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Abstract Background Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. Methods This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. Discussion This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. Trial registration ClinicalTrials.gov Identifier: NCT02537509, first received: 1 September 2015.

Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice. [ABSTRACT FROM AUTHOR]

Researchers active in the field of inflammatory skin diseases from the spectrum of dermatitis and eczema are well aware of a considerable overlap in the clinical pictures and proposed sets of diagnostic criteria for these diseases, which can hardly be overcome through the clinical or epidemiological research. In effect, patients are included in studies based on vague and overlapping criteria, while heterogeneous study populations may, in turn, lead to non-representative outcomes and continued confusion. In this narrative review, a systematics of diseases from the spectrum of dermatitis and eczema is proposed based on the origins of causative factors and the pathomechanisms involved. Difficulties in differentiating between these diseases are discussed, and the extent to which advances in the "omics" sciences might help to overcome them is considered. Of all the "omics" research in this field, more than 90% of the published papers were devoted to atopic dermatitis, with a striking underrepresentation of other diseases from the spectrum of dermatitis and eczema, conditions which collectively exceed the rates of atopic dermatitis by far. A greater "omics" research effort is urgently needed to tackle other dermatitides, like allergic, irritant and protein contact dermatitis, as well as radiation, seborrheic, stasis or autoimmune dermatitis. Atopic dermatitis findings should be validated not only against healthy donors but also other dermatitides. A clinic-oriented approach is proposed for future "omics" studies in the field of dermatitis and eczema. [ABSTRACT FROM AUTHOR]

The efficacy and safety of baricitinib for treatment of atopic dermatitis have been demonstrated in clinical trials; however, very few real-life studies have been published to date. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) registry was initiated to prospectively determine the long-term impairment caused by chronic inflammatory dermatoses on patients’ lives. The study included 88 patients starting baricitinib for treatment of atopic dermatitis. Clinical evaluation and patient-reported outcomes were recorded at baseline and after 6 and 12 months. After 6 months and 1 year of follow-up, 65 and 47 patients, respectively, were still being treated with baricitinib. Treatment failure was the main reason for discontinuation. Only 1 patient stopped baricitinib because of a side-effect. After 1 year of follow-up, the mean Eczema Area and Severity Index score decreased significantly from 20.7 to 6.4; the percentage of patients with severe atopic dermatitis decreased from 42.9% to 6.5% and a significant improvement in most patientreported outcomes was noted. There was no difference in terms of efficacy whether or not patients were previously treated with dupilumab. The results remained stable after 6 and 12 months of treatment, which suggests a sustained efficacy of the treatment in patients who initially responded well. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic, relapsing and inflammatory skin disease. The impact of atopic dermatitis on the partners living with patients has been poorly investigated. The objective of this study was to evaluate the impact of atopic dermatitis in the daily lives of adult patients and to assess the burden of the disease on their partners. A population-based study was conducted on a representative sample of the general population of French adults aged 18 years of age using stratified, proportional sampling with a replacement design. Data were collected on 1,266 atopic dermatitis patient-partner dyads (mean age of patients 41.6 years, 723 (57.1%) women). The mean age of partners was 41.8 years. Patient burden, measured by the Atopic Dermatitis Burden Scale for Adults (ABS-A) score, was closely related to the objective atopic dermatitis severity: the mean score in the mild group (29.5) was significantly lower than in the moderate (43.9) and severe groups (48.6) (p<0.0001). Partner burden, measured by the EczemaPartner score, was highly related to atopic dermatitis severity (p<0.0001). Daytime sleepiness, measured by the Epworth Sleepiness Scale, showed a mean score of 9.24 in patients and 9.01 in their partners, indicating impaired sleep. Atopic dermatitis was found to decrease sexual desire in 39% and 26% of partners and patients respectively. [ABSTRACT FROM AUTHOR]

Epicutaneous exposure to protein allergens, such as papain, house dust mite (HDM), and ovalbumin (OVA), represents an important mode of sensitization for skin diseases including protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. These diseases are inducible by re-exposure to an allergen at both original skin sensitization and distant skin sites. In this study, we examined the serum IgE/IgG1 response, differentiation of T-helper (TH) cells, and epicutaneous TH recall response in mice pre-sensitized with protein allergens through the back skin and subsequently challenged on the ear skin. Repeated epicutaneous sensitization with allergenic proteins including papain, HDM, OVA, and protease inhibitor-treated papain, but not bovine serum albumin, induced serum allergen-specific antibody production, passive cutaneous anaphylaxis responses, and TH2 differentiation in the skin draining lymph node (DLN) cells. Sensitization with papain or HDM, which have protease activity, resulted in the differentiation of TH17 as well as TH2. In papain- or HDM-sensitized mice, a subsequent single challenge on the ear skin induced the expression of TH2 and TH17/TH22 cytokines. These results suggest that allergenic proteins induce the differentiation of TH2 in skin DLN cells and an antibody response. These findings may be useful for identifying proteins of high and low allergenic potential. Moreover, allergenic proteins containing protease activity may also differentiate TH17 and induce TH2 and TH17/TH22 recall responses at epicutaneous challenge sites. This suggests that allergen protease activity accelerates the onset of skin diseases caused by protein allergens. [ABSTRACT FROM AUTHOR]

The evaluation of global atopic dermatitis control is key to minimizing disease burden. The Atopic Dermatitis Control Tool (ADCT) has been developed for this purpose. Participants (diagnosed by a physician) were recruited to this observational cross-sectional study using real-life methodology and completed a questionnaire on sociodemographic and personal information. The ADCT algorithm, described by Pariser, was used to categorize patients as having controlled or uncontrolled atopic dermatitis. Data were collected for 1,606 patients. Median age of the patients was 40 years, and 1,023 (63.7%) patients were women. A total of 1,146 (71.4%) patients had uncontrolled atopic dermatitis according to the ADCT score. Patients with uncontrolled disease were at significantly higher risk of a high stress level and were more likely to be absent from work than those with controlled disease. In conclusion, a key factor for predicting disease burden in atopic dermatitis is patient self-assessed disease control in terms of multiple dimensions: stress, sleep, quality of life, work absenteeism and loss of productivity. [ABSTRACT FROM AUTHOR]

It is important to understand patients' and dermatologists' perceptions of various aspects of atopic dermatitis, but there is a lack of studies on quality of life and stakeholder viewpoints in this therapy area. The aim of this study was to compare patients' and dermatologists' viewpoints regarding the impact of atopic dermatitis that is uncontrolled by topical corticosteroids. Data were collected from 348 adult patients who responded to self-administered questionnaires, and 150 telephone interviews with the dermatologists who selected them. Patients and dermatologists reported both convergent and divergent assessments of the impact of atopic dermatitis and its treatment. Notable areas of agreement were regarding the safety of emollients, the time required and difficulty of applying topical corticosteroids, especially to certain parts of the body. Divergent views involved the perceived efficacy of available treatments and the impact of atopic dermatitis on professional life. A greater understanding of these differences would help dermatologists to optimize patient care. [ABSTRACT FROM AUTHOR]

Lime (Citrus aurantiifolia) is a plant belonging to the family of Rutaceae and to the genus Citrus. The fruit is widely used in the United States, Mexico, Southeast Asia, Latin America, but is increasingly widespread all over the world. It is used as a fresh fruit, in the preparation of foods, sweets and drinks and its oils are used in the cosmetic and pharmaceutical industry. The main adverse reactions to lime seem to be represented by contact dermatitis, allergic and phototoxic type. In the context of allergic forms, several allergens have been identified in the citrus family, the main one being limonene, but no noteworthy cross-reactivity has been identified. However, a case of fruit protein contact dermatitis has been described, showing sensitization to other fruits, such as kiwi, avocado, pineapple and apple. There are several molecules responsible for phototoxic reactions and mainly belonging to the coumarin and furocoumarins families. Reactions related to ingesting the fruit or inhaling pollen from the tree appear to be rare, as there are no known cases reported in the literature. The increasing diffusion of lime in Europe must pay attention to possible adverse reactions due to contact with this fruit, which seem destined to increase in future years. Further importance must be placed on patch tests and on the possibility of using alternative extracts to classic fragrance mixes. [ABSTRACT FROM AUTHOR]

Pruritus in atopic dermatitis has been studied extensively; however, evaluation of skin pain has been very limited. The aim of this study was to evaluate the presence, frequency and characteristics of skin pain in patients with atopic dermatitis. A survey was conducted of a representative sample of 5,000 18-80-year-old individuals selected from the French population according to sex, age, geographical area and socioprofessional status. Data on socio-demographic status and the presence of any skin disease were collected. Pain in the past month and health-related quality of life were evaluated. Mean intensity of skin pain during the previous month was assessed with a horizontal visual analogue scale (0-10). Skin pain was reported by more than half of the patients with atopic dermatitis, at a pain intensity of almost 6/10. A neuropathic component was suggested by the Douleur Neuropathique - 4 questions (DN4) questionnaire (a tool for detection of neuropathic pain), as well as the presence of pain inside and outside of skin lesions. Severe alterations to health-related quality of life were assessed with the Dermatology Life Quality Index and Short Form 12 Health Survey (SF-12). Pain is reported frequently by patients with atopic dermatitis. Healthcare professionals should question patients about pain and provide effective treatments. Future clinical trials must take skin pain into account. [ABSTRACT FROM AUTHOR]

The prevalence of psychological disorders in patients with common skin diseases was assessed in a large representative sample of the French adult population. General health, as measured by the EQ5D score, was significantly lower if patients reported having rosacea, atopic dermatitis, urticaria, fungal infections, psoriasis or acne. The proportions of participants reporting being extremely anxious or depressed were higher in those who reported having rosacea, atopic dermatitis or contact dermatitis. Difficulties in sexual and conjugal life were frequently reported by people with psoriasis, atopic dermatitis, contact dermatitis, urticaria and, in particular, acne. Sleep disorders were present in 30-50% of those who reported having acne, rosacea, eczema, psoriasis or urticaria. Sleep disorders may be related not only to pruritus, but also to disfiguring skin diseases. Anxiety and depression complications were mainly reported by those with disfiguring diseases. Sexual and conjugal dysfunctions were associated with all dermatoses (with the exception of warts). [ABSTRACT FROM AUTHOR]

The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. There was substantial progress in 2019 in the identification of basic mechanisms of allergic and respiratory disease and the translation of these mechanisms into clinics. Better understanding of molecular and cellular mechanisms, efforts for the development of biomarkers for disease prediction, novel prevention and intervention studies, elucidation of mechanisms of multimorbidities, entrance of new drugs in the clinics as well as recently completed phase three clinical studies and publication of a large number of allergen immunotherapy studies and meta‐analyses have been the highlights of the last year. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore characteristics of pruritus in atopic dermatitis (AD) in relation to the severity of AD. A web-questionnaire was used, which included the Patient-Oriented SCORing Atopic Dermatitis index, the 5-D itch scale and the Brest questionnaire. A total of 170 participants were included (86.5% women, mean age 30.9 years). Severity of AD was mild for 8.2% of patients, moderate for 38.2% and severe for 53.5%. Mean 5-D itch scale was 13.2. The mean intensity of pruritus was 5.8, and mean sleep loss was 4.7 (from 0 to 10). The participants frequently described burning (61.8%) and stinging (58.8%); these symptoms suggest a neuropathic component. Pruritus was worse in severe AD compared with moderate AD, exhibiting a higher impact on sleep and more associated symptoms. The majority of participants reported sleep disturbance as a result of pruritus. The characteristics of pruritus varied depending on the severity of AD. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis commonly affects patients with chronic venous leg ulcers and can contribute to impaired wound healing. Many allergens have been identified, and despite the use of advanced dressings, the incidence of allergy has remained high. We discuss an unusual presentation of allergic contact dermatitis in a patient with a chronic wound. The patient's history was consistent with a recurrent venous leg ulcer, but on this occasion, the wound continued to deteriorate despite optimal treatment. This prompted further investigation, which included patch testing. Although the clinical features were not suggestive of allergy, the patch test was positive for several allergens, including Atrauman® dressings, which the patient was using at the time. This case highlights the importance of regular reassessment and accurate diagnosis for the management of chronic wounds. It also demonstrates that allergic contact dermatitis can contribute to delayed wound healing without causing the classical clinical features of inflammation of the surrounding skin, and even hypoallergenic, non‐adherent dressings can be sensitising. [ABSTRACT FROM AUTHOR]

Throughout life, it is necessary to adapt to the Earth's environment in order to survive. A typical example of this is that the daily Earth cycle is different from the circadian rhythm in human beings; however, the ability to adapt to the Earth cycle has contributed to the development of human evolution. In addition, humans can consume and digest Earth-derived foods and use luxury materials for nutrition and enrichment of their lives, as an adaptation to the Earth's environment. Recent studies have shown that daily lifestyles are closely related to human health; however, less attention has been paid to the fact that obesity due to excessive energy intake, smoking, and alcohol consumption contributes to the development of inflammatory skin diseases. Gluten or wheat protein, smoking and alcohol, sleep disturbance, and obesity drive the helper T (Th)1/Th2/Th17 immune response, whereas dietary fiber and omega-3 fatty acids negatively regulate inflammatory cytokine production. In this review, we have focused on daily lifestyles and the mechanisms involved in the pathogenesis of inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer globally. Immunosuppression raises cSCC incidence rates, while high immunogenicity of the cutaneous tissue enables topical immunotherapy. Intriguingly, expanded applications of programmed death-1 (PD-1) blockade therapies have revealed cSCC to be one of the most amenable targets. These clinical observations prompted us to redefine cSCC biology and review current knowledge about cSCC from multiple viewpoints that involve epidemiology, clinicopathology, molecular genetics, molecular immunology, and developmental biology. This synthesis reinforces the following hypothesis: PD-1 blockade effectively restores the immunity specially allowed to exist within the fully cornified squamous epithelium, that is, the epidermis. Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer globally. Because most cSCC cases are manageable by local excision/radiotherapy and hardly become life-threatening, they are often excluded from cancer registries in most countries. Compared with cutaneous melanoma that originates from the melanin-producing, neural crest-derived epidermal resident, keratinocyte (KC)-derived cancers are influenced by the immune system with regards to their pathogenetic behaviour. Congenital or acquired immunosurveillance impairments compromise tumoricidal activity and raises cSCC incidence rates. Intriguingly, expanded applications of programmed death-1 (PD-1) blockade therapies have revealed cSCC to be one of the most amenable targets, particularly when compared with the mucosal counterparts arisen in the esophagus or the cervix. The clinical observation reminds us that cutaneous tissue has a peculiarly high immunogenicity that can evoke tumoricidal recall responses topically. Here we attempt to redefine cSCC biology and review current knowledge about cSCC from multiple viewpoints that involve epidemiology, clinicopathology, molecular genetics, molecular immunology, and developmental biology. This synthesis not only underscores the primal importance of the immune system, rather than just a mere accumulation of ultraviolet-induced mutations but also reinforces the following hypothesis: PD-1 blockade effectively restores the immunity specially allowed to exist within the fully cornified squamous epithelium, that is, the epidermis. [ABSTRACT FROM AUTHOR]

The European Academy of Allergy and Clinical Immunology (EAACI) owns three journals: Allergy, Pediatric Allergy and Immunology and Clinical and Translational Allergy. One of the major goals of EAACI is to support health promotion in which prevention of allergy and asthma plays a critical role and to disseminate the knowledge of allergy to all stakeholders including the EAACI junior members. There was substantial progress in 2019 in the identification of basic mechanisms of allergic and respiratory disease and the translation of these mechanisms into clinics. Better understanding of molecular and cellular mechanisms, efforts for the development of biomarkers for disease prediction, novel prevention and intervention studies, elucidation of mechanisms of multimorbidities, entrance of new drugs in the clinics as well as recently completed phase three clinical studies and publication of a large number of allergen immunotherapy studies and meta-analyses have been the highlights of the last year. [ABSTRACT FROM AUTHOR]