Publications

BACKGROUND: Hidradenitis suppurativa (HS), also known as acne inversa, is a recurring, painful, chronic, and sometimes disfiguring inflammatory skin disease.

OBJECTIVES: Our objective was to report the baseline clinical characteristics, natural history, and associated outcomes of patients with HS from the ongoing, prospective, non-interventional UNITE registry that is collecting data regarding the natural history and associated outcomes of HS.

METHODS: Patients with inflammatory HS lesions were enrolled, including adolescents (aged 12 to < 18 years) and adults (aged ≥ 18 years). None had participated in previous or current originator-adalimumab studies/registries. Patients received treatment consistent with site-specific, routine clinical practice. HS disease status was assessed by HS lesions and disease flare; treatment and outcomes data were collected at enrolment and every 6 months for ≤ 4 years.

RESULTS: Enrolment (N = 594; 89.1% adults; 10.9% adolescents) occurred from 29 October 2013 to 29 December 2015 at 73 sites in 12 countries. At baseline, the majority were female (69.7%) and White (81.2%), had moderate-to-severe disease (Hurley stage II or III; 93.3%), and had undergone prior procedures/surgery for HS (68.7%). In total, 61.6% of adults and 49.2% of adolescents were obese; 40.2% of patients reported current tobacco use. Scarring due to lesions occurred in 91.2% of patients. The prevalence of comorbidities of interest was as follows: depression (13.3%), other psychiatric disorders (9.6%), inflammatory bowel disease (2.7%), diabetes (9.1%), and polycystic ovary syndrome (5.2%).

CONCLUSIONS: In this population from the UNITE HS registry, obesity and smoking were common, and disease burden was high, manifesting as multiple lesions, scarring, surgical history, and considerable comorbidities.

BACKGROUND: Increased interest in hidradenitis suppurativa (HS) research is encouraging. A critical analysis of the state of HS literature may demonstrate the strength of existing knowledge and highlight current gaps.

OBJECTIVES: To analyse changes in HS literature from 2008 to 2018 with focus on quantity and quality of annual publications.

METHODS: Review of all indexed publications reporting on HS on PubMed. Publications were categorized based on study design, study topic and treatment type where applicable. Publications were dichotomized into high level of evidence and low level of evidence groups. Linear regression analyses were performed to investigate the change in publication number over time. Annual average growth rate and distribution of high versus low level of evidence publications were calculated.

RESULTS: Publication number increased over time overall (R2  = 0.64, P = 0.003) and for all publication types except randomized clinical trials. Case reports and case series represented the majority of HS publications (n = 479, 40.3%). Treatment was the main focus of publications (n = 445, 37.6%) with increasing interest in medical management evident in recent years. Distribution of low level of evidence studies (n = 974) compared with high level of evidence studies over time (n = 209) was significant (x2 : 11.45, P = 0.0007). High level of evidence studies had a higher average annual growth rate (49.9%) compared with low level of evidence studies (23.7%). Few randomized clinical trials were performed (n = 16), focusing equally on medical or procedural treatments.

CONCLUSIONS: Hidradenitis suppurativa research is undergoing a tremendous shift, suggesting rapid maturation of the field. Current HS literature, however, remains primarily based on limited clinical observation data, with a particular lack of randomized clinical trials. Despite this, the increase in high level of evidence studies is encouraging and may herald a shift towards improved disease understanding and treatment paradigms.

Alterations in metabolism in skin are accelerated by environmental stressors such as solar radiation, leading to premature aging. The impact of aging on mitochondria is of interest given their critical role for metabolic output and the finding that environmental stressors cause lowered energy output, particularly in fibroblasts where damage accumulates. To better understand these metabolic changes with aging, we performed an in-depth profiling of the expression patterns of dermal genes in face, forearm, and buttock biopsies from females of 20-70 years of age that encode for all subunits comprising complexes I-V of the mitochondrial electron transport chain. This complements previous preliminary analyses of these changes. "Oxidative phosphorylation" was the top canonical pathway associated with aging in the face, and genes encoding for numerous subunits had decreased expression patterns with age. Investigations on fibroblasts from older aged donors also showed decreased gene expression of numerous subunits from complexes I-V, oxidative phosphorylation rates, spare respiratory capacity, and mitochondrial number and membrane potential compared to younger cells. Treatment of older fibroblasts with nicotinamide (Nam) restored these measures to younger cell levels. Nam increased complexes I, IV, and V activity and gene expression of representative subunits. Elevated mt-Keima staining suggests a possible mechanism of action for these restorative effects via mitophagy. Nam also improved mitochondrial number and membrane potential in younger fibroblasts. These findings show there are significant changes in mitochondrial functionality with aging and that Nam treatment can restore bioenergetic efficiency and capacity in older fibroblasts with an amplifying effect in younger cells.

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30-April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as "the only inflammatory skin disease than can be healed". This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future.

BACKGROUND: Hormonal therapy is a potential treatment for hidradenitis suppurativa (HS). However, few data exist describing the efficacy of spironolactone in treatment of HS.

OBJECTIVE: To assess whether spironolactone treatment improves HS disease severity and patient-reported pain.

METHODS: We performed a single-center chart review of female patients with HS who were treated with spironolactone between 2000 and 2017. Primary outcome measurements included the HS Physician's Global Assessment (HS-PGA), Hurley staging, inflammatory lesion count, fistula count, and a numeric rating scale for pain.

RESULTS: On average, subjects were exposed to 75 mg of spironolactone daily over a 7.1-month follow-up period. Patients achieved significant disease improvement with regard to pain (Δ-1.5 [P = .01]), inflammatory lesions (Δ-1.3 [P = .02]), and HS-PGA score (Δ-0.6 [P < .001]). As expected, no change was found for Hurley stage (Δ0 [P = .32]) or fistulas (Δ0 [P = .73]). There was no difference in improvement between subjects who received less than 75 mg of spironolactone daily (n = 25; average dose, 45 mg/d) and those who received more than 100 mg daily (n = 21; average dose, 112 mg/d).

LIMITATIONS: Retrospective nature, limited sample size, and variations in severity measures documented were limiting factors.

CONCLUSIONS: Management of HS with spironolactone reduces lesion count, HS-PGA score, and pain. Lower doses appear to be effective and may be an appropriate option for patients with tolerability concerns.

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.

BACKGROUND: Psoriasis in many patients is a chronic and recalcitrant disease that requires long-term treatment, reinforcing the importance of long-term safety data. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, is approved for treating patients with moderate-to-severe plaque psoriasis.

OBJECTIVE: To determine long-term safety of ixekizumab in psoriasis.

METHODS: Integrated safety data are presented from 12-week induction period, 12-60-week maintenance period, and from all ixekizumab-treated patients from 11 clinical studies. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported.

RESULTS: Overall, 5689 patients accounted for 12 061.5 patient-years of ixekizumab exposure from 11 studies. Over 156 weeks, a total of 83.9% (n = 4775) of patients reported treatment-emergent adverse events (AEs). Most opportunistic infections (IR [95% confidence interval; CI] 1.8 [1.6, 2.1]) reported were mucocutaneous candidiasis. The IR (95% CI) for oral Candida infection was 0.9 (0.8, 1.1). There was no trend of increase in IR of AEs of special interest. Serious AEs were reported in 11.8% of patients; death occurred in 0.4% (n = 23) of patients.

CONCLUSION: The 3-year, long-term maintenance treatment with ixekizumab did not show any new safety signals in patients with moderate-to-severe plaque psoriasis.