Exacerbation Of Atopic Dermatitis Research Articles

Repeated topical application of glucocorticoids augments irritant chemical-triggered scratching in mice

Topical glucocorticoids, widely used for the treatment of a variety of dermatitises, are known to exacerbate atopic dermatitis after long-term or inappropriate use. In some animal models, topical glucocorticoids augment the allergic cutaneous inflammation after repeated application, suggesting a relationship between these and clinical observations. We investigated whether topical glucocorticoids augment itching, rather than inflammation, resulting in the exacerbation of atopic dermatitis. Mice receiving repeated topical application of glucocorticoids, betamethasone valerate or dexamethasone, to the ear for 1 week showed significantly higher scratching frequency after application of an irritant chemical, 2,4-dinitrofluorobenzene (DNFB) or 12-O-tetradecanoilphorbol 13-acetate (TPA) than those receiving either a glucocorticoid or irritant chemical alone. In contrast, the increase in ear thickness induced by application of TPA was significantly suppressed by dexamethasone. Substance P (SP) and nerve growth factor (NGF) levels were higher in the ear receiving betamethasone valerate followed by DNFB application than in that receiving DNFB alone. In addition, histopathological studies revealed an increased density of nerve fibers in the ear receiving betamethasone valerate or dexamethasone followed by DNFB application. Oral administration of betamethasone valerate was not associated with an increase in either scratching frequency or SP or NGF level in the ear. These results suggest that repeated topical application of glucocorticoids may augment irritant chemical-triggered scratching through an increase in SP and NGF levels and nerve fiber density at the application site. These findings might explain the etiology of the exacerbation of atopic dermatitis and other dermatitises, occurring after long-term or inappropriate use of topical glucocorticoids.

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Efficacy of Ultraviolet A1 Phototherapy in Recalcitrant Skin Diseases

Ultraviolet (UV) radiation has been used for decades to treat a variety of skin diseases. UVA1 was used initially as an effective treatment for acute exacerbated atopic dermatitis. Since then, UVA1 has been attempted for recalcitrant skin diseases. This study examined the efficacy of UVA1 phototherapy in three recalcitrant skin diseases. This retrospective study reviewed the efficacy and follow-up of 26 patients with atopic dermatitis (AD), mycosis fungoides (MF) and localized scleroderma (LS). SUPUVASUN 3000 (Mutzhas Co., Munich, Germany) and SELLAMED 3000 (Sellas Medizinische Gerate GmbH, Gevelsberg, Germany) were the UVA1 equipment used. Irradiation was performed in accordance with the disease. Low-dose (20 J/cm(2)), medium-dose (65 J/cm(2)) and high-dose regimens (100 J/cm(2)) of UVA1 therapy were employed. The frequency of the therapy ranged from 3 to 5 times weekly. The therapeutic effectiveness was assessed according to the clinical examination before and after the last treatment. In patients with AD, complete and partial remission was achieved in four (80%) and one (20%) patient, respectively. In patients with MF, complete and partial remission was observed in thirteen (86.7%) and two (13.3%) patients, respectively. In patients with LS, complete and partial remission was observed in three (50%) and three (50%) patients, respectively. UVA1 phototherapy is an effective treatment modality for acute exacerbated AD, MF and LS.

PATHOGENETIC FEATURES OF BALNEOLOGICAL RESPONSE IN PATIENTS WITH ATOPIC DERMATITIS ON INTAKE OF NATURAL HIGH MINERALIZED WATER DURING MEDICAL REHABILITATION

Background. To study pathogenetic features of the normal type balneological response on intake of natural high mineralized water during medical rehabilitation in atopic dermatitis (AD) patients in comparison with relapse of the disease. Materials and methods. There were studied some clinical, morphological and immunological parameters and nature of correlative interlinks between their values in AD patients with different immunopathogenetic forms of the disease (IgE-dependent and IgE-independent AD) during both the relapse of the disease and development of the normal type balneological response at the treatment with natural high mineralized water. Results. The highest interlinks were between the clinical indices of disease severity during exacerbation of IgE-dependent AD and IgE, IL4, TNFб, IL 1в levels, dense infiltrate in derma; at exacerbation period of IgE-independent AD - TNFб and IL 1в dense inflammatory infiltrates in derma and number of degranulating mastocytes in their composition; at developing of the balneological response - only the number of degranulating mastocytes in composition of inflammatory infiltrates and a slightly increased TNFб level. Conclusion. The treatment of AD patients with natural high mineralized water is followed with the normal type balneological response characterized with slightly increased THFб level and is not associated with immunopathological processes, typical for the relapse of the disease, and therefore, it's medical correction is not required.

Serum mucosa‐associated epithelial chemokine (MEC/CCL28) in atopic dermatitis: a specific marker for severity

Mucosa-associated epithelial chemokine (MEC; CCL28) is considered to be pivotal in mediating the migration of CC chemokine receptor 3- and 10- (CCR3- and CCR10)-expressing, skin-homing, memory, cutaneous lymphocyte-associated antigen-positive (CLA(+)) T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases, such as atopic dermatitis (AD). This controlled longitudinal study was designed to evaluate the expression of CCL28 in serum in childhood AD and bronchial asthma (BA), and its possible relationship to disease severity and activity. Serum CCL28 levels were measured in 36 children with AD, 23 with BA, 14 with both conditions, and 21 healthy age- and sex-matched controls. Sixteen patients in the AD group were followed up and resampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables. Serum CCL28 levels in AD, whether during flare [median, 1530 pg/mL; mean +/- standard deviation (SD) = 1590.4 +/- 724.3 pg/mL] or quiescence (median, 1477 pg/mL; mean +/- SD = 1575.2 +/- 522.1 pg/mL), were significantly higher than those in healthy children (median, 301 pg/mL; mean +/- SD = 189.6 +/- 92.8 pg/mL); however, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median, 340 pg/mL; mean +/- SD = 201.6 +/- 109.5 pg/mL) were significantly lower than those in the AD group, and comparable with those in healthy controls. Serum CCL28 levels in severe AD were significantly higher than those in mild and moderate cases, and correlated positively with the calculated severity scores [Leicester Sign Score (LSS) and Scoring Atopic Dermatitis (SCORAD)]. CCL28 levels during the exacerbation of AD were positively correlated with the corresponding values during remission, the peripheral absolute eosinophil counts, and serum lactate dehydrogenase levels. Serum CCL28 levels were not correlated with the serum total immunoglobulin E values in AD. Our data reinforce the concept that CCL28 might contribute to the pathogenesis of AD, probably through the selective migration and infiltration of effector/memory T-helper-2 cells in the skin. CCL28 may also represent an objective prognostic marker for disease severity. Further studies may pave the way for CCL28 antagonism among adjuvant therapeutic strategies.

Efficacy and safety of fluticasone propionate 0.005% ointment in the long‐term maintenance treatment of children with atopic dermatitis: Differences between boys and girls?

Treatment of atopic dermatitis (AD) in children tends to stabilize the condition in the short term. 'Maintenance' treatment options in children are limited. To assess the efficacy and safety of twice daily treatment with fluticasone propionate 0.005% (FP) ointment during 4 wk and the efficacy and safety of twice weekly maintenance treatment with FP in preventing exacerbations or remissions of AD during a 16 wk follow-up period. Ninety children (aged 4-10 yr) with moderate to severe AD were included in a randomized, multi-centre study and received FP ointment twice daily during the acute phase. Children whose AD was in remission after 4 wk of treatment, entered the maintenance phase. In addition to twice daily emollient, children were randomly allocated to receive FP or placebo ointment twice weekly on consecutive days. Efficacy was assessed by the objective SCORAD. Eighty-seven (97%) completed the 4-wk acute study period. Extensive remission was achieved in 78 (87%) children, and 75 children entered the maintenance phase. Intermittent treatment with FP resulted in less severe AD and significantly reduced risk of further relapse as compared with placebo. The risk of an exacerbation of AD was more than twice as high in the placebo group as in the FP group (hazard ratio 2.182, 95% CI). AD in girls was better controlled than in boys. This long-term study shows that the addition of twice weekly FP to standard maintenance therapy significantly reduces the risk of relapse in children with moderate severe AD.

Stressors Associated with the Exacerbation of Atopic Dermatitis

Stressors Associated with the Exacerbation of Atopic Dermatitis

Serum mucosa-associated epithelial chemokine in atopic dermatitis : A specific marker for severity

Background:Mucosa-associated epithelial chemokine (MEC; CCL28) is considered pivotal in mediating migration of CCR3 and CCR10-expressing skin-homing memory CLA+ T cells. CCL28 is selectively and continuously expressed by epidermal keratinocytes, but highly upregulated in inflammatory skin diseases such as atopic dermatitis (AD).Aims:This controlled longitudinal study was designed to evaluate the expression of CCL28 serum levels in childhood AD and bronchial asthma (BA) and its possible relations to disease severity and activity.Methods:Serum CCL28 levels were measured in 36 children with AD, 23 children with BA, and 14 children who had both conditions as well as in 21 healthy age and gender-matched subjects serving as controls. Sixteen patients in the AD group were followed-up and re-sampled for serum CCL28 after clinical remission. Serum CCL28 levels were correlated with some AD disease activity and severity variables.Results:Serum CCL28 levels in patients with AD whether during flare (median = 1530; mean ± SD = 1590.4 ± 724.3 pg/ml) or quiescence (median = 1477; mean ± SD = 1575.2 ± 522.1 pg/ml) were significantly higher than the values in healthy children (median = 301; mean ± SD = 189.6 ± 92.8 pg/ml). However, the levels during flare and quiescence were statistically comparable. The serum levels in BA (median = 340; mean ± SD = 201.6 ± 109.5 pg/ml) were significantly lower than the AD group and comparable with the healthy control values. Serum CCL28 levels in severe AD were significantly higher as compared with mild and moderate cases and correlated positively to the calculated severity scores (LSS and SCORAD). CCL28 levels during exacerbation of AD could be positively correlated to the corresponding values during remission, the peripheral absolute eosinophil counts, and the serum lactate dehydrogenase levels. Serum CCL28 did not vary with the serum total IgE values in AD.Conclusion:Our data reinforce the concept that CCL28 might share in the pathogenesis of AD probably through selective migration and infiltration of effector/memory Th2 cells into the skin. It may also represent an objective prognostic marker for disease severity. Further studies may pave the way for CCL28 antagonism among the adjuvant therapeutic strategies.

Effectiveness and safety of a prevention‐of‐flare‐progression strategy with pimecrolimus cream 1% in the management of paediatric atopic dermatitis

This study was performed to investigate the efficacy and safety of a prevention-of-flare-progression strategy with pimecrolimus cream 1% in children and adolescents with atopic dermatitis (AD). A 26-week multi-centre, randomized, double-blind, vehicle-controlled study was conducted in 521 patients aged 2-17 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n = 256) or vehicle cream (n = 265). Twice-daily treatment with study medication was started at the first signs and/or symptoms of recurring AD. If, despite the application of study medication for at least 3 days, AD worsened (as confirmed by the investigator), treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy end point was the number of days on study without TCS use for a flare. The mean number of TCS-free days was significantly higher (P < 0.0001) in the pimecrolimus cream 1% group (160.2 days) than in the control group (137.7 days). On average, patients on pimecrolimus cream 1% experienced 50% fewer flares requiring TCSs (0.84) than patients on vehicle cream (1.68) (P < 0.0001). Patients on pimecrolimus cream 1% also had fewer unscheduled visits (87) than patients on vehicle cream (246). In children and adolescents with a history of mild or moderate AD but free/almost free of signs or symptoms of the disease, early treatment of subsequent AD exacerbations with pimecrolimus cream 1% prevented progression to flares requiring TCS, leading to fewer unscheduled visits and reducing corticosteroid exposure.

Staphylococcal toxin-induced T cell proliferation in atopic eczema correlates with increased use of superantigen-reactive Vbeta-chains in cutaneous lymphocyte-associated antigen (CLA)-positive lymphocytes.

Staphylococcal superantigens have been implicated in the pathogenesis of atopic dermatitis (AD). This may occur through superantigenic activation of T lymphocytes and their subsequent induction of the skin homing receptor CLA on activated cells. We investigated the proliferative responses of peripheral blood mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD and six normal controls to the staphylococcal superantigens, staphylococcal enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed CLA and T cell receptor (TCR) Vbeta-chain expression by immunofluorescence and flow cytometry before and after stimulation. PBMC from AD patients showed two-fold increased proliferation to SEA and SEB (P < 0.01) compared with normals, whereas the response to mitogenic stimulation was identical. Analysis of (TCR) Vbeta-chain expression demonstrated increased use of superantigen-reactive Vbeta families in freshly isolated PBMC in AD patients compared with controls. This pattern of Vbeta-chain expression was only observed in the CLA+ but not the total population of T cells. Furthermore, there was a positive correlation between the enhanced PBMC proliferative response and increased expression of superantigen-reactive Vbeta families in atopic patients. These data support the concept that superantigens are important in the pathogenesis of this common condition, and also provide evidence that the increased use of certain Vbeta families in circulating, CLA+, skin homing lymphocytes is of functional significance.

Proactive disease management with 0·03% tacrolimus ointment for children with atopic dermatitis: results of a randomized, multicentre, comparative study

Long-term treatment for atopic dermatitis (AD) using low-dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent exacerbations. This 12-month, European, multicentre, randomized study investigated if proactive, twice-weekly application of 0.03% tacrolimus ointment can keep AD in remission and reduce the incidence of disease exacerbation (DE) in children. During the initial open-label period, 267 children with AD applied 0.03% tacrolimus ointment twice daily for up to 6 weeks to all affected areas. When an Investigator Global Assessment (IGA) score of <or=2 was achieved, the patient entered the disease control period (DCP) and was randomized to receive tacrolimus (n=125) or vehicle ointment (n=125) twice weekly for 12 months. Exacerbations were treated with 0.03% tacrolimus ointment twice daily until an IGA<or=2 was regained, then randomized treatment was restarted. The outcome measure was the number of DEs during the DCP that required substantial therapeutic intervention. Proactive application of 0.03% tacrolimus ointment significantly reduced the number of DEs during the DCP that required substantial therapeutic intervention (median difference: 1.0; P<0.001; Wilcoxon rank-sum test), the percentage of DE treatment days (median difference: 6.2; P<0.001; Wilcoxon rank-sum test), and increased the time to first DE requiring intervention (median: 173 vs. 38 days; P<0.001; stratified log-rank test). Differences in quality of life scores were not significant between groups. The adverse event profile was similar for both treatment approaches. Twice-weekly proactive application of 0.03% tacrolimus ointment over 12 months was effective for most paediatric study patients in preventing, delaying and reducing the occurrence of AD exacerbations.

What's new in atopic dermatitis?

What's new in atopic dermatitis?

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment

Long-term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent relapses. This 12-month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE). During the initial open-label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of <or=2 was achieved, the patient entered the disease control period (DCP) and was randomized to either proactive tacrolimus (n = 116) or vehicle ointment (n = 108) twice weekly for 12 months. Exacerbations were treated with 0.1% tacrolimus ointment b.i.d. until an IGA <or=2 was regained, then randomized treatment was restarted. The primary endpoint was the number of DEs during the DCP that required a substantial therapeutic intervention. Proactive tacrolimus 0.1% ointment application significantly reduced the number of DEs requiring substantial therapeutic intervention (median difference 2; P < 0.001; Wilcoxon rank sum test), the percentage of DE treatment days (median difference: 15.2%; P < 0.001; Wilcoxon rank sum test) and increased the time to first DE (median 142 vs 15 days; P < 0.001; stratified log-rank test). The adverse event profile was similar for the two treatment approaches. A 12-month, twice weekly proactive tacrolimus ointment application was an effective treatment in most study patients which prevented, delayed and reduced the occurrence of AD exacerbations

Heme oxygenase 1 attenuates the development of atopic dermatitis–like lesions in mice: Implications for human disease

Oxidative stress has been implicated in the exacerbation of atopic dermatitis (AD). We sought to investigate the pathophysiologic roles of inducible antioxidant heme oxygenase (HO) 1 in the development of AD. Serum HO-1 levels of patients with AD (n = 100) and age-matched healthy control subjects (n = 72) were determined by means of ELISA. The relationships between serum HO-1 levels and clinical severities, laboratory parameters, and cytokines/chemokines were assessed. Skin lesions of patients with AD and psoriasis were analyzed by means of immunohistochemistry. A murine AD model, DS-Nh, was used to further investigate localization and function of HO-1. Evaluation of symptoms, serum IgE and IL-18 levels, immunoblotting results, and histologic analyses of skin were performed. The effect of intraperitoneally administered hemin, a potent HO-1 inducer, or zinc protoporphyrin IX, an inhibitor of HO, was monitored. Serum HO-1 levels were significantly increased in patients with AD compared with those seen in healthy control subjects and were associated with AD disease severity. Serum HO-1 levels correlated with serum IgE, lactate dehydrogenase, IL-18, and thymus and activation-regulated chemokine levels. HO-1-expressing cells were accumulated in skin lesions of patients with AD and DS-Nh mice. Immunofluorescence of mouse skin lesions revealed that HO-1-positive cells were macrophages and dendritic cells. Treatment with hemin, but not with zinc protoporphyrin IX, attenuated the development of the skin lesions in DS-Nh mice and reduced serum IL-18 levels. HO-1 levels were increased in sera and skin lesions of patients with AD. Enhancement of HO-1 attenuated the development of skin lesions in mice, suggesting that HO-1 induction offers a promising therapeutic strategy for AD.

The role of food allergy in atopic dermatitis

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disease affecting more than 10% of all children. Sensitization to foods triggers isolated skin symptoms in about 30% of children. These symptoms include immediate reactions within minutes after ingesting food without exacerbation of AD and early and late exacerbations of AD. It is important to identify clinically relevant sensitizations to foods using skin prick tests, a specific IgE blood test (ImmunoCAP; Phadia, Portage, MI, USA), and double-blind, placebo-controlled food challenges to initiate appropriate dietary interventions and avoid unnecessary dietary restrictions. Children with AD triggered by food allergens demonstrate a distinct immune response upon stimulation of their peripheral blood mononuclear cells with food allergen. A defective skin barrier and increased intestinal permeability appear to facilitate allergen sensitization. Appropriate skin care to maintain skin barrier function and dietary avoidance of highly allergenic foods during infancy may help to prevent allergen sensitization, thereby reducing the severity of AD and food allergies.

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment

Background: Long‐term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti‐inflammatory agents may control acute disease and prevent relapses. This 12‐month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE).Methods: During the initial open‐label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of ≤2 was achieved, the patient entered the disease control period (DCP) and was randomized to either proactive tacrolimus (n = 116) or vehicle ointment (n = 108) twice weekly for 12 months. Exacerbations were treated with 0.1% tacrolimus ointment b.i.d. until an IGA ≤2 was regained, then randomized treatment was restarted. The primary endpoint was the number of DEs during the DCP that required a substantial therapeutic intervention.Results: Proactive tacrolimus 0.1% ointment application significantly reduced the number of DEs requiring substantial therapeutic intervention (median difference 2; P &lt; 0.001; Wilcoxon rank sum test), the percentage of DE treatment days (median difference: 15.2%; P &lt; 0.001; Wilcoxon rank sum test) and increased the time to first DE (median 142 vs 15 days; P &lt; 0.001; stratified log‐rank test). The adverse event profile was similar for the two treatment approaches.Conclusion: A 12‐month, twice weekly proactive tacrolimus ointment application was an effective treatment in most study patients which prevented, delayed and reduced the occurrence of AD exacerbations.

Effect of Dexamethasone on the Cutaneous Late Phase Response

The cutaneous late phase response (LPR) demonstrates characteristics of the inflammatory response associated with acute onset or exacerbations of atopic dermatitis (AD). The current study describes the characterization of the cutaneous LPR in monkeys. Ascaris suum (Asc) sensitive, male cynomolgus monkeys (6-10 kg, n = 4-6) were anesthetized and intradermal injections (40 μL) of PBS or Asc were administered over the thorax/abdominal area. The early phase response (EPR), wheal and flare, was measured 15 minutes post Asc. The LPR was evaluated by analyzing the cellular infiltrate from punch biopsies obtained 20 h after allergen exposure. During treatment studies, monkeys were administered dexamethasone (1 mg/kg; i.m.) 1 h prior to allergen. Asc exposure resulted in a wheal and flare that was significantly (p ≤ 0.04) larger than the paired PBS response. At 20 h post Asc injection a moderate inflammatory response in the upper and deep dermis (p = 0.03) was observed. The LPR was characterized by dermal eosinophilia, and an increase in CD4+ and CD25+ cells, indicative of infiltration and activation of T cells. Pretreatment with dexamethasone had no effect on the Asc-induced EPR, but inhibited the LPR. Dexamethasone significantly inhibited upper dermal inflammation associated with the LPR (p = 0.05) and eosinophilia in both the upper (p = 0.001) and deep (p = 0.05) dermis. With Asc intradermal injection, both an EPR and LPR cutaneous response is observed in the cynomolgus monkey. Acute administration of dexamethasone significantly inhibited the cutaneous LPR. These data elucidate the potential utility of this model for the evaluation of novel therapeutics for AD.

Is topical antimycotic treatment useful as adjuvant therapy for flexural atopic dermatitis: randomized, double‐blind, controlled trial using one side of the elbow or knee as a control

Certain factors are known to cause exacerbation of atopic dermatitis (AD), e.g. soap, detergent, dry skin, staphylococcal colonization, and herpes infection. Other factors are suspected, but not yet proven, e.g. yeasts belonging to the Malassezia genus. It is known that antimycotics may be beneficial in a small subset of adult patients with dermatitis affecting the head and neck region; however, it is not known whether AD patients, many of whom also have head and neck involvement, may also find antimycotics useful. A previous study has demonstrated no treatment difference in adult AD patients; however, the measurement method was criticized and 1% hydrocortisone cream may have too weak an effect in adult patients. Therefore, we designed this randomized, double-blind, controlled trial to examine this question. Younger AD patients were recruited and different methods of measuring outcomes were used. To evaluate the usefulness of topical antimycotic treatment as adjuvant therapy for flexural AD. Methods This was a randomized, double-blind, controlled trial in AD patients using one side of the elbow or knee as a control. There were three independent outcomes: (i) to compare the ability to relieve symptoms; (ii) to compare the ability to improve clinical signs; and (iii) to compare the ability to provide lasting clinical effects. All three outcomes showed unequivocally that the addition of antimycotic did not provide extra benefit to the standard treatment. The addition of antimycotic does not seem to provide extra benefit to AD patients, and the beneficial effect of this medication seems to be restricted to a small subset of adult patients with dermatitis affecting the head and neck region.

The role of selected neuropeptides in pathogenesis of atopic dermatitis

Atopic dermatitis (AD) is an inflammatory skin disease of a chronic course. The role of neuropeptides in pathogenesis of this disorder is probably not crucial; however, there is evidence that these substances influence the development and course of AD. The aim of this study was to evaluate the plasma level of substance P, neuropeptide Y (NPY) and calcitonin gene related peptide (CGRP) in AD patients during exacerbation and remission of the disease. Forty-nine patients with AD, aged 17 to 56 years, participated in the study. Among this group, there were 25 males (51%) and 24 females (49%). The disease lasted from 1 to 55 years. The severity of the disease was assessed with SCORAD index. The severity of pruritus was evaluated with Visual Analog Scale and a specially designed questionnaire. Neuropeptides plasma level was detected with radioimmunoassay. Substance P plasma level in AD patients during exacerbation and remission was significantly higher than in the control group. There was a negative correlation between substance P plasma level and total IgE level. CGRP plasma level during exacerbation of AD was significantly lower than in healthy controls and increased in the remission. Significantly higher CGRP concentration was observed in patients suffering from severe pruritus; however, both in patients with more and less severe pruritus, CGRP plasma level was lower than in controls. Higher CGRP plasma level was also observed in patients with more severe disease. NPY plasma level in patients with AD was significantly increased both during exacerbation and remission. During remission of AD, NPY concentration was higher than during exacerbation.

Role of Bacterial Pathogens in Atopic Dermatitis

The skin of atopic dermatitis (AD) patients exhibits a striking susceptibility to colonization and infection with Staphylococcus aureus. This review summarizes our understanding about the role of S. aureus in AD. Indeed, S. aureus colonization is both a cause and a consequence of allergic skin inflammation. The mechanisms that allergic skin inflammation of AD promotes the increase of S. aureus colonization include skin barrier dysfunction, increased synthesis of the extracellular matrix adhesins for S. aureus, and defective innate immune responses due to decreased production of endogenous antimicrobial peptides. On the other hand, the exotoxins secreted by S. aureus are superantigens. Staphylococcal superantigens (SsAgs) may penetrate the skin barrier and contribute to the persistence and exacerbation of allergic skin inflammation in AD through the stimulation of massive T cells, the role of allergens, direct stimulation of antigen-presenting cells and keratinocytes, the expansion of skin-homing cutaneous lymphocyte-associated antigen-positive T cells, and the augmentation of allergen-induced skin inflammation. SsAgs also induce corticosteroid resistance. In therapeutic interventions, anti-inflammatory therapy alone is very effective in reducing S. aureus colonization on the skin, but antibiotic treatment alone is unable to improve the allergic skin inflammation of AD. Therefore, we recommend the combination therapy of anti-inflammatory drugs and antibiotics in the AD patients with secondary bacterial infection, exacerbated AD, or poorly controlled AD. However, when AD is well controlled by anti-inflammatory drugs alone, we do not recommend the antibiotic therapy.