Atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense pruritus and frequent relapsing courses. It occurs mostly in patients who have a personal or family history of other atopic conditions, such as asthma or allergic rhinitis. The prevalence of AD is high, particularly in children, with rapidly increasing numbers in the past few decades. The chronicity of this disease, along with its relapsing nature, presents treatment and management challenges for clinicians and frustration for patients and their families.     

CX3CL1 (fractalkine) and its receptor CX3CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin

Atopic dermatitis (AD) is a chronic allergic dermatosis characterized by epidermal thickening and dermal inflammatory infiltrates with a dominant Th2 profile during the acute phase, whereas a Th1 profile is characteristic of the chronic stage. Among chemokines and chemokine receptors associated with inflammation, increased levels of CX₃CL1 (fractalkine) and its unique receptor, CX₃CR1, have been observed in human AD. We have thus investigated their role and mechanism of action in experimental models of AD and psoriasis. AD pathology and immune responses, but not psoriasis, were profoundly decreased in CX₃CR1-deficient mice and upon blocking CX₃CL1–CX₃CR1 interactions in wild-type mice. CX₃CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX₃CR1 expression by both Th2 and Th1 cells was required to induce AD. Surprisingly, unlike in allergic asthma, where CX₃CL1 and CX₃CR1 regulate the pathology by controlling effector CD4⁺ T cell survival within inflamed tissues, adoptive transfer experiments established CX₃CR1 as a key regulator of CD4⁺ T cell retention in inflamed skin, indicating a new function for this chemokine receptor. Therefore, although CX₃CR1 and CX₃CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases.Atopic dermatitis (AD) is a common, chronic inflammatory dermatosis that frequently occurs in individuals with a personal or family history of atopic diseases. AD pathophysiology is complex and results from skin barrier dysfunction and a dysregulated immune response, influenced by genetic and environmental factors (Guttman-Yassky et al., 2011a,b). Indeed, most patients with AD have increased serum IgE levels, with specific IgE directed against allergens or microbial proteins such as Staphylococcus aureus (Leung et al., 2004). Lesions in AD are characterized by increased epidermal thickness and a dermal inflammatory cell infiltrate, consisting of mast cells, eosinophils, and T lymphocytes. In acute AD lesions a preferential recruitment of Th2 cells occurs, whereas in the chronic lesions a Th1 profile is predominant (Grewe et al., 1998); allergic asthma or allergic rhinitis are more exclusively Th2-dominated diseases.Chemokines and their receptors play a key role in leukocyte recruitment to inflamed skin (Schall and Proudfoot, 2011). Eotaxins 1, 2, and 3 (CCL11, -24, and -26) bind to CCR3 and attract eosinophils, and CCL26 appears to be particularly involved in AD (Kagami et al., 2003; Owczarek et al., 2010). CCL27 together with CCR10 and CCR4 expression ensures T cell skin domiciliation (Reiss et al., 2001; Homey et al., 2002). More recently, CCR8 and CCL8 have been elegantly demonstrated to direct Th2 cell recruitment into allergen-inflamed skin and draining LNs in a murine model of AD (Islam et al., 2011).Besides chemoattraction, chemokine–chemokine receptor interactions also regulate other functions. Indeed, we have recently demonstrated that CX₃CR1, the receptor for CX₃CL1 (fractalkine [CX₃]), identified also as a receptor for CCL26 (Nakayama et al., 2010) in humans, controls the development of allergic asthma by providing a survival signal to the CD4⁺ effector T lymphocytes in the inflammatory airways (Mionnet et al., 2010; Julia, 2012). In AD patients, CX₃CL1 is up-regulated in both endothelial cells and skin lesions, and serum CX₃CL1 levels are positively associated with disease severity (Echigo et al., 2004). Another study reported that, although CX₃CR1 mRNA expression is consistently up-regulated in AD skin, CX₃CL1 mRNA levels are only increased in some patients with a significant correlation to the disease severity (Nakayama et al., 2010), a result likely to explain the earlier failure to detect CX₃CL1 in skin lesions (Fraticelli et al., 2001). Furthermore, two CX₃CR1 single nucleotide polymorphisms have been associated with asthma and atopy in French-Canadian populations (Tremblay et al., 2006) and German children (Depner et al., 2007).Thus, to functionally delineate the role of CX₃CL1–CX₃CR1 in AD, we used a mouse model of epicutaneous sensitization, by a protein antigen in the absence of adjuvant, faithfully mimicking features of human AD. Unexpectedly, we found that CX₃CL1–CX₃CR1 controlled AD to an even greater extent than allergic asthma through a new and distinct mechanism.     

Atopic dermatitis--more than a simple skin disorder

PURPOSE: To describe atopic dermatitis (AD) in relation to a case study, the diagnostic criteria, complications, prevalence, future implications, and management for the primary care provider. DATA SOURCES: Extensive literature review on the condition, supplemented with an actual case study. CONCLUSIONS: Although there are many scientific studies done on AD, the exact pathogenesis and cure for this condition are still to be discovered. It is usually chronic and has some fatal sequelae in those who have been exposed to viral infections. Asthma, allergic rhinitis (AR), and AD are considered the atopic triad. Further studies that may help improve medical providers' understanding of AD are going on and offer hope to those afflicted by this disorder. IMPLICATIONS FOR PRACTICE: Children over 5 years old may have outgrown their symptoms, so it is best to diagnose this condition at an early age to provide better management outcomes. Because it is part of an atopic triad, the nurse practitioner must think beyond the presenting skin condition to consider possible respiratory system conditions. AD may herald the onset of asthma and AR.     

Bronchial asthma. Mechanisms and management of a complex obstructive airway disease

Airway hyperreactivity to physical, chemical, and pharmacologic stimuli is a hallmark of bronchial asthma. In patients with extrinsic (allergic) asthma, in whom an immunologic mechanism of the IgE type can be demonstrated, specific sensitivity develops to a variety of common environmental substances, including pollen, fungus spores, house dust mites, and animal danders. Persons with intrinsic asthma, in whom immunologic mechanisms are hard to demonstrate, often have chronic sinus disease and nasal polyps and manifest clinical intolerance to nonsteroidal antiinflammatory agents. Evaluation of asthma includes a history and complete physical examination, skin tests, radioallergosorbent tests, pulmonary function tests, blood gas determination, and inhalation challenge tests. Treatment is focused on environmental control, pharmacotherapy, and immunotherapy.     

Periostin promotes chronic allergic inflammation in response to Th2 cytokines

Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with αv integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or αv integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.     

New insights into atopic dermatitis

Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.     

Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy: a multicenter,investigator-blinded,randomized, parallel group controlled trial (PACI Study)—protocol for a randomized controlled trial

Background

Atopic dermatitis is the first clinical manifestation of the atopic march, with the highest incidence in the first year of life. Those affected often go on to develop other allergic diseases including food allergy, asthma, and allergic rhinitis. Recent evidence suggests that sensitization to foods may occur through a defective skin barrier which is common in atopic dermatitis in early life. We hypothesize that therapeutic aggressive intervention to treat new onset atopic dermatitis may prevent the development of later allergen sensitization, and associated food allergy, asthma, and allergic rhinitis.

Methods

This study is a multi-center, pragmatic, two-parallel group, assessor-blind, superiority, individually randomized controlled trial. Atopic dermatitis infants (N?=?650) 7–13 weeks old who develop an itchy rash within the previous 28 days are randomly assigned to the aggressive treatment or the conventional treatment in a 1:1 ratio. The primary outcome is oral food challenge-proven IgE-mediated hen’s egg allergy at the age of 28 weeks.

Discussion

This is a novel pragmatic RCT study to examine the efficacy of early aggressive treatment for atopic dermatitis to prevent later food allergy. If our hypothesis is correct, we hope that such a strategy might impact on disease prevention in countries where food allergy is common, and that our results might reduce the frequency and associated costs of all food allergies as well as hens egg food allergy. Long-term follow and other similar studies will help to determine whether such a strategy will reduce the burden of other allergic diseases such as asthma and allergic rhinitis.Trial registration UMIN-CTR: UMIN000028043

     

Therapeutic modulation of allergic airways disease with leukotriene receptor antagonists

Although asthma is one of the most common chronic respiratory conditions, it often remains unrecognized and undertreated, while patients are often reluctant to comply with regular inhaled anti-inflammatory and bronchodilator therapy. Allergic rhinitis co-exists with asthma in as many as 40% of patients, and can be regarded as a continuum of the same inflammatory disease process. Corticosteroids are the 'gold standard' first-line treatment for both conditions, and have a significant impact upon underlying inflammation, symptoms and long-term outcome. Cysteinyl leukotrienes are potent airway inflammatory mediators, suggesting that treatment antagonizing their effects could play a role in disease management. In recent years, leukotriene receptor antagonists have provided a further therapeutic option in the management of allergic airways disease. These drugs are orally active, can be administered once daily, and provide a systemic approach to the management of patients with asthma and allergic rhinitis. We review the pharmacology of leukotriene receptor antagonists, their potential role in clinical practice in patients with allergic airways disease, and likely areas for further research.     

Allergic multimorbidity is associated with self‐reported anaphylaxis in adults—A cross‐sectional questionnaire study

BackgroundAnaphylaxis has increased over the last two decades in Europe, reaching an estimated prevalence of 0.3% and an incidence of 1.5–7.9 per 100,000 person‐years. Allergic multimorbidity is associated with asthma severity, yet its role in anaphylaxis is not fully understood. Our aim was to study association between allergic multimorbidity and anaphylaxis in adults.MethodsWe used population‐based data from the Finnish Allergy Barometer Study (n = 2070, age range: 5–75). Food allergy (FA), atopic dermatitis (AD), allergic rhinitis (AR) and allergic conjunctivitis (AC), were defined from a self‐completed questionnaire. A logistic regression adjusted on potential confounders (sex, age, smoking status) was applied to estimate the anaphylaxis risk associated with allergic multimorbidity.Results1319 adults with at least one allergic disease (FA, AD, AR, AC) with/without asthma (AS) were included. Of these, 164 had self‐reported anaphylaxis [mean (SD, min‐max) 54 (14, 22–75) years, 17% men]. AS, FA, AR, AC, or AD were reported by 86.0%, 62.2%, 82.3%, 43.3%, and 53.7% of subjects with anaphylaxis and respectively by 67.8%, 29.5%, 86.2%, 29.4%, and 34.4% of subjects without anaphylaxis. Compared with subjects exhibiting only one allergic disease, the risk of anaphylaxis increased with the number of allergic diseases; adjusted odds ratios (OR) [CI95%] for two, three, four and five coinciding allergic diseases were 1.80 [0.79–4.12], 3.35 [1.47–7.66], 7.50 [3.25–17.32], and 13.5 [5.12–33.09], respectively. The highest risk of anaphylaxis (6.47 [4.33–9.92]) was associated with FA + AS or their various variations with AR/AC/AD embodied, when compared with AR, AC, and AS separately or their combinations.ConclusionsAnaphylaxis was positively associated with the number of allergic diseases a subject exhibited and with subgroups including FA and/or AS. The results can be applied when estimating the risk of anaphylaxis for individual patients.     

Costimulation and allergic responses: immune and bioinformatic analyses

Asthma is a complex polygenic disease, the prevalence of which has been on the rise for last few decades. Defining the underpinnings of allergic immune responses and the factors predisposing to asthma are fundamental investigative challenges. T cell costimulatory pathways play critical roles in the pathogenesis of asthma. In this review, we analyze the current state of the art of T cell costimulation in allergic airway inflammation. Also, we discuss both immune and bioinformatic approaches as potential strategies for analyzing multiple costimulatory pathways relevant to asthma.     

Seasonal Changes of Streptococci

Although the theory that bronchial asthma is a manifestation of allergy is often true, there are many patients with asthma in whom no allergen can be identified as the cause of paroxysms. This paper discusses methods of differentiating between allergic and nonallergic asthma and offers procedures to be followed in treating the latter type of the disease.     

Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen

The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for the vascular adhesion molecule E-selectin, and it has been proposed to be involved in the selective targeting of memory T cells reactive with skin-associated Ag to cutaneous inflammatory sites. To further investigate the relation of CLA and cutaneous T cell responses, we analyzed the CLA phenotype of circulating memory T cells in patients with allergic contact dermatitis and atopic dermatitis (AD) alone vs in patients manifesting bronchopulmonary atopy (asthma with or without AD) and nonallergic individuals. Significant T cell proliferative responses to Ni, a contact allergen, and to the house dust mite (HDM), an allergen to which sensitization is often observed in AD and/or asthma, was noted only in allergic and atopic individuals, respectively. When the minor circulating CLA+CD3+CD45RO+ subset was separated from the major CLA-CD3+CD45RO+ subpopulation in Ni-sensitive subjects, the Ni- dependent memory T cell response was largely confined to the CLA+ subset. A similar restriction of the T cell proliferative response to the CLA+ memory subset was observed for HDM in patients with AD alone. In HDM-sensitive patients with asthma with or without AD, however, the CLA- subset exhibited a strong antigen-dependent proliferation, in contrast to patients with AD alone, whose CLA- subset proliferated very weakly to HDM. In asthma with or without AD, the HDM-dependent proliferation slightly predominated in the CLA- when compared to the CLA+ subset. The functional linkage between CLA expression and disease- associated T cell effector function in AD was also demonstrated by the finding that the circulating CLA+ T cell subset in AD patients, but not nonatopic controls, selectively showed both evidence of prior activation (human histocompatibility antigen-DR expression) and spontaneous production of interleukin 4 but not interferon-gamma. Taken together, these observations demonstrate the correlation of CLA expression on circulating memory T cells and disease-associated memory T cell responses in cutaneous hypersensitivity, and they suggest the existence of mechanisms capable of sorting particular T cell Ag specificities and lymphokine patterns into homing receptor-defined memory subsets.     

Role of IL‐17 in atopy—A systematic review

Purpose of ReviewAtopy is defined as the genetic predisposition to react with type I allergic diseases such as food‐, skin‐, and respiratory allergies. Distinct molecular mechanisms have been described, including the known Th2 driven immune response. IL‐17A (IL‐17) is mainly produced by Th17 cells and belongs to the IL‐17 family of cytokines, IL‐17A to F. While IL‐17 plays a major role in inflammatory and autoimmune disorders, more data was published in recent years elucidating the role of IL‐17 in allergic diseases. The present study aimed to elaborate specifically the role of IL‐17 in atopy.MethodsA systematic literature search was conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, regarding IL‐17 and atopy/allergic diseases.ResultsIn total, 31 novel publications could be identified (food allergy n = 3, allergic asthma n = 7, allergic rhinitis [AR] n = 10, atopic dermatitis [AD] n = 11). In all allergic diseases, the IL‐17 pathway has been investigated. Serum IL‐17 was elevated in all allergic diseases. In AR, serum and nasal IL‐17 levels correlated with the severity of the disease. In food allergies, serum IL‐17E was also elevated in children. In AD, there is a trend for higher IL‐17 values in the serum and skin specimen, while it is more expressed in acute lesions. In allergic asthma, serum IL‐17 levels were increased. In two studies, higher serum IL‐17 levels were found in severe persistent asthmatic patients than in intermittent asthmatics or healthy controls. Only one therapeutic clinical study exists on allergic diseases (asthma patients) using a monoclonal antibody against the IL‐17 receptor A. No clinical efficacy was found in the total study population, except for a subgroup of patients with (post‐bronchodilator) high reversibility.SummaryThe role of IL 17 in the pathogenesis of allergic diseases is evident, but the involvement of the Th17 cytokine in the pathophysiological pathway is not conclusively defined. IL‐17 is most likely relevant and will be a clinical target in subgroups of patients. The current data indicates that IL‐17 is elevated more often in acute and severe forms of allergic diseases.     

Allergen-induced inflammation and the role of immunoglobulin E (IgE).

The prevalence of common allergic disorders such as asthma, allergic rhinitis, and atopic dermatitis has increased significantly in the past 30 years. The impact of these atopic diseases on the patient and the health care system is considerable: Allergic disorders are associated with a high degree of morbidity, which can profoundly impact patient quality of life and health care resource use. Existing strategies to treat allergic disorders beyond simple allergen avoidance focus on diminishing or eliminating the recurrent and/or persistent signs and symptoms that characterize the allergic response. A new strategy has been developed that uses antibodies directed against immunoglobulin E (IgE) to prevent it from binding to cells bearing its receptors and thus neutralizing the allergic response before it begins. These new agents reduce allergic responses in atopic individuals and improve their symptoms while reducing rescue medication and corticosteroid use in patients with allergic asthma or seasonal allergic rhinitis. Thus, anti-IgE antibodies represent proof that IgE plays a central role in allergic reactions and that anti-IgE therapy is a potentially effective treatment for allergic disease.     

Assessment of childhood allergy for the primary care practitioner

PURPOSE: To update the primary care practitioner on the assessment of common childhood allergic illnesses. DATA SOURCES: Relevant scientific literature and published clinical practice guidelines. CONCLUSIONS: Atopic children often develop symptoms that occur in a predictable progression from atopic dermatitis to gastrointestinal disturbances, chronic serous otitis media, rhinitis, and asthma. Evaluation of allergic symptoms should be based on their chronicity, family history of atopy, and knowledge of how the information will change patient management. Both skin and blood testing are accurate and useful tools in establishing a diagnosis of allergic disease. Management includes avoidance/environmental control, medications, and, when necessary, referral to specialists. IMPLICATIONS FOR PRACTICE: As the incidence of allergic disease increases, the human and monetary costs associated with allergies place a major burden on our healthcare system. Early identification of allergies and appropriate intervention are important to prevent progression to more significant disease. The use of objective diagnostic testing aids in implementing appropriate evidence-based medical management.     

Skin Impedance at Acupuncture Point Dingchuan in Subjects with and without Asthma

Objective: Asthma can be a disabling disease and despite advances in pharmacology, the prevalence of this condition globally remains high and accounts for a significant proportion of public health care costs. While pharmacology is the mainstay of asthma managemen4 drug side effects have promoted alternative therapeutic interventions, such as acupuncture. Acupuncture points have a lower skin impedance compared to non-acupuncture points. Health impairment is associated with changes in skin impedance at system-specific acupuncture points. Detection of skin impedance changes may assist in the early diagnosis of asthma and monitoring the effectiveness of therapeutic interventions for this condition. Method: This study compared skin impedance at acupuncture point Dingchuan (EX-BI), in 92 subjects with normal health (47 subjects, age 32.6±1.67yr) and those diagnosed with asthma (45 subjects, age 42.4±1.80 yr). Skin impedance was measured using a 2-electrode impedance meter bilaterally at EX-BI, 0.5 "curt" lateral to the lower border of 7th cervical vertebra. Result: The study showed that skin impedance was significantly higher at acupuncture point EX-B1 in subjects with asthma (29.4±21 kΩ) compared to subjects with normal health (13.8±7.9 kΩ) (P=0.013). Skin impedance was negatively correlated to forced expiratory volume in 1 second (FEV1, r=-0.59, P=0.012 in females; and r=-0.68, P=0.015 in males). A receiver operator characteristic (ROC) curve revealed an optimum cut-off point of 35 kΩ for male and 10 kΩ for female subjects. Conclusion: We conclude that EX-B1 skin impedance is higher in patients with asthma and skin impedance might be a possible adjunctive parameter for assisting diagnosis and monitoring asthmatic status.     

Work-related asthma.

Work-related asthma accounts for at least 10 percent of all cases of adult asthma. Work-related asthma includes work aggravation of preexisting asthma and new-onset asthma induced by occupational exposure. Occupational exposure to very high concentrations of an irritant substance can produce reactive airway dysfunction syndrome, while exposure to allergenic substances can result in allergic occupational asthma. An important step in the diagnosis of work-related asthma is recognition by the physician of the work relatedness of the illness. A thorough history can elucidate the work relation and etiology. Objective tests, including pulmonary function, nonspecific and specific bronchial hyperresponsiveness, serial peak expiratory flow rates, and skin allergies, should be performed to confirm the diagnosis of asthma and demonstrate a work correlation. Treatment for occupational asthma--use of anti-inflammatory medications such as inhaled steroids and bronchodilators--is the same as that for nonoccupational asthma. Prevention is an integral part of good medical management. In patients with work-aggravated or irritant-induced asthma, reduction of exposure to aggravating factors is essential. In patients with allergic occupational asthma, exposure should be eliminated because exposure to even minute concentrations of the offending agent can trigger a potentially fatal allergic reaction.     

Predicting the development of early skin test sensitization in offspring of parents with asthma

BACKGROUND: The direct causal relationship between skin sensitization and asthma are controversial until now and remains to be further researched. Our aim is to analyse the role of parental asthma in the development of skin sensitization in offspring. MATERIALS AND METHODS: This study was performed among nuclear families (determined by index of asthma patients), and subjects included parents and offspring. Parents were subdivided into four phenotypes on the basis of skin sensitization (SPT+ or SPT-) and asthma status (AST+ or AST-) and offspring were subdivided into three age groups: 3-8, 9-14 and 15-20 years. The main tests included a standard questionnaire and skin prick tests. RESULTS: Offspring's skin sensitization differed among parental phenotypes at all ages (P < 0.05). In the SPT+/AST-, SPT-/AST+ and SPT+/AST+ groups, offspring were significantly more likely to be allergic than the ones in SPT-/AST- group at 3-8 years. Offspring with at least one parent with asthma were significantly more likely to have positive skin prick test response than those with non-asthmatic parents at age 3-8 years and 9-14 years, but not at 15-20 years among offspring with allergic parents. Results were independent of asthma in the children and of the characteristics of atopy in the parents. CONCLUSION: Parent asthma history is an independent risk factor for allergic sensitization in their offspring in a Chinese population.     

The risk of allergy in asthma

The prevalence of atopy among asthmatics is more than 70 per cent. Atopy is more prevalent among older children and young asthmatic adults. It is inherited, but the pattern of inheritance is not well defined. Increase in total IgE is one manifestation of atopy, and increase in IgE in early infancy is a predictor of atopic illness, including asthma. Sensitization to allergens and repeated exposure is one of the triggers of developing asthma in atopic patients. Allergy even without asthma (allergic rhinitis) is associated with an increase in bronchial reactivity. Allergy is a risk factor in occupational asthma and in exercise induced asthma. In fact, many non-asthmatic allergic rhinitis patients wheeze with exercise. Allergen avoidance and environmental control may contribute to the well-being of many asthmatics. Allergy hyposensitization (immunotherapy) may help control asthma in allergic patients.