirteen patients (12.6%) were classified as Hurley I, 48 (46.6%) as Hurley II, and 42 (40.8%) as Hurley III stage. There were signifi- cant differences in Hurley stage frequencies between sexes: most men (50.8%), had Hurley stage III, whereas most women (57.5%) had Hurley stage II (p = 0.032). Regarding localization, genital and inguinal areas were most commonly involved, present in 81 (78.6%) patients. Differences between the sexes were also ob- served, with more frequent trunk involvement in women and the back of the neck in men (30.2% vs. 7.5%, p = 0.006). In 40 patients (38.8%), three regions were involved, and seven patients (6.8%) had lesions in all five areas. The number of affected regions was similar in both sexes. Major comorbidities, further subclassified by sex, are pre- sented in Table 2. Women had a higher prevalence of increased fasting glucose levels (p = 0.046), obesity (p = 0.051), and thyroid disease (p = 0.005). However, there was no significant difference regarding the presence of metabolic syndrome between sexes (p = 0.192). Acne was the most commonly associated skin disease in our patients (in 29.1%), and women had atopic dermatitis (AD) more frequently than men (12.5% vs. 0%, p = 0.008). Approximate- ly one in 10 patients had psoriasis along with HS. Two patients had associated acne and pyoderma gangrenosum, constituting PASH syndrome (pyoderma gangrenosum, acne, suppurative hi- dradenitis). One patient had follicular occlusion triad syndrome. Table 3 contains the list of therapeutic modalities and their dis- tribution according to the sex of the patients. The most common treatment modality, used in 99% of patients, was topical clinda- mycin. Systemic treatment options most frequently included anti- biotics, either alone or in combination with other modalities. Dif- ferences between sexes in treatment choices were observed: men were more likely to be treated with rifampicin plus clindamycin IQR = interquartile range. Significant p values showed in bold. Data are shown as amean ± standard deviation and bmedian (IQR). Table 1 | Main sociodemographic characteristics, history, and clinical data of hidradenitis suppurativa patients. Total (n = 103) Men (n = 63) Women (n = 40) p-value Agea 37.7 ± 14.3 40.0 ± 13.3 33.9 ± 15.1 0.020 Age at onset (years)a 28.3 ± 12.6 30.2 ± 11.0 25.2 ± 14.4 0.004 0–19, n (%) 30 (29.1) 9 (14.3) 21 (52.5) 20–29, n (%) 33 (32.0) 27 (42.9) 6 (15.0) 30–39, n (%) 21 (20.4) 14 (22.2) 7 (17.5) 0.001 40–49, n (%) 9 (8.7) 7 (11.1) 2 (5.0) 50–59, n (%) 10 (9.7) 6 (9.5) 4 (10.0) Disease duration before first hospitalization (years)b 6 (3–11) 5 (2–10) 6 (3–13) 0.288 Smoking, ever, n (%) 82 (79.6) 58 (92.1) 24 (60.0) < 0.001 Hurley stage, n (%) I 13 (12.6) 6 (9.5) 7 (17.5) II 48 (46.6) 25 (39.7) 23 (57.5) 0.032 III 42 (40.8) 32 (50.8) 10 (25.0) Localization of lesions, n (%) Axilla 72 (69.9) 47 (74.6) 25 (62.5) 0.192 Genital and groin 81 (78.6) 49 (77.8) 32 (80.0) 0.789 Trunk 51 (49.5) 26 (41.3) 25 (62.5) 0.036 Gluteal 64 (62.1) 40 (63.5) 24 (60.0) 0.722 Occipital and neck 22 (21.4) 19 (30.2) 3 (7.5) 0.006 No. of regions involvedb 3 (2–3) 3 (2–4) 3 (2–3) 0.530 165 Acta Dermatovenerol APA | 2024;33:163-169 Hidradenitis suppurativa: fifteen-year experience (p = 0.004) and retinoids (p = 0.004), whereas women received tetracyclines (p = 0.016) and systemic steroids (0.023) more fre- quently. Surgery was twice as frequent as a treatment option in men compared to women (p = 0.001). Differences according to Hurley stages Table 4 provides insight into the characteristics of patients clas- sified according to Hurley disease stages. In addition to the dif- ference in sex distribution, it is possible to note differences in the frequency of hypertension and dyslipidemia across Hurley stages, both being more common in patients staged as Hurley I. Interest- ingly, we observed a lower prevalence of metabolic syndrome with increasing Hurley stages (p = 0.277), whereas the highest percent- age of smokers was seen among Hurley stage I patients (92.3%, p overall = 0.241). The involvement of specific lesion localizations across Hurley stages is displayed in Figure 1. Significant differences in distribu- tions were observed regarding the genital (p overall = 0.008) and axillary (p overall = 0.048) localizations of lesions. The genital and groin localizations were more common in both the Hurley II and Hurley III groups than in Hurley I (p = 0.011 and 0.003, re- spectively). As for the axillae, the difference among groups could be attributed to higher prevalence in Hurley stage III compared to stage II (p = 0.017). Almost one-third of all patients (31.1%) were treated only with systemic antibiotics in addition to different topical treatment op- tions. More than half of Hurley I patients received only systemic antibiotics. The trend for Hurley stages II and III was more toward combinations of different systemic options, as shown in Figure 2. Twenty-one (20.4%) patients were treated with three or more sys- temic modalities. There was a statistically significant trend toward increased use of rifampicin plus clindamycin (p = 0.010), systemic retinoids (p = 0.019), and surgical therapy (p = 0.013) with increas- ing disease severity across the Hurley stages. The final aim of this study was to identify factors associated with greater disease severity as measured by Hurley stages. For the purpose of binary logistic regression, Hurley stages I and II were analyzed together, corresponding to milder disease. As presented in Table 5, the univariate analysis identified male sex HS = Hidradenitis suppurativa, TG = triglycerides, HDL = high-density cholesterol, PCOS = polycystic ovary syndrome, IBD = inflammatory bowel disease, PASH = pyoderma gangrenosum, acne, hidradenitis suppurativa syndrome. Significant p values are in bold. p < 0.050, according to the chi-squared test / Fisher’s exact test. Table 2 | Main comorbidities of hidradenitis suppurativa patients. Total (n = 103) Men (n = 63) Women (n = 40) p-value Associated metabolic diseases, n (%) Diabetes mellitus 14 (13.6) 10 (15.9) 4 (10.0) 0.397 Dyslipidemia 18 (17.5) 11 (17.5) 7 (17.5) 0.996 Metabolic syndrome, n (%) 17 (16.5) 8 (12.7) 9 (22.5) 0.192 Obesity 37 (35.9) 18 (28.6) 19 (47.5) 0.051 Increased TG or treatment 22 (21.4) 15 (23.8) 7 (17.5) 0.446 Low HDL 18 (17.5) 13 (20.6) 5 (12.5) 0.289 Hypertension or treatment 22 (21.4) 10 (15.9) 12 (30.0) 0.088 Increased morning glucose 32 (31.1) 15 (23.8) 17 (42.5) 0.046 Associated systemic diseases, n (%) Hypo/hyperthyroidism 8 (7.8) 1 (1.6) 7 (17.5) 0.005 Anemia 7 (6.8) 5 (7.9) 2 (5.0) 0.564 PCOS — — 7 (17.5) — IBD 2 (1.9) 1 (1.6) 1 (2.5) 1.000 Vasculitis 2 (1.9) 2 (3.2) 0 (0.0) 0.520 Lupus erythematosus 1 (1.0) 0 (0.0) 1 (2.5) 0.388 Associated skin diseases, n (%) Acne 30 (29.1) 14 (22.2) 16 (40.0) 0.056 Psoriasis vulgaris 10 (9.7) 6 (9.5) 4 (10.0) 0.937 Pyoderma gangrenosum 9 (8.7) 8 (12.7) 1 (2.5) 0.074 Atopic dermatitis 5 (4.9) 0 (0.0) 5 (12.5) 0.008 Alopecia areata 5 (4.9) 3 (4.8) 2 (5.0) 1.000 PASH 2 (1.9) 1 (1.6) 1 (2.5) 1.000 Follicular occlusion syndrome 1 (1.0) 1 (1.6) 0 (0.0) 1.000 SD = standard deviation. Significant p values are in bold. p < 0.050, according to the chi-squared test / Fisher’s exact test for categorical data, or Mann–Whitney test for numerical data. Table 3 | Therapeutic modalities in patients with hidradenitis suppurativa at our center. Total (n = 103) Men (n = 63) Women (n = 40) p-value Antibiotics, n (%) Topical clindamycin 102 (99.0) 63 (100.0) 39 (97.5) 0.388 Oral tetracyclines 44 (42.7) 21 (33.3) 23 (57.5) 0.016 Oral rifampicin + clindamycin 64 (62.1) 46 (73.0) 18 (45.0) 0.004 Other oral antibiotics 83 (80.6) 51 (81.0) 32 (80.0) 0.905 Systemic retinoids 52 (50.5) 39 (61.9) 13 (32.5) 0.004 Systemic corticosteroids 26 (25.2) 11 (17.5) 15 (37.5) 0.023 Systemic dapsone 10 (9.7) 7 (11.1) 3 (7.5) 0.546 Biologic treatment 11 (10.7) 7 (11.1) 4 (10.0) 0.859 Surgical treatment 46 (44.7) 36 (57.1) 10 (25.0) 0.001 Total treatment modalities, n (mean ± SD) 3.4 ± 1.1 3.6 ± 1.0 3.0 ± 1.2 0.005 Systemic treatment modalities, n (mean ± SD) 1.9 ± 0.9 2.0 ± 0.8 1.8 ± 1.0 0.197 166 Acta Dermatovenerol APA | 2024;33:163-169D. Živanović et al. (p = 0.009, odds ratio [OR] 3.097) and axillary localization of le- sions (p = 0.014, OR 1.507) as the predisposing factor toward se- vere clinical presentations. Upon inclusion of variables with uni- variate p < 0.100 in the regression model, male sex (p = 0.017, OR 3.251) and trunk lesions (p = 0.029, OR 2.736) emerged as signifi- cant predictors of more severe clinical presentation of HS. Discussion To the best of our knowledge, this is the first study from southeast- ern Europe examining the characteristics of HS patients hospital- ized at a tertiary university clinic. Compared to studies with a similar methodology, a French study had a male-to-female ratio of 1:3 (7). A male-to-female ratio of nearly 1:1, described in Canadian and Lithuanian studies, was the finding most similar to ours (8, 9). This may signify that in our study HS in men presented with more severe clinical forms, requiring hospital treatment. As in previous studies, the age of HS onset in our series of pa- tients was in the third decade of life (10). However, in women we found a markedly earlier onset, which is even earlier than report- ed in the study by Schrader et al. (11), supporting the theory that early-onset HS may be more frequent than previously believed (12, 13). In addition, the number of regions affected in our early-onset HS group and smoking status were in line with a study conducted in the Netherlands (12). Cigarette smoking is a well-established environmental factor with an important impact on HS. A recent meta-analysis found that HS patients are about four times more likely to be smokers (7, 14). A high percentage of active/former smokers is found among our patients, as reported in many other studies (7, 14). This per- centage was even more striking when comparing men and women (92% vs. 60%), in line with another study that found a significant- ly higher percentage of male smokers (8). The authors explained these differences with smoking being a possibly more potent risk factor in men than in women, or that the prevalence of male Table 4 | Main demographic, clinical, and laboratory data of hidradenitis suppurativa patients, classified by Hurley stage of the disease. Variables Hurley I(n = 13) Hurley II (n = 48) Hurley III (n = 42) p-value overall Sex, male, n (%) 6 (46.2) 25 (52.1) 32 (76.2) 0.032 Age at hospitalization (years)a 43.3 ± 12.1 36.2 ± 14.7 37.6 ± 14.3 0.217 Age at onset (years)a 32.1 ± 13.9 27.4 ± 13.5 28.1 ± 11.2 0.444 Disease duration (years)a 12.1 ± 10.4 8.7 ± 9.4 8.8 ± 9.6 0.453 Smoking, n (%) 12 (92.3) 35 (72.9) 35 (83.3) 0.241 Associated metabolic and systemic diseases, n (%) Diabetes 1 (7.7) 9 (18.8) 4 (9.5) 0.356 Dyslipidemia 6 (46.2) 6 (12.5) 6 (14.3) 0.014 Metabolic syndrome 4 (30.8) 8 (16.7) 5 (11.9) 0.277 Obesity 4 (30.8) 19 (39.6) 14 (33.3) 0.759 Increased TG 4 (30.8) 11 (22.9) 7 (16.7) 0.521 Low HDL 4 (30.8) 4 (8.3) 10 (23.8) 0.063 Hypertension/treatment 7 (53.8) 8 (16.7) 7 (16.7) 0.009 Increased blood glucose 5 (38.5) 16 (33.3) 11 (26.2) 0.633 Vasculitis 0 (0.0) 2 (4.2) 0 (0.0) NA PCOS 0 (0.0) 4 (8.3) 3 (7.1) NA Lupus erythematosus 0 (0.0) 1 (2.1) 0 (0.0) NA IBD 1 (7.7) 1 (2.1) 0 (0.0) NA Anemia 1 (7.7) 3 (6.3) 3 (7.1) NA Hypo/hyperthyroidism 3 (23.1) 3 (6.3) 2 (4.8) 0.085 Associated skin diseases, n (%) Psoriasis 1 (7.7) 6 (12.5) 3 (7.1) 0.670 Acne 2 (15.4) 16 (33.3) 12 (28.6) 0.448 Pyoderma gangrenosum 1 (7.7) 5 (10.4) 3 (7.1) 0.852 Atopic dermatitis 1 (7.7) 4 (8.3) 0 (0.0) NA Alopecia areata 1 (7.7) 2 (4.2) 2 (4.8) NA PASH 0 (0.0) 1 (2.1) 1 (2.4) NA Follicular occlusion syndrome 0 (0.0) 0 (0.0) 1 (2.4) NA HS = hidradenitis suppurativa, TG = triglycerides, HDL = high-density cholesterol, PCOS = polycystic ovary syndrome, IBD = inflammatory bowel disease, PASH = pyoderma gangrenosum, acne, hidradenitis suppurativa syndrome, NA = not applicable due to low frequencies. Significant p values are in bold. p < 0.050, according to the chi-squared test / Fisher’s exact test for nominal data, or Kruskal–Wallis test for numerical data. aData are shown as mean ± standard deviation. Table 5 | Univariate and multivariate binary logistic regression analysis for predictors of disease severity (Hurley stage III vs. stages I and II). Variables Univariate Multivariatep-value OR (95% CI) p-value OR (95% CI) Sex† Men 0.009 3.097 (1.298–7.389) 0.017 3.251 (1.240–8.525) Women Ref. Ref. Localization Trunk 0.092 1.320 (0.950–1.835) 0.029 2.736 (1.111–6.738) Axillary 0.014 1.507 (1.122–2.022) 0.094 2.389 (0.861–6.631) Atopic dermatitis 0.057 0.571 (0.481–0.678) 0.999 0.000 (0.000) OR = odds ratio, CI = confidence interval. Male sex, trunk and axillary lesions, and absence of atopic dermatitis, taken altogether, were significant predictors of more severe hidradenitis suppurativa (logistic regression p = 0.001, Nagelkerke R² = 0.230, Hosmer and Lemeshow coefficient = 0.725, correctly classified 67.0%). Significant p values are in bold. †For statistical purposes, female sex was used as a reference (Ref.) for calculating the odds ratio. 167 Acta Dermatovenerol APA | 2024;33:163-169 Hidradenitis suppurativa: fifteen-year experience smokers in the general population is higher. Our study supports these two theories, but it must be considered that in the Serbian population there is just a slightly higher percentage of male com- pared to female smokers (34% vs. 30%, respectively) (15), which favors the first theory. Moreover, the number of cigarettes smoked per day might be an important element in assessing the relevance of this factor in the severity of HS and expression of the diseases among men and women. Comorbidities found with HS in our series were comparable with the literature data (16–20). A high percentage of metabolic syndrome (MS) and its components in our group of patients was noted. Nevertheless, when comparing the presence of MS and each of the MS criteria to the Hurley stage, we did not find that MS had an impact on HS severity. This finding was already men- tioned in the literature (21, 22). Our results further support the theory that chronic inflammation caused by HS does not promote the development of MS, but MS and its components might be the primary pathological event. Sabat et al. explained this connec- tion with the hypothesis that “hypoxia, resulting from metabolic alterations, induces production of interleukin (IL)-10, which in turn decreases the production of IL-22 and IL-20, which are an- tibacterial proteins in epithelia. Hypoxia and reduced antibacte- rial properties in the epithelia then result in bacterial persistence and promote HS outbreak” (22). An additional finding in our study that showed a tendency toward significance was the percentage of overweight patients, with female patients being found to fall into the overweight category more frequently. Combining this with the finding that female sex predisposed to milder disease in our study, we can further support this hypothesis. Acne was the primary associated condition overall, with al- most 29% of our patients having a history of or current acne. A recent study found that HS patients had a 2.7-fold increase in the chance of having psoriasis (23); in our series, 9.7% of HS patients had psoriasis (in Serbia, the prevalence rate of psoriasis is 2%, meaning that in our series HS patients have a five-fold increase in the chance of having psoriasis). AD was present in 5% of our cohort—however, exclusively in women. Similar to our findings, Sherman et al. also found a female predominance in association of HS and AD, and interestingly concluded that a history of AD led to a 40% increase in the odds of HS (24). A recent meta-analysis found that patients with HS have a 4.1-fold increase in odds of having AD compared to healthy controls (25). In our study group, two patients fulfilled the criteria for PASH syndrome (26): one female patient and one male patient. The female patient had polycystic ovarian syndrome in addition to PASH syndrome (27). The male patient had gonadotropic hypoan- drogenism and was receiving testosterone supplementation. The exact relationship of this co-occurrence remains to be elucidated. Finally, it is essential to note the higher frequencies of many as- sociated dermatological comorbidities in our study compared to a recent meta-analysis (19), which are probably due to our study population. Namely, only HS cases that were hospitalized at a ter- tiary center were analyzed, with more severe clinical presentation overall, including other skin comorbidities. The role of sex, with female sex predisposing to milder dis- ease, was already reported in the literature and recorded in our study as well (7, 12). However, this finding still needs to be fully elucidated. One proposed theory is that tobacco has a potential role in the severity of clinical presentation affecting the T helper 17 cell/regulatory T-cell axis, thus more frequently promoting a progression from Hurley II to Hurley III in the men in our study (28). Nonetheless, other mechanisms could have a simultaneous role because the higher percentage of male smokers is found only in our research and could be an incidental finding. Few studies have discussed clinical presentation and locali- zation of lesions as factors for disease severity. We have found a statistical significance regarding trunk involvement (more commonly involved in women) and the occipital and neck area (mostly observed in men). This is partially in line with the study by Canoui-Poitrine et al., who proposed that the front part of the body could be a hallmark of HS in women, whereas involvement of the back was characteristic for men, later confirmed in another study (7, 12). In our study, axillary localization was found to be more prevalent in the most advanced stage of HS, which is also reported in a Dutch study by Schrader et al. (12) After multivariate analysis, we found that trunk involvement also plays a role in the severity of HS, announcing a more severe clinical form. Despite the different classification system used in our study, the French study found comparable results (7). Although significant advances have been made in the treat- ment of HS (European S1 guideline) (3), many newer treatment modalities are still in the approval phase or unavailable in Serbia. Only a relatively narrow spectrum of treatment modalities was used, with biologic drugs being available only for patients with other comorbidities (psoriasis and inflammatory bowel disease). Figure 1 | Involvement of specific anatomical regions across different Hurley stages of hidradenitis suppurativa, highlighting significant variations in lesion localization within the genital, groin, and axillary areas among stages. Figure 2 | Frequency of various systemic therapeutic regimens used in hidrad- enitis suppurativa treatment, sorted by their usage frequency and further categorized by Hurley stage. The most common treatments included systemic antibiotics, combinations of antibiotics with oral retinoids, and antibiotics with systemic corticosteroids. 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J Am Acad Dermatol. 2020;82:1006–11. 15. Department for Informatics and Biostatistics. Health Indicators in Republic of Serbia [Internet]. [cited 2024 Nov 7]. Available from: https://www.batut.org.rs/ download/zdravstveni_pokazatelji_rs_2020.html. 16. Kohorst JJ, Kimball AB, Davis MDP. Systemic associations of hidradenitis sup- purativa. J Am Acad Dermatol. 2015;73:27–35. 17. Wertenteil S, Strunk A, Garg A. Overall and subgroup prevalence of acne vulgaris among patients with hidradenitis suppurativa. J Am Acad Dermatol. 2019;80: 1308–13. 18. Kimball AB, Sundaram M, Gauthier G, Guérin A, Pivneva I, Singh R, et al. The comorbidity burden of hidradenitis suppurativa in the United States: a claims data analysis. Dermatol Ther (Heidelb). 2018;8:557–69. 19. Garg A, Malviya N, Strunk A, Wright S, Alavi A, Alhusayen R, et al. Comorbidity screening in hidradenitis suppurativa: evidence-based recommendations from the US and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Derma- tol. 2022;86:1092–101. 20. Phan K, Huo YR, Charlton O, Smith SD. Hidradenitis suppurativa and thyroid dis- ease: systematic review and meta-analysis. J Cutan Med Surg. 2020;24:23–7. 21. Gold DA, Reeder VJ, Mahan MG, Hamzavi IH. The prevalence of metabolic syn- drome in patients with hidradenitis suppurativa. J Am Acad Dermatol. 2014;70: 699–703. 22. Sabat R, Chanwangpong A, Schneider-Burrus S, Metternich D, Kokolakis G, Kurek A, et al. Increased prevalence of metabolic syndrome in patients with acne inversa. PLoS One. 2012;7:e31810. 23. Gau SY, Preclaro IAC, Wei JC, Lee CY, Kuan YH, Hsiao YP, et al. Risk of psoriasis in people with hidradenitis suppurativa: a systematic review and meta-analysis. Front Immunol. 2022;13:1033844. 24. Sherman S, Kridin K, Bitan DT, Leshem YA, Hodak E, Cohen AD. Hidradenitis sup- purativa and atopic dermatitis: a 2-way association. J Am Acad Dermatol. 2021; 85:1473–9. 25. Gau SY, Chan WL, Tsai JD. Risk of atopic diseases in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies. Dermatology. 2023;239:314–22. 26. Braun-Falco M, Kovnerystyy O, Lohse P, Ruzicka T. Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)—a new autoinflammatory syndrome distinct from PAPA syndrome. J Am Acad Dermatol. 2012;66:409–15. Therefore, our patients’ most common treatment options were oral and topical antibiotics, retinoids, and surgical treatment. We recorded a clear predominance of men being prescribed oral retinoids and surgical treatment. This provides a valuable clue that there was significant restraint in prescribing retinoids in female patients because of well-known teratogenicity. The risk and fear of scarring and recurrence rates after surgical proce- dures, shown to be 13% for wide excision and 27% for deroofing in a recent meta-analysis, was a significant factor in treatment, which is found to be especially important for women in our study group (29). In addition, we found a statistically higher total num- ber of treatment modalities (p = 0.005) in men, which can lead to the conclusion that men were a therapeutic challenge in our study group. Furthermore, in light of the current understanding of the pathogenesis of HS, familial cases of HS may be a subset of patients with more severe clinical presentation and inadequate therapeutic responses to currently used therapeutics. This is de- scribed in a study by Zouboulis et al., in which 28.6% of patients unresponsive to adalimumab had a familial occurrence of HS (30, 31). In addition to genetic factors, epigenetic variations also in- fluence certain enzyme profiles, such as methylation profiles of cytochrome P450 (CYP450). It is shown that variations in these en- zymes can affect the extent of the disease in HS and the presence of other comorbidities, and can influence the response to the ther- apeutics used in HS patients. What is of particular significance is that certain CYP450 subtypes may influence a poor response to isotretinoin, one of the most commonly used conventional drugs for HS (32). Therefore, changing methylation profiles of CYP450 and recently described telomere-related genes (TRGs) could have potential disease-modifying implications, all of which could im- pact the therapeutic response in our study population (33, 34). A critical aspect of managing patients with HS was deficient adherence to treatment and follow-ups, with limited resources for treatment and often unsatisfying outcomes. With biologics being more accessible, we believe significant change to this trend could occur. Conclusions According to our data, HS patients have a five-fold increase in the chance of having psoriasis. Women were diagnosed with HS at an earlier age than men; however, female sex was associated with milder clinical presentation. HS in men was more therapeutically challenging. Severe clinical presentation in men might be attrib- uted to the higher prevalence of male smokers. The presence of metabolic syndrome and its components did not correlate with the severity of the disease. Funding DS, DZ, and MN were partially supported by grant no. 175065, Ministry of Science of the Republic of Serbia. 169 Acta Dermatovenerol APA | 2024;33:163-169 Hidradenitis suppurativa: fifteen-year experience 27. Zivanovic D, Masirevic I, Ruzicka T, Braun-Falco M, Nikolic M. Pyoderma gan- grenosum, acne, suppurative hidradenitis (PASH) and polycystic ovary syn- drome: coincidentally or aetiologically connected? Australas J Dermatol. 2017; 58:54–9. 28. Melnik BC, John SM, Chen W, Plewig G. T helper 17 cell/regulatory T-cell imbal- ance in hidradenitis suppurativa/acne inversa: the link to hair follicle dissec- tion, obesity, smoking and autoimmune comorbidities. Br J Dermatol. 2018;179: 260–72. 29. Mehdizadeh A, Hazen PG, Bechara FG, Zwingerman N, Moazenzadeh M, Bashash M, et al. Recurrence of hidradenitis suppurativa after surgical management: a systematic review and meta-analysis. J Am Acad Dermatol. 2015;73:70–7. 30. Duchatelet S, Miskinyte S, Delage M, Ungeheuer MN, Lam T, Benhadou F, et al. Low prevalence of GSC gene mutations in a large cohort of predominantly Cauca- sian patients with hidradenitis suppurativa. J Invest Dermatol. 2020;140:2085– 8.e14. 31. Zouboulis CC, Hansen H, Caposiena Caro RD, Damiani G, Delorme I, Pascual JC, et al. Adalimumab dose intensification in recalcitrant hidradenitis suppurativa/ acne inversa. Dermatology. 2020;236:25–30. 32. Radhakrishna U, Ratnamala U, Jhala DD, Vadsaria N, Patel M, Uppala LV, et al. Cytochrome P450 genes mediated by DNA methylation are involved in the resist- ance to hidradenitis suppurativa. J Invest Dermatol. 2023;143:670–3. 33. Radhakrishna U, Ratnamala U, Jhala DD, Uppala LV, Vedangi A, Patel M, et al. Hi- dradenitis suppurativa presents a methylome dysregulation capable to explain the pro-inflammatory microenvironment: are these DNA methylations potential therapeutic targets? J Eur Acad Dermatol Venereol. 2023;37:2109–23. 34. Radhakrishna U, Ratnamala U, Jhala DD, Uppala LV, Vedangi A, Saiyed N, et al. Hidradenitis suppurativa associated telomere-methylome dysregulations in blood. J Eur Acad Dermatol Venereol. 2024;38:393–403.