Irritant Contact Research Articles

A Light-Emitting Mouse to Image Skin Inflammation

The mouse ear swelling test is a well-accepted method for quantitating the inflammatory response to contact irritants and sensitizing agents. However, this assay measures edema rather than the cellular component of skin inflammation. To develop a quantitative and noninvasive assay of inflammatory cell infiltration in contact dermatitis. We bred a transgenic bioluminescent mouse that emits light proportional to cutaneous infiltration of inflammatory cells. We characterized this model by correlating luminescence with edema and histologic analysis of affected skin. A mouse strain expressing cyclization recombinase enzyme (cre) recombinase exclusively in myeloid cells was crossed with a reporter strain containing an inactivated form of the luciferase gene. In progeny mice, cre-mediated recombination repaired the luciferase gene, causing light emission from myeloid cells. Light emission and swelling from the inflamed ear was quantitated and compared to the contralateral ear. Light intensity correlated with the inflammatory cell infiltration in the dermis. In sensitized mice challenged with squaric acid, luminescence increased about 2.2-fold while swelling increased about 1.5-fold. Our model may serve as a useful screening assay for topical antiinflammatory molecules. Moreover, this approach allows real-time imaging of skin infiltration by specific inflammatory cell lineages in living animals.

Patient responses to vacuum formed splints compared to heat cured acrylic splints: pilot study

Vacuum formed and heat cured acrylic splints have been used in the diagnosis and treatment of temporomandibular disorders. The aim of this study was to evaluate patient's preference to either the vacuum formed or the heat cured acrylic splint. Twenty patients planned to receive splints were chosen from the dental school. Both types of occlusal splints were fabricated for each of them. Each patient used the splints alternatively on a nightly basis for 3 weeks. After 3 weeks, each patient completed a questionnaire regarding the comfort, fit, retention, occlusal contact, taste, gingival and lip irritation, smoothness and smelling. Statistical analysis was conducted by the MacNemar's Chisquare test. There was no statistical difference in patient's responses to the different splint materials except for the comfort of wearing through the night. The vacuum formed and heat cured acrylic splint may be equally worn in patient preference for treatment of temporomandibular disorders.

Occupational allergic contact dermatitis among construction workers in India

Background:Allergic contact dermatitis is one of the important occupational hazards in construction workers and it often leads to poor quality of life of the workers with substantial financial loss. However, this is often a neglected entity. There are no past studies on the construction workers in Indian subcontinent.Objective:This pilot study has been done to assess the allergological profile among the workers engaged in construction of roads and bridges.Materials and Methods:The study was conducted among the workers working on construction of a bridge, flyover, and roads in West Bengal, India. Sixteen workers were selected on clinical suspicion. Ten were selected randomly and patch tested with Indian standard battery of patch test allergens. Analysis of reactions and relevance of positive test was assessed as per standard guidelines.Results:All the workers were men. Average age of workers was 24.8 years (range, 19-34 years). Dermatitis affected exposed parts in 93.75% and covered areas in 62.5%. Total positive test was 24 and relevant 11. Most common allergens were chromate (relevant allergy/RA: in 60% of patch tested workers), epoxy resin (RA: 30%), cobalt (RA: 20%), nickel (RA: 20%), thiuram mixture (RA: 10%) and black rubber mix (RA: 10%). Two cases (20%) had irritant contact dermatitis.Conclusion:The result indicated that chromate is the most frequent allergen among construction workers in this part of India. High frequency of involvement of the covered areas as well as the exposed areas highlighted the fact that the allergens had access to most body parts of the workers.

Low‐cobalt diet for dyshidrotic eczema patients

Dyshidrotic eczema is a type of chronic intermittent dermatitis characterized by vesicles, dystrophic fingernail changes, and rarely bullae that affects the hands and feet. Many exogenous factors may trigger a flare including dermatophyte infections, contact irritants, and metal hypersensitivity. Although metal hypersensitivity does not play a role in all cases of dyshidrotic eczema, high oral ingestion of nickel and/or cobalt should be considered, regardless of patch test results. We updated and simplified existing published guidelines for low-cobalt diets. A recent review of the literature showed that dietary cobalt restriction, a safe yet burdensome treatment option for dyshidrosis, is referenced to dated sources. We have analysed current data for the cobalt content in common food items. We propose a revised, point-based diet that will eliminate much of the dietary cobalt (and nickel) and reduce dyshidrotic eczema flares.

Gene expression analysis in chemical-treated dendritic cells: Discriminating contact sensitisers and irritants employing the immune toxicity chip and a whole genome array

Gene expression analysis in chemical-treated dendritic cells: Discriminating contact sensitisers and irritants employing the immune toxicity chip and a whole genome array

Establishment and characteristics of Gottingen minipig skin in organ culture and monolayer cell culture: relevance to drug safety testing

Skin from Gottingen minipigs was used as a source of tissue for organ and cell culture and compared to human skin for growth conditions and sensitivity to irritants. Optimal organ culture conditions were determined, based on the preservation of the histological structure. These included serum-free, growth factor-free conditions with a calcium concentration of 1.5mM. Formulations in which the calcium concentration were low (0.075-0.15mM) failed to support tissue viability (even in the presence of dialyzed serum). Epidermal keratinocytes were grown from tissue explants and as single cells from enzyme-disrupted tissue. Optimal keratinocyte growth was achieved using a serum-free, growth factor-supplemented culture medium with a calcium concentration of 0.15mM. Fibroblasts were optimally grown from explant cultures using a medium with 1.5mM calcium and 10% fetal bovine serum. The conditions that were optimal for maintenance of intact pig skin, as well as for the isolated cells, are the same conditions that have been shown previously to be optimal for intact human skin and skin cells. In additional studies, pig skin keratinocytes and fibroblasts were exposed to a panel of contact irritants and contact sensitizers. Using growth inhibition as the response, the median effective dose values with each agent were very similar to the values previously determined for human epidermal keratinocytes and human dermal fibroblasts. Taken together, these data suggest that the skin from the Gottingen minipig can be used as a surrogate for human skin in ex vivo skin safety studies.

Loss-of-Function Mutations in the Filaggrin Gene and Allergic Contact Sensitization to Nickel

Allergic contact dermatitis is one of the most frequent dermatological problems affecting 7% of the general population. Impaired skin barrier function facilitates the penetration of contact allergens and irritants into the epidermal layer and is regarded as an important cofactor promoting the process of allergic contact sensitization. Filaggrin is crucial for the maintenance of the skin barrier function. Loss-of-function mutations within the filaggrin (FLG) gene are associated with skin barrier diseases such as ichthyosis vulgaris and atopic eczema (AE). To assess the impact of FLG on allergic contact sensitization and plausible intermediate traits, the two prevalent FLG mutations R501X and 2282del4 were typed in 1,502 individuals of the KORA C population-based cohort with extensive dermatologic phenotyping. Associations of FLG mutations with AE could be replicated. Strong associations were seen with dry skin, palmar hyperlinearity, and keratosis pilaris. In addition, an association with contact sensitization to nickel and contact sensitization to nickel combined with intolerance to fashion jewelry, but not with other contact allergens, was observed. From these data, we conclude that a genetically determined FLG deficiency manifests as dry skin and features of ichthyosis vulgaris. In addition, FLG deficiency may also represent a risk factor for contact sensitization to allergens.

RESPUESTA CONDUCTUAL DE Aedes aegypti (Linnaeus, 1762) FRENTE A ADULTICIDAS PIRETROIDES DE USO FRECUENTE EN SALUD PÚBLICA

Objectives. To assess the behavioural response of the F1 generation of Aedes aegyti (L) collected in the Metropolitan area of Monterrey (Nuevo Leon, Mexico) vs. three adulticides pyrethroids frequently used in public health. Materials and methods. We used a novel modular system called HITSS (High-Throughput Screening System) to evaluate two behavioral responses (contact irritation and spatial repellency), as well as the toxicity of three insecticides DDT, permeathrin and bifenthrin at different concentrations (0.025, 0.25, 25 and 250 nmol/cm 2 ). Results. In the concentration 2.5 nmol/cm 2 , DDT (4.3 ± 2.4) and permethrin (8.0 ± 1.4) were the insecticides that are more irritating effect (p <0.05); the bifenthrin requires 20 times higher doses to achieve similar effects. In spatial repellency, the three insecticides tested have had a similar responses at all concentrations; DDT: 7 to 14%, permethrin: 9 to 15% and bifenthrin: 19% to 27%. Permethrin and bifenthrin in 0.025 nmol/cm 2 concentrations, effects knockdown above 34%, with a mortality rate 19%, DDT requires 10 times higher concentrations to achieve similar effects. Conclusions. HITTS system can be used to assess the behavioural response to insecticides.

Microarray-Based In Vitro Test System for the Discrimination of Contact Allergens and Irritants: Identification of Potential Marker Genes

Animal tests have been used to characterize the potential of chemicals to produce allergic contact dermatitis, but this approach is increasingly a matter of public and political concern. Our aim was to develop and validate an alternative in vitro test that can identify contact allergens. We developed a targeted microarray containing oligonucleotide probes for 66 immune-relevant genes and analyzed gene expression in monocyte-derived dendritic cells (Mo-DCs) treated with 1 irritant (SDS) and 2 prominent contact allergens, nickel and Bandrowski's base (BB), which is the oxidation product of the most important hair dye allergen, p-phenylenediamine. Comparing RNA amounts in chemical-treated and solvent-treated cells, we identified significant changes in the expression of 21 genes and 10 genes after exposure of immature DCs (iDCs) to nickel and BB, respectively, but not after exposure to SDS. Eight genes were differentially expressed after application of both nickel and BB. Real-time PCR was used to confirm the results for selected genes. We propose a microarray-based in vitro test that might allow the identification of contact allergens. Independently from donor variability, several immune-relevant genes were up- or downregulated after the application of the tested sensitizers to iDCs, therefore presenting potential marker genes. While reducing the number of laboratory animals used, this test would also enable reliable analysis of chemicals using a human system.

Discrimination of contact allergens and irritants employing the immune toxicity chip

Discrimination of contact allergens and irritants employing the immune toxicity chip

A new classification system for the actions of IRS chemicals traditionally used for malaria control.

Knowledge of how mosquitoes respond to insecticides is of paramount importance in understanding how an insecticide functions to prevent disease transmission. A suite of laboratory assays was used to quantitatively characterize mosquito responses to toxic, contact irritant, and non-contact spatial repellent actions of standard insecticides. Highly replicated tests of these compounds over a range of concentrations proved that all were toxic, some were contact irritants, and even fewer were non-contact repellents. Of many chemicals tested, three were selected for testing in experimental huts to confirm that chemical actions documented in laboratory tests are also expressed in the field. The laboratory tests showed the primary action of DDT is repellent, alphacypermethrin is irritant, and dieldrin is only toxic. These tests were followed with hut studies in Thailand against marked-released populations. DDT exhibited a highly protective level of repellency that kept mosquitoes outside of huts. Alphacypermethrin did not keep mosquitoes out, but its strong irritant action caused them to prematurely exit the treated house. Dieldrin was highly toxic but showed no irritant or repellent action. Based on the combination of laboratory and confirmatory field data, we propose a new paradigm for classifying chemicals used for vector control according to how the chemicals actually function to prevent disease transmission inside houses. The new classification scheme will characterize chemicals on the basis of spatial repellent, contact irritant and toxic actions.

Human Skin in Organ Culture and Human Skin Cells (Keratinocytes and Fibroblasts) in Monolayer Culture for Assessment of Chemically Induced Skin Damage

Human skin cells (epidermal keratinocytes and dermal fibroblasts) in monolayer culture and human skin in organ culture were exposed to agents that are known to produce irritation (redness, dryness, edema and scaly crusts) when applied topically to skin. Among the agents used were three well accepted contact irritants (i.e., all-trans retinoic acid [RA], sodium lauryl sulfate [SLS] and benzalkonium chloride) as well as the corrosive organic mercury compound, aminophenyl mercuric acetate (APMA), and 5 contact sensitizers (oxazolone, nickel sulfate, eugenol, isoeugenol and ethylene glycol dimethacrylate [EGDM]). As a group, the contact irritants (including the corrosive mercuric compound) were cytotoxic for keratinocytes and fibroblasts and suppressed growth at lower concentrations than the contact sensitizers. The contact irritants also produced histological changes (hyperplasia, incomplete keratinization, loss of the granular layer, acantholysis and necrosis) in organ-cultured skin at dose levels at which the contact sensitizers appeared to be inert. Finally, the profile of secreted molecules from organ-cultured skin was different in the presence of contact irritants versus contact sensitizers. Taken together, these data suggest that the use of organ-cultured skin in conjunction with cells derived from the skin in monolayer culture may provide an initial approach to screening agents for deleterious changes in skin.

Atopic Dermatitis and Contact Dermatitis in the Emergency Department

Atopic dermatitis and contact dermatitis are common dermatologic conditions that may be encountered in the emergency department (ED). Atopic dermatitis is a chronic inflammatory skin disease with an undulating course characterized by remissions and exacerbations. Patients may present to the ED because of chronic disease or acute flares that fail to respond to routine treatments or because of secondary infections. The article reviews the ED management of exacerbations of atopic dermatitis as well as various common skin infections associated with this disorder, including specifically Staphylococcus aureus and eczema herpeticum. Although contact dermatitis can be chronic, patients usually present with acute symptoms. The article discusses the diagnosis and ED management of common types of contact dermatitis, including allergic and irritant chronic dermatitis, photodermatitis, and contact urticaria.

Skin Contact Irritation Conditions the Development and Severity of Allergic Contact Dermatitis

Irritant contact dermatitis (ICD) is a frequent inflammatory skin disease induced by skin contact with low molecular weight chemicals such as haptens endowed with proinflammatory properties. Allergic contact dermatitis (ACD) is a frequent complication of ICD and is mediated by hapten-specific T cells primed in lymph nodes by skin emigrating dendritic cells. The aim of this study was to analyze the relationship between ICD and ACD to 2,4-dinitrofluorobenezene (DNFB) in C57BL/6 and BALB/C mice, which develop a severe and a moderate skin inflammation, respectively. Upon a single skin painting with DNFB, C57BL/6 developed within hours a more severe dose-dependent ICD response as compared to BALB/C mice, which was associated with enhanced upregulation of IL-1beta, IL-6, and IL-10. Skin exposure to a low dose of DNFB resulted, in both strains, in a low ICD that resolved in a few hours. Alternatively, skin painting with either an intermediate or a high DNFB concentration induced an ICD that subsequently gave rise to an ACD reaction whose intensity was proportional to the magnitude of the ICD response and was more severe in C57BL/6 mice than in BALB/C mice. In conclusion, the hapten-induced skin contact irritation conditions the development and the severity of ACD.

Prostaglandin E 2 and interleukin-8 production in human epidermal keratinocytes exposed to marine lipid-based liposomes

In response to exogenous stimuli such as non-sensitizing contact irritants, human keratinocytes produce various types of soluble pro-inflammatory mediators including prostaglandin E 2 (PGE 2) and interleukin 8 (IL-8). Polyunsaturated fatty acids of the n − 3 series ( n − 3 PUFA) are known to play a role in the prevention of the inflammatory response. In this work, n − 3 PUFA were supplied to keratinocytes through Marinosomes ® that are liposomes based on a natural marine lipid extract. Marinosomes ® contributed to reduce inflammation induced by croton oil by regulating PGE 2 and IL-8 production in human keratinocyte cultures. However, the preventing effect of Marinosomes ® was highly dependent on the lipid concentration used and the liposome mean diameter.

Molecular Events on Experimental Skin Inflammation and Modulation by Topical Anti-inflammatory Flavonoids

There have been various animal models of skin inflammation. These models have been used for establishing anti-inflammatory activity of the topical agents including cosmetics. Here, the molecular mechanisms of most widely-used animal models of skin inflammation including contact irritation, acute and chronic inflammation, and delayed-type hypersensitivity are summarized. Against these animal models, varieties of plant flavonoids showed anti-inflammatory activity. The action mechanisms of anti-inflammation by topical flavonoids are presented. A therapeutic potential of flavonoids is discussed.

Noninvasive Evaluation of Allergic and Irritant Contact Dermatitis by In Vivo Reflectance Confocal Microscopy

The clinical differentiation of allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD) is often difficult to accomplish. Reflectance-mode confocal microscopy (RCM) is an imaging technique that has previously been used to examine ACD and ICD noninvasively in vivo. To determine characteristic features of ACD and ICD and their kinetic evolution over time. Ethnic susceptibility to contact irritants such as sodium lauryl sulfate and Ivory dishwashing liquid was evaluated noninvasively, and the sensitivity and specificity of RCM parameters were analyzed in a clinical context and in reference to patch testing. Subjects were patch-tested with allergens, irritants, and controls. Clinical scoring and RCM evaluation were performed at various time points, assessing stratum corneum (SC) disruption, spongiosis, exocytosis, vesicle formation, and epidermal thickness. RCM features of both ACD and ICD include spongiosis, exocytosis, vesicle formation, and blood vessel dilatation. SC disruption, epidermal necrosis, and hyperproliferation are hallmarks of ICD whereas ACD more typically presents with vesicle formation. Patients with ICD showed a more rapid recovery than those with ACD. When tested with Ivory soap at selected concentrations, Caucasians, when compared to African Americans, showed significantly lower clinical thresholds for ICD and features that were more severe. RCM may be a promising new technology for longitudinal noninvasive studies of contact dermatitis (CD). Using a diagnostic algorithm and those parameters with high sensitivity for CD, RCM may facilitate the differentiation of acute ACD and ICD. RCM can reliably visualize cutaneous changes at subclinical degrees of CD, which suggests a possible role for RCM as an adjunctive tool in CD diagnosis. The results of this pilot study also indicate ethnic differences in the response to contact irritants. However, further studies are needed to substantiate the relevance and clinical applicability of our findings.

Powered Endoscopic Septoplasty for Septal Deviation and Isolated Spurs

Septoplasty is commonly performed for nasal airway obstruction or rhinologic headache due to contact irritation, often in conjunction with other nasal procedures, including cosmetic rhinoplasty and endoscopic sinus surgery.Traditionally, it is performed before these procedures via a "headlight" technique. This article describes the use of the microdebrider in 29 cases of endoscopic septoplasty. Many of the procedures were performed in conjunction with functional endoscopic sinus surgery; however, several were performed as an isolated procedure or with inferior turbinoplasty. The technique is described in detail. All 29 patients had significant improvement in their symptoms, and no patient developed a perforation or postoperative hematoma. Conversion to a traditional septoplasty was required in 1 case because of the severity of the deviation. Power-assisted endoscopic septoplasty is a useful adjunct in cases involving isolated septal spurs or moderate septal deviations. Patients with severe nasal obstruction due to caudal deflection of the septum off the nasal spine are better served with traditional headlight septoplasty.

Vulvar susceptibility to contact irritants and allergens: a review

Vulvar tissue differs from cutaneous epithelia in structure, morphology and biophysical characteristics. For example, the skin of the labia majora exhibits elevated hydration, occlusion and frictional properties, which may increase susceptibility to irritants and contact sensitizers. Furthermore, the nonkeratinized vulvar vestibule is likely to be more permeable than keratinized regions. These differences heighten vulvar susceptibility to topical agents. This reviews the structure and properties of vulvar tissue, emphasizing their impact on susceptibility contact irritants and allergens.

Atopic Dermatitis

Atopic dermatitis is one of the more common inflammatory dermatologic disorders with an estimated prevalence of 15%. It is thought to be primarily an inherited disease associated with a multitude of clinical manifestations; age at onset varies. Atopic dermatitis may coexist with allergic rhinitis/conjunctivitis and asthma, and these 3 conditions are referred to as the atopic triad. Some patients may develop 1, 2, or all 3 of these disorders, which do not necessarily have a parallel course. Atopic dermatitis is usually diagnosed on the basis of clinical findings obtained from the history and physical examination. Occasionally, laboratory tests such as determination of total or specific IgE levels are helpful, as is skin biopsy. Most affected patients have dry skin, are intolerant of harsh soaps and detergents, and report that wool clothing creates an itchy sensation on the skin. Pruritus may be severe and is often maximal in the fold or flexural areas of the sides of the neck and in the antecubital and popliteal fossae. Scratching the skin often causes thickened or “lichenified” areas, and secondary impetiginization from gram-positive bacteria (Staphylococcus aureus) is common. Other physical findings include excessive wrinkling of the skin over the extensor aspects of the hands and around the eyes, particularly the lower eyelid. This latter finding is referred to as Dennie-Morgan folds. Some patients have subtle circumoral pallor and may demonstrate white dermatographism on stroking of the skin, as opposed to the normal triple response of Lewis. Hand eczema may be the presenting sign, especially in persons who must wash their hands repeatedly throughout the day. Patients with atopic dermatitis have altered skin immunity manifested by increased susceptibility to infection with herpesvirus and bacteria. Rarely, those with severe atopy may develop a widespread herpetic infection of the skin known as eczema herpeticum or Kaposi varicelliform eruption. Patients with atopic dermatitis also have increased eosinophils in the skin and sometimes in the peripheral blood. Serum IgE levels are often elevated, and specific IgE levels to allergens may be increased. Furthermore, patients with atopic dermatitis have diminished ability for sensitization to topically applied allergens. This seems somewhat paradoxical but is another reflection of the altered immune status of such patients. The treatment of atopic dermatitis requires recognition of factors that aggravate and exacerbate the condition in a specific patient, including environmental and infectious factors. Contact irritants and allergens must be identified and removed. Treatment of the skin consists of hydrating lotions and creams, and topical corticosteroid or immunomodulating creams/ointments are used to decrease inflammation. Antihistamines may be therapeutic in some patients.