Remission Of Atopic Dermatitis Research Articles

ALLERGIC CONTACT DERMATITIS AND ATOPIC DERMATITIS: HIGHLIGHTS OF THE OVERLAP SYNDROME

Introduction. The combination of atopic dermatitis (AD) with allergic contact dermatitis (ACD) or the occurrence of ACD on the background of atopic dermatitis is called the overlap syndrome. Studies have demonstrated several reasons why patients with AD have a similar or even increased risk of developing ACD compared to those without AD. Allergens and haptens are trigger factors in a group of patients with AD and ACD overlap syndrome. The aim of the study. To confirm the diagnosis of ACD in a group of patients with AD – diagnose the overlap syndrome and analyze which allergens and haptens were the trigger factors in this group. Materials and methods. To confirm IgE-dependent sensitization in atopic dermatitis, skin prick tests or determination of specific IgE in blood serum were performed. Skin patch tests (European series S-1000) were performed to determine the mechanisms of delayed-type hypersensitivity. Results. It was found that the highest specific weight of positive allergic reactions has been recorded in response to the following allergens: ticks, ticks/ambrosia, birch and mold. The absolute majority of patients demonstrated positive specific IgE-dependent sensitization to Dermatophagoides pteronyssinus and Dermatophagoides farinae – 24 (50%), in turn, on Ambrósia – 14 (29.2%), and on Alternaria alternata – 8 (16.7%). Also, the reaction was most often recorded to haptens: cobalt, nickel, formaldehyde, PPD, textile dyes. Deterioration of the clinical course and shortening of AD remission periods were observed due to the formation of ACD against the background of impaired skin barrier function and the presence of chronic immune inflammation. Conclusions. Patients with AD are more often diagnosed with ACD, which predictably worsens the course of AD. Patients with confirmed overlap syndrome "AD + ACD" most often show reactions to haptens: Cobalt, Nikel, Formaldehyde, PPD, Textile dye mix – and in the vast majority to 2 haptens or more in one patient.

Regulatory T Cell-Targeted Immunomodulatory Therapy for Long-Term Clinical Improvement of Atopic Dermatitis: Hypotheses and Perspectives.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disorder characterized by itching and eczematous lesions. It is often associated with a personal or familial history of allergic diseases. Allergic inflammation induced by immunoglobulin E and T-helper type 2 (Th2) cell responses to common environmental agents has been suggested to play an essential role in AD pathogenesis. The standard therapies for AD, including topical or systemic agents, focus on controlling skin inflammation. Recently developed monoclonal antibody to interleukin-4 receptor alpha or Janus kinase inhibitors can provide significant clinical improvements in patients with AD by inhibiting Th2 cell-mediated skin inflammation. However, the clinical efficacy of the Th2 cell-targeted therapy is transient and incomplete in patients with AD. Patients with AD are seeking a permanent cure. Therefore, the development of novel immunomodulatory strategies that can improve a long-term clinical outcome and provide a long-term treatment-free clinical remission of AD (disease-modifying therapy) is needed. Regulatory T (Treg) cells play a critical role in the maintenance of immune tolerance and suppress the development of autoimmune and allergic diseases. This review provides three working hypotheses and perspectives for the treatment of AD by Treg cell activation. (1) A decreased number or function of Treg cells is a critical event that causes the activation of Th2 cells, leading to the development and maintenance of AD. (2) Activation of Treg cells is an effective therapeutic approach for AD. (3) Many different immunomodulatory strategies activating Treg cells can provide a long-term clinical improvement of AD by induction of immune tolerance. The Treg cell-targeted immunomodulatory therapies for AD include allergen immunotherapy, microbiota, vitamin D, polyvalent human immunoglobulin G, monoclonal antibodies to the surface antigens of T cell or antigen-presenting cell, and adoptive transfer of autologous Treg cells or genetically engineered Treg cells expanded in vitro.

KIR Allelic Variation and the Remission of Atopic Dermatitis Over Time.

Atopic dermatitis (AD) is a common chronic skin disease. Although generally thought to be a disease of T-cell dysregulation, recent studies have suggested that immune dysregulation of NK cells is also important. Killer cell Ig-like receptors (KIRs) are involved with NK cell regulation. The Pediatric Eczema Elective Registry is a U.S. nationwide longitudinal cohort with up to 10 y of follow-up in which 655 children had DNA available for full allelic KIR sequencing. Every 6 mo, AD activity was reported by Pediatric Eczema Elective Registry children. Using generalized estimating equations, we evaluated the association of KIR allelic variation in concert with known HLA binding ligands and whether the child reported AD in "remission" (no skin lesions and not using AD medication). KIR2DS4*001:01 (odds ratio 0.53, 95% CI [0.32, 0.88]) and KIR2DL4*001:02 (0.54, [0.33, 0.89]) in the presence of C*04:01 had the largest effect on decreasing the likelihood of AD remission. The haplotype KIR 2DL4*001:02 ∼ 2DS4*001:01 ∼ 3DL2*002:01 (0.77, [0.60, 0.99]) was also associated with a decreased likelihood of AD remission. Our findings add to the general body of evidence of a growing literature on the importance of NK cells with respect to the immunopathogenesis and natural history of AD.

Successful use of a janus kinase inhibitor for the treatment of atopic dermatitis

The article presents a clinical report of the use of a new drug of the janus kinase inhibitor, upadacitinib, possessing of the effect on the intracellular JAK/STAT system, the role of which in the pathogenesis of atopic dermatitis (AD) is being actively studied. JAK/STAT includes janus kinases JAK1, JAK2, JAK3, tyrosine kinase, protein-transductor and transcription activator (STAT). When the cytokine interacts with the corresponding receptor, janus kinases phosphorylate STAT proteins inducing transcription of genes that mediate the action of key cytokines to trigger the development of an inflammatory response in the shock organ. Upadacitinib is recommended for uncontrolled AD patients older 12 years. The use of upadacitinib in a 17-year-old patient at a dose of 15 mg in tablets, daily, has shown high efficacy in achieving clinical remission of AD and complete relief of the skin itching.

Stratum Corneum Ceramide Profiles Provide Reliable Indicators of Remission and Potential Flares in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Prevention of exacerbation of AD is a crucial issue for all physicians. However, exacerbation of AD often is seen during reduction of AD treatment, even with appropriate follow-up by tapered topical corticosteroids and daily topical moisturizers, indicating the need for good indicators of AD remission. We hypothesized that the presence of mutations in FLG or the stratum corneum ceramide profile on AD remission phase may predict the ease of AD exacerbation. This study examined the differences in the frequency of FLG mutations or stratum corneum ceramide profiles (stratum corneum levels and carbon chain length for 11 ceramide classes [ceramides containing nonhydroxy fatty acids and dihydrosphingosines; nonhydroxy fatty acids and sphingosines; nonhydroxy fatty acids and 6-hydroxysphingosines; nonhydroxy fatty acids and phytosphingosines; a-hydroxy fatty acids and dihydrosphingosines; a-hydroxy fatty acids and sphingosines; a-hydroxy fatty acids and 6-hydroxysphingosines; a-hydroxy fatty acids and phytosphingosines; ester-linked fatty acids, o-hydroxy fatty acids, and sphingosines; ester-linked fatty acids, o-hydroxy fatty acids, and 6-hydroxysphingosines; and ester-linked fatty acids, o-hydroxyfatty acids, and phytosphingosines]) at AD remission phase between the two AD study groups: subsequent exacerbation (‒) and (+) of AD. The frequency of FLG mutations did not differ between the study groups. On the other hand, the carbon chain lengths of ceramides containing nonhydroxy fatty acids and dihydrosphingosines, nonhydroxy fatty acids and sphingosines, and nonhydroxy fatty acids and 6-hydroxysphingosines were shorter in the exacerbated AD group than in the maintained-AD group. Thus, the stratum corneum ceramide profile at the remission phase of AD is a potential biomarker, predicting the likelihood of substantial AD remission or subsequent AD exacerbation.

Uncommon variants in FLG2 and TCHHL1 are associated with remission of atopic dermatitis in a large longitudinal US cohort.

Atopic dermatitis (AD) is a relapsing inflammatory skin disease; filaggrin (FLG) variation has been consistently associated with its pathogenesis. Filaggrin-2 (FLG2) and trichohyalin-like-1 (TCHHL1) are members of the same protein family (S100 fused-type proteins), are similar in structure to FLG, and may be involved in AD pathogenesis. We sought to evaluate the association between variation in FLG2, TCHHL1 and AD remission. We sequenced FLG2 and TCHHL1 in a longitudinal AD cohort using targeted capture-based massively parallel sequencing. Association between individual alleles and AD remission was evaluated with generalized estimating equations for binary outcomes. Association between groups of alleles and AD remission was evaluated using a genetic algorithm to group alleles. We identified two loss-of-function (LoF) mutations in FLG2 (Ser2377Ter,Arg2207Ter) and 2 LoF mutations in TCHHL1 (Gln656Ter, Gln294Ter), none of which were associated with AD remission. Common (MAF > 5%) alleles in FLG2 were similarly unassociated with AD. No common alleles in TCHHL1 were associated with AD remission after multiple testing correction. Among self-described whites, a group of 34 uncommon alleles in FLG2 were associated with increased AD remission (OR 7.64e17; 95% CI 4.41e17-1.32e18; adjusted p < 1.0e-16). Twelve uncommon alleles in TCHHL1 trended toward association with increased AD remission (OR 23.46; 95% CI 7.07-77.89; adjusted p = 0.064). Among self-described African Americans, 13 uncommon FLG2 alleles were associated with increased AD remission (OR 21.01; 95% CI 11.90-37.09; adjusted p < 1.0e-16). No TCHHL1 uncommon allele groups were associated with AD remissionamong African Americans. Our study supports the role of uncommon alleles in FLG2 and TCHHL1 in AD pathogenesis.

Altered skin microbiome: The most important symptom of atopic dermatitis

The progressively increased incidence of atopic dermatitis among children and increased persistence in adulthood, combined with an inevitably decreased quality of life of patients, determine the relevance of studying the development mechanisms of this disease not only for dermatology but also for the entire health care system. Thus, the prerequisites for the emergence of new pathogenetic concepts and the search for the most effective therapeutic modalities arise. Currently, atopic dermatitis is considered as the interaction of endogenous (impaired immune response and insufficient epidermal barrier function) and exogenous (exposure to allergens, chemical or physical irritants, and microorganisms) factors.&#x0D; Environmental factors, such as temperature and humidity, genetic makeup, antibiotic use, and good hygiene, play a critical role in skin microbiome maintenance and stability. Normally, the skin microbiota is mainly formed by bacteria of the genus Staphylococcus, Propionibacterium, Corynebacterium, and Streptococcus. In 70% of patients with atopic dermatitis, colonization of Staphylococcus aureus is observed on the affected skin, whereas on the unaffected skin in 39%, which secondarily contributes to the development of immune imbalance and increased skin xerosis. This fact determines the importance of basic therapy, which, on one hand, helps to strengthen the epidermal barrier, and on the other, normalizes the microbiome of the skin, thereby reducing the colonization of Staphylococcus aureus.&#x0D; The normal skin microbiome suppresses the activity of immune-inflammatory responses and regulates pH, lipid synthesis, and transepidermal water loss. Thus, skin microbiome normalization is the key to successful therapy and long-term remission of atopic dermatitis.

Efficacy of Heparinoid Cream Containing Pseudo-Ceramide for Remission of Atopic Dermatitis

PurposeAtopic dermatitis (AD) is characterized by chronic inflammation, which frequently recurs, is exacerbated, and enters remission. A maintenance remission period is important for AD patients. We developed a formulation for use during AD remission, containing heparinoid and pseudo-ceramide that forms a lamellar structure. We evaluated the allergen permeability and examined the formulation’s efficacy in maintaining remission in patients with AD.Materials and MethodsSeventeen AD patients applied a cream containing 0.3% heparinoid and pseudo-ceramide (test cream group, n = 10), or a general cream containing 0.3% heparinoid (control cream group, n = 7) to their arm for four weeks after inducing remission with the application of a steroid cream for two weeks.ResultsThe lamellar structure of the test cream was confirmed with small- and wide-angle x-ray scattering analysis and observation by transmission electron microscopy. The test cream inhibited the penetration of V8 protease significantly compared to the control cream in vitro. According to AD severity score by dermatologists, the effects remission maintenance of the test cream group were comparable to those of the control cream group. However, the test cream group had a significantly increased skin hydration value compared to the control cream group. A significant decrease in transepidermal water loss, an indicator of skin barrier function, was shown in the test cream group compared to the control cream group.ConclusionThe cream with lamellar structures containing heparinoid and pseudo-ceramides may inhibit allergen penetration. Moreover, skin properties improved during the remission period; thus, the formulation we developed was suitable for use during the AD remission period.

101 Uncommon alleles in FLG2 and TCHHL1 are associated with remission of atopic dermatitis

Atopic dermatitis (AD) is a relapsing inflammatory skin disease; filaggrin (FLG) variation has been consistently associated with its pathogenesis. Filaggrin-2 (FLG2) and trichohyalin-like-1 (TCHHL1) are members of the same protein family (S100 fused type proteins), are similar in structure to FLG, and may be involved in AD pathogenesis. We sought to evaluate the association between variation in FLG2, TCHHL1 and AD remission. We sequenced FLG2 and TCHHL1 in a longitudinal cohort of individuals with AD using targeted capture based massively parallel sequencing. The association between individual alleles and AD remission was evaluated with generalized estimating equations (GEE) for binary outcomes, assuming an exchangeable working correlation structure with empirical standard errors. The association between groups of alleles and AD remission was evaluated using a genetic algorithm, implemented via the rbga.bin function in R, to group alleles and GEE models to evaluate group associations with AD remission. We identified 3 loss-of-function (LoF) mutations in FLG2 (Ser2377Ter, Ter2392Ser, Arg2207Ter) and 2 LoF mutations in TCHHL1 (Gln656Ter, Gln294Ter), none of which were associated with AD remission. Common (MAF>5%), non-LoF alleles in FLG2 were similarly unassociated with AD. One common allele in TCHHL1, 152057002A>G, was associated with increased AD remission (OR 1.48; 95%CI 1.06-2.06; p=0.022). Within the self-described white population, a group of 34 uncommon alleles in FLG2 were associated with increased AD remission (OR 7.64e17; 95%CI 4.41e17-1.32e18; adjusted p<1.0e-16). 12 uncommon alleles in TCHHL1 were associated with increased AD remission (OR 23.46; 95%CI 7.07-77.89; adjusted p=0.064). Within the self-described African American population, 13 uncommon FLG2 alleles were associated with increased AD remission (OR 21.01; 95%CI 11.90-37.09; adjusted p<1.0e-16). No TCHHL1 uncommon allele groups were associated with AD remission. Our study supports the role of uncommon alleles in FLG2 and TCHHL1 in AD pathogenesis.

Dupilumab effectiveness for the treatment of patients with concomitant atopic dermatitis and chronic rhinosinusitis with nasal polyposis.

Dupilumab is a fully human monoclonal antibody targeting interleukin (IL) 4 and IL13 pathways. We performed a retrospective observational study to evaluate the efficacy of dupilumab for the treatment of adult patients referred to our department, from January 2019 to May 2021, with a diagnosis of moderate to severe atopic dermatitis (AD) and concomitant chronic rhinosinusitis with nasal polyps (CRSwNP), with a clinical indication for dupilumab treatment. Skin disease activity was assessed using EASI, Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), and Dermatology Life Quality Index (DLQI). The CRSwNP activity was evaluated using 22-item Sino-Nasal Outcome Test (SNOT-22), endoscopic nasal polyp score (ENPS), nasal congestion or obstruction score (scale 0-3), loss-of-smell score (scale 0-3), and rhinosinusitis disease severity (visual analog scale 0-10cm). A significant improvement of all the score values was recorded assessing patients at baseline, week (W)16, and W24. In particular, concerning the CRSwNP, a reduction of ENPS score (baseline: 4.9 ± 1.85; W16: 2.49 ± 1.42, p < 0.01; W24: 1.68 ± 1.25, p < 0.01) and SNOT-22 (baseline: 35.9 ± 19.11; W16: 12.85 ± 6.31, p < 0.01; W24: 10.71 ± 7.29, p < 0.01) was observed. Furthermore, dupilumab is a labeled drug for the treatment of both AD and CRSwNP. The use of a single drug to obtain the improvement up to the near remission of AD and CRSwNP increases not only patient's compliance with the treatment, but also the benefits in terms of health cost related to these chronic diseases.

Using a Machine Learning Approach to Identify Low-Frequency and Rare FLG Alleles Associated with Remission of Atopic Dermatitis

Atopic dermatitis (AD) is a common relapsing inflammatory skin disease. FLG is the gene most consistently associated with AD. Loss-of-function variants in FLG have been previously associated with AD. Low-frequency and rare alleles (minor allele frequency < 5%) in this gene have been given less attention than loss-of-function variants. We fine sequenced the FLG gene in a cohort of individuals with AD. We developed a machine learning‒based algorithm to associate low-frequency and rare alleles with the disease. We then applied this algorithm to the FLG data, searching for associations between groups of low-frequency and rare FLG alleles and AD remission. A group of 46 rare and low-frequency FLG alleles was associated with increased AD remission (P = 2.76e-11). Overall, 16 of these 46 FLG variants were identified in an independent cohort and were associated with decreased AD incidence (P = 0.0007). This study presents an application of statistical methods in AD genetics and suggests that low-frequency and rare alleles may play a larger role in AD pathogenesis than previously appreciated.

LB727 Using a machine learning approach to identify rare and low-frequency filaggrin variants associated with remission of Atopic Dermatitis

Rare and low-frequency variants (minor allele frequency (MAF)<5%) within diseased populations are traditionally given less attention than common variants (MAF>5%), primarily because of insufficient statistical power, and because existing methods (burden tests and variant component tests) are primarily useful for examining whether a whole gene, and not particular variants, are implicated in disease. Atopic dermatitis (AD) is a common relapsing inflammatory skin disease, for which common variants, primarily in the skin barrier protein filaggrin (FLG), have been associated with disease presence and remission.

Duration of topical therapy in the maintenance of atopic dermatitis remission in paediatric age.

BACKGROUND Topical corticosteroids (TCS) are the first-choice treatment for atopic dermatitis (AD) flares. In literature there are clear advice about the potency, dosage and frequency of application of TCS, but there are no shared indications about duration of the treatment during a flare. The aim of the study is to demonstrate if the use of a steroid cream for less than or 5 days, could be equal or more effective than the application for more than 5 days during a flare episode, in keeping a remission state of AD. METHODS The study population (N.=122) was selected according to the following inclusion criteria: at least one specialist allergological and dermatological examination in the period November 2015 to February 2017, age between 1 and 11 years; mild to moderate atopic dermatitis. All patients were given a standardized telephone questionnaire, which concerns on multiple aspects: parents' self-reported perceptions of the severity of their child's condition; actual use of emollients, moisturizers and steroid creams; number of consecutive days of using of topical steroid cream during an exacerbation of AD; average number of AD exacerbations per month in the last year; total number of AD exacerbations in the last year. RESULTS Data from 96 patients was examined. We classified three groups of patients from data collected: group 1 (N.=40): use of TCS for ≤5 consecutive days during an exacerbation event of AD; group 2 (N.=12): use of TCS for >5 consecutive days during an exacerbation event of AD; group 3 (N.=44): nonuse of TCS or use of TCS with a different posology. We found a further subgroup in group 3 (3a, N.=27) with patients using only emollient creme in AD management. In group 1, 27 patients (67.5%) did not show a good AD control; on the contrary, 13 patients (27.5%) reported a good AD control. In group 2, 4 patients (25%) did not show a good AD control; on the contrary, 8 patients (75%) reported a good AD control. By comparing the data obtained in the presence of good AD control, the difference between the percentages obtained was found to be statistically significant (P=0.034). CONCLUSIONS The results obtained show that a therapeutic pattern based on the use of TCS for a duration of more than 5 consecutive days during an episode of AD exacerbation is more efficient than the proposed alternative therapeutic scheme in the maintenance of AD remission.

Duration of topical therapy in the maintenance of atopic dermatitis remission in pediatric age.

Topical corticosteroids (TCS) are the first-choice treatment for atopic dermatitis (AD) flares. In literature there are clear advice about the potency, dosage and frequency of application of TCS, but there are no shared indications about duration of the treatment during a flare. The aim of the study is to demonstrate if the use of a steroid cream for less than or 5 days, could be equal or more effective than the application for more than 5 days during a flare episode, in keeping a remission state of AD. The study population (N.=122) was selected according to the following inclusion criteria: at least one specialist allergological and dermatological examination in the period November 2015 to February 2017, age between 1 and 11 years; mild to moderate atopic dermatitis. All patients were given a standardized telephone questionnaire, which concerns on multiple aspects: parents' self-reported perceptions of the severity of their child's condition; actual use of emollients, moisturizers and steroid creams; number of consecutive days of using of topical steroid cream during an exacerbation of AD; average number of AD exacerbations per month in the last year; total number of AD exacerbations in the last year. Data from 96 patients was examined. We classified three groups of patients from data collected: group 1 (N.=40): use of TCS for ≤5 consecutive days during an exacerbation event of AD; group 2 (N.=12): use of TCS for >5 consecutive days during an exacerbation event of AD; group 3 (N.=44): nonuse of TCS or use of TCS with a different posology. We found a further subgroup in group 3 (3a, N.=27) with patients using only emollient crème in AD management. In group 1, 27 patients (67.5%) did not show a good AD control; on the contrary, 13 patients (27.5%) reported a good AD control. In group 2, 4 patients (25%) did not show a good AD control; on the contrary, 8 patients (75%) reported a good AD control. By comparing the data obtained in the presence of good AD control, the difference between the percentages obtained was found to be statistically significant (P=0.034). The results obtained show that a therapeutic pattern based on the use of TCS for a duration of more than 5 consecutive days during an episode of AD exacerbation is more efficient than the proposed alternative therapeutic scheme in the maintenance of AD remission.

PERSISTENT SUBCLINICAL INFLAMMATION IN THE SKIN AS A RISK FACTOR FOR RELAPSE IN ATOPIC DERMATITIS: FROM PATHOPHYSIOLOGY TO TREATMENT

Lowgrade cutaneous inflammation, which persists after induction of remission of atopic dermatitis (AD), determines the risk of repeated relapses and progression of the disease. It has been well established that subclinical inflammation in the skin of atopic patients may be inhibited by topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), and proactive courses of these drugs prolong remission of the disease. In terms of prolonged application, TCI have some advantages over TCS in the context of safety. However, the routine use of TCI in AD is constrained by many practitioners who do not accept the concept of subclinical chronic inflammation and the strategy of maintenance antiinflammatory therapy on areas prone to repeated relapses, as well as obsolete myths about the association of TCI application with increased risk of cutaneous lymphoma. The review presents modem data on the pathophysiology of AD with a focus on subclinical skin inflammation, which persists after regression of acute manifestations of the disease, and the possibilities of suppressing this inflammation with TCI. Data on the safety of TCI for longterm use and the absence of prooncogenic potential are given. In addition, the relevance and expediency of pimecrolimus use in children under 2 years of age are emphasized.

Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: A randomized, investigator-blinded, controlled study.

Proactive therapy for atopic dermatitis (AD) effectively prevents exacerbation. However, its role in preventing subsequent sensitization to allergens has not been prospectively studied. We investigated whether proactive therapy for AD can effectively impact immunological parameters in a randomized, investigator-blinded, parallel group study. Thirty patients aged 3 months to 7 years with moderate to severe AD who had undergone an AD educational program were allocated to a proactive treatment group or a reactive treatment group. During the disease control period, patients in the proactive group performed intermittent preventive application of topical corticosteroid for 1 year. Changes in the severity scoring, quality of life measures and immunological parameters (serum thymus and activation regulated chemokine [TARC], total immunoglobulin E [IgE] and house dust mite-specific IgE levels) were evaluated and compared between the proactive and reactive treatment groups. Although the average topical corticosteroid ointment use per day in both groups was not significantly different, the severity and quality of life scores were significantly lower in the proactive group than in the reactive group at the final visit. In addition, compared with baseline levels, serum TARC levels remained significantly lower during proactive therapy, while house dust mite-specific IgE levels were significantly increased only in the reactive group. The results suggest that in addition to controlling the severity of AD, intermittent preventive administration of topical corticosteroids may prevent an increase in aeroallergen-specific IgE levels in patients with childhood AD. The use of TARC levels as a biomarker for AD remission is also supported.

Plasma α-defensins are elevated during exacerbation of atopic dermatitis.

There is no currently no information regarding the role of α-defensins in the pathophysiology of atopic dermatitis (AD). To investigate levels of plasma α-defensins at exacerbation and remission of AD, and to assess their association with clinical severity of AD. Patients with AD during exacerbation were recruited from the Dermatology department at the Chita Medical Academy (Chita, Russian Federation). SCORAD (SCORing Atopic Dermatitis), itch intensity, plasma concentrations of α-defensins, and serum total IgE, interleukin (IL)-1β, IL-8 and IL-10 levels were measured at study entry and after 4 months. In total, 82 patients with AD [35 (45.1%) female and 47 (54.9%) male patients, mean ± SD age 42.2 ± 11.5 years, range 15-40] and 30 healthy controls (HCs) were included. Mean objective SCORAD score was 48.8 ± 19.4 and 16.1 ± 8.3 during AD during exacerbation and remission, respectively (P < 0.01). Plasma α-defensin levels in patients with AD (1.41 ± 0.32 μg/L) were significantly higher than in HCs (0.91 ± 0.34 μg/L) (P < 0.001). Significant correlations were found between plasma α-defensin levels with objective SCORAD (r = 0.55, P < 0.001), itch severity (r = 0.25, P < 0.05) and serum IgE levels (r = 0.38, P < 0.001) during AD exacerbation. Serum concentrations of IL-1β, IL-4 and IL-8 were significantly higher and levels of IL-10 were lower at AD exacerbation in patients than in HCs, with a weak negative correlation between plasma α-defensin and serum IL-10 levels (r = -0.22; P < 0.05). During AD exacerbation, plasma α-defensin levels are elevated, and are positively correlated with AD clinical severity, itch intensity and serum IgE levels.

Factors Associated with the Development and Remission of Allergic Diseases in an Epidemiological Survey of High School Students in Japan

Allergic diseases are an important health problem for children and adults. It is important to know how allergic diseases develop and remit from infancy to adolescence. Early intervention is effective in treating allergic diseases. We performed a large-scale questionnaire survey of high school students in Fukui Prefecture, Japan, and analyzed the factors associated with the development and remission of allergic diseases. A total of 21,802 students participated in the epidemiologic survey, and the valid response rate was 89.3% (19,461). We applied an inverse probability weighting method with propensity scores. The present prevalence rate of allergic rhinitis (AR) was 19.2%. The remission rate of AR was 15.3%. Only children and firstborns had a significantly higher risk of developing symptoms of allergic diseases [only child: AR, 1.37; bronchial asthma (BA), 1.30; food allergy (FA), 1.33 and firstborn: AR, 1.38; BA, 1.10]. Constipation was an associated factor for development of atopic dermatitis (AD) (1.17) and AR (1.17), regular intake of lactic acid bacteria was not an associated factor for development of allergic diseases but was a factor for remission of AD (1.22). Hypohidrosis was an associated factor for development of AD (1.25). High academic performance was an associated factor for development of AR (1.20) but was a negative factor for development of BA (0.89). The values in parentheses are significant adjusted odds ratios. This epidemiologic survey showed that the hygiene hypothesis and intestinal bacterial flora might influence the development of symptoms and remission of allergic diseases.

The natural course of childhood atopic dermatitis: a retrospective cohort study.

Atopic dermatitis (AD) is generally considered to be the initial step of the so-called atopic march, which following steps are allergic rhinitis (AR) and asthma. There are few data about the progression of AD, including factors associated with the remission of AD in Asians and further research is needed. To study the progression and factors associated with the remission of childhood AD diagnosed by pediatric dermatologists. This study included 303 AD patients who visited the pediatric dermatology unit at King Chulalongkorn Memorial Hospital, Thailand, between 2002 and 2010. An interview, performed by a physician via telephone using a preformed questionnaire, was completed for 205 children. A total of 205 children were observed, with a median observation time of 5.2 (3.5-8.0) years, and an initial AD severity score of mild (61.0%), moderate (29.3%) and severe (9.7%). The prevalence of AD during the first two years of life was 64.4%. AD completely disappeared in 102 cases (49.8%) by the median age of 3.5 (1.5-7.8) years. Early onset and severity of AD were major determinant of prognosis. The prevalence of AR and asthma was 36.6%, and 9.3%, respectively. The risk factors associated with respiratory allergy were the onset of AD after aged two years, a family history of atopy, increased serum IgE level, and sensitization to inhalant allergens. Half of AD had completely disappeared at preschool age. Good prognosis was mostly determined by early onset AD and mild severity. Late onset, family history of atopy and increased serum IgE level are associated with respiratory allergy.

ATOPIC DERMATITIS: NEW TARGETS OF THERAPY

Treatment of atopic dermatitis (AD) is most often based on the relief of symptoms. Two fundamental basis of AD — dry skin and itching — determine the main objectives of treatment of this chronic inflammatory diseases of the skin. With this purpose, the patients are recommended to use moisturizers (emollients) and topical anti-inflammatory drugs — corticosteroids, and/or calcineurin inhibitors. However, there are studies conclusively proving the existence of subclinical inflammation associated with impaired barrier function of the skin, production of cytokines and infiltration of lymphocytes. The new strategy of treatment — proactive therapy aimed at achieving control and maintenance of remission of atopic dermatitis. This will allow you to achieve faster control the symptoms of AD and to reduce the risk of recurrence of the disease.