Real-World Clinical Experience of Dupilumab in the Treatment of Chronic Palmo-Plantar Eczema in Patients with Moderate-Severe Atopic Dermatitis: 52-Week Follow-Up.

Background: Hand-foot eczema (HFE) are special locations of dermatitis, which are often associated with atopic dermatitis (AD) and have a significant negative impact on the quality of life, demanding a clinically relevant improvement. Objectives: To evaluate the effectiveness and safety of dupilumab in the treatment of eczema localized in hands and/or feet in patients with moderate-to-severe AD. Methods: Retrospective multicenter study of adult patients with HFE treated with dupilumab for their AD. Patients with other concomitantly systemic immunosuppressive treatments did not undergo a washout period. The severity of palmar and/or plantar involvement was assessed using the Physician Global Assessment (PGA) scale on a scale of 0 ( = clear) to 5 ( = very severe). Eczema Area and Severity Index (EASI) and NRS-pruritus scales were also evaluated. One hundred percent of patients reached week 16, while 67/84 reached week 52 of follow-up. Results: A total of 84 patients were included 86.69% of patients showed a reduction in PGA-Hand, and 80.34% in PGA-Foot at week 52, EASI improvement was reached by 83.55% of patients at week 16 and 87.35% at week 52. Reduction of pruritus (≥4 points in NRS-pruritus scale) was 73.01% at week 16 and 80.67% at week 52. No differences in response to dupilumab were observed in the different subtypes of palmo-plantar dermatitis. Conclusions: The results obtained in our study suggest that dupilumab may be an effective and safe therapeutic option for the treatment of dermatitis localized in hands and/or feet.

Upadacitinib for moderate to severe atopic dermatitis.

Atopic dermatitis is an inflammatory skin disease, the prevalence of which has increased in the last decade. It affects all age groups, with adult involvement being a major focus of interest in recent years. The unmet needs of the disease, such as pruritus, sleep quality impairment and eczematous skin lesions, have undergone a therapeutic revolution following the commercialization of drugs such as JAK inhibitors. Upadacitinib, a selective JAK1 inhibitor, has been positioned by both clinical trial results and those observed in clinical practice as the fastest and most effective drug in reducing both pruritus and Eczema Area and Severity Index and validated Investigator Global Assessment. Although the safety profile may be initially alarming, it is advisable to update the actual data in this regard for proper management. New perspectives for upadacitinib in nonatopic comorbidities such as psoriasis and alopecia areata are beginning to be described, and interest in learning more about its peculiarities is growing.

Atopic dermatitis is the most common inflammatory skin disease. The inflammation happens when the body's defense system attacks the body's tissue. People with atopic dermatitis often have itching and red and scaly parts of the skin. The inflammation tends to be long-lasting and comes back repeatedly. The main goal of treatment is controlling the inflammation, which occurs because of a certain group of proteins called cytokines. Receptors called JAKs are involved in the inflammation that happens through cytokines, so they play an important role in this disease. A medicine called upadacitinib has been approved for the treatment of moderate to severe atopic dermatitis. In this article, you will find the most relevant published information on upadacitinib, including how effective and safe the medicine is based on both clinical studies and real-life cases.

Validation of a Questionnaire to Assess the Perception of Women with Atopic Dermatitis in Family Planning.

INTRODUCTION: Atopic dermatitis (AD) is a highly frequent chronic inflammatory skin disease. It is important to know how women with AD approach family planning together with their disease. The aim of the present research is to develop and validate a questionnaire for women diagnosed with AD in order to measure their level of desire and gestational information. MATERIALS AND METHODS: A multicenter cross-sectional study was conducted. Women between 18 and 45 years old with mild, moderate, and severe forms of the disease were included and disease-free controls. An exploratory factorial analysis of the primary components and varimax rotation was used to measure the validity of the construct. Cronbach's α was used to measure the reliability of the individual scales and the global questionnaire. RESULTS: In total, 150 valid questionnaires were included. The final questionnaire consisted of 23 items that converged on six factors. The six scales had adequate reliability: "Pregnancy" (Cronbach's alpha = 0.95), "Conception" (Cronbach's alpha = 0.93), "Concern-information" (Cronbach's alpha = 0.82), "Breastfeeding" (Cronbach's alpha = 0.81), "Sexual life" (Cronbach's alpha = 0.79), and "Family planning" (Cronbach's alpha = 0.67). The total Cronbach's alpha of the questionnaire was 0.94. DISCUSSION: This questionnaire is the first specific measurement instrument developed for women with AD of childbearing age that has demonstrated adequate levels of reliability and construct validity. We consider it useful and valuable to study aspects such as family planning in this patient profile, and that can influence their decision to have offspring.

Long-Term Effectiveness and Safety of Biologic and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review.

INTRODUCTION: Atopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD. METHODS: A literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48-60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109. RESULTS: A total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3-92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3-89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7-75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs. DISCUSSION: Today, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis.

Atopic Dermatitis: Background, Objectives and Future Perspectives (Superresponders).

In this Special Issue entitled Atopic Dermatitis: New Perspectives, we have tried to collect research of special interest related mainly to the incorporation of pathophysiological aspects and therapeutic novelties in this regard [...].

Inter- and intra-observer variability in the selection of therapy for infantile hemangiomas among pediatric dermatologists in Spain.

BACKGROUND: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. OBJECTIVE: The objective was to analyze the inter- and intra-observer agreement among pediatric dermatologists in the choice of treatment for IH. METHODS: We performed a cross-sectional inter-rater and intra-rater agreement study within the Spanish infantile hemangioma registry. Twenty-seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra-rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). RESULTS: Twenty-four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter-rater agreement on the treatment decision was fair (AC1  = 0.39, 95% confidence interval [CI]: 0.30-0.47). When stratified by risk category, good agreement was reached for high-risk hemangiomas (AC1  = 0.77, 95% CI: 0.51-1.00), whereas for intermediate- and low-risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16-0.46 and AC1  = 0.38, 95% CI: 0.27-0.48, respectively). Propranolol was the main option for high-risk hemangiomas (86.4%), timolol for intermediate-risk (36.8%), and observation for low-risk ones (55.9%). The intra-rater agreement was good. The inter-rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate- and low-risk hemangiomas.

Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Some Network Meta-analysis (NMA) has been published regarding atopic dermatitis (AD). These studies have considered drugs under investigation both in monotheraphy or in combination with topical corticosteroids, as well as systemic immunosuppressant therapies. The objective of this study is to evaluate the efficacy and safety of biological agents and small molecules in AD. METHODS: A systematic review and NMA of biologics agents and small molecules in AD was performed. A literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical trials and systematic reviews between January 2000 and 19 December 2020. Only randomized clinical trials (RCTs) were included. It was limited to English language and adult human subjects. Two networks were evaluated: monotherapy and combination with TCS. The two primary outcomes were Eczema Area and Severity Index (EASI) 75 and EASI 90 change from baseline to week 12-16, depending on source study cut-off. The Cochrane's Risk of Bias tool 2011 update was used to analyze the risk of bias, focused on the primary objectives. RESULTS: 30 RCTs (included in 26 publications) were included in the systematic review. Finally, 23 RCTs were included in the quantitative analysis (14 RCTs including 3582 patients in monotherapy; and 9 RCTs including 3686 patients with TCS). In monotherapy, a higher percentage of patients achieving EASI-75 was obtained with Upadacitinib 30 mg [OR: 18.90 (13.94; 25.62)] followed by Abrocitinib 200 mg [OR = 11.26 (7.02; 18.05)] and Upadacitinib 15 mg [OR: 10.89 (8.13; 14.59)]. These results were also observed in studies where the use of topical corticosteroid (TCS) was allowed (OR Upadacitinib 30 mg = 9.43; OR Abrocitinib 200 mg = 6.12; OR Upadacitinib 15 mg = 5.20). Regarding IGA, the percentage of patients achieving IGA0/1 was higher with both doses of Upadacitinib 30 mg [OR: 19.13 (13.14; 27.85)] and 15 mg [OR = 10.95 (7.52; 15.94). In studies where the use of TCS were allowed, however, the dose of Abrocitinib 200 mg [OR = 6.10 (3.94; 9.44)] showed higher efficacy than Upadacitinib 15 mg [OR = 5.47 (3.57; 8.41)]. Regarding safety, the drugs with the highest probability of presenting adverse effects were the Janus kinases (JAK) inhibitors, Upadacitinib and Abrocitinib in monotherapy and Baricitinib in combination with TCS. DISCUSSION: Some risks of bias have been found, which must be taken into account when interpreting the results. The funnel plot shows a possible publication bias that may underestimate the efficacy of drugs. Upadacitinib and Abrocitinib are the drugs with the highest efficacy, both in monotherapy and in association with TCS. However, they were also those associated with the highest risk of adverse effects, showing monoclonal antibodies better safety profile. LIMITATIONS: We have included molecules still in the development phase as well studies completed and presented at conferences and with data available in Trialsgov® but not published yet. Several molecules' development had included a small number of patients from 12 to 17 years of age, without being able to differentiate the results from the adult population. Other: Founding: None. PROSPERO database registration number CRD42021225793.

Direct-to-consumer, store-and-forward teledermatology with dermoscopy using the pharmacist as patient point-of-contact.

OBJECTIVE(S): To evaluate the frequency of nonmelanoma skin cancer (NMSC), NMSC precursors, and melanoma on a store-and-forward dermatology model featuring the pharmacist as the patient's point-of-contact. The secondary objective was to define lesion changes and symptoms perceived by patients (clinical prediction rules by nonexpert observers) that can be predictive of malignity. METHODS: A cross-sectional study of teledermatology consultation was performed. All patients who underwent a teledermatology consultation between September 2018 and March 2020 were included. A patient could have more than 1 lesion per consultation. The object of the study was a defined dermatologic lesion. The differences between the variables were analyzed using a univariate model based on the chi-square test for independent qualitative variables and Fisher exact test in cases when the expected values in any of the cells of a contingency table were less than 5. Statistical significance was set at P < 0.05 (2-tailed). RESULTS: A total of 225 lesions in 218 patients were considered for this study; 53.8% (n = 121) of the lesions were classified as benign, 16.4% (n = 37) as dubious, 23.1% (n = 52) as NMSC precursors, 5.8% (n = 13) as NMSC, and 0.9% (n = 2) as melanomas. Of the reported clinical lesion changes, spontaneous pain, pruritus, surface texture changes, color changes, or form changes had no statistically significant relationship with the diagnostic group, whereas the presence of spontaneous bleeding (P = 0.015) and size changes (P = 0.026) were more frequently observed in the "dubious lesion" and "of oncological relevance lesion" groups. CONCLUSION: This "direct-to-consumer," store-and-forward teledermatology with dermoscopy model featuring the pharmacist as the patient's point-of-contact is useful for the diagnosis of melanoma, NMSC, and NMSC precursors when backed by a robust dermatology service.

Development and validation of a questionnaire to measure empowerment in adult patients with atopic dermatitis. The DATEMP questionnaire.

BACKGROUND AND OBJECTIVES: In recent years, the hypothesis that increasing the empowerment of patients can help to improve health outcomes and rationalize the use of health services has become relevant, especially for chronic diseases. Developing validated measurement tools is necessary to achieve this goal. In the field of dermatology, there are few studies related to empowerment of the patient. The aim of the present research is to develop and validate a self-administered questionnaire for adult patients diagnosed with atopic dermatitis (AD) in order to measure their level of empowerment. METHODS: After a literature review and the establishment of consulting groups of patients and dermatologists, a large battery of 35 items was generated, based on the dimensions included in previous empowerment descriptions. A multidisciplinary group selected the 20 most suitable items to include in the questionnaire. A cross-sectional study was carried out with the items included in the questionnaire as well as demographic and clinical characteristics. To reduce the number of items and measure the construct validity, an exploratory factorial analysis (EFA) of the primary components and varimax rotation were used. Cronbach's α was used to measure the reliability of the individual scales and the global questionnaire. RESULTS: 242 valid questionnaires were included. After completion of the EFA, the final Dermatitis Atópica EMPoderamiento (DATEMP) questionnaire was composed of 17 items that converged on four factors. The four scales had adequate reliability: "Knowledge" (Cronbach's alpha = 0.808), "Abilities" (Cronbach's alpha = 0.744), "Intention to change" (Cronbach's alpha = 0.798) and "Coping skills" (Cronbach's alpha = 0.772). The overall Cronbach's α of the questionnaire was 0.764. CONCLUSIONS: The DATEMP questionnaire is the first specific empowerment measurement instrument developed for patients with AD that has demonstrated adequate levels of reliability and construct validity. It is a self-administered questionnaire that is simple and quick to answer.

Fifty-two week follow-up safety and effectiveness results of dupilumab treatment of moderate-to-severe atopic dermatitis from a retrospective, multicentric series.

Atopic dermatitis (AD) is a chronic, systemic disease that has a multifactorial etiology, where immune system disorders and epidermal barrier dysfunction are added to the influence of genetic and environmental factors. Dupilumab has been approved by United States and the European Union regulatory agencies in 2017 for the treatment of moderate-to-severe AD in adult patients who are candidates for systemic treatment. In this short report, we present a retrospective, multicentric study, in which five hospitals in Andalusia, Spain, have taken part. Our objective is to evaluate the safety and effectiveness of dupilumab in patients with moderate-to-severe AD treated with dupilumab with at least 52 weeks of follow-up.

"Sky Full of Stars" Pattern: Dermoscopic Findings in a Desmoplastic Giant Congenital Melanocytic Nevus.

Desmoplastic giant congenital melanocytic nevus (DGCN) is an uncommon variant of congenital nevus, presenting as a progressive induration and hypopigmentation of the lesion that occasionally causes hair loss and even total or partial disappearance of the nevus. A 6-month-old girl with a giant congenital melanocytic nevus that involved the entire posterior side of the right thigh was seen in our department. Nine months later, the peripheral area of the nevus presented as a marked induration with hypopigmentation. Dermoscopy demonstrated a reticular pattern exclusively located in the perifollicular areas, with a radial distribution from the follicular ostium that mimicked a "sky full of stars." We report a case of DGCN, including a dermoscopic description of the findings noted in the indurated and hypopigmented areas that appear as a "sky full of stars" image.

Oral Nadolol for Children with Infantile Hemangiomas and Sleep Disturbances with Oral Propranolol.

BACKGROUND/OBJECTIVE: Oral propranolol has been shown to be safe and effective in infants with infantile hemangioma (IH). Side effects such as sleep disturbances have been associated with propranolol. The aim of this study was to evaluate the efficacy and safety of oral nadolol in a small series of patients whose propranolol therapy was discontinued due to sleep disturbances. METHODS: A retrospective study of patients with IHs who were treated with oral nadolol due to propranolol-related sleep disturbances at a pediatric tertiary care center between July 2008 and March 2013. Clinical response to oral nadolol and disappearance of propranolol-related side effects were analyzed. RESULTS: A total of 97 patients presenting IH received oral propranolol. Nine patients (9.3%) developed sleep disturbances. Oral propranolol was discontinued in seven patients and switched to oral nadolol, with resolution of these side effects in 5 (71%) of the cases. One patient developed sleep disturbances again after four months of oral nadolol. LIMITATIONS: The sample size was too small to draw generalizable conclusions and to draw any statistical inference as to the incidence of sleep disturbances with nadolol therapy. CONCLUSIONS: The use of oral nadolol in the treatment of IH in our series of 7 patients, resolved the propranolol-related sleep disturbances in 5 (71%), while in one patient the symptoms recurred after 4 months of oral nadolol at a dose of 2 mg/kg/day. In most cases, switching beta-blockers did not compromise efficacy, and is recommended when sleep disturbance necessitates discontinuation of beta-blocker therapy of IH.

The role of accessibility policies and other determinants of health care provision in the initial prognosis of malignant melanoma: a cross-sectional study.

BACKGROUND: The prognostic benefit of health care service provision and delivery policies for patients with malignant melanoma (MM) is not yet clear. OBJECTIVE: To analyze the role of health care provision determinants in the initial prognosis of MM. METHODS: A multicenter cross-sectional study was conducted at 14 public hospitals and recruited 3550 patients with MM between 2000 and 2009. The study variables were analyzed using univariate and multivariate models to identify their role in the variations observed. RESULTS: In a 10-year period, the number of patients with MM increased by 78.54%, with primary in situ MM (Tis) or MMs with a Breslow thickness <1 mm (T1) representing 51.72% of the total number of MMs in 2000, increasing to 62.23% by the end of the study period (P = .005). Among the variables that explained the variation in MM frequency the year of diagnosis after 2004 (univariate odds ratio [OR], 1.43 [P < .001]; multivariate OR, 1.36 [P = .005]) and diagnosis in centers with specific fast-track referral systems (univariate OR, 1.24 [P = .01]; multivariate OR, 1.59 [P = .025]) were shown to explain the increasing frequency of Tis-T1 MM. LIMITATIONS: The primary potential limitation of this study is its retrospective nature. CONCLUSION: Health care provision policies and interventions aimed at improving accessibility to specialized care appear to explain the increasing frequency of Tis-T1 MM.