Atopic dermatitis (eczema)

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Molecular analysis of Malassezia microflora in seborrheic dermatitis patients: comparison with other diseases and healthy subjects.

J Invest Dermatol. 2008 Feb;128(2):345-51

Authors: Tajima M, Sugita T, Nishikawa A, Tsuboi R

Malassezia species colonize the skin of normal and various pathological conditions including pityriasis versicolor (PV), seborrhoeic dermatitis (SD) and atopic dermatitis (AD). To elucidate the pathogenic role of Malassezia species in SD, Malassezia microflora of 31 Japanese SD patients was analyzed using a PCR-based, culture-independent method. Nested PCR assay using the primers in the rRNA gene indicated that the major Malassezia species in SD were M. globosa and M. restricta, found in 93 and 74% of the patients, respectively. The detection rate and number of each species varied similarly in SD, PV and healthy subjects (HSs), whereas AD showed higher values. Real-time PCR assay showed that the lesional skin harbored approximately three times the population of genus Malassezia found in nonlesional skin (P<0.05), and that M. restricta is a significantly more common species than M. globosa in SD (P<0.005). Genotypic analysis of the rRNA gene showed that the M. globosa and M. restricta from SD patients fell into specific clusters, and could be distinguished from those collected from HSs, but not from those colleted from AD patients. Our results indicate that certain strains of M. restricta occur in the lesional skin of SD patients.

PMID: 17671514 [PubMed - indexed for MEDLINE]

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Transglutaminase autoantibodies in dermatitis herpetiformis and celiac sprue.

J Invest Dermatol. 2008 Feb;128(2):332-5

Authors: Marietta EV, Camilleri MJ, Castro LA, Krause PK, Pittelkow MR, Murray JA

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disorder that is associated with intestinal gluten sensitivity. Epidermal transglutaminase (TGe) and closely related tissue transglutaminase (tTG) are considered to be autoantigens in DH, because a majority of DH patients have IgA specific for TGe and for tTG. It is unknown where and how these autoantigen-specific IgAs are generated in DH. Results reported in this paper on nine DH patients on a gluten containing diet demonstrate that the levels of circulating anti-tTG IgA and anti-TGe IgA in DH are correlated with each other and that both appear to be correlated with the degree (extent) of enteropathy. An analysis of 15 untreated celiac sprue (CS) patients demonstrated that approximately 33% of CS patients had elevated levels of anti-TGe IgA. These results would indicate that intestinal damage is associated with the production of anti-tTG IgA and anti-TGe IgA in DH patients.

PMID: 17762854 [PubMed - indexed for MEDLINE]

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Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice.

J Invest Dermatol. 2008 Feb;128(2):434-46

Authors: Pavlovic S, Daniltchenko M, Tobin DJ, Hagen E, Hunt SP, Klapp BF, Arck PC, Peters EM

A neurogenic component in atopy and allergy is evident and potentially of great pathogenic relevance. Stress was recently shown to activate elements of this component and is vividly discussed as a cause of exacerbation. However, to date, scientific proof of stress-induced neuronal plasticity and neuro-immune interaction in atopy or allergy remains lacking. Here we show early evidence that exposure to sound stress and atopic dermatitis-like allergic dermatitis (AD) equipotently raise the number of cutaneous nerve fibers containing the prototypic stress neuropeptide substance P (SP) in mice. Stress increases AD readout parameters by at least 30% (eosinophil infiltration, vascular cell adhesion molecule-positive blood vessels, epidermal thickness). This dramatic pathologic exacerbation is associated with increased neurogenic inflammation (degranulated mast cells; interstitial neuropeptidergic dense core granules, mast cell apoptosis, endothelial gaping). Key features of AD exacerbation could not be induced in mice lacking the neurokinin-1 SP receptor (NK1). Interestingly, stress had no significant additional effect on CD4+ cell number, but shifted the cytokine profile toward TH2 in skin. Thus, we conclude that stress primarily exacerbates AD via SP-dependent cutaneous neurogenic inflammation and subsequent local cytokine shifting and should be considered as a therapeutic target, while it offers a convincing pathogenic explanation to affected patients and their frustrated physicians alike.

PMID: 17914449 [PubMed - indexed for MEDLINE]

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Hypersensitivity to aeroallergens in adult patients with atopic dermatitis develops due to the different immunological mechanisms.

Eur J Dermatol. 2007 Nov-Dec;17(6):520-4

Authors: Samochocki Z, Owczarek W, Rujna P, Raczka A

Atopic dermatitis (AD) is a disease with a complex pathomechanism, it is very difficult to establish the exact factors which can either trigger or exacerbate the disease. Knowledge of the mechanisms involved in AD development can be increased by, among others, applying new diagnostic tests and careful assessment of the results obtained. The aim of this study was to determine the allergic mechanisms of hypersensitivity to selected aeroallergens in patients with AD. The study comprised 109 AD patients. In all the patients the total IgE level was measured and atopy patch tests and skin prick tests were performed. We also assessed the presence of specific IgE against house dust mite, birch-tree, mixed grass pollen and cat dander. The highest incidence of positive results was found for house dust mite allergens, irrespective of the test employed. Analysing hypersensitivity to all the examined allergens we revealed the presence of allergic mechanisms in 85.3% of the patients. In 30.2% of the examined individuals we proved a type I immunological response, in 45.9% — both types I and IV in 9.2% — only type IV in one patient. In 14.7% of the patients the results of all the tests performed were negative. Analysing hypersensitivity to particular aeroallergens, negative test results to house dust mite were observed in 25.8% of the patients. The percentage of positive results for birch pollen, grass pollen and cat dander were 45.0, 44.1 and 53.2, respectively. Analysis of the results showed that allergic reactions to the same aeroallergens may develop via different mechanisms. We also revealed that the coexistence of various mechanisms involved in the development of hypersensitivity to a particular aeroallergen may occur in individual patients.

PMID: 17951133 [PubMed - indexed for MEDLINE]

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Diffuse dermatitis: An unexpected initial presentation of cystic fibrosis.

J Am Acad Dermatol. 2008 Feb;58(2 Suppl):S1-4

Authors: Lovett A, Kokta V, Maari C

Cystic fibrosis is an autosomal recessive disease that typically presents with pulmonary symptoms. Diffuse rash related to protein energy malnutrition can rarely be a presenting sign of cystic fibrosis in infancy. We report such a case and relate the difficulties of establishing a diagnosis. We also discuss possible pathophysiological mechanisms, histopathology, prognosis, and treatment.

PMID: 18191689 [PubMed - indexed for MEDLINE]

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A retrospective case series review of the peroxisome proliferator-activated receptor ligand rosiglitazone in the treatment of atopic dermatitis.

Arch Dermatol. 2008 Jan;144(1):84-8

Authors: Behshad R, Cooper KD, Korman NJ

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are expressed in a variety of cells, including keratinocytes and cells of the immune system. The gamma subtype, activated by the antidiabetic thiazolidinediones, was originally identified as a regulator of adipogenesis and glucose homeostasis. Recent data, however, have linked PPAR-gamma to several genes involved in inflammation. Among others, these pathways reduce certain inflammatory mediators in the skin and regulate epidermal barrier homeostasis, alterations of which contribute to the inflammation associated with atopic dermatitis (AD). To our knowledge, the addition of rosiglitazone maleate to the standard treatment of AD has not been evaluated. OBSERVATIONS: Severe adverse events were not observed, although 1 patient experienced weight gain. All patients responded to rosiglitazone therapy with decreased total body surface area involvement, severity of lesions, and number of flares. CONCLUSIONS: Rosiglitazone, a drug that has an excellent safety profile, may offer a well tolerated systemic treatment option for AD. However, its role should be further assessed in controlled trials to establish its efficacy and safety in this disease.

PMID: 18209172 [PubMed - indexed for MEDLINE]

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Frequency of allergic contact dermatitis to isoeugenol is increasing: a review of 3636 patients tested from 2001 to 2005.

Br J Dermatol. 2007 Sep;157(3):580-2

Authors: White JM, White IR, Glendinning A, Fleming J, Jefferies D, Basketter DA, McFadden JP, Buckley DA

BACKGROUND: Isoeugenol is an important fragrance allergen. The cosmetic industry was recommended voluntarily to reduce concentrations of isoeugenol in finished cosmetic products from 0.2% to 0.02% in 1998. It was suspected that this would reduce the incidence of patch test positivity in individuals undergoing routine patch testing after approximately 2-3 years (the Dillarstone effect). OBJECTIVES: To review our patch test data since the change in practice by industry, to see if there has been an observable decrease in isoeugenol contact sensitivity. METHODS: We retrospectively analysed all subjects patch tested to isoeugenol 1% pet. in the St John’s Department of Cutaneous Allergy over a period of 5 years, commencing 3 years after the changes. RESULTS: We identified 3636 subjects, 97 of whom were positive for isoeugenol. Year-on-year incidence shows an increasing trend, with an overall incidence of 2.67%. Using the exact Cochran-Armitage test, this ascending trend is statistically significant (P = 0.0182). Seventy-two of 97 isoeugenol-positive subjects were also positive to fragrance mix I. Other fragrances positive in these 97 patients included Myroxylon pereirae (30%), Evernia prunastri (22%) and eugenol (15%). CONCLUSIONS: We suspect that the increasing trend may be due to allergen substitution with compounds chemically related to isoeugenol, or which hydrolyse to isoeugenol itself.

PMID: 17573874 [PubMed - indexed for MEDLINE]

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On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis.

Br J Dermatol. 2007 Sep;157(3):441-9

Authors: Hoffjan S, Stemmler S

Undisturbed epidermal differentiation is crucial for an intact skin barrier function. The epidermal differentiation complex (EDC) is a cluster of genes on chromosome 1q21 encoding proteins that fulfil important functions in terminal differentiation in the human epidermis, including filaggrin, loricrin, S100 proteins and others. Recently, evidence emerged that variation within EDC genes plays an important role in the pathogenesis of three common skin disorders, ichthyosis vulgaris, atopic dermatitis (AD) and psoriasis. Two loss-of-function mutations in the filaggrin (FLG) gene, R501X and 2282del4, were identified as causative for ichthyosis vulgaris in 15 affected European families, and the mode of inheritance was found to be semidominant. As ichthyosis vulgaris and AD often occur concomitantly in affected individuals, these two mutations were subsequently investigated in AD patients and found to be strongly associated with the disease. Following this first report, seven replication studies have been performed that all confirm an association of these two mutations with AD (or AD subtypes) in several European cohorts. Additionally, two unique loss-of-function mutations in the FLG gene were identified in Japanese ichthyosis vulgaris families and found to be associated with AD in a Japanese cohort. Thus, the FLG mutations are among the most consistently replicated associations for AD. Additionally, linkage analysis has suggested that variation within the EDC might also predispose for psoriasis but the exact susceptibility variation(s) have not yet been elucidated. Taken together, these findings convincingly demonstrate the important role of barrier dysfunction in various common skin disorders.

PMID: 17573887 [PubMed - indexed for MEDLINE]

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Increased lipopolysaccharide-induced tumour necrosis factor-alpha, interferon-gamma and interleukin-10 production in atopic dermatitis.

Br J Dermatol. 2007 Sep;157(3):583-6

Authors: Simon D, Braathen LR, Simon HU

BACKGROUND: Atopic dermatitis (AD) is based on a genetic predisposition, but environmental factors may trigger skin inflammation. According to the hygiene hypothesis, decreased exposure to microbial products in early childhood does not allow sufficient maturation of the immune system that is associated with an increased risk of atopic sensitization. OBJECTIVES: The effect of lipopolysaccharide (LPS) on the cytokine production of peripheral blood mononuclear cells (PBMC) of AD patients and nonatopic controls was studied. PATIENTS AND METHODS: PBMC were isolated from heparinized blood of 10 patients with AD and 10 nonatopic individuals, suspended in culture medium and stimulated with LPS. Cytokine levels in the supernatants were measured by immunoassays. Results Upon stimulation with LPS, PBMC from AD patients produced significantly higher amounts of tumour necrosis factor-alpha, interferon-gamma and interleukin (IL)-10 compared with control PBMC. LPS stimulation blocked the increased spontaneous production of IL-4 and IL-5 by PBMC from AD patients, but had no effect on IL-13 production. CONCLUSIONS: These results demonstrate that the effects of LPS stimulation depend on both the type of cytokine and the origin of PBMC. Endotoxin exposure is suggested to modulate the disease course of AD.

PMID: 17596153 [PubMed - indexed for MEDLINE]

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Occupational dermatitis related to chromium and cobalt: experience of dermatologists (EPIDERM) and occupational physicians (OPRA) in the U.K. over an 11-year period (1993-2004).

Br J Dermatol. 2007 Sep;157(3):518-22

Authors: Athavale P, Shum KW, Chen Y, Agius R, Cherry N, Gawkrodger DJ,

BACKGROUND: Chromium and cobalt (and their compounds) are well recognized as being important causes of occupational contact dermatitis (OCD), particularly of the hands, although their exact contribution to occupational hand dermatitis varies between different studies. In some European studies, cases of chromium-related dermatitis have decreased following the addition of ferrous sulphate to cement to reduce the amount of available chromium. OBJECTIVES: To examine, using data from the U.K. occupational skin surveillance schemes, the proportionate reported incidence and changing trends in OCD considered to be related to chromium and cobalt for the 11-year period from February 1993 to December 2004. METHODS: Surveillance data collected by the two British occupational health surveillance schemes, EPIDERM and OPRA, from February 1993 to December 2004 were studied. These are occupational health surveillance schemes in the U.K. to which physicians voluntarily and anonymously report new cases of skin disease suspected to be work related. RESULTS: Over the 11-year period, dermatologists reported 22 184 cases of OCD, comprising 77% of all types of occupational skin diseases that were disclosed. Chromium was recorded as being thought to play a role in 1226 (6%) of these, with cobalt identified as being likely to be implicated in 823 (4%). The numbers fluctuated on a year-on-year basis but there were no overall trends during the period of study. The male/female ratio was 5 : 1 for chromium and 1 : 1 for cobalt. Overall, the male/female ratio for OCD was 1.4 : 1. The rates of dermatitis believed to be related to both metals generally increased with age. In women, the highest rate for chromium was seen in the > 60 years age group, whereas conversely, for cobalt the rate decreased with age. For chromium-related OCD the most common occupations were builders and building contractors, bricklayers, construction workers and plasterers. For cobalt-related OCD, the commonest occupations were hairdressers/barbers, builders/building contractors, retail cash/checkout operators, machine operatives and domestic cleaners. Occupational physicians reported 15 016 cases of OCD (82% of all occupational skin diseases reported by them) for the period May 1994-December 2004. Of these, only 38 cases were thought to be related to chromium and 30 to cobalt (25 of the latter were processing labourers). CONCLUSIONS: In this series, chromium was reported by dermatologists as potentially being involved in 6% of all cases of OCD in the U.K., and cobalt in 4%. Our data support the view that chromium-related dermatitis has an onset in later working life and often affects those in the building trades, whereas cobalt-related dermatitis seems to have an earlier onset and may affect a wide range of employments.

PMID: 17596174 [PubMed - indexed for MEDLINE]

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