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Urinary biomarker of oxidative stress in patients with psoriasis vulgaris and atopic dermatitis.

J Eur Acad Dermatol Venereol. 2009 Dec;23(12):1405-8

Authors: Nakai K, Yoneda K, Maeda R, Munehiro A, Fujita N, Yokoi I, Moriue J, Moriue T, Kosaka H, Kubota Y

BACKGROUND: The involvement of oxidative stress in the pathogenesis of various skin disorders has been suggested for decades. However, few clinical studies have assessed oxidative stress in skin diseases. The easiest and least invasive method to assess oxidative stress in patients may be the measurement of oxidation products in urine. OBJECTIVE: This study aims to assess oxidative stress in psoriasis and atopic dermatitis patients. METHODS: Urine samples were collected from 29 psoriasis patients (25 males and 4 females), 21 atopic dermatitis patients (14 males and 7 females) and 20 healthy controls (16 males and 4 females). The severity and extent of psoriasis and atopic dermatitis was assessed by their area and severity index. We measured nitrate as a metabolite of nitric oxide, malondialdehyde as a major lipid oxidation product, and 8-hydroxydeoxyguanosine (8-OHdG) as a DNA oxidation marker. RESULTS: Urinary nitrate and 8-OHdG levels, but not malondialdehyde, were significantly higher in psoriasis patients than those in healthy controls. On the contrary, only urinary nitrate level was significantly higher in atopic dermatitis patients than those in healthy controls. The severity and extent of both psoriasis and atopic dermatitis significantly correlated with urinary nitrate level and malondialdehyde level, but it did not correlate with urinary 8-OHdG level. CONCLUSIONS: Measurement of these three urinary oxidative products is non-invasive. Above all, measurement of urinary nitrate may be most useful in the clinical assessment of oxidative stress in both psoriasis and atopic dermatitis patients. There is a possibility that urinary 8-OHdG level may indicate the different pathogenesis between psoriasis and atopic dermatitis.

PMID: 20205355 [PubMed - in process]

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IKKbeta Leads to an Inflammatory Skin Disease Resembling Interface Dermatitis.

J Invest Dermatol. 2010 Mar 4;

Authors: Page A, Navarro M, Garín M, Pérez P, Casanova ML, Moreno R, Jorcano JL, Cascallana JL, Bravo A, Ramírez A

IKKbeta is a subunit of the IkappaB kinase (IKK) complex required for NF-kappaB activation in response to pro-inflammatory signals. NF-kappaB regulates the expression of many genes involved in inflammation, immunity, and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. In this study we report the alterations caused by increased IKKbeta activity in skin basal cells of transgenic mice. These animals suffered chronic inflammation with abundant macrophages and other CD45(+) infiltrating cells in the skin, which resulted in epidermal basal cell injury and degeneration of hair follicles. They showed histological features characteristic of interface dermatitis (ID). This phenotype is accompanied by an increased production of inflammatory cytokines by transgenic keratinocytes. Accordingly, transcriptome studies show upregulation of genes associated with inflammatory responses. The inflammatory phenotype observed as a consequence of IKKbeta overexpression is independent of T and B lymphocytes, as it also arises in mice lacking these cell types. In summary, our data indicate the importance of IKKbeta in the development of ID and in the homeostasis of stratified epithelia. Our results also support the idea that IKKbeta might be a valid therapeutic target for the treatment of skin inflammatory diseases.Journal of Investigative Dermatology advance online publication, 4 March 2010; doi:10.1038/jid.2010.28.

PMID: 20200541 [PubMed - as supplied by publisher]

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Polymorphisms in human histamine receptor H4 gene are associated with atopic dermatitis.

Br J Dermatol. 2010 Mar 1;

Authors: Yu B, Shao Y, Zhang J, Dong XL, Liu WL, Yang H, Liu L, Li MH, Yue CF, Fang ZY, Zhang C, Hu XP, Chen BC, Wu Q, Chen YW, Zhang W, Wan J

Summary Background Atopic dermatitis (AD) is a chronic skin disease affecting more than 15% of children and 2% of adults. A strong connection between genetic factors and AD has been described for a long time. Histamine receptor H4 (HRH4) has been shown to be related to different kinds of allergic and autoimmune disorders. However, an association between HRH4 and AD has not yet been reported. Objectives To examine a possible association between HRH4 and AD. Methods Genomic DNA from 301 patients with AD and 313 healthy controls was extracted and three exons of HRH4 were sequenced. Results We found three new single nucleotide polymorphisms (SNPs) in HRH4 which were significantly associated with AD: ss142022671 [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.24-2.81; P = 0.002], ss142022677 (OR 4.40, 95% CI 2.42-8.00; P = 1.5 x 10(-7)) and ss142022679 (OR 4.26, 95% CI 2.38-7.61; P = 1.3 x 10(-7)). The SNPs ss142022677 and ss142022679 were found to be in strong linkage disequilibrium (D’ = 0.98; r(2) = 0.92). Two-SNP haplotype analysis (ss142022677 and ss142022679) showed that the major AA haplotype was protective against AD (OR 0.22, 95% CI 0.12-0.40; P = 3.1 x 10(-8)) and the minor TT haplotype was significantly associated with AD (OR 4.13, 95% CI 2.27-7.54; P = 6.6 x 10(-7)). In addition, in a three-SNP haplotype analysis (ss142022671, ss142022677 and ss142022679), the major TAA haplotype was protective against AD (OR 0.46, 95% CI 0.31-0.69; P = 0.0001), while the complementary ATT haplotype was found to be significantly associated with AD (OR 3.81, 95% CI 2.03-7.14; P = 8.3 x 10(-6)). Conclusions Polymorphisms of ss142022671, ss142022677 and ss142022679 in HRH4 are associated with AD.

PMID: 20199554 [PubMed - as supplied by publisher]

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A double-blind, randomized study to assess the effectiveness of different moisturizers in preventing dermatitis induced by hand washing to simulate healthcare use.

Br J Dermatol. 2010 Mar 1;

Authors: Williams C, Wilkinson SM, McShane P, Lewis J, Pennington D, Pierce S, Fernandez C

Summary Background Healthcare-associated infection is an important worldwide problem that could be reduced by better hand hygiene practice. However, irritant contact dermatitis of the hands as a result of repeated hand washing is a potential complication that may be preventable by the regular use of an emollient. Objectives To assess the effect of moisturizer application after repeated hand washing (15 times daily) vs. soap alone. Methods In a double-blind, randomized study, the effect of five different moisturizers on skin barrier function was determined by assessment after repeated hand washing over a 2-week period in healthy adult volunteers. Assessments of transepidermal water loss (TEWL), epidermal hydration and a visual assessment using the Hand Eczema Severity Index (HECSI) were made at days 0, 7 and 14. Results In total, 132 patients were enrolled into the study. A statistically significant worsening of the clinical condition of the skin as measured by HECSI was seen from baseline to day 14 (P = 0.003) in those subjects repeatedly washing their hands with soap without subsequent application of moisturizer. No change was seen in the groups using moisturizer. Subclinical assessment of epidermal hydration as a measure of skin barrier function showed significant increases from baseline to day 14 after the use of three of the five moisturizing products (P = 0.041, 0.001 and 0.009). Three of the five moisturizers tested led to a statistically significant decrease in TEWL at day 7 of repeated hand washing. This effect was sustained for one moisturizing product at day 14 of hand washing (P = 0.044). Conclusions These results support the view that the regular application of moisturizers to normal skin offers a protective effect against repeated exposure to irritants, with no evidence of a reduction in barrier efficiency allowing the easier permeation of irritant substances into the skin as has been suggested by other studies. Regular use of emollient in the healthcare environment may prevent the development of dermatitis.

PMID: 20199550 [PubMed - as supplied by publisher]

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Systematized contact dermatitis and montelukast in an atopic boy.

Pediatr Dermatol. 2009 Nov 1;26(6):739-43

Authors: Castanedo-Tardan MP, González ME, Connelly EA, Giordano K, Jacob SE

Upon ingestion, the artificial sweetener, aspartame is metabolized to formaldehyde in the body and has been reportedly associated with systemic contact dermatitis in patients exquisitely sensitive to formaldehyde. We present a case of a 9-year-old Caucasian boy with a history of mild atopic dermatitis that experienced severe systematized dermatitis after being started on montelukast chewable tablets containing aspartame. Patch testing revealed multiple chemical sensitivities which included a positive reaction to formaldehyde. Notably, resolution of his systemic dermatitis only occurred with discontinuation of the montelukast chewables.

PMID: 20199453 [PubMed - in process]

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Recent Microbiological Shifts in Perianal Bacterial Dermatitis: Staphylococcus aureus Predominance.

Pediatr Dermatol. 2009 Nov;26(6):696-700

Authors: Heath C, Desai N, Silverberg NB

Traditionally, bacterial infections of the anal skin have been found to be caused by Streptococcus. The aim of this study was to determine the breakdown of bacterial isolates and the current presentation of bacterial diseases involving the perineum. From the chart review of children who had bacterial cultures of the anus from 2005 to 2008 in a pediatric dermatology practice population in New York City, 26 pediatric patients (ages 5 months to 12 yrs) who had the indications of anal erythema or recurrent buttocks dermatitis were identified. Bacterial cultures of 17 patients grew pathogens, that of 14 (82% of identifiably infected patients) grew Staphylococcus aureus, in 11 as a solo pathogen (6 MSSA and 5 MRSA in 2 family clusters). Streptococcus was identified in three patients, two on culture and one on latex agglutination test; and two patients were identified as having both group A beta hemolytic Streptococcus and Staphylococcus aureus (2 MSSA and 1 MRSA). In patients with S. aureus perianally, concurrent small papules and pustules of the buttocks or extension of the erythema to adjacent buttock skin was the primary clinical feature distinguishing this condition from isolated streptococcal disease. Whereas Streptococcal infections of the anus and buttocks occur commonly, Staphylococcus aureus has become the leading cause of anal bacterial infection in the setting of skin involvement; therefore, antibacterial therapy for anal and buttock bacterial infections should be tailored accordingly.

PMID: 20199443 [PubMed - in process]

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The frequency and intensity of topical pimecrolimus treatment in children with physician-confirmed mild to moderate atopic dermatitis.

Pediatr Dermatol. 2009 Nov;26(6):682-7

Authors: Kapoor R, Hoffstad O, Bilker W, Margolis DJ

Atopic dermatitis (AD) is often treated with multiple modalities, including topical medications such as corticosteroids and topical calcineurin inhibitors (TCIs). The aim of this study was to describe the natural history of the utilization characteristics of topical treatment in those with AD. We conducted a longitudinal study of the first 4,105 children with physician-confirmed mild to moderate AD enrolled in an ongoing postmarketing safety study of pimecrolimus. Information was obtained from participants every six months using a questionnaire. Drug utilization was solely determined by the physician and patient. Over the three years of our study, an increasing number of individuals reported at least 6 months of complete control of their disease, without the continued use of a topical medication. While all study participants used pimecrolimus at the start of the study less than 40% continued to use it after 3 years of study participation. If an individual was still using a topical medication after three years of follow-up, it was most likely a topical corticosteroid. For those who continued to use pimecrolimus, the use was limited to about 60 grams of pimecrolimus in 6 months. Community-based use of topical pimecrolimus to treat AD is limited both with respect to the duration of exposure and amount or total dose of the exposure. If a topical therapy is persistent, it is most likely to a topical corticosteroid.

PMID: 20199441 [PubMed - in process]

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Sporadic blau syndrome with onset of widespread granulomatous dermatitis in the newborn period.

Pediatr Dermatol. 2010 Jan 1;27(1):69-73

Authors: Stoevesandt J, Morbach H, Martin TM, Zierhut M, Girschick H, Hamm H

Blau syndrome is a dominantly inherited, chronic autoinflammatory disorder characterized by the clinical triad of granulomatous dermatitis, symmetric arthritis, and recurrent uveitis with onset below 4 years of age. It is caused by activating mutations in the nucleotide-binding oligomerization domain 2 (NOD2) gene, previously referred to as CARD15 gene. Noncaseating granulomas in affected tissues are the pathologic hallmark of the condition. We report the lifelong severe disease course in a 14-year-old Caucasian boy with sporadic Blau syndrome. Unusually, granulomatous dermatitis started in the first week of life. Whereas skin involvement faded away spontaneously in subsequent years, polyarthritis and anterior uveitis appeared in the second and third year of life respectively. Mutational analysis of the NOD2 gene revealed a missense mutation (R334W) previously detected in other Blau syndrome pedigrees. With this report, we would like to stress the rare possibility of Blau syndrome in generalized papular rashes of infancy and the importance of histopathologic study for clarification. The finding of early-onset widespread granulomatous dermatitis should prompt eye and joint examination in regular intervals and entail mutational analysis of the NOD2 gene.

PMID: 20199415 [PubMed - in process]

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Related Articles

A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis.

J Am Acad Dermatol. 2010 Feb 15;

Authors: Victor FC, Cohen DE, Soter NA

BACKGROUND: Retrospective chart reviews are periodically needed to update allergen series to detect changes in photoallergic contact dermatitis (PACD) over time. OBJECTIVE: We sought to evaluate photopatch test results during a 13-year period and extend the observations to 20 years. METHODS: A retrospective chart review was conducted in patients who were photopatch tested. RESULTS: In all, 76 patients were evaluated. A total of 69 positive photopatch and 45 positive patch test reactions were detected in 30 and 23 patients, respectively. The frequencies of the positive photopatch test reactions were sunscreens 23.2%, antimicrobial agents 23.2%, medications 20.3%, fragrances 13%, plants and plant derivatives 11.6%, and pesticides 8.7%. Of the positive photopatch reactions to antimicrobial agents, 60% were caused by Fentichlor. LIMITATIONS: This study was a retrospective chart analysis, and the number of patients was small. CONCLUSIONS: Sunscreens and antimicrobial agents were the most frequent allergens eliciting PACD, and there was a decrease in PACD caused by fragrances. The number of reactions to medications increased. This study also demonstrated that pesticides can be a cause of PACD. The detection of reactions to Fentichlor was unexpected and, although they have been attributed in some studies to cross-reactions to sulfanilamides and bithionol, such a robust association was not observed in this study. This study extends our experience of the changes in the allergens that elicit PACD to 20 years.

PMID: 20163891 [PubMed - as supplied by publisher]

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Twice-weekly treatment with tacrolimus 0.03% ointment in children with atopic dermatitis: clinical efficacy and economic impact over 12 months.

J Eur Acad Dermatol Venereol. 2010 Feb 10;

Authors: Thaci D, Chambers C, Sidhu M, Dorsch B, Ehlken B, Fuchs S

Abstract Background Rational healthcare decision-making based on clinical and economic evidence is essential to provide the best possible care for patients with atopic dermatitis (AD). Objective To evaluate treatment outcomes, resource use and cost associated with twice-weekly tacrolimus 0.03% ointment treatment vs. standard flare-only therapy in children with moderate-to-severe AD. Methods In a pan-European, Phase III multicentre randomized clinical trial, children with mild-to-severe AD were randomized to 0.03% tacrolimus ointment or vehicle twice weekly for 12 months. Disease flares were treated using open-label tacrolimus 0.03% ointment twice daily. Clinical efficacy data were evaluated in a subgroup of 153 children with moderate-to-severe AD, with resource use data - collected prospectively using caregiver questionnaires - available from 146 children. Pooled costs of resource use were determined using German unit cost data. Direct and indirect costs were considered from third-party payer, patient and caregiver, and societal perspectives. Results Twice-weekly tacrolimus ointment reduced the number of flares compared with standard therapy (P < 0.001) and prolonged time to first flare (146 vs. 17 days, P < 0.001). Mean +/- SD annual costs per patient for standard and twice-weekly therapy respectively were euro2002 +/- 2315 vs. euro1571 +/- 1122 for severe AD and euro1136 +/- 1494 vs. euro1233 +/- 1507 for moderate AD. Conclusions In children with AD, twice-weekly treatment with tacrolimus 0.03% ointment reduces the number of flares and prolongs time spent free from flares with no additional cost in children with moderate AD, and may be cost-saving in those with severe AD.

PMID: 20158589 [PubMed - as supplied by publisher]

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