Atopic dermatitis

ABSTRACT:  Atopic dermatitis (AD) is a common dermatologic disease that can occur at different ages with different clinical manifestations. The etiologic factors and the pathogenetic pathways of AD have been thoroughly investigated but as often happens, something more has to be yet elucidated before the statement, that we possess the overall comprehension of the disease, could be considered the truth. Treatment of AD is often challenging, because of the chronic course of the disease and the fact that even the best of therapies is affected by adverse events, intolerances, or the possible occurrence of contraindications resulting from a sudden change in the overall health status of the patient (e.g., the onset of some comorbidities). Hence, the need to know "how, when, with what, and why" to treat AD patients with the many therapeutic modalities is now in the hands of the dermatologists.     

Atopic contact dermatitis

Contact urticaria appears either as wheal and flare reactions or as dermatitis resembling other types of contact dermatitis. A nonimmunologic form of contact urticaria is seen more frequently than the allergic form of the disease in experimental conditions. However, the immunologic form of contact urticaria is clinically more important. It is often seen in atopic persons working in the food industry or in kitchens.
We can prevent many cases of occupational anaphylactic hand eczema by choosing proper jobs for atopic persons. Especially handling food seems to produce hypersensitivity reactions in atopic more frequently than in nonatopic persons.     

特应性皮炎的遗传学及免疫学研究进展

特应性皮炎(AD)为遗传过敏性疾病,患者及其家族的基因筛选结果显示,AD与其他炎症性皮肤病、自身免疫疾病存在染色体区域的交迭。候选基因的研究为探讨AD的发病机理提供了新的视野。由皮肤浸润的T细胞、树突状细胞、肥大细胞和血管内皮细胞所产生的多种趋化细胞因子配体(CCL)和受体(CCR)在AD的发病机制中起到了重要作用。细胞因子的不同表达状态和基因识别的高效方法将有助于进一步仔细研究AD的综合特点,也有助于定义AD的诊断标准和治疗。     

Atopic background in patients with occupational hand eczema

Of 368 patients with hand eczema examined during the years 1978-79, at a Department of Occupational Dermatology, 39% had a history of atopic disease (dermatitis, asthma, or rhinitis). 28% of the patients had or had had atopic dermatitis. The % of atopics in the patient material was highest in the age range 20-24 years, in which 57% of the patients had a history of atopic dermatitis, compared with only 11% in the age range above 35 years. Of all patients with a history of atopy, 22% had developed allergic contact dermatitis, while the corresponding figure for non-atopics was 45% (p less than = 0.001). Positive patch test reactions occurred in a significantly smaller number of individuals with past or present atopic disease than in non-atopics. Atopics had not changed jobs because of hand eczema to a greater extent, but had healed to a lesser extent after change of occupation than non-atopics (p less than 0.01).     

Atopic Dermatitis

Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.     

Atopic dermatitis and melanocytic naevi

A study was performed to test the clinical impression that adults with severe atopic dermatitis (AD) have a low number of common naevi (CN). The number of CN > or = 2 mm was investigated in 51 Caucasian patients aged 20-63 years with severe AD since early childhood. The control group consisted of 379 randomly selected subjects, aged 30-50 years, investigated in an earlier study. Patients with AD had a significantly (P < 0.0001) lower total body count of CN (mean 9, median 5) compared with the control group (mean 67, median 53). It was also found that in the AD group there was a significant (P < 0.001) negative correlation between serum IgE and number of CN [r(s) = -0.50, 95% CI (-0.69; -0.24)]. The explanation for the low number of naevi that we have found in this highly selected subgroup of AD patients is not known. The atopic inflammation in the skin, genetics and treatment used for eczema are possible factors that may influence the formation of melanocytic naevi.     

Atopic dermatitis and cancer risk

BACKGROUND: Epidemiological studies have provided growing evidence of a link between atopy and cancer risk. OBJECTIVES: To review the evidence from case-control studies and cohort studies on a possible association between atopic dermatitis (AD) and cancer risk, with particular attention to the case definition of AD. METHODS: Studies with quantitative data on the association between AD (eczematous disease) and cancer risk were obtained from MEDLINE in combination with a review of cited references. RESULTS: In 23 publications, AD was implicated in the risk of haematological [childhood leukaemia (n = 3), adult leukaemia (n = 3), non-Hodgkin lymphoma (NHL; n = 4) and different haematological cancers (n = 1)], pancreatic (n = 5), skin (n = 2) and brain malignancies (n = 5). The overall picture of the results of these studies shows that a history of AD may be associated with a decreased risk of pancreatic cancer, brain tumour and childhood leukaemia, although in most instances the findings were not statistically significant. No consistent associations were observed for skin cancer or NHL. The definition of AD had varying quality, and was imprecise in the majority of publications. CONCLUSIONS: The findings of the epidemiological studies tend to support a lower risk of cancer among persons with a history of AD. Although a more careful definition of AD is needed, these epidemiological studies could provide an estimate of the background cancer risk in patients with AD when the long-term effects of treatments for AD are assessed.     

Atopic eczema or atopiform dermatitis

Please cite this paper as: Atopic eczema or atopiform dermatitis. Experimental Dermatology 2010. Abstract: Age period prevalence of atopic eczema (AE), a very common skin disease, has increased during the past decennia. This expansion seems to be ending in wealthy countries, while an increase is observed in developing nations, for which there is no firm explanation. Recent steps in understanding AE are the detection of skin barrier related filaggrin null mutations in approximately 25% of patients and the recognition of IL‐31 as a molecule possibly involved in the itch (pruritus). Also interesting are the recognition of thymus and activation‐regulated chemokine (TARC) and proliferating‐inducing ligand (APRIL), as being associated with AE severity and activity. Immunocentric and corneocentric views on pathogenesis (the inside‐outside paradigm) and the diagnostic entity atopiform dermatitis (AFD) are discussed here. We emphasize that diagnosing AE is not simple but challenging. We accentuate that a diagnosis of AE is only possible when there is allergen‐specific IgE. Advice as to the need for elimination of allergens and adjustment of lifestyle are only proficient in patients having atopy and true AE, not in those having AFD.     

老年特应性皮炎

【摘要】 近年国内外指南更新了特应性皮炎（AD）类别,增加了老年AD分型。老年AD的病因与遗传、皮肤屏障功能障碍、免疫失调及生活方式有关。但多数老年AD患者临床症状不典型,误诊十分常见。充分认识老年AD的发病机制和临床特征,根据老年AD临床特点制定个体化的诊疗方案,对改善患者生活质量,减轻疾病负担显得尤为重要。     

Atopic dermatitis in older patients: particular points

We review the particular characteristics of atopic dermatitis (AD) in adult life, and compare findings with those of AD in childhood. AD affects 1–3% of adults world‐wide, and can present as adult‐onset AD, or as infantile/childhood AD that persists, or recurs after many years. Eczema in adults usually exists for years, compromising quality of life, sex life and occupational choices. The flexural areas, shoulders, head‐and‐neck, and hands are typically affected. In elderly adults, eczematous erythroderma is common. The intrinsic (non‐IgE‐allergic) eczema subtype affects 5–15% of cases. Classical food allergy has a low importance, although non‐IgE‐mediated and pseudoallergic reactions can cause eczema. Sensitivity to aeroallergens, especially dust mite, is demonstrated in the majority of adult AD patients, including elderly adults, by immunoglobulin E‐mediated tests and/or atopy patch tests. Occupational allergic and irritant contact dermatitis is increased. In adults, as in children, Staphylococcus aureus colonization is very high, whereas adult skin is more heavily colonized with Malassezia yeasts. Immediate and delayed sensitization to Malassezia sympodialis is specific for intrinsic and extrinsic AD, occurring especially in head‐and‐neck eczema. Concerning therapy, older patients are prone to certain adverse drug effects. In conclusion, differences exist between childhood and adult disease. As we should be seeing more adults with AD in the future, there is a need for more clinical and immunological studies in older patients.     

Atopic dermatitis made easy: The Schachner Ladder

The vast majority of atopic dermatitis follows a mild, chronic relapsing course. In this article, we highlight the art and practice of treating atopic dermatitis based upon a foundation of maintenance care and a ladder of therapy that can teach patients and their families how to best tailor their pharmaceutical options to optimize the management of their disease.     

Atopic dermatitis: review of immunopathogenesis and advances in immunosuppressive therapy

This paper reviews the theories of the pathogenesis of atopic dermatitis (AD), with a particular emphasis on its immunopathogenesis. The contribution of predisposing factors, immunopathogenic factors and provoking factors in the pathogenesis of AD are considered. Predisposing factors explored in this article include genetics and the disturbance of skin function. Immunopathogenic factors reviewed include T cell dysfunction, biphasic cytokine expression and the role of immunoglobulin E. Provoking factors considered include microbial factors, psychosomatic interactions, contact allergens and irritants, inhalant allergens, food and climate. Immunosuppressive treatments reviewed include cyclosporin, azathioprine, methotrexate, tacrolimus, interferon-gamma, phosphodiesterase inhibitors and pimecrolimus (SDZ ASM 981).     

TSLP Polymorphisms in Atopic Dermatitis and Atopic March in Koreans

BackgroundAtopic march (AM) is the progression from atopic dermatitis (AD) to allergic rhinitis and asthma. The development of AD is as high as 20% in children worldwide and continues to increase. AD seems to be caused by both genetic and environmental factors. Recently, polymorphisms of the thymic stromal lymphopoietin (TSLP) gene associated with allergic disorders were reported in ethnic groups from various countries.ObjectiveIdentification of TSLP polymorphisms in Koreans with AD or AM.MethodsWhole-exome sequencing was performed in 20 AD and 20 AM patients.ResultsNine single nucleotide polymorphisms (SNPs) of TSLP were detected (rs191607411, rs3806933, rs2289276, rs2289277, rs2289278, rs139817258, rs11466749, rs11466750, rs10073816). These SNPs have been correlated with susceptibility to allergic diseases in ethnic groups from China, Japan, Turkey, and Costa Rica in previous studies. Remarkably, one of 20 patients in the AD group lacked all SNPs, compared to six of 20 patients in the AM group. Odds ratios showed that Korean patients without the nine TSLP variants had an 8.14 times higher risk of moving from AD to AM. Two haplotype blocks were validated in 60 AD and 59 AM patients using Sanger sequencing. The haplotype blocks (rs3806933 and rs2289276) and (rs11466749 and rs11466750) were in high linkage disequilibrium, respectively (D′=0.97, D′=1).ConclusionThe increase of major allele frequency of respective nine TSLP variants may enhance the risk of AM. These data will contribute to improved genetic surveillance system in the early diagnosis technology of allergic disease.     

Long Term Treatment Concepts and Proactive Therapy for Atopic Eczema

Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.