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.

Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.

Apremilast for moderate hidradenitis suppurativa: Results of a randomized controlled trial.

BACKGROUND: Effective anti-inflammatory treatments for hidradenitis suppurativa (HS) are limited. OBJECTIVE: To evaluate the efficacy and short-term safety of apremilast in patients with moderate HS. METHODS: A total of 20 patients with moderate HS were randomized in a 3:1 ratio to receive blinded treatment with apremilast, 30 mg twice daily, or placebo for 16 weeks. The primary outcome was the Hidradenitis Suppurativa Clinical Response at week 16. Linear mixed effects modeling (analysis of covariance) was used to assess secondary clinical outcomes between treatment groups. RESULTS: The HS clinical response was met in 8 of 15 patients in the apremilast group (53.3%) and none of 5 patients in the placebo group (0%) (P = .055) at week 16. Moreover, the apremilast-treated patients showed a significantly lower abscess and nodule count (mean difference, -2.6; 95% confidence interval, -6.0 to -0.9; P = .011), NRS for pain (mean difference, -2.7; 95% -4.5 to -0.9; P = .009), and itch (mean difference, -2.8; 95% confidence interval, -5.0 to -0.6; P = .015) over 16 weeks compared with the placebo-treated patients. There was no significant difference in the Dermatology Life Quality Index over time between the 2 treatment groups (mean difference, -3.4; 95% confidence interval, -9.0 to 2.3; P = .230). The most frequently reported adverse events in the apremilast-treated patients were mild-to-moderate headache and gastrointestinal symptoms, which did not result in dropouts. LIMITATIONS: Small number of patients, relatively short study duration. CONCLUSION: Apremilast, at a dose of 30 mg twice daily, demonstrated clinically meaningful efficacy and was generally well tolerated in patients with moderate HS.

Hidradenitis Suppurativa: A Systematic Review Integrating Inflammatory Pathways Into a Cohesive Pathogenic Model.

Background: The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways involved in HS as a chronic inflammatory skin disease. Methods: A systematic literature search was performed in PubMed/Medline and EMBASE from January 2013 through September 2017, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Findings on HS pathogenesis were also compared with those of other immune-mediated inflammatory diseases (IMIDs) in a non-systematic review. In addition, current therapeutic options for HS are briefly discussed on the basis of the findings for the inflammatory pathways involved in HS. Results: A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS and related syndromic conditions. First, nicastrin (NCSTN) and PSTPIP1 mutations are directly associated with auto-inflammatory disease. Secondly, the up-regulation of several cytokines including tumor necrosis factor-α and T helper-17/interleukin-23 are connected to auto-inflammatory mechanisms in the pathogenesis of HS. Thirdly, the microbiome of lesional skin differs significantly vs. normal-appearing skin. Fourthly, HS risk is enhanced through physiological and environmental factors such as smoking, obesity, and mechanical friction. There is significant overlap between the pathogenesis of HS, its syndromic forms and other IMIDs, particularly with respect to aberrations in the innate immune response. Conclusions: The evidence presented in this review supports HS as an auto-inflammatory skin disorder associated with alterations in the innate immune system. Based on these most recent data, an integrative viewpoint is presented on the pathogenesis of HS. Current management strategies on HS consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as smoking cessation and weight loss. As large gaps remain in the understanding of the pathogenesis of HS, further research is warranted to ultimately improve the management and treatment of patients with HS and related syndromic conditions.

Assessing Pruritus in Hidradenitis Suppurativa: A Cross-Sectional Study.

BACKGROUND: Pruritus is still a forgotten aspect of hidradenitis suppurativa (HS) and, to date, has never been adequately studied. OBJECTIVE: The aim of this study was to determine the prevalence, and explore the characteristics, of pruritus in a well-defined cohort of HS patients. SETTING: An academic hospital-based cross-sectional study in The Netherlands. METHODS: A numerical rating scale (NRS, 0-10) was used to determine the prevalence of HS-related itch (NRS score ≥3). Candidate predictors for pruritus were subsequently determined using logistic regression models, and the impact of pruritus was assessed using a modified five-dimensional (5-D) itch scale. Associated serological and histological markers of pruritus were (semi-)quantitatively investigated in a subpopulation. RESULTS: The prevalence rate of pruritus in 211 HS patients was 57.3%, with a mean NRS score of 6.1 ± 2.0. Patients with a pruritus NRS score ≥3 had more HS-affected body sites than patients with a score <3 (p < 0.001). The occurrence of a pruritus NRS score ≥3 was associated with Hurley III disease (odds ratio [OR] 7.73; p = 0.003) and pain (OR 1.34; p < 0.001). Pruritus affected sleep and activities of daily living (ADL) in the majority of cases, with an associated modified 5-D itch score of 13.7 ± 3.6 (on a scale from 5 to 25) in 52 HS patients. Histological examination showed eosinophilic granulocytes were present in 25% (2/8) of the perilesional skin and 63% (10/16) of the lesional skin, while a perineural infiltrate was found in 25% (2/8) and 69% (11/16) of the perilesional and lesional skin, respectively. CONCLUSION: Pruritus is a frequent but underreported symptom in patients with HS. Its moderate to severe intensity and significant impact on daily activities have great potential to impair patients' quality of life.

Hidradenitis suppurativa is not associated with the metabolic syndrome based on body type: A cross-sectional study.

A body type with a high waist circumference or elevated waist-to-hip ratio (WHR), known as the "apple" body type, represents central/visceral obesity and is associated with the metabolic syndrome. The aim of this study was to simultaneously investigate the body mass index (BMI) and WHR in order to classify body types in individuals with hidradenitis suppurativa (HS) compared with a general dermatological population. A hospital-based cross-sectional study was performed in the Netherlands. One hundred and six HS patients and 212 controls were included. The BMI was significantly higher in the HS group in comparison with the control group, at 27.8 ± 5.4 and 25.6 ± 4.8, respectively (P < 0.001). The WHR did not significantly differ between HS patients and the control dermatological population (P > 0.05). A more peripheral pattern of bodyweight distribution was seen in 43% of the 37 obese HS individuals, in contrast to 19% of 31 obese patients in the control group (P = 0.036). In conclusion, the body type in obese HS patients, based on the WHR, shows a more peripheral pattern and differs from the WHR in the BMI-matched general dermatological population.

[Porphyria cutanea tarda: the benefit of additional diagnostics]. / Porphyria cutanea tarda: Nut van aanvullende diagnostiek.

The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection. The clinical relevance of the several diagnostic modalities is important in PCT. Diagnostic evaluation is important in order to confirm the diagnosis, but also to evaluate the treatment response in the context of long-term follow-up in the prevention of late complications of PCT, i.e. hepatocellular carcinoma.