Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep‐seated, ...inflamed lesions in the apocrine gland‐bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100 000 person‐years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho‐histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade‐relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered.
Summary
Background
Hidradenitis suppurativa (HS) causes considerable morbidity. The long‐term prognosis is of obvious interest to both patients and physicians. We conducted this study to determine ...the prognosis and risk factors in patients diagnosed with HS.
Objectives
To describe the long‐term prognosis and the clinical course of HS and its association to known risk factors.
Methods
A postal follow‐up survey with uncomplicated factual questions was conducted. As all of the patients were well acquainted with their long‐standing disease, this was thought to be sufficient for meaningful results. All cases were diagnosed by a dermatologist. Overall, 212 patients diagnosed with HS between 1981 and 2001 were studied after a median follow‐up period of 22 years (range 12–32).
Results
The overall response rate was 71·2%, with 60·8% (129/212) valid (fully completed) questionnaires. Remission was reported by 39·4% (50/127) and improvement by 31·5% (40/127). Unchanged severity was reported by 20·5% (26/127), and 8·7% (11/127) experienced worsening disease. Tobacco smoking was reported by 92·2% (119/129). Among nonsmokers, 40% (35/88) reported remission vs. 29% (17/59) of active smokers. A higher proportion of nonobese patients (45%) reported remission than obese patients (23%).
Conclusions
We found that 39·4% of the sample reported remission of HS. Suspected risk factors appeared to influence the prognosis. Smoking and obesity were significantly linked to a lower rate of self‐reported remission. The notion that lifestyle factors play a role in HS appears to be supported by this survey.
What's already known about this topic?
Hidradenitis suppurativa (HS) causes considerable morbidity.
Smoking and obesity are suggested exogenous risk factors, and inheritance has an influence on development of HS.
Some patients with HS experience remission.
What does this study add?
Nonsmoking and nonobesity are linked to a better chance of remission from HS.
In this cohort 39% of patients experienced remission.
New long‐term follow‐up data describing the clinical course of HS are presented.
Summary
Background The pathogenesis of hidradenitis suppurativa (HS) is largely unknown and the disease is difficult to treat. Patients are in high need of an effective treatment. Although it is not ...known whether the levels of tumour necrosis factor (TNF)‐α are aberrant in HS skin, anti‐TNF‐α biologics are used, with variable clinical efficacy.
Objectives To determine the cytokine profile in lesional and perilesional HS skin.
Methods We cultured 20 lesional and 10 normal‐appearing perilesional HS skin samples, seven psoriasis and six healthy control skin samples in a transwell culture system. Two distinct cytokine bead arrays were used to measure the spectrum of inflammatory cytokines in the culture supernatant. Results from HS skin samples were compared with those of healthy and psoriasis skin.
Results The proinflammatory cytokines interleukin (IL)‐1β and TNF‐α as well as the anti‐inflammatory cytokine IL‐10 were significantly elevated in HS skin. Elevated levels of these cytokines were also found in perilesional HS skin. Fold increases relative to control skin of IL‐1β, TNF‐α and IL‐10 in HS were 31, 5 and 34, compared with psoriasis: 4, 1 and 2, respectively. Levels of all three cytokines showed a trend towards a positive correlation with disease severity. IL‐2, IL‐4, IL‐5 and interferon‐γ were hardly detectable in HS or healthy control skin.
Conclusions This study shows for the first time that IL‐1β, TNF‐α and IL‐10 levels are elevated in HS skin. These data provide a rationale for therapies with biologics targeting cytokines such as TNF‐α and IL‐1.
Summary
Background
A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking.
Objectives
To develop and validate a novel dynamic scoring system to ...assess the severity of HS.
Methods
A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round.
Results
Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4–10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36).
Conclusions
The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real‐life and the clinical trials setting.
What's already known about this topic?
The modified Sartorius score, Hurley classification and Physician's Global Assessment have been used to assess severity of hidradenitis suppurativa.
However, these are often either difficult to use in daily clinical practice or static and generally poorly validated.
What does this study add?
The proposed score is a systematically constructed, validated and simple tool to assess disease severity, and can be adapted both to clinical research and daily practice.
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Summary
Background
Biologics are often required for the treatment of hidradenitis suppurativa (HS). However, data on the drug survival of biologics in daily practice are currently lacking.
Objectives
...To assess the drug survival of antitumour necrosis factor biologics in a daily practice cohort of patients with HS and to identify predictors for drug survival.
Methods
A retrospective multicentre study was performed in two academic dermatology centres in the Netherlands. Adult patients with HS using biologics between 2008 and 2020 were included. Drug survival was analysed with Kaplan–Meier survival curves and predictors of survival with univariate Cox regression analysis.
Results
The overall drug survival of adalimumab (n = 104) at 12 and 24 months was 56·3% and 30·5%, respectively, which was predominantly determined by infectiveness. Older age (P = 0·02) and longer disease duration (P < 0·01) were associated with longer survival time. For infliximab (n = 44), overall drug survival was 58·3% and 48·6% at 12 and 24 months, respectively, and was predominantly determined by infectiveness and side‐effects. Surgery during treatment was associated with a longer survival time (P = 0·01).
Conclusions
Survival rates were comparable for adalimumab and infliximab at 12 months, and were mainly determined by ineffectiveness. Age, disease duration (adalimumab) and surgery (infliximab) are predictors for longer survival.
What is already known about this topic?
Adalimumab is the only registered biological drug for the treatment of hidradenitis suppurativa (HS).
Successful treatment with biologics is determined by drug survival.
Data on drug survival in patients with HS in daily practice are lacking.
What does this study add?
The survival rates of adalimumab (56·3%) and infliximab (58·3%) after 1 year are predominantly determined by ineffectiveness and side‐effects.
Age, disease duration (adalimumab) and surgery (infliximab) are predictors for longer survival.
Linked Comment: R. Hambly and B. Kirby. Br J Dermatol 2021; 185:16–17.
Summary
Background
Hidradenitis suppurativa (HS) has a major impact on patients’ quality of life (QoL). Although it has commonly been assumed that HS impairs sexual health, only a single case–control ...study has been performed on sexual functioning in a small group of patients with HS.
Objectives
To investigate the QoL with a particular focus on sexual health in a substantial population of patients with HS.
Methods
In total 916 patients with HS received an invitation to participate in this multicentre cross‐sectional survey.
Results
Three hundred patients completed the questionnaires. This study showed a diminished QoL and sexual health in patients with HS (Female Sexual Function Index: 21·6 ± 9·6, International Index of Erectile Function: 49·7 ± 20·7, Arizona Sexual Experience Scale: 16·7 ± 5·3, Dermatology Life Quality Index: 12·5 ± 7·5). Sexual health was associated with QoL in women but not in men. Female sex and late onset of HS were associated with poor sexual function. Impairment of QoL was associated with anogenital involvement, early onset of HS, disease severity and disease activity.
Conclusions
HS is associated with impaired sexual health and QoL. Physicians should not hesitate to ask patients with HS about their sexual function and, when needed, offer them psychological support.
What's already known about this topic?
Hidradenitis suppurativa (HS) has a major impact on quality of life.
What does this study add?
Sexual health is impaired in patients with HS.
Impairment in sexual health is associated with female sex and late onset of disease.
Clinicians should be aware of the impact of HS on sexual health, and should not hesitate to ask patients with HS about their sexual function and offer them psychological support when needed
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Linked Comment: Ofenloch. Br J Dermatol 2017; 176:861–862
Plain language summary available online
Conjunctivitis in dupilumab clinical trials Akinlade, B.; Guttman‐Yassky, E.; Bruin‐Weller, M. ...
British journal of dermatology (1951),
September 2019, Letnik:
181, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
Background
Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis ...(AD) uncontrolled by topical prescription medicines or who cannot use topical medicines, for patients in Japan whose AD is uncontrolled with existing therapies, for patients with moderate‐to‐severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment of moderate‐to‐severe asthma uncontrolled with their current medicines. AD trials have reported increased incidence of conjunctivitis for dupilumab vs. placebo.
Objectives
To characterize further the occurrence and risk factors of conjunctivitis in dupilumab clinical trials.
Methods
We evaluated randomized placebo‐controlled trials of dupilumab in AD (n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47).
Results
In most AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators. In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase the incidence compared with placebo. In the EoE trial, no patients had conjunctivitis.
Conclusions
Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the incidence of conjunctivitis was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab‐treated patients require further study.
What's already known about this topic?
Ocular disorders, including allergic conjunctivitis, are common in patients with atopic dermatitis (AD).
In most dupilumab AD trials, dupilumab‐treated patients had higher conjunctivitis incidence than those receiving placebo.
Most cases were mild to moderate and recovered or were recovering during study treatment; study treatment discontinuation due to conjunctivitis was rare.
Conjunctivitis incidence was very low and similar for dupilumab and placebo in clinical trials in asthma, chronic rhinosinusitis with nasal polyps and eosinophilic oesophagitis.
What does this study add?
This analysis confirms and extends the results of the individual clinical trials.
Baseline disease‐related factors, including AD severity, prior conjunctivitis history and certain biomarkers (thymus and activation‐regulated chemokine, IgE, eosinophils), were associated with increased incidence of conjunctivitis.
Patients who responded well to dupilumab had reduced incidence of conjunctivitis.
Further study is needed to elucidate the aetiology and treatment of conjunctivitis in dupilumab‐treated patients with AD.
Linked Editorial: Chia‐Yu Chu. Br J Dermatol 2019; 181:436–437.
Plain language summary available online
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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.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent inflammatory nodules mostly located in the armpits and groin. Over the years multiple treatments for HS ...have been proposed; however, to date a cure is still lacking. In this update we provide an overview of most drug treatments reported on for HS, where possible with their mode of action and side effects. In mild cases, clindamycin lotion or resorcinol cream have proven effective. Tetracyclines are a first-line systemic option in more widespread or severe cases, followed by the combination of clindamycin and rifampicin. However, the recurrence rate is high after discontinuation of clindamycin plus rifampicin combination therapy. Long-term treatment with retinoids, especially acitretin is feasible, although teratogenicity has to be taken into account in females of reproductive age. Multiple anti-inflammatory drugs have been suggested for HS, such as dapsone, fumarates or cyclosporine. However, their effectiveness in HS is based on small case series with varying results. If most common treatments have failed, biologics (e.g., infliximab or adalimumab) are the next step. Although not addressed in this review, surgical interventions are often needed to achieve remission.
Summary
Background Hidradenitis suppurativa (HS) is a difficult‐to‐manage disease. Randomized controlled trials with antitumour necrosis factor (TNF)‐α biologics have been conducted and in most ...studies disease activity was reduced. However, the mechanism of action in HS skin is so far unknown.
Objectives To assess whether anti‐TNF‐α treatment affects in situ cytokine production and frequency of inflammatory cell populations in HS lesional skin.
Methods Nine patients with HS, participating in a larger placebo‐controlled, double‐blind phase IIb clinical trial on the efficacy and safety of adalimumab in patients with moderate to severe HS (M10‐467), were randomized and treated for 16 weeks. In a mechanism‐of‐action substudy, biopsies were obtained at fixed time points pre‐ and post‐treatment. One part of the biopsy was cultured for 24 h for cytokine release in the culture medium, while another part was used for in situ analysis.
Results Secretion of cytokines, including interleukin (IL)‐1β, CXCL9 monokine induced by interferon‐γ (MIG), IL‐10, IL‐11, B‐lymphocyte chemoattractant (BLC) and IL‐17A, was significantly elevated in HS. Adalimumab treatment was associated with decreased production of cytokines in HS skin, especially IL‐1β, CXCL9 (MIG) and BLC. Treatment significantly reduced the number of CD11c+, CD14+ and CD68+ cells in HS lesional skin. The numbers of CD3+ and CD4+ T cells, and CD20+ and CD138+ B cells were also reduced by adalimumab treatment.
Conclusions Adalimumab treatment inhibits important cytokines and inflammatory cell numbers in lesional HS skin, especially levels of IL‐1β and numbers of inflammatory CD11c+ dendritic cells.
See also the Commentary by Jemec
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