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Atopic dermatitis and systemic autoimmune diseases: a descriptive cross sectional study.

Atopic dermatitis (AD) has a Th2 (T-helper 2) immune-reactivity pattern. However, the majority of systemic autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and insulin dependent diabetes mellitus show a Th1 (T-helper 1) reactivity pattern. From this, one may hypothesize that AD and the Th1 autoimmune diseases could be inversely associated and AD may be more common in the minority of autoimmune diseases with a Th2 overactivity pattern such as systemic lupus erythematosus. A cross sectional study was designed. Our patients were enrolled from a general university hospital (all systemic autoimmune patients in every medical ward based on definite diagnoses in their medical records). Information on atopic dermatitis was obtained by questionnaires and physical examination by a dermatologist. A total of 63 patients were studied; 17.5 percent of cases had atopic dermatitis in the past or present. There were 31 patients 49.2 %) who carried a diagnosis known to be associated with Th1 reaction, and 21 patients (33.3 %) who had a disease associated with Th2-type reactivity. In 11 patients (17.5 %) the T-cell reaction type was not definitively classified. The relative frequency of AD was 9.7 percent (3 of 31 cases) in Th1-related autoimmune diseases, 28.6 percent (6 of 21 cases) in Th2-related autoimmune diseases and 18.2 percent (2 of 11 cases) in the unclassified category, a difference not statistically significant. Although the power of this study is not high enough to show a statistical significance, AD seems to be uncommon in patients with autoimmune diseases associated with Th1 overactivity.

Adolescent↗

[Immunologic response in patients with atopic dermatitis].

It is a well known fact that atopic dermatitis, as one of the clinical manifestations of atopic syndrome, is characterized by a number of immunologic disorders. In 17 patients with atopic dermatitis we examined: systemic cellular immunity, production of total serum IgE, specific IgE to certain aero-allergens, cutaneous hypersensitivity of an early type to aero-allergens and chemotaxis activity of neutrophils and monocytes. Increased production of IgE proved to be the main disorder which confirms increased values of the total IgE in serum, specific IgE to inhalatory allergens and cutaneous hypersensitivity of an early type to inhalatory allergens in 11 (64.70%) patients. In regard to aero-allergens the most common atopics are pollens and Dermatophagoides pteronyssinus. Decreased number of CD8+ T-lymphocytes and decreased chemotaxis activity of neutrophils was established in some cases.

Adolescent↗

Atopic dermatitis and Sézary syndrome.

A patient with severe atopic dermatitis had pre-Sézary and Sézary syndromes. Although elevated serum IgE values in mycosis fungoides and Sézary syndrome are not infrequent, the direct sequential occurrence of atopic dermatitis and Sézary syndrome is uncommon. The clinical and laboratory changes we observed imply that the relationship of these disorders may be conditioned by changes in immunoresponsiveness.

Adult↗

Comparison of cyclosporin and UVAB phototherapy for intermittent one-year treatment of atopic dermatitis.

Although cyclosporin is effective for the treatment of severe atopic dermatitis, phototherapy is the standard second-line treatment for this disease. An open, randomized, controlled, parallel-group study was conducted to compare the efficacy, influence on quality of life and safety of cyclosporin and UVAB phototherapy during 1 year of intermittent treatment of atopic dermatitis in adult patients. The main endpoints of the study were the number of days in remission and the influence on quality of life. Seventy-two patients were treated, 36 in each group. Cyclosporin produced significantly more days in remission than UVAB phototherapy during the 1-year study period. At the end of the study no difference between the 2 groups was noted in terms of quality of life. A significant increase in serum creatinine occurred in 2 patients and 7 patients developed mild or moderate hypertension during cyclosporin treatment. It can be concluded that intermittent cyclosporin seems to be more effective than UVAB and is reasonably safe for the treatment of atopic dermatitis over a 1-year treatment period.

Administration, Topical↗

Food allergy and atopic dermatitis in low birthweight infants during early childhood.

UNLABELLED: The prevalence rates of food allergy and atopic dermatitis in low birthweight infants were evaluated. In Fukuoka City, Japan, between July 1994 and September 1997, sufficient information including birthweight, gestational age, sex, feeding method and a history of food allergy was obtained from questionnaires at the well-baby check-ups of 21766 infants (18 mo of age) and 4378 children (3 y of age). All the children were examined by pediatricians with regard to the existence of atopic dermatitis. The prevalence rate (8.1%) of food allergy in infants with low birthweight (<2,500 g) was significantly lower than that (11.2%) in infants with normal birthweight (> or = 2,500 g) at 18 mo of age (p = 0.0002). Atopic dermatitis was also observed at a lower prevalence rate (1.2%) in infants with low birthweight than in those with normal birthweight (2.3%) at the same age (p = 0.0041). However, this significance was lost at 3 y of age. Other characteristics including male sex and breast-feeding showed independent risks for the development of food allergy and atopic dermatitis at both ages. CONCLUSION: This study found that low birthweight was significantly associated with a lower risk of both food allergy and atopic dermatitis at 18 mo of age.

Breast Feeding↗

Randomised double-blind placebo-controlled trial of local cyclosporin in atopic dermatitis.

The efficacy of local applications of 10% cyclosporin gel was studied in a randomised double-blind placebo-controlled trial in atopic dermatitis. Twenty atopic patients, presenting with stable symmetrical lesions, participated in the study. They applied cyclosporin gel to one side and placebo gel to the other side twice a day. The lesions were assessed on day 0 and day 14 according to lesional criteria scored from 0 to 3. The mean score for each criterion on day 14 was significantly lower on the sides treated with cyclosporin than on the sides treated with placebo. The total mean score on day 14 was 6.1 +/- 3.9 on the sides treated with CSA and 9.6 +/- 3.9 for placebo (p less than 0.005). These findings suggest the efficacy of local CSA applications on lesions of atopic dermatitis.

Administration, Cutaneous↗

Combined skin prick and patch testing enhances identification of food allergy in infants with atopic dermatitis.

BACKGROUND: Early recognition of dietary allergies in infants with atopic dermatitis is essential for avoidance of unnecessary elimination diets, amelioration of the skin disease, and secondary prevention of the development of multiple food allergies. Simple and accurate methods of identifying provocative foods are urgently needed. METHODS: The usefulness of skin prick and patch tests as indicators of cow milk allergy was evaluated in 183 patients ranging in age from 2 to 36 months with double-blind, placebo-controlled (n = 118) or open (n = 65) cow milk challenges. RESULTS: The oral cow milk challenges were interpreted as positive in 54% of both challenge types. Positive challenge rapidly elicited pruritus, urticaria, and/or exanthema in 49% of cases and delayed-onset eczematous lesions in 51%. The skin prick and patch tests gave markedly discrepant results; prick tests were positive in 67% of the cases with acute-onset reactions to milk challenge, whereas patch tests tended to be negative. Patch tests were positive in 89% of those with delayed-onset reactions, although prick tests were frequently negative. CONCLUSIONS: The observations indicate that IgE and T cell-mediated responses to cow milk can be distinguished in atopic dermatitis. Parallel skin testing with combined prick and patch tests can significantly enhance the accuracy in diagnosis of specific dietary allergies in patients with atopic dermatitis.

Animals↗

Basophil mediator release in atopic dermatitis.

Basophils have been implicated as a source of histamine and pro-inflammatory eicosanoids in atopic dermatitis. However, mechanisms regulating basophil mediator release are not understood. An H3 receptor involved in the control of histamine synthesis and release has been identified in nervous tissue. In this study we have investigated 1) release of histamine, leukotriene C4, and prostaglandin D2 from anti-immunoglobulin E (IgE)-stimulated basophils of adults with atopic dermatitis and unaffected individuals and 2) specific H3 receptor-dependent basophil mediator release, using an H3 receptor agonist and antagonist. Basophil-rich leukocyte fractions were prepared by dextran sedimentation of venous blood from 19 patients with atopic dermatitis (five male, 14 female, mean age 30.6 years, range 19-59 years) and 15 unaffected individuals (five male, 10 female, mean age 27.6 years, range 19-50 years). Anti-IgE (0.78-78.0 micrograms/ml) stimulation of basophils induced a concentration-dependent release of histamine and leukotriene C4, but not prostaglandin D2. Histamine release was maximally induced by 7.8 micrograms/ml anti-IgE with no significant (Mann-Whitney U test) difference between atopic basophils (n = 17; 43.65 +/- 4.16% mean +/- SEM) and normal basophils (n = 13; 52.23 +/- 4.39%). LTC4 release was maximal from atopic basophils incubated with 2.6 micrograms/ml anti-IgE (n = 5; 0.99 +/- 0.29 pg/10(6) cells) and from normal basophils incubated with 0.78 microgram/ml anti-IgE (n = 5; 25.38 +/- 5.79 pg/10(6) cells). Anti-IgE-stimulated release of leukotriene C4 from atopic basophils was significantly less than from normal basophils at all concentrations (p < 0.05). Basophils were co-incubated with anti-IgE (2.6 and 7.8 micrograms/ml) and either the H3 receptor agonist, (R)alpha-methylhistamine (10(-8) and 10(-7) M), or the H3 receptor antagonist thioperamide (10(-6) and 10(-5) M). Neither drug modulated anti-IgE-induced release of histamine (atopics, n = 10; normals, n = 8). These results indicate 1) that basophils from adults with atopic dermatitis release the same amount of histamine as, but less leukotriene C4 than, basophils of unaffected adults and 2) that H3 receptors are not involved in anti-IgE release of histamine from basophils. These data do not support a role for increased basophil release of histamine as a mediator in the itch and erythema of atopic dermatitis in adults.

Adult↗

Expression of dipeptidyl-peptidase IV (CD26) on CD8+ T cells is significantly decreased in patients with psoriasis vulgaris and atopic dermatitis.

T cells play a major role in inflammatory skin disorders such as psoriasis vulgaris and atopic dermatitis. They are both active on the level of cell-to-cell interaction and by the secretion of pro-inflammatory mediators. CD26 is a lymphocyte membrane-associated dipeptidyl peptidase IV (DPP IV), which is able to inactivate chemokines such as RANTES or eotaxin by cleaving dipeptides from the NH2-terminus of proteins. We investigated the expression of CD26 on CD4+ and CD8+ peripheral blood T cells in patients with psoriasis and atopic dermatitis. In addition PASI and SCORAD as a measure of disease severity were determined in each patient at the time of blood drawing. Thirty patients with psoriasis, 15 with atopic dermatitis and 17 age- and sex-matched healthy persons were investigated by two-colour flow cytometry using epitope-specific monoclonal antibodies. Our results revealed, that there is a significant decrease (P<0.05) of CD26 expression on CD8+ T cells in both psoriasis (7.7%+/-3.3, mean and SD, n=30) and atopic dermatitis patients (7.9%+/-3.7, mean and SD, n=15) compared to the control population (11.58%+/-5.0, mean and SD, n=17). However, there was no correlation to disease severity as determined by PASI and SCORAD, respectively. Since CD26 can be regarded as an anti-inflammatory principle the decreased expression in psoriasis and atopic dermatitis patients may lead to a dysbalance in favour of pro-inflammatory mediators in both clinical conditions.

Adolescent↗

Advances in pediatric asthma and atopic dermatitis.

PURPOSE OF REVIEW: Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. RECENT FINDINGS: With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. SUMMARY: Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.

Albuterol↗

Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life.

OBJECTIVES: To determine whether early infectious diseases could explain the association between number of siblings and other markers of microbial exposure and the development of atopic dermatitis before the age of 18 months. DESIGN: Cohort study. Information on atopic dermatitis, infectious diseases occurring before 6 months of age, number of siblings, early day care, pet keeping, farm residence, and background factors was collected in telephone interviews. SETTING: Danish national birth cohort. PARTICIPANTS: 24,341 mother-child pairs. MAIN OUTCOME MEASURES: Incidence rate ratios of atopic dermatitis. RESULTS: 13,070 children (54%) had at least one clinically apparent infectious disease before 6 months of age. At age 18 months, 2638 (10.8%) of the children had had atopic dermatitis. The risk of atopic dermatitis increased with each infectious disease before 6 months of age (incidence rate ratio 1.08, 95% confidence interval 1.04 to 1.13). The risk of atopic dermatitis decreased with each additional exposure to three or more siblings, day care, pet ownership, and farm residence (0.86, 0.81 to 0.93). CONCLUSIONS: Early infections do not seem to protect against allergic diseases. The protective effect of number of siblings, day care, pet ownership, and farm residence remained after adjustment for clinically apparent infectious diseases, suggesting that the effect is established independently early in life.

Age Distribution↗

The morphologic characteristics of dry skin in atopic dermatitis.

Uninvolved skin sites in 436 consecutive patients, 6 to 25 years old, with atopic dermatitis were observed during the winter months (from November to February). Ichthyosis vulgaris occurred in 133 patients. Of the 303 remaining patients, only 11 (4%) had generalized dry skin; 191 (63%) exhibited focal areas of dry skin; and 95 (33%) showed only normal-appearing skin. Microscopically, in 41 patients, dry skin associated with atopic dermatitis showed mild eczematous changes. Dry skin coexistent with ichthyosis in patients with atopic dermatitis revealed ichthyotic changes frequently superimposed on eczematous changes. We suggest that in patients with atopic dermatitis the presence of dry skin may reflect mild eczematous changes, a manifestation of concomitant ichthyosis, or a complex of both of these changes.

Adolescent↗

Dosage and adverse effects of topical tacrolimus and steroids in daily management of atopic dermatitis.

Since 1999, combination therapy with tacrolimus and topical steroids has been widely used for the treatment of adolescent/adult-type atopic dermatitis. In order to determine the clinical doses of topical tacrolimus and steroids for daily treatment of atopic dermatitis and to elucidate their beneficial and adverse effects, we analyzed the clinical data from 215 patients with atopic dermatitis who were more than 16 years old. Less than 70 g of tacrolimus and less than 15 g of steroids were applied to 90% of the patients on the face and neck, and less than 75.8 g of tacrolimus and less than 322 g of steroids were applied to 90% of the patients on the trunk and extremities during the six-month treatment period. Topical tacrolimus is much more frequently used on face and neck lesions (99.1%); in only 39.5% of cases was it used on the trunk and extremities. The majority of patients improved after six months of the combination topical therapy; however, atopic dermatitis was not controlled in 6% of the patients. The combination therapy did not seem to increase the risk of cutaneous infections; however, the incidence of herpes simplex infection on the face and neck was 2.8% at pre-treatment and slightly increased to 4.7% during the therapy. The incidence of all steroid-induced adverse effects was reduced both in frequency and intensity with a decrease in the dose of topical steroids through simultaneous tacrolimus application. Combination therapy with topical tacrolimus and steroids is useful for treating atopic dermatitis, but a small percentage of the patients still cannot be satisfactorily treated. For such patients, adjustments of the dose and rank of topical steroids and tacrolimus and other therapeutic adjuncts are necessary.

Administration, Cutaneous↗

Topical noncorticosteroid immunomodulation in the treatment of atopic dermatitis.

At present, the first-line drugs for treating atopic dermatitis are topical corticosteroids. They are effective when used short-term; however, long-term use of the corticosteroids is associated with suppressive effects on the connective tissue, seen as skin atrophy or resistance to therapy. Currently, two topical noncorticosteroid immunomodulators tacrolimus (FK506) and pimecrolimus (SDZ ASM 981) are under development, or already on the market in some countries for atopic dermatitis. These two compounds show structural similarity. In T lymphocytes they bind to the same cellular receptor, the FK-binding protein (FKBP) or macrophilin-12. Tacrolimus shows a 3-fold greater affinity to FKBP compared with pimecrolimus. The tacrolimus/ pimecrolimus-FKBP complex further binds to calcineurin, an enzyme vital for the early activation of T cells. The consequence of calcineurin binding is a lack of activation of both T helper cell types 1 and 2. Further effects of these compounds have been suggested on other inflammatory cells, such as Langerhans cells and mast cells/basophils. In contrast to corticosteroids, no suppressive effects on connective tissue cells have been observed. Taken together, treatment of inflammation results in healing of the barrier function of the skin. This again results in reduced bioavailability of the drug, as compared with systemic use. Placebo-controlled studies have shown the efficacy of both tacrolimus (at 0.03 and 0.1%) and pimecrolimus (at 0.6 and 1%). The main adverse event in these studies has been a burning sensation and increased pruritus at the site of application. Typically, these adverse events are observed only during the first days of treatment. Long-term safety studies, of up to one year, have not revealed any new adverse events. So far, long-term use of topical noncorticosteroid compounds has not been associated with signs of immune deficiency. Although there is currently no evidence for clinically relevant, prolonged adverse effects, some of these, such as an increased risk of photocarcinogenesis, need to be monitored. There is evidence from tacrolimus studies that monotherapy results in better long-term results when compared with combination therapy with corticosteroids. Tacrolimus and pimecrolimus could replace topical corticosteroids as the first-line treatment of atopic dermatitis.

Adjuvants, Immunologic↗

Reduced histamine reaction in atopic dermatitis.

Vascular reactivity to intracutaneously injected histamine phosphate was examined in both the normal and affected skin of 50 patients with atopic dermatitis and 30 patients with allergic contact dermatitis. Reduced histamine reactions occurred consistently in the slightly lichenified skin of patients with atopic dermatitis and in skin sites of allergic contact dermatitis. The normal skin of patients with atopic dermatitis usually showed normal erythematous reactions to intracutaneously injected histamine. It seems likely that the reduced histamine reaction seen in the lesions of atopic dermatitis is a secondary phenomenon.

Adolescent↗

IL-16 serum level in children with atopic dermatitis.

IL-16 is a natural ligand of CD4 molecules and induces chemotaxis in CD4-expressing cells. It amplifies the inflammatory reaction by stimulating cytokine production in monocytes and activating T-cells. There is evidence that IL-16 plays a role in the pathogenesis of atopic dermatitis, and increased serum levels of IL-16 have been detected in allergic diseases. However, few data are available on IL-16 serum levels in atopic dermatitis. The aim of our study is to measure IL-16 serum levels in childhood atopic dermatitis before and after treatment and to evaluate a possible correlation between IL-16 serum levels and disease severity. IL-16 serum levels were measured by an ELISA approach in 34 children (19 males and 15 females; mean age 6.8 years) with moderate to severe atopic dermatitis, at their first visit and after 3 months of treatment, and in 10 non-atopic healthy controls of the same age group. The severity of atopic dermatitis was measured by SCORAD index. IL-16 serum levels were significantly higher in patients affected by atopic dermatitis than in controls before and after treatment with tacrolimus ointment. No clear correlation was found between IL-16 serum levels and atopic dermatitis severity. IL-16 serum levels are increased in atopic dermatitis but do not seem to correlate with disease severity.

Adolescent↗

A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients.

The safety and efficacy of 0.03% and 0.1% tacrolimus ointment for the treatment of atopic dermatitis were evaluated in a 12-week, randomized, double-blind, vehicle-controlled study of 351 children 2 to 15 years of age with moderate to severe atopic dermatitis. The mean age of patients was 6.1 years. A total of 61.5% of patients had severe atopic dermatitis at baseline. The mean percentage of body surface area affected was 47.7%, and 83.5% of patients were affected on the head and/or neck. Significantly more patients (P<.001) achieved clinical improvement of 90% or better with 0.03% or 0.1% tacrolimus ointment compared with vehicle. Significant improvements in the signs and symptoms of atopic dermatitis, percent body surface area affected, and the patient's assessment of pruritus were also observed early in treatment and were maintained throughout the study. Adverse events with a statistically significantly greater incidence in the 0.03% tacrolimus ointment treatment group compared with vehicle were limited to the sensation of skin burning, pruritus, varicella, and vesiculobullous rash ("blisters"). Varicella and vesiculobullous rash occurred at a low incidence (<5%). No adverse event occurred at a statistically higher incidence in the 0.1% tacrolimus ointment-treated group compared with vehicle. Tacrolimus ointment was equally safe for younger (2-6 years) and older (7-15 years) children. Both tacrolimus ointment concentrations (0.03% and 0.1%) were safe and significantly more effective than vehicle for the treatment of atopic dermatitis in children.

Adolescent↗

Absence of association between a variant of the mast cell chymase gene and atopic dermatitis in an Italian population.

Atopic dermatitis (AD) is a chronic dermatitis which belongs to the group of atopy-related diseases together with asthma and rhinitis. IgE and mast cell chymase (MCC) play a key role in atopic or allergic inflammation of the skin. An association between AD and a genetic variant of the MCC has been reported in a Japanese population, but failure of confirmation has rendered this association questionable. We have tested for genetic association to an MCC variant in relation to AD in an Italian population. No significant association was found between AD and MCC genotypes. These data suggest that BstXI MCC polymorphism may not be involved in AD.

Adolescent↗