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IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis.

BACKGROUND: IL-31 is a newly discovered T-cell cytokine that, when overexpressed in mice, results in pruritus and skin dermatitis resembling human atopic dermatitis (AD). OBJECTIVE: We sought to investigate the expression of IL-31 and IL-31 receptor A (IL-31RA) in skin biopsy specimens and peripheral blood cells from patients with AD and healthy individuals. METHODS: Expression of IL-31 and IL-31RA was evaluated in skin biopsy specimens from patients with AD and healthy individuals by means of immunohistochemistry and RT-PCR. IL-31 protein production by skin-homing cutaneous lymphocyte antigen (CLA)-positive T cells was also assessed. RESULTS: IL-31RA protein was expressed by keratinocytes and infiltrating macrophages in skin biopsy specimens from patients with AD. Comparisons between skin from patients with AD and healthy skin showed IL-31RA expression at higher levels on epidermal keratinocytes in AD samples. Infiltrating cells, more numerous in skin from patients with AD compared with that of healthy individuals, expressed IL31 mRNA. Histomorphometric analysis of these cells indicated they were of the lymphocytic lineage, with the majority of cells staining positive for CLA and CD3. IL31 mRNA and protein expression is largely restricted to CD45RO(+) (memory) CLA(+) T cells in peripheral blood of patients with AD and healthy volunteers. Moreover, circulating CLA(+) T cells from patients with AD, but not from patients with psoriasis, are capable of producing higher levels of IL-31 compared with CLA(+) T cells from healthy individuals. However, the average levels of IL-31 were not significantly different between patients with AD and healthy individuals. CONCLUSION: We provide evidence that IL-31 expression is associated with CLA(+) T cells and might contribute to the development of AD-induced skin inflammation and pruritus.

Adult↗

Childhood atopic dermatitis: a measurement of quality of life and family impact.

Atopic dermatitis is the commonest skin disease in children, causing psychological, social and functional disability to them and their families. This study assessed the family impact and quality of life using the translated Malay version of The Dermatology Family Impact (DFI) and The Children's Dermatology Life Quality Index (CDLQI) questionnaires. Seventy-two children, aged between 6 months and 16 years attending the Paediatric Dermatology Clinic at the Paediatric Institute and the Dermatology Department, Hospital Kuala Lumpur participated in this study. Thirty-nine patients (54.2%) were males and 33 patients (45.8%) were females. The median age of the patients was 74 months (Q1 6, Q3 104 months). The median age of diagnosis was 22 months (Q1 1, Q3 36 months). The median disease duration was 44 months (Q1 3, Q3 65). The severity of eczema was assessed using the SCORAD severity index (maximum score = 83). The median SCORAD (European Task Force On Atopic Dermatitis) score was 36 (n = 72, SD = 16.2). The majority of patients in this study suffered from moderately severe eczema (n = 40, mean, SCORAD = 29.3) followed by severe eczema (n = 27, mean SCORAD = 54.3). The mildly affected patients formed the minority group (n = 5, mean SCORAD = 9.0). The family impact was shown to be greater in severe atopic dermatitis compared to moderate atopic dermatitis (Anova, p = 0.02). The children's quality of life impairment was also greater in severe atopic dermatitis compared to moderate atopic dermatitis (Anova p = 0.08). This study confirms that quality of life and family impact are related to the severity of atopic dermatitis.

Adolescent↗

Clinical improvement and significant reduction of total serum IgE in patients suffering from severe atopic dermatitis treated with oral azathioprine.

Atopic dermatitis (AD) is a common inflammatory skin disease: the incidence is increasing in many countries and treatment can be difficult. The aim of this retrospective case series was to examine the effect of oral azathioprine on the clinical severity and serum IgE levels in 38 patients with severe atopic dermatitis. The AD was well-controlled in nearly 80% (30/38). The maintenance dose required was in the range 25-200 mg per day. Four patients withdrew because of adverse affects, including one case of pancytopenia, and a further four ceased azathioprine after 4 months because of a lack of clinical improvement. Total serum IgE levels were measured before commencing azathioprine and after two years of treatment in 26 patients. IgE levels decreased in almost all patients and this was statistically significant (P = 0.012).

Administration, Oral↗

[Do breast-feeding and "diet" milks have any preventive or curative effect in the management of atopic dermatitis in children?].

A) The preventive interest of infants' food in the onset of atopic dermatitis. Measures of prevention of atopic dermatitis concern predisposed children. Most studies agree on the protective effect of breast feeding for at least 3 to 4 months, compared with industrial milk products, on the onset of atopic dermatitis. Partial breast feeding is not protective. There is no preventive effect of breast feeding on the onset of atopic dermatitis in the absence of a family history of atopy. However, a few studies have raised the question of the aggravation of eczema during prolonged breast feeding. The "breast fed" group is probably not a homogenous group. Mothers' milk contains IgA, TGFb-type cytokines and long-chain polyinsaturated fatty acids that may play an important part in the acquisition of tolerance to food and the prevention of atopic dermatitis. The administration of a protein hydrolysate is preferable in terms of prevention of an allergy to a formula based on cow's milk, but does not provide any benefit compared with breast feeding. The preventive effect on atopic dermatitis of a casein hydrolysate is greater than that of a partial hydrolysate, which itself is greater than a formula based on cow's milk. In conclusion, the first preventive measure is breast feeding for 3 to 4 months, associated with intensive protein hydrolysate in the case of mixed feeding. In the absence of breast feeding, intensive hydrolysate is recommended in children at high risk. B) The curative interest of infants' food in the management of atopic dermatitis. The curative interest implies the responsibility of food in the triggering-off or maintenance of atopic dermatitis. This concerns non-diversified infants exhibiting severe or moderate eczema concomitant to digestive disorders. In such cases, the diagnosis of food allergy should be evoked. If the infant is fed on industrial milk, a test diet should be proposed with a hydrolysate or based on amino acids, followed by the re-introduction of the formula used previously. If the infant is exclusively breast fed, diagnosis of an allergy to one of the foodstuffs ingested by the mother should be searched for and treated. Early diagnosis of food allergy in infants, before diversification, is the optimal factor of prognosis.

Breast Feeding↗

Production of interleukin-5 and the suppressive effect of cyclosporin A in childhood severe atopic dermatitis.

A child with severe atopic dermatitis had marked improvement with oral cyclosporin A (CyA) therapy. The function of activated T lymphocytes and serum interleukin-5 concentrations were reduced. The expression and production of interleukin-5 were high, but were suppressed during CyA therapy and by CyA in vitro. Oral CyA therapy may be useful for severe atopic dermatitis.

Child, Preschool↗

Differences in lymphocyte proliferative responses to food antigens and specific IgE antibodies to foods with age among food-sensitive patients with atopic dermatitis.

BACKGROUND: Clinical symptoms of patients with food-sensitive atopic dermatitis often improve with increasing age. OBJECTIVE: To investigate this tendency and the underlying mechanism. METHODS: We selected and divided 194 food-sensitive atopic dermatitis patients into three age groups. The proliferative responses of peripheral blood mononuclear cells (PBMCs) to food antigens and specific IgE antibodies to foods then were evaluated with respect to age. We also followed up 55 food-sensitive patients with atopic dermatitis and examined their improvement ratio after 1 year. Further, we investigated changes in lymphocyte proliferative responses to food antigens and specific IgE antibodies to foods in food-sensitive patients with atopic dermatitis during elimination diets. RESULTS: Proliferative responses of PBMCs to ovalbumin of patients in the over 6-years-old group were significantly (P < .05) lower than those of the less than 1-year-old group. Proliferative responses of PBMCs to bovine serum albumin of patients in the over 6-years-old group were significantly (P < .05) lower than those in the 1 to 5-year-old group and in the less than 1-year-old group. RAST values for hen egg in the over 6-years-old group were significantly (P < .05) lower than those for the less than 1-year-old group. Improvement was shown by 13 of the 33 hen egg-sensitive patients with atopic dermatitis, an improvement ratio of 39%, and by 9 of the 22 cow milk-sensitive patients with atopic dermatitis, an improvement ratio of 41%. Proliferative responses of PBMCs to food antigens in food-sensitive patients with atopic dermatitis decreased rapidly after patients were placed on elimination diets. CONCLUSION: The PBMC proliferative responses to food antigens and RAST values were higher for young children and lower for older ones who suffered from food-sensitive atopic dermatitis. Oral tolerance, in addition to the development of digestive and absorptive functions, may be responsible for these immunologic changes.

Adolescent↗

Contact sensitivity to flavourings and perfumes in atopic dermatitis.

16 children with atopic dermatitis and 4 nonatopics were skin tested with flavourings and perfumes. Immediate reactions to balsam of Peru and fragrance-mix were found in 9 atopics, and none among nonatopics. An irritant is more probable than an immunologic mechanism. Allergen solutions should probably be assayed at a lower concentration in atopic patients. This study points to a possible aggravating factor from perfumes and flavourings ingested, inhaled, or used as cosmetics.

Child↗

How epidemiology has challenged 3 prevailing concepts about atopic dermatitis.

We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple cause-and-effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgE-mediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a co-manifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.

Asthma↗

The development of a practical and reliable assessment measure for atopic dermatitis (ADAM).

Previous measures of Atopic Dermatitis (AD) have not been adequate for research purposes. This paper describes a study conducted in dermatology clinics of the Royal Children's Hospital, Melbourne, Australia, to develop a reliable, valid and practical measure. A pool of items to describe both site and morphology of AD was generated from a literature survey and expert opinion. Selected items were incorporated into a measure with each item rated on a four point scale. The measure was piloted and revised to a simpler format and called the Atopic Dermatitis Assessment Measure (ADAM). Unidimensionality was established. Reliability was determined by comparing two doctors blind ratings on 51 patients (mean age = 70 months). Agreement varied depending upon site and morphology with more agreement on "mild" AD than on "severe" AD. These results imply that operational definitions of the scales need to be defined more clearly. The measure satisfies the assumptions for a partial credit analysis.

Adolescent↗

Double-blind crossover trial comparing systemic chromosome-carboxylic acid with placebo in patients with atopic dermatitis.

35 adult patients with atopic dermatitis were included in a double-blind crossover trial comparing chromone-2-carboxylic acid, FPL 57787 18 mg x 4, with placebo. Each treatment period lasted for 6 weeks with clinical assessment every 3 weeks. 28 patients completed 3 weeks of each period. Significant differences at the 5% level in favour of FPL 57787 were seen in the group starting on placebo. 17 patients completed the study. After 6 weeks there were no significant differences. 10 patients experienced dyspeptic side-effects. Further studies are warranted on clearly allergic sub-groups of atopic dermatitis patients.

Adolescent↗

Canine atopic dermatitis: new targets, new therapies.

Atopic dermatitis is a common allergic skin disease of complex etiopathogenesis in both humans and dogs. Immediate-type hypersensitivity to environmental allergens that arises as a result of environmental and genetic factors is a major part of the pathogenesis in most but not all patients. Alterations in epidermal barrier function, priming of cutaneous antigen-presenting cells with IgE, intrinsic keratinocyte defects, and even development of autoimmunity are also factors that contribute to the primary disease. Secondary factors, especially infections with Staphylococcus and yeast organisms, strongly influence the course of this skin disease. The relatively recent understanding of the complexities of atopic dermatitis has resulted in changes in diagnostic and therapeutic strategies for the disease. We now know that the best therapeutic approach is to use combinations of multiple modalities individualized for each patient over the course of his or her lifetime.

Animals↗

Alpha interferon treatment in atopic dermatitis.

Eight patients suffering from atopic dermatitis were treated with interferon alpha 2b. They received low or intermediate doses (9-15 x 10(6) U/week) for a short period of time (4-8 weeks), with a moderate improvement of skin lesions in 4 of them and no change or an exacerbation of the disease in the other 4. Among the 4 patients who slightly improved at 4 weeks, 3 did not show any beneficial effect of interferon after 8 weeks. Serum IgE levels, which were increased in all patients before treatment, were not reduced under interferon therapy. This study shows that intermediate doses of interferon alpha 2b are not effective in the short-term treatment of atopic dermatitis.

Adult↗

Efficacy of gamma-linolenic acid in the treatment of patients with atopic dermatitis.

Of 60 patients with atopic dermatitis (30 males and 30 females, 15-30 years old) 30 were treated with gamma-linolenic acid of (C18:3 n-6) at a dosage of 274 mg twice a day; the other 30 patients were given placebo. The patients were treated for 12 weeks, during which their symptoms were assessed on a linear scale both by a dermatologist and by themselves every 4 weeks. The patients who received gamma-linolenic acid, showed gradual improvements in pruritus, erythema, vesiculation and oozing, which were statistically significant compared with the control group (P < 0.001). Only one patient had presented with scaling at the beginning of the study and this symptom appeared to be less influenced by the effects of gamma-linolenic acid. The assessments of symptoms made by the dermatologist were generally consistent with those made by the patients themselves. gamma-linolenic acid was found to be effective and without side-effects for the treatment of atopic dermatitis.

Adolescent↗

Effect of Mycobacterium vaccae on cytokine responses in children with atopic dermatitis.

The increasing prevalence of atopic diseases over the last few decades is thought to be due to reduced exposure to environmental microbes that normally down-regulate allergic responses (hygiene hypothesis). We have shown previously that administration of the environmental microbe Mycobacterium vaccae ameliorates atopic dermatitis in school-age children at 3 months post-treatment. The present study tested the hypothesis that M. vaccae suppresses Th2-type cytokine activity and increases transforming growth factor (TGF)-beta(1) immunomodulatory activity in these children. Interleukin (IL)-4, IL-5, TGF-beta(1) and interferon (IFN)-gamma activity were assessed in resting and stimulated peripheral blood mononuclear cells (PBMC) isolated from 12 of the children who received M. vaccae in our original clinical trial. A cDNA expression array was used to examine a broader range of cytokine pathway transcripts. There were no significant changes in either Th2-type or TGF-beta(1) activity. A 5- to 10-fold increase in Th1-type activity was found at 1 month post-M. vaccae administration (P < 0.05), but it had returned to baseline by 3 months. The results do not support the hypothesis that M. vaccae reduces Th2-type or increases TGF-beta(1) activity of PBMC isolated from children with atopic dermatitis. The transient surge in IFN-gamma at 1 month is unlikely to explain any improvement in eczema score at 3 months.

Adolescent↗

[A double blind study of the effectiveness of ketotifen in preventing the development of asthma in atopic dermatitis patients].

Many asthmatic children have experienced atopic dermatitis in their younger days. As it is very difficult to cure childhood asthma we attempted to determine the anti-allergic drug effects in preventing the development of asthma by using ketotifen on atopic dermatitis patients. The study was designed as a placebo controlled double blind trial of 128 atopic dermatitis patients aged from 2-34 months. 91 patients were given complete analysis in the study, 33 patients were given only a safety rate and 4 patients were dropped. The 91 patients were followed for 52 weeks. Our primary finding was that the development of bronchial asthma was inhibited in the ketotifen group compared to the placebo controlled group with a statistically significant degree (p less than 0.001). We also found that clinical symptoms of atopic dermatitis were significantly improved in the ketotifen group (p less than 0.001). Only 5 patients complained of mild side effects.

Age Factors↗

Monocyte phosphodiesterase abnormalities and dysregulation of lymphocyte function in atopic dermatitis.

The immunologic aberrations associated with atopic dermatitis include the paradox of reduced cell-mediated immune responses in the setting of increased cell-mediated immunity features that resemble allergic contact dermatitis. In this review, we present evidence that abnormalities in monocytes and Langerhans cells alter the function of T-helper-cell subpopulations to cause the immunologic defects associated with atopic dermatitis. Increased monocyte prostaglandin E2 production inhibits Th1 responses, accentuating interleukin (IL)-4 secretion by Th2 cells. Elevated prostaglandin E2 secretion correlates with abnormally increased cyclic adenosine monophosphate-phosphodiesterase activity in monocytes and this, along with other defective inflammatory cell responses, can be normalized in vitro by phosphodiesterase inhibitors. It appears that in addition to prostaglandin E2, IL-10 acts to regulate the balance between Th1 and Th2 functional responses accounting for many atopic features, including increased IL-4, IL-5, and IL-6 production by T cells; increased IgE synthesis; decreased interferon-gamma production; and impaired cell-mediated immune responses. All of these abnormalities can be related to increased phosphodiesterase activity in atopic monocytes, and inhibition of this key enzyme appears to reverse atopic dermatitis inflammatory abnormalities in vitro and in vivo.

Animals↗

Interleukin-1 release from peripheral blood monocytes and soluble interleukin-2 and CD8 receptors in serum from patients with atopic dermatitis.

In 31 adult patients with atopic dermatitis, the capacity to secrete interleukin-1 (IL-1) from peripheral blood mononuclear cells and from purified monocytes was investigated following stimulation with lipopolysaccharide. We also measured soluble interleukin-2 receptor levels (sIL-2R) and CD-8 receptor in serum from some of the patients in order to estimate the degree of lymphocyte stimulation in vivo. We observed that purified monocytes from patients with atopic dermatitis released more IL-1 than unseparated blood mononuclear cells did and also had significantly greater IL-1 activity than non-atopic donors. Addition of histamine in concentrations of 10(-7) to 10(-4) M did not suppress, but rather augmented the IL-1 activity release. An increased monocyte-IL-1 release could lead to increased T lymphocyte activity. We observed that 60% of the patients had increased sIL-2R concentrations in serum. There was no correlation between serum IgE and sIL-2R. Our observations indicate that monocytes in atopic dermatitis patients release increased quantities of IL-1, supporting an augmented T lymphocyte activation in the patients.

Adult↗

Impaired responses of peripheral blood mononuclear cells to staphylococcal superantigen in patients with severe atopic dermatitis: a role of T cell apoptosis.

Staphylococcus aureus colonization is an almost universal feature of atopic dermatitis. In order to investigate the role of staphylococcal enterotoxin B in the pathogenesis of atopic dermatitis, we assessed the correlation between clinical disease severity and proliferative response of peripheral blood mononuclear cells to staphylococcal enterotoxin B in patients with atopic dermatitis. Peripheral blood mononuclear cells from patients with mild atopic dermatitis showed significantly increased proliferative responses to staphylococcal enterotoxin B compared to controls. In contrast, peripheral blood mononuclear cells from patients with severe atopic dermatitis showed markedly suppressed proliferative responses. Additionally, longitudinal evaluation of peripheral blood mononuclear cell samples from the same patient demonstrated that proliferative responses were suppressed only at times of severe disease exacerbation. Mixing experiments, using autologous T cells and antigen presenting cells that were isolated at different time points from the same patient, demonstrated that T cells of severe atopic dermatitis patients were dysfunctional, but their antigen presenting cell function remained intact. We found no significant differences of interleukin-2 levels in the culture supernatants between healthy controls and atopic dermatitis groups. Fluorescence-activated cell sorter analysis for APO2.7 antigen, an early apoptosis cell marker, demonstrated that approximately 60% of staphylococcal-enterotoxin-B-stimulated T cells expressed APO2.7 antigen in severe atopic dermatitis cases. By contrast, 5%-20% of T cells expressed APO2.7 after staphylococcal enterotoxin B stimulation in cases of mild atopic dermatitis and in healthy controls. Nuclear staining with Hoechst 33258 also showed approximately 40% apoptotic cells in the CD19-CD16-PBMC of severe atopic dermatitis patients, compared with only 5%-10% in the mild atopic dermatitis group and in healthy controls. Blocking monoclonal antibody to Fas ligand partially prevented the staphylococcal-enterotoxin-B-induced apoptosis detected by APO2.7 expression and Hoechst 33258 staining. Suppressed proliferation of peripheral blood mononuclear cells in severe atopic dermatitis patients may be secondary to T cell death by apoptosis. These results suggest that an infection of S. aureus producing staphylococcal enterotoxin B may play a role in aggravation of atopic dermatitis by inducing apoptosis in T cells.

Adult↗