Background
The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch‐related ...prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat.
Objective
To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross‐sectional EPP were discussed and agreed upon.
Methods
Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members.
Results
Twenty‐four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch‐scratch cycle.
Conclusion
This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross‐sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP.
Summary
Background
The relevance of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in the management of psoriasis has not been studied previously. GM‐CSF is important in the initiation and ...maintenance of chronic inflammatory processes.
Objectives
To investigate the clinical use of GM‐CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM‐CSF inhibitor, in patients with moderate‐to‐severe plaque psoriasis.
Methods
A phase II, multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐finding, proof‐of‐concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point – the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) – was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777.
Results
In total, 122 patients were enrolled and 106 (86·9%) completed the double‐blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration–time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment‐related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis.
Conclusions
GM‐CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis.
What's already known about this topic?
Blockade of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) signalling is effective in rheumatoid arthritis.
Potential relevance for psoriasis has been indicated by the presence of GM‐CSF in psoriasis‐related skin blister fluid and the serum of patients with psoriasis, and also by elevated expression in psoriatic skin lesions.
What does this study add?
This is the first clinical investigation into the efficacy and safety of an anti‐GM‐CSF antibody in plaque psoriasis.
This study provides no evidence of benefit for GM‐CSF neutralization in the treatment of plaque psoriasis.
Safety profiles were comparable in the placebo and anti‐GM‐CSF treatment groups, and no incidences of pulmonary alveolar proteinosis or clinically significant changes in lung function were recorded throughout the short‐term duration of study treatment.
Overall, the findings point to key differences in the role of GM‐CSF in the pathogeneses of psoriasis and rheumatoid arthritis.
Linked Comment: Crowley. Br J Dermatol 2019; 180:1286–1287.
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Background Itching is a cardinal symptom of atopic dermatitis (AD).
Objective The study aim was to evaluate the relationships between pruritus and stress, health‐related quality of life (HRQoL) and ...depression in adult patients with AD.
Methods Eight‐nine patients (30 men and 59 women) with AD were included. Demographic and clinical data were collected. The intensity of pruritus was assessed according to the 10‐point Visual Analogue Scale (VAS) and the 4‐Item Itch Questionnaire, HRQoL according to Dermatology Life Quality Index, and depression symptoms with Beck’s Depression Inventory (BDI). Stress experienced by patients was evaluated with Social Readjustment Rating Scale and Stress Self‐assessment Scale.
Results The mean intensity of pruritus according to VAS was 7.9 ± 2.2 points, and according to 4‐Item Itch Questionnaire 14.0 ± 4.4 points. The intensity of pruritus was related to the stress experienced by the patients prior to disease exacerbation (ρ = 0.37, P < 0.001). A significant correlation between pruritus and HRQoL was also found (VAS: ρ = 0.5, P < 0.001, 4‐Item Itch Questionnaire: ρ = 0.5, P < 0.001) as well as between pruritus and BDI (VAS: ρ = 0.44, P < 0.001, 4‐Item Itch Questionnaire: ρ = 0.51, P < 0.001). Patients with symptoms suggesting depression had more intense pruritus compared with the rest of patients (VAS: 9.1 ± 1.6 vs. 7.6 ± 2.2 points, P = 0.004; 4‐Item Itch Questionnaire: 17.3 ± 2.5 vs. 13.1 ± 4.4 points, P < 0.001).
Conclusions Itching intensity in AD plays an important role in determining patients’ psychosocial well‐being. Patients with atopic dermatitis require an effective, long‐term antipruritic therapy to improve their QoL and reduce the potential risk of depression.
The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were ...held between December 2020 and July 2021. Twenty‐nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti‐inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.
Chronic itch is a common and distressing symptom that arises from a variety of skin conditions and systemic diseases. Despite this, there is no clinically based classification of pruritic diseases to ...assist in the diagnosis and cost-effective medical care of patients with pruritus. The proposed classification focuses on clinical signs and distinguishes between diseases with and without primary or secondary skin lesions. Three groups of conditions are proposed: pruritus on diseased (inflamed) skin (group I), pruritus on non-diseased (non-inflamed) skin (group II), and pruritus presenting with severe chronic secondary scratch lesions, such as prurigo nodularis (group III). The next part classifies the underlying diseases according to different categories: dermatological diseases, systemic diseases including diseases of pregnancy and drug-induced pruritus, neurological and psychiatric diseases. In some patients more than one cause may account for pruritus (category "mixed") while in others no underlying disease can be identified (category "others"). This is the first version of a clinical classification worked out by the members of the International Forum for the Study of Itch. It is intended to serve as a diagnostic route for better evaluation of patients with chronic pruritus and aims to improve patients' care.
Background
Dermatophytosis is a world‐wide distributed common infection. Antifungal drug resistance in dermatophytosis used to be rare, but unfortunately the current Indian epidemic of atypical ...widespread recalcitrant and terbinafine‐resistant dermatophytosis is spreading and has sporadically been reported in Europe.
Objectives
To explore the occurrence of clinical and mycological proven antifungal drug resistance in dermatophytes in Europe.
Methods
A standardized questionnaire was distributed through the EADV Task Force of Mycology network to dermatologists in Europe.
Results
Representatives from 20 countries completed the questionnaires of which 17 (85 %) had observed clinical and/or mycological confirmed antifungal resistance, two countries published cases of antifungal resistance and one country had no known cases.
Conclusions
This pilot study confirms that both clinical and mycological antifungal resistance exist in Europe.
The special interest group on sensitive skin of the International Forum for the Study of Itch previously defined sensitive skin as a syndrome defined by the occurrence of unpleasant sensations ...(stinging, burning, pain, pruritus and tingling sensations) in response to stimuli that normally should not provoke such sensations. This additional paper focuses on the pathophysiology and the management of sensitive skin. Sensitive skin is not an immunological disorder but is related to alterations of the skin nervous system. Skin barrier abnormalities are frequently associated, but there is no cause and direct relationship. Further studies are needed to better understand the pathophysiology of sensitive skin – as well as the inducing factors. Avoidance of possible triggering factors and the use of well‐tolerated cosmetics, especially those containing inhibitors of unpleasant sensations, might be suggested for patients with sensitive skin. The role of psychosocial factors, such as stress or negative expectations, might be relevant for subgroups of patients. To date, there is no clinical trial supporting the use of topical or systemic drugs in sensitive skin. The published data are not sufficient to reach a consensus on sensitive skin management. In general, patients with sensitive skin require a personalized approach, taking into account various biomedical, neural and psychosocial factors affecting sensitive skin.
Background
Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed.
Objective
To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu ...opioid antagonist nalbuphine extended release (NAL‐ER) tablets in a phase 2, multicentre, randomized, double‐blind, placebo‐controlled trial with an open‐label, 50‐week extension phase.
Methods
Subjects with moderate‐to‐severe PN were randomized to NAL‐ER 81 mg (NAL‐ER81) or 162 mg (NAL‐ER162) tablets twice‐daily or placebo for 8 weeks of stable dosing following a 2‐week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI‐NRS) score ≥5 at the time of rollover (or during the observation period) were eligible for open‐label treatment.
Results
Of 63 randomized subjects, 62 were treated and comprised the modified intent‐to‐treat population (MITT), 50 completed 10 weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL‐ER162 (P = 0.32) and 6 (27.3%) treated with NAL‐ER81 (P = 0.78) achieved ≥30% reduction from baseline in 7‐day WI‐NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8/12 (66.7%) subjects completing Week 10 treated with NAL‐ER162 vs. placebo (8/20, 40.0%; P = 0.03). Additionally, 6 subjects (33.3%) treated with NAL‐ER162 and 3 (13.6%) treated with NAL‐ER81 achieved ≥50% reduction from baseline in 7‐day WI‐NRS at Week 10 (coprimary endpoint). Extended open‐label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild‐to‐moderate severity. The safety profile did not change with extended open‐label treatment.
Conclusion
In adult subjects with PN, oral treatment with NAL‐ER 162 mg twice daily provided measurable anti‐pruritic efficacy in subjects completing ≥10 weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419).
Background
Chronic pruritus (CP) is a subjective symptom, and it is necessary to assess its intensity with validated patient‐reported outcome tools in order to allow determination of the treatment ...course.
Objectives
So far, the itch intensity scales were validated in small cohorts and in single languages. Here, we report the validation of the numerical rating scale, the verbal rating scale and the visual analogue scale for the worst and average pruritus intensity in the last 24h in several languages across Europe and across different pruritic dermatoses.
Methods
After professional translation, the intensity scales were digitized for use as a tablet computer application. Validation was performed in clinics for Dermatology in Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland and Turkey.
Results
A total of 547 patients with contact dermatitis, chronic nodular prurigo, psoriasis vulgaris, lichen planus or cutaneous T‐cell lymphoma were included. The intensity scales showed a high level of reproducibility and inter‐correlations with each other. The correlation with the Dermatology Life Quality Index was weak to strong in nearly all countries and dermatoses with the exception of France and patients with chronic nodular prurigo, for which no statistically significant correlations were found.
Conclusions
The numerical rating scale, the verbal rating scale und the visual analogue scales are valid instruments with good reproducibility and internal consistency in German (Germany, Austria, Switzerland), French, Italian, Polish, Russian, Spanish and Turkish for different pruritic dermatoses. VAS worst was the best reproducible and consistent measuring instrument in all countries.
Introduction
Overweight is a well‐established risk factor for hidradenitis suppurativa (HS). In this cross‐sectional study, we compare HS patients with a high body mass index (BMI) with HS patients ...with a low BMI to investigate differences in disease characteristics.
Materials and method
Patients were recruited from 17 dermatological centres from four continents. A total of 246 patients with a BMI below 25 were compared to 205 patients with a BMI of above 35.
Results
Patients with a high BMI suffered more severe disease (Hurley, physician global assessment, number of areas affected and patient‐reported severity (PRS), P < 0.001 for all). There was no difference in smoking (P = 0.783) nor in family history (P = 0.088). In both low and high BMI patients, early onset of HS was a predictor of positive family history (P < 0.001, for each). For low BMI patients, an increase in BMI significantly increased PRS (P < 0.001). For patients with a high BMI, number of pack‐years significantly increased PRS (P = 0.001). Cluster analysis of eruption patterns was location specific for low BMI patients but severity specific for high BMI patients.
Discussion
Patients with a low and high BMI could represent two clinically different subtypes. We suggest a non‐linear relationship between BMI and impact of HS. As patients go from a low BMI patient to a high BMI patient (or from high to low), eruption patterns and risk factors may change.
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