Hidradenitis suppurativa: impact of environmental factors and new treatment options

Hidradenitis suppurativa (HS) is a chronic and diverse skin disease characterized by recurrent inflammation in body folds. It predominantly affects women, and its cause is complex and multifactorial. HS has a significant impact on the quality of life and is challenging to treat due to its complexity.The first part of this thesis focuses on understanding the epidemiology of HS, the lifestyle of patients, and their mental health. A study of 135,950 participants revealed that the prevalence of HS in Northern Netherlands was higher than previously thought, at 2.1%. HS patients had a lower socioeconomic status and were more likely to smoke. Furthermore, new associations were discovered between HS and conditions such as fibromyalgia and irritable bowel syndrome.Chapter three examined the lifestyle of HS patients and found lower scores for healthy nutrition and physical activity among them. This suggests that a healthy lifestyle may be protective against HS and underscores the need for prevention strategies.Chapter four investigated the mental health of HS patients and found a higher prevalence of depression, anxiety, and loneliness. However, there was no link between developing HS and mental health, indicating shared causes.Chapter five focused on the survival of biological treatments (adalimumab and infliximab) in HS patients. The study showed that the effectiveness of these treatments was limited, primarily due to ineffectiveness.Chapter six explored the use of retinoids in HS patients and found similar survival rates for isotretinoin and acitretin after 12 months. Some HS phenotypes may respond better to acitretin.The final chapter examined the use of guselkumab, a biological treatment, in HS. Approximately 65% of patients showed clinical improvement after 16 weeks of treatment. However, there were no consistent correlations between clinical and molecular responses.In summary, these studies demonstrate that HS is underdiagnosed, and more attention is needed for early diagnosis and treatment. A multidisciplinary approach, including consideration of lifestyle and mental health, is crucial. Treatment options vary, but biological treatments have limited effectiveness. Future research is needed to develop better treatment strategies for this complex condition

Assessment tools and phenotype classification for hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a heterogeneous chronic relapsing skin disease. Several assessment tools are used to assess disease severity and to classify disease phenotype; however, no consensus exists. This review evaluates the various assessment tools and phenotypes, assessing their validity and reliability. Numerous assessment tools and phenotype classifications have been proposed for identifying various subtypes within the hidradenitis suppurativa disease spectrum. Each has a different purpose, such as use in daily practice or in clinical trial settings. Several assessment tools and phenotype classifications have been validated but not always with satisfactory results and often with studies showing divergent intra-rater reliability results. A consensus is needed for a validated, easy-to-use, and timesaving assessment tool for routine daily practice. For clinical trials, a validated and extensive assessment tool that also measures response to treatment is also needed.</p

Guselkumab for hidradenitis suppurativa:a phase II, open-label, mode-of-action study

BACKGROUND: The effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are needed. OBJECTIVES: To investigate the efficacy and mode of action of guselkumab [an anti-interleukin (IL)-23p19 monoclonal antibody] 200 mg subcutaneously every 4 weeks for 16 weeks in patients with HS. METHODS: An open-label, multicentre, phase IIa trial in patients with moderate-to-severe HS was carried out (NCT04061395). The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. The protocol was reviewed and approved by the local institutional review board (METC 2018/694), and the study was conducted in accordance with good clinical practice guidelines and applicable regulatory requirements. RESULTS: Thirteen of 20 patients (65%) achieved HiSCR with a statistically significant decrease in median IHS4 score (from 8.5 to 5.0; P = 0.002) and median AN count (from 6.5 to 4.0; P = 0.002). The overall patient-reported outcomes did not show a similar trend. One serious adverse event, likely to be unrelated to guselkumab treatment, was observed. In lesional skin, transcriptomic analysis revealed the upregulation of various genes associated with inflammation, including immunoglobulins, S100, matrix metalloproteinases, keratin, B-cell and complement genes, which decreased in clinical responders after treatment. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. CONCLUSIONS: Sixty-five per cent of patients with moderate-to-severe HS achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study were the small sample size and absence of a placebo arm. The large placebo-controlled phase IIb NOVA trial for guselkumab in patients with HS reported a lower HiSCR response of 45.0-50.8% in the treatment group and 38.7% in the placebo group. Guselkumab seems only to be of benefit in a subgroup of patients with HS, indicating that the IL-23/T helper 17 axis is not central to the pathophysiology of HS.</p

New Insights in Hidradenitis Suppurativa from a Population-based Dutch Cohort:Prevalence, Smoking Behaviour, Socioeconomic Status and Comorbidities

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic, auto-inflammatory skin condition and is associated with several comorbidities. Previous studies report variable prevalence rates of HS, depending on the methodology, however the exact prevalence remains unknown. OBJECTIVES: To estimate the prevalence of HS in a large population-based cohort in the Northern Netherlands, and to compare HS patients to the general population, investigate characteristics and identify potential associated comorbidities. METHODS: Data was collected through a cross-sectional survey-based study within the Lifelines Cohort Study (n=167,729), based on the general population located in the Northern Netherlands. A digital self-reported questionnaire was developed consisting of validated questions for determining HS. RESULTS: Among 56,084 respondents, the overall prevalence of HS was 2.1% [95% CI 2.0 to 2.2]. The respondents with HS had a lower socioeconomic status than the controls (p<0.001) and were more frequently current smokers (p<0.001). Several new significant associations in HS patients were revealed, such as fibromyalgia [OR=2.26; 95%CI 1.64 to 3.11], irritable bowel syndrome [OR 1.63; 95%CI 1.18 to 2.26], chronic fatigue syndrome [OR=1.72; 95%CI 1.06 to 2.78] and migraine [OR=1.48; 95%CI 1.11 to 1.96]. Fibromyalgia and chronic fatigue syndrome remained significantly associated with HS in the multivariate analysis after adjusting for age, sex, BMI, smoking status and socioeconomic status. CONCLUSION: Our study showed a higher prevalence of HS in the Northern Netherlands compared to the overall estimated prevalence of 1% and identified several new associated comorbidities

Drug Survival of Oral Retinoids in Hidradenitis Suppurativa: A Real-Life Cohort Study

Introduction Cohort studies on the use of retinoids for hidradenitis suppurativa (HS) have yielded contradicting results. As the clinical presentation of HS is heterogeneous, with different predilection sites and hallmark features, it can be hypothesized that HS phenotypes are associated with the effectiveness of specific retinoid treatments. Objectives The aim of this study was to evaluate the drug survival of oral retinoids in the treatment of HS and to establish predictors for longer treatment duration. Methods A retrospective, dual-center study was conducted in the Netherlands in adult HS patients treated with oral retinoids between 2011 and 2021. Drug survival analyses were performed through Kaplan-Meier survival curves. Additionally, Cox regression models were used to determine predictors for a longer drug survival. Results In total, 102 patients were included. Overall drug survival of (low-dose) isotretinoin (n = 66) at 12 and 24 months was 44.2% and 15.5%, respectively. Termination of treatment was mostly due to ineffectiveness (26%). Presence of widespread comedones (p = 0.03) and the use of concomitant systemic medication (p = 0.04) were associated with a prolonged treatment duration. For acitretin (n = 36), the overall drug survival was 42.0% at 12 months and 37.4% at 24 months, and was also predominantly determined by ineffectiveness (28%). Interestingly, the scarring folliculitis phenotype (p < 0.05) was associated with prolonged drug survival time for acitretin treatment relative to the regular phenotype. Conclusion Comparable drug survival rates at 12 months for isotretinoin and acitretin were found. HS patients with widespread comedones and the scarring folliculitis phenotype could benefit from treatment with isotretinoin or acitretin, respectively