Atopic dermatitis (eczema)

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Does autonomic dysfunction play a role in atopic dermatitis?

Br J Dermatol. 2008 Jul 22;

Authors: Cicek D, Kandi B, Berilgen MS, Bulut S, Tekatas A, Dertlioglu SB, Ozel S, Saral Y

Background Atopic dermatitis (AD) is a chronic dermatitis characterized by intense itching and excessive skin dryness. The factor most commonly blamed for the pathogenesis of skin dryness in the disease is impaired barrier function of the stratum corneum. However, there are findings indicating that the autonomic nervous system, and the sympathetic nervous system in particular, is affected negatively in AD, and thus, autonomic dysfunction can be an important factor leading to skin dryness. Objective In this study we aimed to evaluate the functioning of the autonomic nervous system electrophysiologically using R-R interval variation (RRIV) and the sympathetic skin response (SSR) in patients with AD, and to examine whether there is an underlying autonomic nervous system dysfunction. Patients and methods The study registered a total of 38 (12 males and 26 females) patients with AD, of whom 24 had active and 14 inactive disease, and 20 (10 males and 10 females) healthy control subjects. RRIV was used in our study as the electrophysiological test to evaluate the parasympathetic system. The SSR method, which is a noninvasive electrophysiological test with a significant role in evaluating the sudomotor activity of skin, as well as that of the unmyelinated fibres that take a part in this activity, was employed to assess the sympathetic nervous system. Results Our study revealed a significantly prolonged SSR latency and amplitude of the upper extremity in the patient group, relative to the control group (P < 0.05). When the group with active skin lesions was compared with the control group, the former was found to have prolonged SSR latency and amplitude in the upper extremity. The prolongation in SSR latency of the upper extremity was statistically significant (P < 0.05), while the prolongation in amplitude was not (P = 0.5). An evaluation of RRIV results did not show a significant difference between the patient and control groups. Conclusions These findings demonstrate that the sudomotor activity controlled by the sympathetic nervous system, as well as unmyelinated fibres that play a role in this activity are affected in patients with AD. We think that the involvement of sudomotor activity may be one of the causes that leads to dysfunction in sweat glands and skin dryness.

PMID: 18652587 [PubMed - as supplied by publisher]

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Prophylactic effect of oral administration of Lactobacillus johnsonii NCC533 (La1) during the weaning period on atopic dermatitis in NC/NgaTnd mice.

Eur J Dermatol. 2008 Mar-Apr;18(2):136-40

Authors: Tanaka A, Fukushima Y, Benyacoub J, Blum S, Matsuda H

Bacterial exposure in infancy may be one of the determinants of atopic dermatitis (AD) morbidity in later life. Some clinical studies have shown that an intake of probiotics reduced the risks of AD in children; however, the timing and duration of administration for the prevention of AD still remain unclear. The aim of this study was to evaluate the effects on AD development of the administration of Lactobacillus johnsonii NC553 (La1) during the weaning period, using an animal model of human AD, NC/NgaTnd mice. La1 suspended in drinking water was administered to 4-week-old NC/NgaTnd mice for 4 weeks. Mice were kept up to 16 weeks of age in an air uncontrolled conventional condition. Clinical skin severity, scratching behaviour, histological features, and production of regulatory or inflammatory cytokines in spleens were analyzed. The results indicated that oral administration of La1 suppressed exacerbation of the clinical severity of dermatitis when compared to the controls. Scratching duration, which is the most important cause of skin damage, was also suppressed in mice fed with La1. La1 supplementation also suppressed epidermal hyperplasia and infiltration of inflammatory cells in skin. This study showed that exposure to La1 from the early stages might be beneficial to reduce the exacerbation of AD in children at high-risk of allergy.

PMID: 18424371 [PubMed - indexed for MEDLINE]

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Facing psoriasis and atopic dermatitis: are there more similarities or more differences?

Eur J Dermatol. 2008 Mar-Apr;18(2):172-80

Authors: Wilsmann-Theis D, Hagemann T, Jordan J, Bieber T, Novak N

Atopic dermatitis (AD) and psoriasis vulgaris (Pso) represent the most frequent chronic inflammatory skin diseases. It has been assumed for a long time that these diseases have a completely different background. Recent findings about the genetic, epidemiologic and pathophysiologic factors of both diseases have remarkably improved our knowledge about the complex mechanisms underlying AD and Pso. Beyond that, in view of these findings, the question arises, which similarities and differences between AD and Pso exist. In order to address this point, we provide an overview about the current knowledge in the field of AD and Pso.

PMID: 18424378 [PubMed - indexed for MEDLINE]

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Alefacept for moderate to severe atopic dermatitis: a pilot study in adults.

J Am Acad Dermatol. 2008 Jun;58(6):984-9

Authors: Moul DK, Routhouska SB, Robinson MR, Korman NJ

BACKGROUND: Atopic dermatitis is a common inflammatory skin condition with acute and chronic phases showing a prevalence of memory T cells. Alefacept is a fully human LFA-3/IgG1 fusion protein that inhibits T-cell activation and selectively reduces memory T cells, which may prove to be effective in the treatment of atopic dermatitis. OBJECTIVE: We sought to evaluate clinical response of alefacept intramuscular (IM) injection for 16 weeks in adults with atopic dermatitis. METHODS: This was an open-label study of a 16-week treatment regimen of alefacept IM injection in adults with moderate to severe inflammatory atopic dermatitis. Patients received alefacept (30 mg IM) weekly for the first 8 weeks. At week 9, patients who did not achieve a 50% reduction in their Eczema Area Severity Index (EASI) score continued on alefacept (30 mg IM) weekly; those patients with a 50% reduction in their EASI (EASI 50) score or higher had their weekly dose decreased (15 mg IM) for the remaining 8 weeks. RESULTS: Nine patients with moderate to severe atopic dermatitis were enrolled and treated. At the primary end point, week 18, 1 patient achieved EASI 50 score and 1 patient achieved EASI 90 score; 4 patients had a decrease in EASI score of less than 50%, 1 patient had an increase in EASI score, and 2 patients withdrew early before the primary end point because of worsening disease. A Physician Global Assessment score of mild was achieved in 2 patients and 1 patient achieved a Physician Global Assessment score of almost clear. Minimal pruritus was reported by 3 patients and 1 patient reported no pruritus. The 16-week course of alefacept was well tolerated. LIMITATIONS: The study was inherently limited by its small sample size, concomitant use of antihistamines, and open-label design, which increases the likelihood of observer and self-assessment bias. CONCLUSION: The treatment regimen of alefacept for 16 weeks was well tolerated by our patients. Although, in this study, only 2 of the 9 patients with atopic dermatitis responded to treatment with alefacept, the study was inherently limited by the small sample size. Additional studies with a larger sample size, continued weekly use, or concomitant use of ultraviolet-B light therapy may be warranted to evaluate the possibility of alefacept as a therapy for patients with chronic atopic dermatitis.

PMID: 18395294 [PubMed - indexed for MEDLINE]

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Intermittent therapy for flare prevention and long-term disease control in stabilized atopic dermatitis: a randomized comparison of 3-times-weekly applications of tacrolimus ointment versus vehicle.

J Am Acad Dermatol. 2008 Jun;58(6):990-9

Authors: Breneman D, Fleischer AB, Abramovits W, Zeichner J, Gold MH, Kirsner RS, Shull TF, Crowe AW, Jaracz E, Hanifin JM,

BACKGROUND: Intermittent dosing of a topical calcineurin inhibitor for preventing atopic dermatitis (AD) disease relapse in patients with stabilized AD has not been evaluated. OBJECTIVE: We sought to evaluate the long-term efficacy and safety of 3-times-weekly use of tacrolimus ointment in preventing AD disease relapse. METHODS: Adult and pediatric patients with moderate to severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were randomized in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment (0.03% or 0.1%) or vehicle for 40 weeks. The primary end point was the number of flare-free treatment days. RESULTS: A total of 125 patients were randomized to tacrolimus and 72 patients to vehicle. The mean number of flare-free treatment days was 177 for tacrolimus and 134 for vehicle (P = .003). Median time to first relapse was 169 days for tacrolimus and 43 for vehicle (P = .037). LIMITATIONS: Generalizability to all patients seen in clinic may be limited because only patients who responded to tacrolimus ointment in the stabilization phase were randomized into the maintenance phase of the trial. CONCLUSIONS: Maintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle, and a significantly longer time until first disease relapse.

PMID: 18359127 [PubMed - indexed for MEDLINE]

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A 4-year follow-up study of atopic dermatitis therapy with 0.1% tacrolimus ointment in children and adult patients.

Br J Dermatol. 2008 Jul 15;

Authors: Reitamo S, Rustin M, Harper J, Kalimo K, Rubins A, Cambazard F, Brenninkmeijer EE, Smith C, Berth-Jones J, Ruzicka T, Sharpe G, Taieb A,

Background For the treatment of a chronic disease like atopic dermatitis, sustained tolerability and efficacy of the applied medication are essential. Objectives The present open-label, noncomparative study was conducted to obtain information on the long-term safety and efficacy of 0.1% tacrolimus ointment. Methods Patients aged 2 years or older with an affected body surface area of more than 5%, who previously participated in a clinical trial on tacrolimus ointment, were eligible for this study. The treatment area was defined by the investigator at study entry. Both children and adults applied continuously or intermittently 0.1% tacrolimus ointment twice daily during episodes of active disease plus an additional week after remission over a follow-up period of up to 4 years. Results The intent-to-treat population comprised 782 patients, with a median age of 22 years (range 2-72). Patients remained in the study for up to 4 years. Approximately half of the patients discontinued the study prematurely; the median follow-up was 1422 days. Median tacrolimus ointment use was 31.2 g during the first week; ointment use decreased during the first year and then remained stable for the remainder of the study. The median cumulative tacrolimus use was 271.5 g at month 6, 462.5 g at month 12, 739.9 g at month 24, 1029.3 g at month 36 and 1320.8 g at month 48. Altogether 51.8% of patients discontinued the study prematurely; the main reasons were withdrawal of consent (13.3%), loss to follow-up (11.3%) and lack of efficacy (9.4%). Adverse events led to study discontinuation in 3.7% of the patients. The most frequent application site events were skin burning and pruritus. These events were most often reported in adult patients during the initial treatment period; prevalence decreased after the first week and remained at a low level throughout the study. Nonapplication site events occurred with stable incidences throughout the study period. In general, calculated daily hazard rates did not indicate an increased risk of adverse events with prolonged treatment. The total affected body surface area decreased substantially upon onset of treatment and efficacy of treatment was maintained until the end of the study with smaller but continuous improvements throughout the follow-up period. Overall, 75% of the patients and 76% of the investigators rated their satisfaction with the treatment as excellent, very good or good at the end of the study or at the time of premature discontinuation. Conclusions The safety profile of intermittent or continuous long-term application of 0.1% tacrolimus ointment for up to 4 years was consistent with that which has been established from shorter studies and gave no reason for concern. In addition, 0.1% tacrolimus ointment demonstrated sustained efficacy as reflected by the expression of high satisfaction with treatment by both patients and investigators.

PMID: 18637898 [PubMed - as supplied by publisher]

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Loss-of-function polymorphisms in the filaggrin gene are associated with an increased susceptibility to chronic irritant contact dermatitis: a case-control study.

Br J Dermatol. 2008 Jul 10;

Authors: de Jongh CM, Khrenova L, Verberk MM, Calkoen F, van Dijk FJ, Voss H, John SM, Kezic S

Background Polymorphisms in the filaggrin (FLG) gene, which result in loss of filaggrin production, may alter the skin barrier and are a well-known predisposing factor for atopic dermatitis. Objectives As a compromised skin barrier and atopic dermatitis are risk factors for chronic irritant contact dermatitis (CICD), our objective was to determine whether polymorphisms in the FLG gene contribute towards susceptibility to occupational CICD. Methods In a case-control study, the FLG polymorphisms R501X and 2282del4 were determined in 296 patients with CICD. Two hundred and seventeen apprentices in vocational training for high-risk occupations for CICD were chosen as controls. Data on skin diseases and conditions were collected by dermatologists from patients and by means of questionnaires from controls. Results Heterozygotes for R501X and 2282del4, FLG null alleles, were more frequent among patients with CICD (12.5%) compared with controls (6.9%), resulting in an odds ratio of 1.91 (95% confidence interval 1.02-3.59). Among patients who were carriers of a FLG null allele, we found a higher lifetime prevalence of flexural eczema (62% vs. 46%; P = 0.04) and a higher atopy score (13 vs. 10 points; P = 0.05) compared with noncarriers. In the apprentice group, signs of dermatitis before the start of the vocational training were four times more prevalent in carriers (43%) than in noncarriers (10%; P < 0.001). Conclusions Our study shows that FLG null alleles are associated with increased susceptibility to CICD; whether or not the FLG null allele is an independent risk factor needs further study.

PMID: 18637008 [PubMed - as supplied by publisher]

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Common misconceptions in contact dermatitis counseling.

Dermatol Online J. 2008;14(4):2

Authors: Katta R

Both physicians and patients hold many misconceptions when it comes to allergen avoidance. Ten commonly held misconceptions are exposed, allowing more accurate approach to the individual with cutaneous allergies.

PMID: 18627724 [PubMed - in process]

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

J Eur Acad Dermatol Venereol. 2008 Jun 24;

Authors: Sigurgeirsson B, Ho V, Ferrándiz C, Andriano K, Grinienko A, Jimenez P,

Objective 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). Methods 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. Results 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). Conclusions 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.

PMID: 18624866 [PubMed - as supplied by publisher]

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A multicentre randomized controlled trial of ion-exchange water softeners for the treatment of eczema in children: protocol for the Softened Water Eczema Trial (SWET) (ISRCTN: 71423189).

Br J Dermatol. 2008 Jun 26;

Authors: Thomas KS, Sach TH,

Background There is epidemiological evidence linking increased water hardness with increased eczema prevalence. A number of plausible mechanisms can be forwarded to suggest why hard water could exacerbate eczema. The most likely explanation is increased soap usage in hard water areas, the deposits of which can cause skin irritation in individuals with eczema. Objectives To assess the cost and cost-effectiveness of ion-exchange water softeners for the treatment of eczema in children. Patients/Methods Three hundred and ten children aged 6 months to 16 years, with moderate to severe eczema. The children must live in hard water areas (>/= 200 mg L(-1) of calcium carbonate) and have a home that is suitable for the installation of a water softener. This is a single-blind, parallel-group, randomized controlled trial of 12 weeks duration followed by a 4-week cross-over period. Results/Analysis Plan Primary outcome: difference in the mean change in disease severity (Six Area, Six Sign Atopic Dermatitis score) at 12 weeks compared with baseline. Secondary outcomes: (i) proportion of time spent moving during the night; (ii) self-reported global changes in eczema severity; (iii) amount of topical treatment used; (iv) Patient Oriented Eczema Measure; (v) number of totally controlled and well controlled weeks; (vi) impact on health-related quality of life for the child (EQ-5D) and the family (Dermatitis Family Impact questionnaire); and (vii) cost-effectiveness. It is planned that recruitment will be completed by the end of 2008 and results will be available towards the end of 2009.

PMID: 18616772 [PubMed - as supplied by publisher]

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