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A comparative study of the expression of cytotoxic proteins in allergic contact dermatitis and psoriasis: spongiotic skin lesions in allergic contact dermatitis are highly infiltrated by T cells expressing perforin and granzyme B.

Recent reports indicate that cytotoxic T cells are critically involved in contact hypersensitivity reactions in animals. In this study we sought to investigate the in vivo expression of cytotoxic granule proteins in the elicitation phase of allergic contact dermatitis in humans. Skin biopsy specimens were obtained from patients with allergic contact dermatitis (n = 8) and psoriasis (n = 6) and from controls with normal skin (n = 6). Expression of perforin and granzyme B was investigated by in situ hybridization and immunohistochemistry. In contrast to normal skin and psoriasis, a significant enhancement of perforin and granzyme B gene expression and immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. Immunoreactivity for perforin and granzyme B was mainly found in the cytoplasm of lymphocytic cells, which were located in the dense perivascular infiltrate as well as at sites of marked spongiosis in the epidermis. Double immunostaining revealed that both CD4+ and CD8+ T cells are capable of expressing perforin and granzyme B. In conclusion, our data suggest that T-cell-mediated mechanisms involving cytotoxic granule proteins may elicit epidermal cell injury in vivo and thereby strongly contribute to the development of allergic contact dermatitis in humans.

Adult↗

Adhesion molecule profiles in atopic dermatitis vs. allergic contact dermatitis: pharmacological modulation by cetirizine.

BACKGROUND: Experimental data suggest that there is an imbalance between Th1 and Th2 cells in atopic dermatitis (AD) skin compared to allergic contact dermatitis (ACD). This imbalance (Th2 and Th1 predominance, respectively) implies the production of different cytokines in these two conditions leading to different expression of adhesion molecules on skin endothelial cells. OBJECTIVE: The expression of VCAM-1 (IL-4/Th2-dependent) and ICAM-1 (INF-gamma/IL-1) on dermal vessels was compared in six patients with AD and six patients with ACD. The effect of cetirizine, a highly selective H1-receptor antagonist on the expressions was studied. METHODS: Six patients with AD were challenged with Dermatophagoides pteronyssimus (DPT patch tests applied to clinically normal skin) and six patients with ACD challenged in the same way with allergens of the European standard series. Skin biopsies at challenged sites were performed before and 6, 24 and 48 h after challenge. The experiment was carried out under double-blind cross-over conditions during a 4-day treatment with a placebo and cetirizine. RESULTS: In AD patients, the scores for both VCAM-1 and ICAM-1 were high before and after challenge. In ACD patients, the ICAM-1 score was high at each experimental time, but the VCAM-1 score, which was significantly lower before challenge, increased at 6, 24 and 48 h after challenge. The administration of cetirizine significantly reduced the VCAM-1 expression in AD patients at each experimental time. CONCLUSION: It is concluded that the increased VCAM-1 expression in AD patients compared to ACD may reflect greater IL-4 and/or IL-13 production in situ. The study also confirms the existence of a modulating effect of cetirizine in vivo on adhesion molecule expression.

Adult↗

Effect of age and sex on the elicitation of irritant contact dermatitis.

Irritant contact dermatitis causes significant disability to numerous consumers and individuals in industry. Knowledge of the prevalence of this disease remains inadequate. Irritant contact dermatitis occurs in workers engaged in occupations where the subjects are exposed to different types and doses of irritants. The intensity of the reaction depends on the quality and the quantity of exposure. Irritant thresholds and dose responses depend on many different factors. This article reviews the clinical and physiological parameters that affect the age and sex related differences in irritant contact dermatitis.

Adolescent↗

Allergic contact dermatitis.

Allergic contact dermatitis is a common skin condition that can be difficult to diagnose without the aid of a specific diagnostic tool called patch testing. The pathophysiology, clinical features, diagnosis, and treatment of allergic contact dermatitis are summarized in this review. The process of patch testing, the gold standard for diagnosing allergic contact dermatitis, is discussed in detail.

Administration, Oral↗

Recent developments in the pathogenesis of allergic contact dermatitis.

Allergic contact dermatitis is both an important clinical problem and a model system for lymphocyte-mediated pathologic changes. Elicitation of allergic contact dermatitis requires interaction of antigen with epidermal Langerhans cells, followed by migration of the Langerhans cells to the lymph nodes to present antigen to T lymphocytes. These activated T lymphocytes must then home to the antigen-exposed skin. Adhesion molecules such as LFA-1 and ICAM-1 have a role in this homing. Only a small proportion of the T lymphocytes in the skin lesion are specific for the inducing antigen. Studies of poison ivy (urushiol dermatitis) have determined this fraction to be less than one per 100 infiltrating lymphocytes. By a variety of amplification mechanisms, it is possible for this small number of antigen-specific T lymphocytes to induce the pathologic changes of allergic contact dermatitis. Improved understanding of this condition should result in increased knowledge of the pathogenesis of a variety of T lymphocyte-mediated skin conditions.

Dermatitis, Contact↗

An epidemic outbreak of papular and follicular contact dermatitis to tocopheryl linoleate in cosmetics. Swiss Contact Dermatitis Research Group.

BACKGROUND: In Spring 1992, an epidemic outbreak of papular and follicular rashes caused by a new line of cosmetics occurred throughout Switzerland. OBJECTIVE: Epidemiological and clinical data were collected in order to identify the offending agent and to specify the pathophysiological mechanisms. METHODS: The data concerning 263 patients seen by dermatologists plus 642 additional cases directly reported by consumers to the manufacturer were analyzed. Seventy-seven patients were patch-tested, 26 extensively, and 15 performed a repeated open application test for a duration of 4 weeks. Control patch and use tests were performed in 73 and 25 patients, respectively. The results were analyzed statistically. In addition, 12 skin biopsies were performed for histological examination. Biochemical studies on the cosmetics (final products and offending ingredient) supplemented the clinical studies. RESULTS: The lesions were mainly papular and follicular, widely distributed, with pronounced pruritus, which was aggravated by sweating or heat exposure, and were long lasting. In a few cases, the papules were located on intensely erythematous, well-defined plaques, suggesting irritation rather than allergy. Both immediate and delayed onsets of the lesions were observed. Skin biopsies showed signs of folliculitis and perifolliculitis with little alteration of the interfollicular epidermis. Patch and use testing disclosed vitamin E linoleate (a mixture of tocopheryl esters, mainly tocopheryl linoleate) as the offending agent. An in vitro time-dependent formation of oxidative products under storage or oxidation-stimulating conditions was observed. CONCLUSION: Though vitamin E esters have been widely and safely used for decades in dermatological preparations and in cosmetics, vitamin E linoleate was the cause of about 1,000 cases of unusual papular mainly follicular contact dermatitis. Oxidized vitamin E derivatives could act in vivo as haptens and/or irritants, possibly with synergistic effects.

Adolescent↗

Role of protective gloves in the causation and treatment of occupational irritant contact dermatitis.

Irritant contact dermatitis of the hands is a significant occupational problem. Management primarily involves cessation of exposure to hazardous substances. Protective gloves can reduce or eliminate exposure of the hands to hazardous substances if used correctly, but if not selected and used correctly, protective gloves can actually cause or worsen irritant contact dermatitis of the hands by increasing exposure of the hands to hazardous chemicals. We present two cases of occupational irritant contact dermatitis of the hands caused by incorrect use of protective gloves. Glove failure can occur by penetration, permeation, or contamination, and all 3 mechanisms were operative in these cases. These cases demonstrate that correct use of gloves is at least as important as selection of gloves made of the appropriate material. By understanding mechanisms of glove failure, clinicians can make more appropriate recommendations for the selection and use of protective gloves in the workplace.

Adult↗

The significance of previous contact dermatitis for elicitation of contact allergy to nickel.

In 2 earlier studies, we found increased nickel re-test reactivity at earlier experimentally induced nickel eczema sites. The aim of this study was to investigate if earlier contact dermatitis caused by another allergen or earlier irritant contact dermatitis also influenced the reactivity when nickel was applied topically on earlier but healed dermatitis sites. Twenty-three females with contact allergy to both nickel and cobalt were involved in the study. Experimental contact dermatitis from nickel, cobalt and SLS was induced on the lower back. One month later, challenge patch testing with a serial dilution of nickel on the previous but healed dermatitis sites, and on a control area, was done. The tests were read blindly. Significantly higher test reactivity was found at the site with previous allergic contact dermatitis from nickel, and significantly lower test reactivity was observed at the previous SLS dermatitis site.

Adult↗

Topical pimecrolimus in the treatment of human allergic contact dermatitis.

BACKGROUND: Contact dermatitis is a common clinical problem, with prevalent sensitizers being cosmetics, metals, medicines, and plants. Plants of the Toxicodendron species cause allergic contact dermatitis (ACD) in 50% to 70% of the population. Pimecrolimus is an ascomycin macrolactam developed for the treatment of inflammatory skin diseases and approved by the US Food and Drug Administration for atopic dermatitis. There are studies supporting the effectiveness of macrolactams when administered before antigen challenge, but there are no studies describing the effectiveness of these drugs in the treatment of established human ACD. OBJECTIVE: To investigate the effect of topical pimecrolimus in the treatment of Toxicodendron-induced ACD once rash is evident. METHODS: Poison ivy tincture was applied to the bilateral anterior forearms of 12 subjects with Finn Chambers (Allerderm Diagnostic Products, Petaluma, CA). After dermatitis was evident, volunteers treated each arm twice daily with either 1% topical pimecrolimus cream or placebo in a blinded fashion. Outcomes measured were a dermatitis grading score and time to rash and itch resolution. RESULTS: The median +/- SEM time for rash resolution was 16.55 +/- 1.59 days in the treatment group and 16.27 +/- 1.82 days in the placebo group (P = 0.601). The median time for itch resolution was 4.73 +/- 1.56 days in the treatment group and 4.91 +/- 1.59 days in the placebo group (P = 0.167). The average dermatitis score was 2.26 +/- 0.17 in the treatment group and 2.32 +/- 0.15 in the placebo group (P = 0.62). CONCLUSIONS: The application of topical pimecrolimus is ineffective in the treatment of ongoing Toxicodendron-induced ACD.

Administration, Topical↗

Allergic contact dermatitis in children. A multicenter study of the Portuguese Contact Dermatitis Group (GPEDC).

The authors report a study of allergic contact dermatitis in 329 Portuguese children of 14 years or younger. 170 children (64 male and 106 female) reacted to 1 or more allergens. Most of these were in the 11-14 years group. The main allergens were nickel, thimerosal, cobalt, mercury, fragrance-mix and potassium dichromate. Nickel reactivity predominated in females over the whole group, but a greater number of males younger than 5 years reacted to nickel. The number of positive reactions increased with age, but this was not accompained by an increase in the % of relevant tests. 12 children, all of them 13 or 14 years-old, had an occupational allergic contact dermatitis.

Adolescent↗

Bronopol allergic contact dermatitis.

Bronopol (2-bromo-2-nitropropane-1, 3-diol) is an antimicrobial compound widely used as a preservative, primarily in cosmetic formulations. Analysis of patch tests performed on our patients revealed an incidence of 12.5% relevant positive results to 0.5% and/or 0.25% bronopol. This result reflects a history of prolonged use of bronopol-containing lubricants in our referral population of patients with different types of severe, extensive dermatitis. Contact sensitization to bronopol in this population is probably facilitated by abnormal cutaneous barrier function. Our findings emphasize the need for further clinical study of the potential for bronopol to produce contact sensitivity, and suggest caution with regard to its use in patients with dermatitis.

Adult↗

Circulating allergen-reactive T cells from patients with atopic dermatitis and allergic contact dermatitis express the skin-selective homing receptor, the cutaneous lymphocyte-associated antigen.

The cutaneous lymphocyte-associated antigen (CLA) is the major T cell ligand for the vascular adhesion molecule E-selectin, and it has been proposed to be involved in the selective targeting of memory T cells reactive with skin-associated Ag to cutaneous inflammatory sites. To further investigate the relation of CLA and cutaneous T cell responses, we analyzed the CLA phenotype of circulating memory T cells in patients with allergic contact dermatitis and atopic dermatitis (AD) alone vs in patients manifesting bronchopulmonary atopy (asthma with or without AD) and nonallergic individuals. Significant T cell proliferative responses to Ni, a contact allergen, and to the house dust mite (HDM), an allergen to which sensitization is often observed in AD and/or asthma, was noted only in allergic and atopic individuals, respectively. When the minor circulating CLA+CD3+CD45RO+ subset was separated from the major CLA-CD3+CD45RO+ subpopulation in Ni-sensitive subjects, the Ni-dependent memory T cell response was largely confined to the CLA+ subset. A similar restriction of the T cell proliferative response to the CLA+ memory subset was observed for HDM in patients with AD alone. In HDM-sensitive patients with asthma with or without AD, however, the CLA- subset exhibited a strong antigen-dependent proliferation, in contrast to patients with AD alone, whose CLA- subset proliferated very weakly to HDM. In asthma with or without AD, the HDM-dependent proliferation slightly predominated in the CLA- when compared to the CLA+ subset. The functional linkage between CLA expression and disease-associated T cell effector function in AD was also demonstrated by the finding that the circulating CLA+ T cell subset in AD patients, but not nonatopic controls, selectively showed both evidence of prior activation (human histocompatibility antigen-DR expression) and spontaneous production of interleukin 4 but not interferon-gamma. Taken together, these observations demonstrate the correlation of CLA expression on circulating memory T cells and disease-associated memory T cell responses in cutaneous hypersensitivity, and they suggest the existence of mechanisms capable of sorting particular T cell Ag specificities and lymphokine patterns into homing receptor-defined memory subsets.

Adult↗

Mechanisms involved in allergic contact dermatitis.

Allergic contact dermatitis is a common inflammatory skin disease caused by agents such as plants, chemical compounds, and topical medications. Histologic features typically include edema within the epidermis and dermis and a lymphohistiocytic infiltrate with an admixture of basophils. Langerhans cells and keratinocytes play pivotal roles in allergic contact dermatitis reactions. Langerhans cells synthesize and express class II molecules that allow the presentation of exogenous antigens to T lymphocytes. Additionally, keratinocytes and Langerhans cells produce interleukin-1, which is thought to be a second signal that activates T cells. Mast cells and basophils also may play a proinflammatory role. Treatment primarily consists of removal of the offending agent. At times, systemic corticosteroids may be required, especially in the acute phase. In more chronic cases, topical corticosteroids may be beneficial. Antihistamines may be useful because of their soporific effects, but their usefulness is limited.

Dermatitis, Contact↗

Dissection of antigenic and irritative effects of epicutaneously applied haptens in mice. Evidence that not the antigenic component but nonspecific proinflammatory effects of haptens determine the concentration-dependent elicitation of allergic contact dermatitis.

Allergic contact dermatitis differs from most other immune reactions by its strict dose dependence during the elicitation phase. Moreover, almost all known contact allergens can also induce dose-dependent irritative dermatitis and in general only elicit allergic contact dermatitis in sensitized individuals when applied within a narrow dose range. Therefore, we hypothesized that elicitation of contact hypersensitivity (CHS) may require two signals, antigen-specific effector cell activation and a non-antigen-specific proinflammatory signal, both of which are provided by application of a sufficient dose of hapten. To dissociate these putative two signals, oxazolone-sensitized mice were ear challenged with a dose of the specific hapten which was too low to elicit CHS. At the same time, an unrelated hapten was applied in a conventional concentration to the same skin site. Whereas neither treatment alone elicited a significant CHS response, application of both compounds together resulted in a strong CHS response that was indistinguishable from that elicited by the full dose of the specific hapten. Upon coadministration of the irrelevant hapten, allergic contact dermatitis could be elicited even when the dose of the specific hapten was further reduced by a factor of 10(3). In contrast, a dose reduction of the irrelevant hapten by a factor of two resulted in the loss of the CRS response. These data indicate that non-antigen-specific effects of epicutaneously applied haptens significantly contribute to the elicitation of CHS responses and that the capacity of the hapten to evoke this proinflammatory stimulus rather than its antigenicity is responsible for the strict concentration dependence.

Administration, Cutaneous↗

Persistent light reaction associated with photoallergic contact dermatitis to musk ambrette and allergic contact dermatitis to fragrance mix.

A 57-year-old man suffering from persistent light reaction with photocontact allergy to musk ambrette and contact allergy to fragrance mix was evaluated. A lowered minimal erythema dose to UV-B (MED-UV-B) was seen. Reactions to long-wave UV-A and visible radiation were normal. A skin biopsy from one MED-UV-B, taken 24 h after irradiation, showed acute spongiotic dermatitis.

Dermatitis, Contact↗

Mechanisms of drug-induced allergic contact dermatitis.

Allergic contact dermatitis is induced by a wide variety of drugs that trigger specific immune responses following topical exposure. Identified chemical structures involved in such reactions include the mercuric and thiosalicylic acid groups of thimerosal, the diphenylketone group of the anti-inflammatory drug ketoprofen, the amide or ester structure of local anesthetics, and the side-chain and thiazolidine ring of beta-lactams. The T cell responses to such compounds involve CD4+ and CD8+ alphabeta+ T lymphocytes and also CD4 /CD8 gammadelta+ T cells. Although "T helper 2" cytokine production by drug-specific human T cells from patients with allergic contact dermatitis has been described, T helper 1-like and T cytotoxic 1-like responses clearly play key roles in this cutaneous reaction.

Allergens↗