Effectiveness of dupilumab for the treatment of nummular eczema phenotype of atopic dermatitis in adults

Nummular eczema (NE) is currently considered as one of the clinical phenotypes of atopic dermatitis (AD) of the adult. In this multicentre study, 30 adult patients (age ≥ 18 years) affected with nummular‐like AD were treated with dupilumab, a monoclonal antibody against the receptor for interleukin(IL)‐4 and IL‐13. The evaluation of the results after 16 weeks of treatment showed a significant improvement of the disease, as demonstrated by reduction in Eczema Area Severity Score (EASI), visual analogue score (VAS) of pruritus, and Dermatology Life Quality Index (DLQI) scores. Conjunctivitis in one patient was the only side effect. In conclusion, dupilumab seems to be an effective and safe treatment in NE phenotype of AD of the adult.     

Effect of dupilumab on hand eczema in patients with atopic dermatitis: An observational study

Systemic treatment options for chronic hand eczema are limited. Dupilumab is used in atopic dermatitis (AD) but is not licensed for (isolated) hand eczema. In this observational prospective study we aimed to determine the response of hand eczema to dupilumab in patients with AD. Adult patients with hand eczema and AD received dupilumab s.c. at a 600 mg loading dose, followed by 300 mg every 2 weeks. Primary outcome was a minimum improvement of 75% on the Hand Eczema Severity Index after 16 weeks (HECSI‐75). Secondary outcomes were severity, measured using the Photographic guide; quality of life improvement as patient‐reported outcome, measured using the Dermatology Life Quality Index (DLQI); and AD severity, measured using the Eczema Area and Severity Index (EASI). Forty‐seven patients were included (32 males; mean age, 45 years). HECSI‐75 was achieved by 28 (60%). Mean HECSI score reduction was 49.2 points (range, 0–164; 95% within‐subject confidence interval, 46.4–52.0), which was already significantly decreased after 4 weeks (P < 0.001). DLQI score mean improvement was 8.8 points (standard deviation [SD], 6.0) or 70.0% decrease (SD, 26.4) (P < 0.001). Eighteen patients (38%) were classified as responders on the Photographic guide. There was no difference in response between chronic fissured and recurrent vesicular clinical subtypes. Similar percentages of patients achieving EASI‐75 and HECSI‐75 were seen after 16 weeks. In conclusion, this study shows a favorable response of hand eczema to dupilumab in patients with AD. This raises the question whether a response will also be seen in isolated hand eczema.     

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.     

Childhood atopic dermatitis—An Indian perspective

Developing countries such as India can offer unique perspectives on and contributions to knowledge of and the literature on atopic dermatitis, including information on epidemiology, the role of environmental factors, clinical features, and treatment strategies in resource‐poor settings using indigenous methodologies. This report will help in understanding atopic dermatitis in the Indian diaspora as well.     

Comparison of psoriasis and atopic dermatitis guidelines—an argument for aggressive atopic dermatitis management

The development of effective systemic treatments has revolutionized the treatment of inflammatory skin diseases. The availability of safe new treatments and the understanding of psoriasis as a systemic disease with comorbidities and effects on quality of life have driven the current aggressive treatment paradigm of psoriasis. Historically the morbidity of atopic dermatitis (AD) has been dismissed, given the perception of AD as “just” a rash. Differences in the guidelines for psoriasis and AD management may suggest variations in the current conceptualization of disease severity and effects on quality of life. Published guidelines from the American Academy of Dermatology for the management of psoriasis and AD were reviewed. We recorded the similarities and differences in disease assessment and therapy. The threshold to use biologic agents for moderate to severe psoriasis highlights the aggressive nature of modern psoriasis treatment. AD guidelines include an assessment of quality of life but do not designate a disease severity threshold for systemic treatment. AD and psoriasis have a tremendous effect on quality of life. The AD guidelines have a less aggressive approach to disease management than the psoriasis guidelines. We should think critically about rapid advancement to systemic agents in AD management, especially now that more and better agents are being developed.     

The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group

OBJECTIVE: To test the reliability of the eczema area and severity index (EASI) scoring system by assessing inter- and intra-observer consistency. DESIGN: Training of evaluators, application, and assessment over 2 consecutive days. SETTING: An academic center. PATIENTS: Twenty adults and children with atopic dermatitis (AD); cohort 1 (10 patients > or = 8 years) and cohort 2 (10 patients < 8 years). INTERVENTIONS: None. MAIN OUTCOME MEASURE: The EASI was used by 15 dermatologist evaluators to assess atopic dermatitis in cohort 1 and cohort 2 on 2 consecutive days. Inter- and intraobserver reliability were analyzed. RESULTS: Overall intra-evaluator reliability of the EASI was in the fair-to-good range. Inter-evaluator reliability analyses indicated that the evaluators assessed the patients consistently across both study days. CONCLUSIONS: This study demonstrated that the EASI can be learned quickly and utilized reliably in the assessment of severity and extent of AD. There was consistency among the evaluators between consecutive days of evaluation. These results support the use of the EASI in clinical trials of therapeutic agents for AD.     

Circadian rhythm in atopic dermatitis—Pathophysiology and implications for chronotherapy

Circadian rhythm is a biological clock that controls a wide range of physiological functions throughout the body, including various skin functions. A 24‐h diurnal cycle, governed by an endogenous clock in the brain, largely controls cutaneous diurnal rhythm, which external factors, including temperature, humidity, diet, and stress, also modulate locally. Circadian rhythm influences cutaneous blood flow and properties of skin barrier function, such as transepidermal water loss and capacitance, and has important implications in atopic dermatitis (AD). This review explores how aberrations in circadian rhythm may play a role in the pathogenesis of AD and proposes implementation of chronotherapy to improve treatment outcomes in patients with AD.     

ETFAD/EADV eczema task force 2009 position paper on diagnosis and treatment of atopic dermatitis

Background The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. Methods EADV eczema task force developed its guideline for atopic dermatitis diagnosis and treatment based on literature review and repeated consenting group discussions. Results and Discussion Basic therapy relies on hydrating topical treatment and avoidance of specific and unspecific provocation factors. Anti‐inflammatory treatment based on topical glucocorticosteroids and topical calcineurin antagonists is used for exacerbation management and more recently for proactive therapy in selected cases. Topical corticosteroids remain the mainstay of therapy, but the topical calcineurin inhibitors, tacrolimus and pimecrolimus are preferred in certain locations. Systemic anti‐inflammatory treatment is an option for severe refractory cases. Microbial colonization and superinfection may induce disease exacerbation and can justify additional antimicrobial/antiseptic treatment. Systemic antihistamines (H1) can relieve pruritus, but do not have sufficient effect on eczema. Adjuvant therapy includes UV irradiation preferably of UVA1 wavelength or UVB 311 nm. Dietary recommendations should be specific and given only in diagnosed individual food allergy. Allergen‐specific immunotherapy to aeroallergens may be useful in selected cases. Stress‐induced exacerbations may make psychosomatic counselling recommendable. ‘Eczema school’ educational programmes have been proven to be helpful.     

New emergent therapies for atopic dermatitis: A review of safety profile with respect to female fertility,pregnancy, and breastfeeding

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Systemic treatment is usually mandatory in moderate‐to‐severe AD of the adult; these patients need to be informed about safe and effective management of AD also regarding the reproduction. Treating a pregnant woman with AD with systemic drugs may affect the unborn child. While effects of traditional systemic treatments for AD on female fertility, pregnancy, and breastfeeding are largely known, data about new emergent therapies for AD are still poor. Treating pregnant or lactating women with AD can be a challenge since no large clinical studies on its possible effects and side‐effects on conception, pregnancy, the unborn child and lactation are currently available for new AD treatments.     

The millennium criteria for the diagnosis of atopic dermatitis

Abstract: Atopic dermatitis forms an active area of basic and clinical research, where important new knowledge about genetics and immunopathogenesis has surfaced over the past years, and where simultaneous development of new and innovative therapies is under way. However, the inclusion of any patient in an atopic dermatitis study, whether it is on its genetics, pathogenesis or therapy, requires a diagnosis which is irrefutable. Since there is no simple and also no complicated laboratory procedure to reach a diagnosis of atopic dermatitis, different sets of clinical criteria have been developed for the purpose of making the diagnosis uniformly in different studies as well as in different study centers. The most commonly used are Hanifin and Rajka's set of diagnostic features, which have major and minor clinical criteria to be fulfilled in order to establish a diagnosis of atopic dermatitis. Recent developments in the immunology of atopy have clearly established the major abnormality in this syndrome, the preferential production of allergen-specific IgE. In this contribution, it is suggested that the presence of such antibodies in a given patient should be a mandatory criterium for the diagnosis of atopic dermatitis. Such a diagnostic test however establishes a diagnosis of atopic syndrome, not atopic dermatitis. Thus, for atopic dermatitis we have to rely, for the time being, on additional clinical criteria. The clinical features described in the literature are critically evaluated, and it is suggested that in addition to the mandatory presence of allergen-specific IgE, 2 of 3 principal criteria (pruritus, typical morphology and distribution, chronic or chronically relapsing) should be present for such a diagnosis. Finally, the minor features originally described by Hanifin and Rajka and later evaluated by others are revised and divided over 4 subcategories; a) related to subclinical eczema; b) related to dry skin; c) extra skin folds; and d) ophthalmological pathology. They are suggested to be used as additional criteria only, needed when clinical suspicion is high but the new mandatory and principal diagnositic criteria described here are inconclusive. For study purposes, we suggest that the mandatory and principal criteria are sufficient. They are now evaluated and validated in ongoing atopic dermatitis treatment studies.     

Association between non‐atopic hand eczema and interleukin‐13 gene polymorphism in Taiwanese nursing population

Chronic hand eczema is an important occupational skin disease with atopic dermatitis (AD) and wet work being the most important risk factors. This study was launched to analyse the potential association between AD‐related inflammation genes and development of non‐atopic hand eczema among nurses in University Hospital. Atopic eczema, non‐atopic hand dermatitis and control groups were identified. The association between occurrence of non‐atopic hand eczema and interleukin (IL)‐13, IL‐4 and IL‐5 gene variants was analysed. IL13 rs20541 A allele [assuming recessive model; odds ratio (OR) = 3.38, 95% CI: (1.63–7.00)] showed association with development of non‐atopic hand eczema. Additive score analyses showed combination of this gene variant with previously identified risk factors including certain SPINK5 polymorphism and more than 10 years of work experience conferred highest risk for development of non‐atopic hand eczema. As non‐atopic hand eczema made up significant portion of occupational skin diseases, further studies should be focused on this commonly encountered skin condition.     

Treatment of moderate and severe adult chronic atopic dermatitis with narrow‐band UVB and the combination of narrow‐band UVB/UVA phototherapy

The phototherapy is a safe and effective technique for the treatment of adult patients with atopic dermatitis (AD). The treatment of chronic forms of the disease is most often done with narrow‐band UVB (NB‐UVB). There also exist effective phototherapy options against the AD. The aim of this study was to asses if the combination of NB‐UVB with UVA was more effective than the treatment with only NB‐UVB against adult chronic AD. We carried out a prospective and observational study. Adult patients with chronic AD with more than 50% of the total body surface area affected (TBSA) were included. The affected TBSA was calculated using the so‐called “rule of nines.” Patients with a clearance rate >75% of the initial affected TBSA or complete clearance rate were considered as complete response (CR). An analogue scale from 0 to 10 was used to measure the improvement grade of the pruritus. The treatments were repeated three times a week. The initial doses of NB‐UVB and UVA were determined by patient's phototype. The treatments were performed using a phototherapy booth (UV7002, Walmann, Villingen‐Schwenningen, Germany^®) with TL01 and UVA fluorescent lamps. Statistical analysis was performed with SPSS^® (IBM, New York, NY) for Windows 21.0. A total of 26 patients with adult chronic AD were included in the study, 16 patients were treated with UVB‐BE and 10 patients with the combined treatment option NB‐UVB/UVA. The mean value of cumulative doses and the mean number of performed treatments were similar between both groups of patients (p > 0.05). The mean value of duration of response was significantly higher in the patients treated only with NB‐UVB, 101 versus 6.8 months (p ≥ 0.05). No differences were observed for the patients that showed complete response (p = 0.42) and in the analogue scale of pruritus (p > 0.005). In our study, the patients treated with the combination of NB‐UVB and UVA were similar to the patient that were only treated with NB‐UVB e. Further prospective and controlled studies have to be performed in order to determine the dosing regimens of phototherapy in adult patients with AD.     

An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema

BACKGROUND: Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. OBJECTIVES: We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. METHODS: All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2.5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. RESULTS: On average, disease activity improved by 52% from baseline (95% confidence interval 45-60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as 'marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. CONCLUSIONS: We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted.     

Consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II

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.     

Consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I

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.     

Omalizumab for treatment of refractory severe atopic dermatitis. A pediatric perspective

Omalizumab is a monoclonal antibody, targeting Fc receptor of IgE, approved for the treatment of allergic asthma and chronic spontaneous urticaria. Its utility in atopic dermatitis appears controversial from data in literature since the molecule is well tolerated but it seems less effective than other medications used in adult patients (eg, Dupilumab). At present, the use of Dupilumab is not approved in pediatric patients therefore there are no second level treatments available in this age group. Here we report two clinical cases of patients (15 and 16 years old) suffering from both atopic dermatitis and asthma, treated with Omalizumab. Our experience suggests that atopic eczema of young patients with allergic comorbidities can benefit from asthma treatment with Omalizumab observing improvement on both conditions.