High Body Mass Index in Adolescent Girls Precedes Psoriasis Hospitalization

Psoriasis is associated with being overweight, but the temporal relationship is not known. This historical cohort study tested whether severe psoriasis resulting in hospitalization in adulthood was preceded by excess increase in age-adjusted body mass index, a known risk factor in childhood for being overweight in adulthood. The study cohort was based on the Copenhagen School Health Records Register, birth years 1930 to 1984 (309,152 schoolchildren). Cases were found through the Danish National Patient Register for the period 1977 to 2001. A total of 1074 (0.36%) of the schoolchildren were identified as having psoriasis, with at least one hospital admission. Multivariate analysis demonstrated an association between excess increase in body mass index and psoriasis in females only. Being overweight in adolescence was the main factor behind this observation. The female group showed a significant association between psoriasis and body mass index at ages 12 (p=0.028) and 13 years (p=0.010). This was not the case for males or for body mass index measured at ages 11 years and below

DHA Improves Cognition and Prevents Dysfunction of Entorhinal Cortex Neurons in 3xTg-AD Mice

Defects in neuronal activity of the entorhinal cortex (EC) are suspected to underlie the symptoms of Alzheimer's disease (AD). Whereas neuroprotective effects of docosahexaenoic acid (DHA) have been described, the effects of DHA on the physiology of EC neurons remain unexplored in animal models of AD. Here, we show that DHA consumption improved object recognition (↑12%), preventing deficits observed in old 3xTg-AD mice (↓12%). Moreover, 3xTg-AD mice displayed seizure-like akinetic episodes, not detected in NonTg littermates and partly prevented by DHA (↓50%). Patch-clamp recording revealed that 3xTg-AD EC neurons displayed (i) loss of cell capacitance (CC), suggesting reduced membrane surface area; (ii) increase of firing rate versus injected current (F-I) curve associated with modified action potentials, and (iii) overactivation of glutamatergic synapses, without changes in synaptophysin levels. DHA consumption increased CC (↑12%) and decreased F-I slopes (↓21%), thereby preventing the opposite alterations observed in 3xTg-AD mice. Our results indicate that cognitive performance and basic physiology of EC neurons depend on DHA intake in a mouse model of AD

Evidence-based approach to the treatment of hidradenitis suppurativa/acne inversa, based on the European guidelines for hidradenitis suppurativa

Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by painful, recurrent nodules and abscesses that rupture and lead to sinus tracts and scarring. To date, an evidence-based therapeutic approach has not been the standard of care and this is likely due to the lack of evidence based treatment guidelines. The purpose of this study was to promote a holistic evidence-based approach which implemented Level of Evidence and Strength of Recommendation for the treatment of HS. Based upon the European Dermatology Forumguidelines for the management of HS, evidence-based approach was explored for the treatment of HS. The diagnosis of HS should be made by a dermatologist or other healthcare professional with expert knowledge in HS. All patients should be offered adjuvant therapy as needed (pain management, weight loss, tobacco cessation, treatment of super infections, and application of appropriate dressings). The treating physician should be familiar with disease severity scores, especially Hurley staging, physician global assessment and others. The routine use of patient’reported outcomesincluding DLQI, itch and pain assessment (Visual Analogue Scale) is strongly recommended. The need for surgical intervention should be assessed in all patients depending upon type and extent of scarring, and an evidence-based surgical approach should be implemented. Evidence-based medical treatment of mild disease consists of topical Clindamycin 1 % solution/gel b.i.d. for 12 weeks or Tetracycline 500 p.o. b.i.d. for 4 months (LOE IIb, SOR B), for more widespread disease. If patient fails to exhibit response to treatment or for a PGA of moderate-to-severe disease, Clindamycin 300 p.o. b.i.d. with Rifampicin 600 p.o. o.d. for 10 weeks (LOE III, SOR C) should be considered. If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present. If the patient fails to exhibit response, then consideration of second or third line therapy is required. A growing body of evidence is being published to guide the treatment of HS. HS therapy should be based upon the evaluation of the inflammatory components as well as the scarring and should be directed by evidence-based guidelines. Treatment should include surgery as well as medical treatment. Future studies should include benefit risk ratio analysis and long term assessment of efficacy and safety, in order to facilitate long term evidence based treatment and rational pharmacotherapy

The Hidradenitis Suppurativa Quality of Life (HiSQOL) score: development and validation of a measure for clinical trials

Background Hidradenitis suppurativa (HS) is a chronic, inflammatory condition that can have a large negative impact on health‐related quality of life (HRQOL). A reliable and validated measure of HS‐specific HRQOL in clinical studies is needed. Objective To develop and validate the Hidradenitis Suppurtiva Quality Of Life (HiSQOL©) scale, for clinical trial measurement of HS‐specific HRQOL. Methods Stage 1: Qualitative concept elicitation (CE) interviews were conducted with HS patients in Denmark (DK) (n = 21) and the United States (US) (n=21). Stage 2: Cognitive debriefing (CD) interviews were performed with US HS patients (n = 30) and Danish HS patients (n=30). Stage 3: Observational study of 222 HS patients in the US was conducted for item reduction, measure validation and assessment of psychometric properties. Stage 4: Observational study of 215 HS patients in Denmark was conducted to confirm the psychometric structure derived in stage 3. In both studies ‐ the Dermatology Life Quality Index, Hospital Anxiety and Depression Scale, and numerical rating scale for pain ‐ were also included. Results In CE, 99 items were generated and reduced to 41 after removing duplicates. In CD, 2 items were added and 1 items removed. A 42‐item instrument was psychometrically assessed. Based on psychometric analyses and patient input, the instrument was reduced to 17 items that had strong psychometric properties in both US and DK samples

A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process

Background There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome reporting bias and limits the ability to synthesise evidence. Objectives To achieve global multi‐stakeholder consensus on a Core Outcome Set (COS) of domains regarding what to measure in clinical trials for HS. Methods Six stakeholder groups participated in a Delphi process which included five anonymous e‐Delphi rounds and four face‐to‐face consensus meetings to reach consensus on the final COS. The aim was for a 1:1 ratio of patients: Health Care Professionals (HCPs). Results A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process which yielded a final COS that included five domains: pain, physical signs, HS specific quality of life, global assessment and progression of course. A sixth domain, symptoms, was highly supported by patients and not by healthcare professionals but is recommended for the core domain set. Conclusions Routine adoption of the COS in future HS trials should ensure that core outcomes of importance to both patients and HCPs are collected

Quality of life measurement in alopecia areata. Position statement of the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes

New treatment options may lead to an increased interest in using reliable and sensitive instruments to assess health-related quality of life in people with alopecia areata (AA). The purpose of this paper is to present current knowledge about quality of life assessment in AA. The dermatology-specific Dermatology Life Quality Index (DLQI) was the most widely reported health-related quality of life instrument used in AA. Three AA-specific (Alopecia Areata Symptom Impact Scale, Alopecia Areata Quality of Life Index and Alopecia Areata Patients'' Quality of Life) and three hair disease-specific instruments (Hairdex, Scalpdex and ‘hair-specific Skindex-29’) were identified with a range of content and validation characteristics: there is little evidence yet of the actual use of these measures in AA. Scalpdex is the best-validated hair disease-specific instrument. Further extensive validation is needed for all of the AA-specific instruments. The European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes recommends the use of the dermatology-specific DLQI questionnaire, hair disease-specific Scalpdex and the alopecia areata-specific instruments the Alopecia Areata Symptom Impact Scale or Alopecia Areata Quality of Life Index, despite the limited experience of their use. We hope that new treatment methods will be able to improve both clinical signs and health-related quality of life in patients with AA. In order to assess the outcomes of trials on these new treatment methods, it would be helpful when further development and validation of AA-specific instruments is being encouraged and also conducted. © 2021 European Academy of Dermatology and Venereology

Exploring the EQ-5D dimension of pain/discomfort in dermatology outpatients from a multicentre study in 13 European countries

Pain and discomfort are important symptoms in dermatology. The aim of this cross-sectional, multicentre study was to describe the prevalence of pain/discomfort and its associations in patients with several dermatological conditions across 13 European countries. The outcome was the prevalence of pain/discomfort according to a question of the EQ-5D questionnaire. Data collected from November 2011 to February 2013 were complete for 3, 509 consecutive outpatients. Moderate or extreme pain/discomfort was reported by 55.5% of patients and 31.5% of controls with no skin conditions. The highest proportions were reported by patients with hidradenitis suppurativa (92.9%), leg ulcer (81.4%), prurigo (80%) and lichen planus (75.6%). Pain/discomfort was associated with older age, low educational level, clinical severity, flare on scalp or hands, itch, depression, anxiety, low quality of life, and thoughts of suicide. It is important to enquire specifically about pain/discomfort during clinical consultations and to address it when planning a patient’s care

Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials

Background: Weekly adalimumab (Humira®) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. Objectives: Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS. Methods: Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE. Results: For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection. Conclusions: Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic?. Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira®) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add?. This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy

The self-assessed psychological comorbidities of prurigo in European patients: a multicentre study in 13 countries

Background Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. Objective The aim of this study was to assess the psychological burden of prurigo in patients of European countries. Methods In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio‐demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. Results There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10 of 27 (37%) suffered from anxiety and 8 of 27 (29%) from depression. Suicidal ideation was reported in 5 of 27 (19%) patients, and for four of these five patients, suicidal ideation was related to their skin disease. These frequencies were higher in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers). The impact on quality of life was severe, with a mean Dermatologic Life Quality Index (DLQI) of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. Conclusion The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments