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Histamine helps development of eczematous lesions in experimental contact dermatitis in mice.

Histamine is released from mast cells in the skin, causing urticaria and itching. However, little is known about the roles of histamine in development of eczematous lesions in contact dermatitis. Effects of histamine on development of eczematous lesions in contact dermatitis were assessed using histamine-deficient mice in which contact dermatitis was developed by repeated application of diphenylcyclopropenone. Development of eczematous lesions in contact dermatitis was suppressed in histamine-deficient mice compared to wild-type mice. H(1) agonist ((6-12-(4-imidazol)ethylamino)-N-(4-trifluoro- methylphenyl)hepatanecarboxamide) promoted development of eczematous lesions in histamine-deficient mice. H(1) receptor antagonist (loratadine) suppressed development of eczematous lesions in wild-type mice, whereas H(2) agonist (dimaprit) and receptor antagonist (cimetidine) were ineffective. These results suggest that histamine facilitates the development of eczematous lesions in a murine model of contact dermatitis via H(1) receptors.

Animals↗

Regulation of peripheral blood mononuclear cell responses to Dermatophagoides farinae by substance P in patients with atopic dermatitis.

Neuropeptides mediate stress-induced cutaneous inflammation such as atopic dermatitis. The effect of substance P on proliferation and cytokine mRNA expression of peripheral blood mononuclear cells in response to Dermatophagoides farinae (Der f) was studied in atopic dermatitis patients with positive RAST scores to Der f. Upon stimulation with Der f peripheral blood mononuclear cells from patients proliferated in a B7-dependent (CD80- and CD86-dependent) manner, while those from the patients with negative scores, nonatopic eczematous dermatitis patients or normal individuals, did not. Based on the reactivity of normal individuals, atopic dermatitis patients with a stimulation index greater than 1.8 were tentatively defined as high responders, who comprised two-thirds of the patients. Proliferation in high responders was associated with upregulation of IL-2 mRNA expression and induction of IL-5 mRNA expression. Substance p at 10(-10) to 10(-8) M promoted the Der f-induced proliferation when added at the start of culture and upregulated IL-10 MRNA expression while downregulating IL-5 mRNA expression. Our results suggest that substance P modifies immune responses of atopic T cells to Der f by promoting proliferation and altering cytokine profiles, and thus modulates the clinical manifestations of atopic dermatitis.

Adolescent↗

Prevention of hand dermatitis in bakers' apprentices: different efficacy of skin protection measures and UVB hardening.

OBJECTIVE: The objective of this controlled intervention study was to quantify the efficacy of skin protection (SP) measures and ultraviolet B (UVB) hardening in the prevention of hand dermatitis in bakers' apprentices. METHOD: SP measures were compared against UVB hardening in a controlled clinical trial of 94 apprentices. The apprentices were assigned to the intervention arms class-wise. Bakers' apprentices involved in a previous follow-up study served as additional controls representing no intervention. The apprentices were interviewed and examined in a standardised way at the beginning of the training and at 4 monthly follow-ups. Transepidermal water loss (TEWL) was measured at the back of the hands. RESULTS: Demographic profile and atopy criteria were equally distributed in the two intervention arms and the control group. Point prevalence of hand dermatitis after 6 months was highest in the controls (29.1%) followed by the UVB (19.4%) and the SP group (13.3%). UVB hardening and SP measures reduced hand dermatitis prevalence by 9.7% (95%CI: -8.5 to 28.1) and 15.7% (95%CI: -2.4 to 33.9), respectively. Application of SP measures reduced the odds ratios (ORs) for hand dermatitis 0.8-fold (95%CI: 0.17-3.70) and 0.33-fold (95%CI: 0.09-1.23) compared with the UVB group and the controls, respectively. These clinical trends were confirmed by statistically significant differences in TEWL values. TEWL values were consistently higher in the UVB group than in the SP group ( P=0.002). CONCLUSIONS: This study provided evidence, based on significant differences in TEWL levels, that general SP measures may be more effective than UV light hardening of the skin, which in turn was more effective than no intervention. This trend was supported by the frequency of development of clinical hand dermatitis, although differences did not reach statistical significance. A multi-centre trial is recommended to confirm the efficacy of SP measures in a larger randomised study.

Adolescent↗

Safety, reactogenicity, and immunogenicity of live attenuated varicella vaccine in children between 1 and 9 years of age with atopic dermatitis.

INTRODUCTION: Infection with varicella-zoster virus (VZV) is known to facilitate secondary bacterial infection, which is cause for particular concern in children with atopic dermatitis. This 2-year study assessed the safety, reactogenicity, and immunogenicity of a live attenuated Oka strain varicella vaccine (Varilrix, GlaxoSmithKline Biologicals) in 160 children aged 1-9 years with atopic dermatitis randomized to vaccination at the start of either the 1st or 2nd study year (VAR-1Y and VAR-2Y, respectively). Mean SCORing Atopic Dermatitis (SCORAD) scores at baseline were 19.3+/-11.1 and 26.0+/-10.4 in the two groups, respectively. RESULTS: Varicella vaccination did not adversely affect the severity of atopic dermatitis, with analysis of variance (ANOVA) confirming equivalence for the change in SCORAD index from baseline to week 8 between vaccinated and unvaccinated subjects. Within-group comparison of post-vaccination changes in SCORAD index from baseline to week 8 and month 12 in the VAR-2Y group showed a greater reduction in mean SCORAD scores following vaccination in year 2 than in year 1 when subjects were unvaccinated. Overall, SCORAD indices fell by approximately 10 points in both study groups over the 2 years of follow-up. Varicella vaccination was well tolerated, with no children withdrawn due to adverse events. Injection site redness was the most frequent solicited adverse event, occurring in 17.1% of subjects. Seroconversion rates were 94.3% at week 8 and 88.9% at month 12. In all, 43.6% of vaccinees reported at least one varicella contact during the course of the study. However, none developed varicella infection after vaccination over the 2 years of follow-up. CONCLUSION: In summary, vaccination with a live attenuated varicella vaccine appears safe and effective in children with atopic dermatitis.

Analysis of Variance↗

Plasma levels of polyunsaturated fatty acids in children with atopic dermatitis and in atopic and nonatopic controls.

BACKGROUND: Atopic dermatitis has been thought to be associated with a disturbance in n-6 polyunsaturated fatty acid (PUFA) metabolism, but randomized trials investigating the clinical efficacy of oral supplementation with gammalinolenic acid have revealed conflicting results. AIM OF THE STUDY: To re-investigate the proposed linkage between PUFA dysregulation and atopic dermatitis. MATERIALS AND METHODS: Plasma levels of linoleic acid (LA), gammalinolenic acid (GLA), dihomogammalinolenic acid (DGLA) and arachidonic acid (AA) were measured using HPLC in 22 children with atopic dermatitis. Patients were subdivided into those with elevated total serum IgE (group A, n = 15, IgE > +1 SD of age-specific normal values) and those with normal IgE (group B, n = 7) and compared with children suffering from allergic rhinitis/asthma (group C, n = 8) and with non-atopic controls (group D, n = 6). RESULTS: GLA levels were significantly lower (p < 0.05) in eczema patients with elevated IgE (A, 0.19 +/- 0.06%) and in atopic controls (C, 0.23 +/- 0.06%) than in eczema patients with low IgE (B, 0.42 +/- 0.19%) and non-atopic controls (D, 0.43 +/- 0.16%). There were no significant differences between groups for LIN, DGLA and AA, except for lower LIN levels in atopic controls. Correlation of individual LA and GLA values showed significantly steeper regression lines in low-IgE responders (B and D, k(x) = 0.058) than in high-IgE responders (A and C, k(x) = 0.012; p < 0.02), suggesting impaired delta-6-desaturase function in the latter. For the study population as a whole, there was a clear negative correlation between total levels of IgE and GLA (r(s) = -0.64) and a moderate negative correlation between total IgE and AA (r(s) = -0.38). CONCLUSIONS: Dysregulation of n-6 PUFA metabolism is neither consistently found in nor specifically associated with atopic dermatitis but rather appears to be associated with IgE production and atopy in general. The finding of decreased GLA levels in eczema patients with elevated total IgE and in children with allergic rhinitis and asthma but not in eczema patients with normal total IgE questions the proposed pathophysiologic role of fatty acid dysregulation in atopic dermatitis.

Asthma↗

HLA and atopic dermatitis with high serum IgE levels.

Patients with atopic dermatitis usually exhibit allergen-specific IgE antibodies against several environmental antigens. HLA restriction is presumed to be involved in the recognition of such antigens, but several previous reports have so far failed to find a significant association between atopic dermatitis and HLA antigens. In this study we examined 38 unrelated Japanese patients with severe atopic dermatitis and high serum IgE levels (greater than 800 U/ml). We investigated the serological HLA types and HLA class II alleles in this group of patients with atopic dermatitis. Frequencies of HLA-A24, A33, Cwblank, B44, DR13 and HLA-DRB1*1302, DQB1*0604, DPB1*0301 alleles were increased in the patients. In contrast, frequencies of HLA-Cw1, Bw6, DR4, DR53, and HLA-DQB1*0302 allele were decreased. However, none of these remained significant after p values were corrected. Further study on HLA association with atopic dermatitis through characterization of specific antigens or antigen epitopes is needed.

Adolescent↗

Eosinophil cationic protein in sera of patients with atopic dermatitis.

Patients with atopic dermatitis frequently show elevated blood eosinophil counts, and eosinophil-derived major basic protein has been demonstrated in the eczematous skin from patients with atopic dermatitis. To evaluate further the role of eosinophils in the pathogenesis of atopic dermatitis, the concentration of eosinophil cationic protein was measured in serum samples of 42 patients with moderate to severe disease. The results were compared with those obtained in 32 patients with psoriasis with (n = 9) or without (n = 23) a history of inhalant allergy, 12 patients with a history of pseudoallergic reactions to acetylsalicylic acid, 14 patients with a history of inhalant allergy, and 31 nonatopic healthy control subjects. Eosinophil cationic protein levels were significantly increased in the serum of patients with atopic dermatitis (p less than or equal to 0.005) and patients with a history of pseudoallergic reactions to acetylsalicylic acid (p less than or equal to 0.01). There was no significant difference between eosinophil cationic protein levels in patients with psoriasis or a history of inhalant allergy and in control subjects. Moreover, eosinophil cationic protein levels did not differ significantly in psoriasis patients with or without inhalant allergy. These studies support the concept of an active participation of eosinophils in atopic dermatitis and point to a possible role for eosinophils in pseudoallergy.

Adolescent↗

High-dose UVA1 therapy in the treatment of patients with atopic dermatitis.

BACKGROUND: Besides glucocorticosteroids, there is currently no known effective therapy for patients with acute atopic dermatitis. OBJECTIVE: The therapeutic effectiveness of high-dose UVA1 irradiation in the management of patients with acute exacerbation of atopic dermatitis was examined. METHODS: Patients in the high-dose UVA1 group (n = 15) were irradiated with 130 joules/cm2 UVA1; the control group (n = 10) was treated with UVA-UVB therapy in a minimal erythema dose-dependent manner (total number of treatments 15). RESULTS: High-dose UVA1 irradiation was found to induce a significant clinical improvement of atopic dermatitis (p less than 0.001). In comparison with UVA-UVB therapy, significant differences in favor of high-dose UVA1 were observed (p less than 0.01). High-dose UVA1, but not UVA-UVB treatment, significantly reduced the elevated serum level of eosinophil cationic protein in patients with atopic dermatitis (p less than 0.003). CONCLUSION: These studies indicate that high-dose UVA1 irradiation may represent a novel phototherapeutic modality for the treatment of patients with an acute exacerbation of atopic dermatitis.

Adult↗

Atopic dermatitis: a genetic-epidemiologic study in a population-based twin sample.

BACKGROUND: Atopic dermatitis is a common multifactorial disease that seems to be increasing in frequency. OBJECTIVE: Our purpose was to evaluate and expand previous findings on the incidence of atopic dermatitis and its concordance rates in twins. METHODS: A mailed questionnaire study was conducted. It involved 812 twin pairs living in Fyn County, Denmark, as of Jan. 1, 1987 and born between 1965 and 1979. Zygosity was determined by the similarity method. RESULTS: The response rate was 92%. The cumulative incidence rate (up to 7 years) of atopic dermatitis increased significantly from 0.06 for the birth cohort 1965-1969 to 0.12 for the birth cohort 1975-1979. The pairwise concordance rate was 0.72 in monozygotic and 0.23 in dizygotic twin pairs. CONCLUSION: The frequency of atopic dermatitis is still increasing but not as rapidly as in the 1960s. The magnitude of the concordance rates indicates that genetic factors are decisive in the development of atopic dermatitis. It is suggested that widespread environmental factors are operating in genetically susceptible persons.

Adolescent↗

Prevention of poison ivy and poison oak allergic contact dermatitis by quaternium-18 bentonite.

BACKGROUND: Poison ivy and poison oak are the most common causes of allergic contact dermatitis in North America. OBJECTIVE: We investigated whether a new topical lotion containing 5% quaternium-18 bentonite prevents experimentally induced poison ivy and poison oak allergic contact dermatitis. METHODS: A single-blind, paired comparison, randomized, multicenter investigation was used to evaluate the effectiveness and safety of quaternium-18 bentonite lotion in preventing experimentally induced poison ivy and poison oak allergic contact dermatitis in susceptible volunteers. One hour before both forearms were patch tested with urushiol, the allergenic resin from poison ivy and poison oak, 5% quaternium-18 bentonite lotion was applied on one forearm. The test patches were removed after 4 hours and the sites interpreted for reaction 2, 5, and 8 days later. The difference in reactions between treated and untreated patch test sites was statistically analyzed. RESULTS: Two hundred eleven subjects with a history of allergic contact dermatitis to poison ivy and poison oak were studied. One hundred forty-four subjects had positive reactions to urushiol. The test sites pretreated with quaternium-18 bentonite lotion had absent or significantly reduced reactions to the urushiol compared with untreated control sites (p < 0.0001) on all test days. When it occurred, the reaction consistently appeared later on treated than on control sites (p < 0.0001). One occurrence of mild, transient erythema at the application site was the only side effect from the quaternium-18 bentonite lotion. CONCLUSION: Quaternium-18 bentonite lotion was effective in preventing or diminishing experimentally produced poison ivy and poison oak allergic contact dermatitis.

Administration, Cutaneous↗

Improvement of skin barrier function during treatment of atopic dermatitis.

BACKGROUND: Active dermatitis causes a disturbance in skin barrier function. This can be evaluated by the measurement of transepidermal water loss (TEWL) and percutaneous absorption of hydrocortisone. OBJECTIVE: The study objective was to evaluate changes in skin barrier function during treatment of atopic dermatitis. METHODS: Nine patients with widespread atopic dermatitis were studied longitudinally by measuring the severity of the dermatitis and TEWL at intervals of 1 to 3 days. Percutaneous absorption of hydrocortisone was measured at entry and during treatment. RESULTS: At entry, both TEWL and percutaneous absorption of hydrocortisone were elevated. Four to six days later, a significant decline was observed in both variables, indicating rapid improvement in skin barrier function. Individual changes in TEWL correlated with the changes in the systemic absorption of hydrocortisone. CONCLUSION: TEWL reflects changes in the systemic absorption of topical hydrocortisone during treatment of atopic dermatitis.

Administration, Topical↗

A speculative view of atopic dermatitis: barrier dysfunction in pathogenesis.

The development of atopy or atopic dermatitis is undoubtedly influenced by immunological abnormality. However, the question of factors which induce tolerance breakthrough and hypersensitivity to non-selective multiple antigens in atopy has remained unanswered. The broad clinical spectrum of this disease cannot be explained simply by allergy or immunological abnormalities. This speculative article is the first attempt to answer these questions and to explain the concept of atopic dermatitis by the barrier dysfunction theory based on our experimental results which demonstrated and increased permeability of the stratum corneum in patients with atopic dermatitis. We consider immunological abnormality and mucocutaneous barrier dysfunction as two major defects of atopy or atopic dermatitis. The wide range of clinical manifestations presented by this disease can be more easily comprehended by partial overlapping of these two core abnormalities. A mucocutaneous barrier defect readily allows penetration of multiple antigens or haptens. Repeated encounters with allergens may induce not only tolerance breakthrough and non-selective hypersensitivities but also enhancement of the allergic inflammation. On the other hand, an allergic inflammation stemming from the immunological abnormalities breaks down barrier functions. This sequence results in a 'vicious circle', which plays the most important role in pathogenesis of atopic dermatitis and probably of other atopic diseases.

Dermatitis, Atopic↗

Allergic contact dermatitis from a natural deodorant: a report of 4 cases associated with lichen acid mix allergy.

BACKGROUND: Botanical ingredients used in personal care products are a significant and underreported cause of allergic contact dermatitis. OBJECTIVE: To evaluate allergic contact dermatitis from a widely-used botanical deodorant. METHODS: We conducted patch testing in four patients who were using the botanical deodorant and were referred to the contact dermatitis clinic; three patients had axillary dermatitis and one had dermatitis of the external ear. RESULTS: All four patients had positive patch test reactions to lichen acid mix and D-usnic acid. Of the three patients who were patch tested to the botanical deodorant, all had positive reactions. LIMITATIONS: We did not test to the specific lichen used in the natural deodorant but rather used our own lichen acid mix and d-usnic acid in addition to testing to the actual product. One of the patients declined to be tested with the natural deodorant, but did test positive to the lichen acid mix and d-usnic acid. CONCLUSION: Personal care products such as deodorants may represent a new route of exposure to lichen extract, a known allergen.

Adult↗

Pilot trial of 1% pimecrolimus cream in the treatment of seborrheic dermatitis in African American adults with associated hypopigmentation.

BACKGROUND: African Americans with seborrheic dermatitis may manifest associated hypopigmenation. Corticosteroids and antifungals are often used for treatment, yet chronic use of corticosteroids may be associated with skin atrophy, increased intraocular pressure, or further hypopigmenation. Pimecrolimus has been used successfully in a few patients with seborrheic dermatitis. OBJECTIVES: This open-label, pilot trial assessed the efficacy and tolerability of pimecrolimus in the treatment of seborrheic dermatitis in African Americans with hypopigmentation. METHODS: Five African American adults with seborrheic dermatitis used a thin layer of pimecrolimus on the involved areas twice per day for 16 weeks. Clinical measures of improvement included erythema, scaling, and pruritus. Hypopigmentation was measured objectively using a mexameter. RESULTS: All participants noted a marked decrease in the severity of their condition. An improvement in hypopigmentation was also noted. For all indicators, the magnitude of improvement was most marked during the initial 2 weeks of treatment. LIMITATIONS: This was an open-label pilot trial limited to just 6 participants, only 5 of whom completed the study. CONCLUSIONS: Topical pimecrolimus cream may be an excellent alternative therapeutic modality for treating seborrheic dermatitis in African Americans, particularly in those with associated hypopigmentation.

Adult↗

Absence of T-regulatory cell expression and function in atopic dermatitis skin.

BACKGROUND: The role of regulatory T cells has been widely reported in the suppression of T-cell activation. A dysfunction in CD4(+)CD25(+) T-regulatory cell-specific transcription factor FoxP3 leads to immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome, often associated with atopic dermatitis. Increasing the number and activity of regulatory T cells in affected organs has been suggested as a remedy in various inflammatory diseases, including allergy. OBJECTIVE: To determine the presence and function of regulatory T cells in atopic dermatitis. METHODS: Immunohistochemistry of lesional atopic dermatitis skin and control skin conditions was used to demonstrate regulatory cells and cytokines in situ. The role of effector and regulatory T cells as well as their specific cytokines in apoptosis in human keratinocyte cultures and artificial skin equivalents was investigated. RESULTS: Human T-regulatory type 1 cells, their suppressive cytokines, IL-10 and TGF-beta, as well as receptors for these cytokines were significantly expressed, whereas CD4(+)CD25(+)FoxP3(+) T-regulatory cells were not found in lesional and atopy patch test atopic dermatitis or psoriasis skin. Both subsets of regulatory T cells suppress the allergen-specific activation of T(H)1 and T(H)2 cells. In coculture and artificial skin equivalent experiments, subsets of T-regulatory cells neither induced keratinocyte death nor suppressed apoptosis induced by skin T cells, T(H)1 cells, IFN-gamma, or TNF-alpha. CONCLUSION: A dysregulation of disease-causing effector T cells is observed in atopic dermatitis lesions, in association with an impaired CD4(+)CD25(+)FoxP3(+) T-cell infiltration, despite the expression of type 1 regulatory cells in the dermis.

Adult↗

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↗

Hyperresponsive TH2 cells with enhanced nuclear factor-kappa B activation induce atopic dermatitis-like skin lesions in Nishiki-nezumi Cinnamon/Nagoya mice.

BACKGROUND: Nishiki-nezumi Cinnamon/Nagoya (NC/Nga) mice raised in nonair-controlled conventional circumstances spontaneously develop atopic dermatitis-like skin lesions; however, the underlying mechanisms remain unclear. OBJECTIVE: We wanted to identify the critical intracellular signaling molecules in T cells that induce atopic dermatitis-like skin legions in NC/Nga mice. METHODS: We examined the levels of signal transduction and cytokine production in T cells, particularly those in atopic dermatitis-like lesions induced by the topical injection of mite antigens in NC/Nga mice under specific pathogen-free conditions. RESULTS: In NC/Nga mice maintained under specific pathogen-free conditions, the capability of T(H)1/T(H)2 and T cytotoxic 1/T cytotoxic 2 (Tc1/Tc2) cell differentiation increased significantly. T-cell antigen receptor-mediated activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase cascade and nuclear factor-kappaB (NF-kappaB) signaling were enhanced in NC/Nga T cells. The expression of T(H)2 cytokines (IL-4, IL-13, and IL-5) and that of GATA-binding protein 3 (GATA3), avian musculoaponeurotic fibrosarcoma (c-Maf), NF-kappaB, and activator protein 1 (AP1) selectively increased in draining lymph node T cells of NC/Nga mice. Moreover, the cell transfer of inhibitory NF-kappaB mutant-infected T(H)2 cells reduced ear thickness in the mite antigen-induced skin lesion of NC/Nga mice. CONCLUSION: Hyperresponsive T(H)2 cells with an enhanced activity of NF-kappaB and AP1 play a crucial role in the pathogenesis of atopic dermatitis-like skin lesions in NC/Nga mice. CLINICAL IMPLICATIONS: These results indicate potential therapeutic usefulness of developing selective inhibitors for NF-kappaB in the treatment of human atopic dermatitis.

Animals↗

Prognosis of infantile seborrheic dermatitis.

Of 191 children who had had infantile seborrheic dermatitis, 88 were reexamined after 10 years. One child had psoriasis, four had atopic dermatitis, and seven had seborrheic dermatitis, which suggests a link with adult seborrheic dermatitis. A familial tendency toward infantile seborrheic dermatitis was noted, as was an increased incidence of allergy within the family.

Child, Preschool↗