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.
Pruritus in psoriasis: An update Szepietowski, J.C.; Reich, A.
European journal of pain,
January 2016, Letnik:
20, Številka:
1
Journal Article
Recenzirano
Background and objective
Psoriasis is one of the most common chronic inflammatory skin diseases, found in about 1–3% of the general population. Pruritus affects about 60–90% of patients with ...psoriasis. The aim of this review was to summarize current knowledge about the pathogenesis and treatment of this symptom in psoriasis patients.
Results
Majority of psoriatic patients consider pruritus as the most bothersome symptom. The pathogenesis of pruritus is still unknown but the major concept of its origin is focused on neurogenic inflammation. Possible itch mediators include neuropeptides released from dermal nerve endings upon various stimuli, which were found to be abnormally expressed in itchy psoriatic plaques. Another important phenomenon supporting the idea of neurogenic inflammation as a key player in pruritus accompanying psoriasis is abnormal innervations of psoriatic skin. Possibly increased innervation density in psoriasis may decrease the threshold for pruritic stimuli. It is also suggested that pruritus in psoriasis might be related to abnormal functioning of the peripheral opioid system. Despite the high frequency of pruritus in psoriasis, to date there is no single antipruritic therapy dedicated specifically to treat itch in this disease.
Conclusions
Neurogenic inflammation seems to be important for itchiness in psoriasis. Treatment of pruritus in patients with psoriasis should be directed towards the resolution of skin lesions, as disease remission usually is linked with pruritus relief.
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available ...evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti‐inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long‐term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long‐term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti‐inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.
This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus‐based guideline, taking available ...evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen‐specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease‐modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen‐specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress‐induced exacerbations. Therapeutic patient education (‘Eczema school’) is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti‐inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.
Summary
Background
Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin‐17A.
Objectives
To assess the efficacy and safety of different maintenance ...dosing regimens of secukinumab 300 mg based on Psoriasis Area and Severity Index (PASI) response at week 24 in patients with moderate‐to‐severe plaque psoriasis.
Methods
OPTIMISE was a randomized, open‐label, rater‐blinded phase IIIb study. Patients (n = 1647) received secukinumab 300 mg at baseline; weeks 1, 2, 3 and 4; and every 4 weeks (q4w) to week 24. At week 24, PASI 90 responders (≥ 90% improvement in PASI; n = 1306) were randomized to secukinumab 300 mg q4w (n = 644) or q6w (n = 662) to week 52, and PASI ≥ 75 to < 90 responders (n = 206) were randomized to secukinumab 300 mg q4w (n = 114) or q2w (n = 92) to week 52.
Results
PASI 90 response was maintained at week 52 by 85·7% of patients with q4w dosing vs. 74·9% with q6w dosing (odds ratio 1·91, 95% confidence interval 1·44–2·55). The primary end point, noninferiority of q6w vs. q4w dosing, was not met. In PASI ≥ 75 to < 90 responders, the proportion of patients with PASI 90 response at week 52 was numerically higher in the q2w vs. the q4w group (57% vs. 46·5%, respectively, P = 0·10). Heavier patients (≥ 90 kg) demonstrated numerically higher PASI 90 response with the q2w (57·1%) vs. the q4w regimen (40%, P = 0·11).
Conclusions
Standard q4w dosing of secukinumab 300 mg is the optimal dosing regimen to achieve and maintain clear or almost clear skin. Patients with body weight ≥ 90 kg not achieving PASI 90 at week 24 may benefit from the q2w dosing regimen.
What's already known about this topic?
Individual responses to biologics in patients with psoriasis vary considerably and there may be a need to individualize treatment.
Dose optimization strategies of currently available biologic drugs have been investigated mainly in rheumatic disorders.
Secukinumab has shown long‐term PASI 90/100 responses (percentage improvement in Psoriasis Area and Severity Index) to year 5 in patients with moderate‐to‐severe plaque psoriasis when used at the dose of 300 mg every 4 weeks.
What does this study add?
Standard every 4 week (q4w) dosing of secukinumab 300 mg is the optimal regimen to achieve and maintain clear or almost clear skin at week 52; the majority of the patients (85·7%) maintain PASI 90 at week 52.
Superiority of intensified (q2w) dosing over the q4w regimen could not be claimed.
However, patients with a higher body weight (≥ 90 kg) not achieving PASI 90 response at week 24 may benefit from q2w dosing.
Linked Comment: Morita and Ikumi. Br J Dermatol 2020; 182:264–266.
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.
Respond to this article
Summary
Background
Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long‐term treatment of adults with moderate‐to‐severe chronic plaque psoriasis. The fixed ...combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient.
Objectives
To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm®, in adults with moderate‐to‐severe chronic plaque psoriasis.
Methods
In this phase III, double‐blind, placebo‐controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012‐000055‐13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of ‘clear’ or ‘almost clear’ in the Physician's Global Assessment (PGA) at week 16.
Results
In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm®; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm®: P < 0·001). Overall, 33% of patients treated with LAS41008 were ‘clear’ or ‘almost clear’ in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm®. Most treatment‐related adverse events were classed as ‘mild’ in severity.
Conclusions
LAS41008 (DMF) is effective in the treatment of adults with moderate‐to‐severe chronic plaque psoriasis.
What's already known about this topic?
A combination of fumaric acid esters (FAEs), including dimethyl fumarate (DMF), is approved for the treatment of moderate‐to‐severe psoriasis in Germany, with a positive risk–benefit profile for long‐term use.
Despite being recommended in international treatment guidelines, FAEs are not available in most European countries.
What does this study add?
This international, randomized, double‐blind trial demonstrates the efficacy and safety of LAS41008 (DMF) for the treatment of adults with moderate‐to‐severe chronic plaque psoriasis.
Linked Comment: Balak. Br J Dermatol 2017; 176:563–564.
Plain language summary available online
Summary
Background
The management of hidradenitis suppurativa (HS) is still challenging, and new treatment methods are necessary. Acitretin seems to be a promising agent in HS management; however, ...literature data are limited.
Objectives
To investigate the clinical efficacy of acitretin monotherapy in 17 patients with long‐standing and recalcitrant HS. Simultaneously, an assessment of quality of life was carried out.
Methods
The study was conducted with a group of 17 patients with HS. Patients were treated with acitretin for up to 9 months and examined at baseline, after 1 month, and then every 3 months from baseline. The clinical extent of disease severity was measured with the HS Severity Index (HSSI), Hurley scoring system, Physician's Global Assessment and Dermatology Life Quality Index (DLQI).
Results
Nine patients (53%) finished the whole 9 months of acitretin treatment. The mean acitretin dose was 0·56 ± 0·08 mg kg−1 daily. A significant improvement of clinical manifestation (HSSI, DLQI) was observed after only 1 month of therapy, and further improvement was recorded during the next few months. Overall, eight subjects (47%) fulfilled the criteria for response (HSSI ≥ 50% reduction from baseline). The dropout rate was 47%, due mostly to drug ineffectiveness and adverse events. Discontinuation of treatment resulted in deterioration or relapse of HS 2–8 months after acitretin cessation, in all but one patient.
Conclusions
HS treatment with acitretin seems to be a promising method of disease management. However, due to the high daily dosage, its usage may be limited.
What's already known about this topic?
In contrast to isotretinoin, acitretin seems to be a promising treatment for management of hidradenitis suppurativa.
What does this study add?
This study is the largest open‐label trial to date on acitretin treatment for hidradenitis suppurativa.
Evaluation of quality‐of‐life aspects during acitretin therapy was also conducted.
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