Allergic Contact Sensitization Research Articles

Perfumes and associated allergens: A brief review

A perfume (Latin, perfumare for smoke through) is essentially a cosmetic product to be used on the human body for its pleasing scent to mask body odor and have a feeling of freshness. A perfume is composed of fragrances which are aromatic compounds and essential oils, and solvents and fixatives. These fragrances are chemicals or are derived mostly from botanical sources. A perfume that usually consists of a few to hundreds of fragrance materials remains a major source of contact allergy from them. Everyone comes in contact with fragrance materials in daily life either directly from the application of a product to the skin, mostly cosmetics, or occasionally after contact with fragrance-containing household or other personal care products. Cosmetics and personal care products such as personal perfume(s), deodorant, aftershave lotion/gel, eau de cologne, and eau de toilette with the highest ever concentrations of fragrances remain the major source of contact sensitivity from fragrances. The adverse effects associated with the use of perfumes are both allergic and irritant contact dermatitis, pigmented contact dermatitis, phototoxicity and photoallergy, and contact urticaria. Systemic toxicity may also occur following inhalation and ingestion of fragrance(s) causing respiratory illness, headache, and attacks of migraine. However, allergic contact dermatitis and pigmented contact dermatitis remain by far the commonest cutaneous adverse effects. Colophony, Myroxylon pereirae, lanolin, formaldehyde, vanillin, musk mix, rose oil, cetostearyl alcohol, and more than 160 fragrances, both single and complex mixtures of chemicals (methyl ionones), or essential oils (Evernia furfuracea (treemoss) extract, E. prunastri (oakmoss) extract, Ferula galbaniflua gum, Narcissus poeticus flower extract, and Viola odorata leaf extract) have caused cosmetic contact sensitivity in most instances. Ylang-ylang oil, jasmine absolute, Cananga oil, benzyl salicylate, hydroxyl citronellal, sandalwood, and geraniol are common fragrances to cause pigmentary changes. This review highlights the composition of perfumes and constituent fragrances identified commonly as allergens. A brief insight is also provided for the diagnosis of allergic contact sensitivity from fragrances and present safety regulatory status.

The frequency of specific contact allergies is reduced in patients with psoriasis.

Earlier studies suggested an inverse association between contact allergy and psoriasis, although the results of clinical studies have been inconsistent. Gene expression studies in human contact allergy focusing on immune responses revealed nickel being an inducer of T helper (Th)1/Th17 and some Th22 immune polarization, whereas fragrances were found to promote a Th2-dominated immune activation. To investigate the epidemiological association between contact allergy and psoriasis in a large multicentre cohort and to analyse the sensitization profile to specific allergens in these patients. Retrospective analysis of patch-tested patients from 56 departments of dermatology (1996-2015), including 2387 patients with psoriasis and 161989 control patients. All patients with atopic dermatitis were excluded from both groups. The odds ratio (OR) for contact allergy was calculated to be 0·55 in patients with psoriasis (95% confidence interval 0·50-0·59). Logistic regression analyses with several independent variables indicated a 'protective effect' of having psoriasis for most allergens, independently of age, sex, affected body site and patch test indication. Fragrance mix II (OR 0·36) and lanolin alcohols (OR 0·38) were found to be among the least common allergens in patients with psoriasis. In contrast, the frequency of contact dermatitis to nickel was only marginally affected in patients with psoriasis compared with controls (OR 0·75). The inverse association between psoriasis and allergic contact sensitization is likely to be not exclusively mediated by psoriasis itself. The polarization of the activated immune response by specific allergens may influence the occurrence and significance of contact allergies in underlying immune-mediated diseases, eventually even beyond the skin.

Neutrophil cathepsin G inhibits hapten-presenting dendritic cell production of IL-12 and skewing of hapten-reactive CD4 T Cell development to IFN-γ- and IL-17-producing effector cells in allergic contact sensitivity

Abstract Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten skin sensitization and challenge. Sensitization of WT mice induces hapten-reactive CD8 cells producing CHS effector cytokines IFN-γ/IL-17 and IL-4-producing CD4 cells that cannot mediate CHS. Although CXCR2-dependent Gr-1+ cell recruitment into hapten challenged skin is required to direct effector CD8 T cell infiltration to elicit CHS, sensitization of CXCR2−/− mice or neutrophil-depleted WT mice induced both hapten-reactive CD4 and CD8 cells producing IFN-γ and IL-17. CD4 T cell-mediated CHS responses were not generated during hapten sensitization of neutrophil depleted WT mice treated with anti-IL-12 mAb or neutrophil depleted IL-12−/−mice. Neutrophil depletion during hapten sensitization of WT mice markedly increased numbers of IL-12-producing hapten-primed dendritic cells (DC), DC-derived p40, and T-bet-expressing CD4 T cells in the skin-draining lymph nodes. Sensitization of mice lacking the neutrophil serine protease cathepsin G induced hapten-reactive CD4 and CD8 T cells producing IFN-γ and IL-17 with elevated and elongated CHS responses to challenge. Few Gr-1+ cells were detected in the skin draining lymph nodes following senstization suggesting this regulation may not be mediated through direct Gr-1-DC interactions. In support of this, induction of CHS effector CD4 T cells producing IFN-γ in neutrophil-depleted WT mice was eliminated by subcutaneous injection of active, but not inactivated, cathepsin G during sensitization. Thus, hapten skin sensitization induces neutrophil release of cathepsin G that systemically inhibits hapten-presenting dendritic cell production of IL-12 and the development of CHS effector CD4 T cells.

Neutrophil Cathepsin G inhibits hapten-presenting dendritic cell production of IL-12 and skewing of hapten-reactive CD4 T cell development to IFN-γ- and IL-17-producing effector cells in allergic contact sensitivity

Abstract Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten skin sensitization and challenge. Sensitization of wild-type (WT) mice induces hapten-reactive CD8 T cells that produce IFN-γ and IL-17 and mediate CHS and hapten-reactive CD4 T cells producing IL-4 that cannot mediate CHS. Although CXCR2-dependent neutrophil recruitment into the hapten challenged skin is required to direct effector CD8 T cell infiltration into the site to elicit CHS in WT mice, CHS was elicited following challenge of hapten sensitized CXCR2−/− mice. Sensitization of CXCR2−/− mice or antibody-mediated depletion of neutrophils during sensitization of WT mice generated hapten-reactive CD4 and CD8 T cells producing IFN-γ and IL-17 and either T cell population could mediate CHS independently of the other. The hapten-reactive CD4 cells producing IFN-γ and IL-17 and their CHS responses were not generated during hapten sensitization of IL-12−/− mice depleted of neutrophils or WT mice depleted of neutrophils and treated with anti-IL-12 mAb. Neutrophil depletion during hapten sensitization of WT mice markedly increased numbers of IL-12-producing dendritic cells in the skin draining lymph nodes. Sensitization of mice lacking the neutrophil serine protease cathepsin G induced hapten-reactive CD4 and CD8 T cells producing IFN-γ and IL-17 with elevated and elongated CHS responses to challenge. Induction of CHS effector CD4 T cells in neutrophil-depleted WT mice was eliminated by subcutaneous injection of recombinant cathepsin G during sensitization. Thus, hapten skin sensitization induces neutrophil production of cathepsin G that regulates hapten-presenting dendritic cell production of IL-12 and the development of CHS effector CD4 T cells.

Comparing reliabilities of strip and conventional patch testing.

The standardized protocol for performing the strip patch test has proven to be valid, but evidence on its reliability is still missing. To estimate the parallel-test reliability of the strip patch test as compared with the conventional patch test. In this multicentre, prospective, randomized, investigator-blinded reliability study, 132 subjects were enrolled. Simultaneous duplicate strip and conventional patch tests were performed with the Finn Chambers® on Scanpor® tape test system and the patch test preparations nickel sulfate 5% pet., potassium dichromate 0.5% pet., and lanolin alcohol 30% pet. Reliability was estimated by the use of Cohen's kappa coefficient. Parallel-test reliability values of the three standard patch test preparations turned out to be acceptable, with slight advantages for the strip patch test. The differences in reliability were 9% (95%CI: -8% to 26%) for nickel sulfate and 23% (95%CI: -16% to 63%) for potassium dichromate, both favouring the strip patch test. The standardized strip patch test method for the detection of allergic contact sensitization in patients with suspected allergic contact dermatitis is reliable. Its application in routine clinical practice can be recommended, especially if the conventional patch test result is presumably false negative.

Contact sensitization in patients with suspected textile allergy. Data of the Information Network of Departments of Dermatology (IVDK) 2007-2014.

Textile dyes, rubber, elements or textile resins carry the risk of inducing allergic contact sensitization. To assess clinical data and patch test results for dermatitis patients with suspected textile allergy. A retrospective analysis of Information Network of Departments of Dermatology data of the years 2007-2014 of patients patch tested because of suspected textile allergy was performed. Patients of the study group (n = 3207) suffered more frequently from leg, trunk and generalized dermatitis than patients of the control group (n = 95210). Among the allergens of the textile dye series, the highest frequency of positive reactions was observed for p-aminoazobenzene (5.1%) and p-phenylenediamine (PPD) (4.5%), followed by Disperse Orange 3 (3.1%), Disperse Blue 124 (2.3%), Disperse Blue 106 (2.0%), Disperse Red 17 (1.1%), and Disperse Yellow 3 (1.1%), partly with concomitant reactions. Patch testing with the patients' own textiles was performed in 315 patients, with positive reactions in 18 patients. These were mostly elicited by blue or black textiles with tight skin contact. Only 2 of these patients also reacted to textile dyes from the German Contact Dermatitis Research Group series. For the comprehensive diagnosis of contact sensitization in patients with suspected textile dermatitis, combined patch testing is indicated, with (i) PPD and a textile dye series and (ii) patients' own clothing.

Inflamed skin predisposes to sensitization to less potent allergens

Irritant dermatitis, caused by genetic barrier dysfunction in atopic dermatitis or wet work in hand dermatitis, induces innate immune response that might predispose to allergic contact sensitization to less potent sensitizers. We sought to determine if positive patch test results to less potent allergens are more prevalent in patients with a history of childhood flexural dermatitis or current wet work. We examined our database of patients presenting to a contact dermatitis clinic tested to potential contact allergens as indicated by their history. Allergens from our most recent standard were studied if they could be classified as weak, moderate, or strong sensitizers based on published data from the local lymph node assay. Patients were stratified by a history of childhood-onset flexural dermatitis as a proxy for atopic dermatitis and by occupation. History of childhood-onset dermatitis predisposed to contact allergy to weak sensitizers and wet work to medium-potency sensitizers. Neither predisposed to contact allergy from strong sensitizers. Association cannot prove causation. We conclude that strong sensitizers do not require wet work or atopy to cause sensitization. Barrier defects associated with childhood eczema and wet work may promote sensitization to weak antigens.

Association of MHC region SNPs with irritant susceptibility in healthcare workers

Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in “wet-work” occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC). Genotyping was performed using Illumina Goldengate MHC panels. A number of SNPs within the MHC Class I (OR2B3, TRIM31, TRIM10, TRIM40 and IER3), Class II (HLA-DPA1, HLA-DPB1) and Class III (C2) genes were associated (p < 0.001) with skin response to tested irritants in different genetic models. Linkage disequilibrium patterns and functional annotations identified two SNPs in the TRIM40 (rs1573298) and HLA-DPB1 (rs9277554) genes, with a potential impact on gene regulation. In addition, SNPs in PSMB9 (rs10046277 and ITPR3 (rs499384) were associated with hand dermatitis. The results are of interest as they demonstrate that genetic variations in inflammation-related genes within the MHC can influence chemical-induced skin irritation and may explain the connection between inflamed skin and propensity to subsequent allergic contact sensitization.

Allergic contact dermatitis to parthenolide

Parthenolide is a sesquiterpene lactone that is found in the fruit and flowers of the plant feverfew (Tanacetum parthenium or Chrysanthemum parthenium). Parthenolide, comprising 85% of the total sesquiterpene content, is located in the superficial leaf glands of the plant. This plant is grown all over the world and is used for its anti-inflammatory effects to treat a wide range of conditions, including migraine headache and arthritis. Parthenolide also occurs in other common flowering plants of the family Asteraceae (Compositae), including daisies and magnolias. We present a case of contact dermatitis to parthenolide. A 76-year-old woman with a history of allergic rhinitis presented with a chronic hand dermatitis for many years. She denied any associated environmental changes, such as changes in detergents, soaps, conditioners, shampoos, or cosmetics. There was no association with any particular foods or specific medications, such as nonsteroidal anti-inflammatory medications or antibiotics. The dermatitis was extremely pruritic and appeared to worsen when she performed gardening activities, especially during the fall, spring, and summer months. She did not perform much gardening in the winter season, and the dermatitis improved during this time. She had previously seen dermatology and was prescribed multiple topical preparations, including clobetasol proprionate 0.05%, triamcinolone acetonide 0.1%, and pimecrolimus 1%, with only temporary benefit. On examination, there was erythema with thickening of the dorsal surface of the hands and fingers, as well as scaling erythema and lichenification of the palms. There were no vesicles noted. T.R.U.E. Test patch testing was performed. At 48 hours after application, there was a 1þ reaction (erythema and infiltration) to parthenolide. The patient cancelled the 96hour patch test read but reported increased pruritis and irritation at the testing site in the days following the 48-hour read. At the 7-day patch test read, there was a 2þ reaction (increased erythema with infiltration and papules) to parthenolide (Figure 1). Based on the history (working extensively with flowering plants), timing (dermatitis worsening with exposure to these plants), and positive patch test result, a diagnosis of allergic contact dermatitis to parthenolide was made. Protective handwear was recommended for the patient with improvement in the dermatitis. Allergic contact sensitization is a frequent cause of chronic hand dermatitis (24%). A “crescendo” (increase in reaction) effect over the timing of the patch test reading, which occurred in our patient, is common in allergic contact dermatitis. Although Alstroemeria (Peruvian lily) is the most common cause of hand dermatitis in floral workers in the United States, parthenolide is the most common cause of plant dermatitis in India. In one study in Denmark, the prevalence of parthenolide-induced contact dermatitis was estimated to be 2.25% of all patients with contact dermatitis. Although direct contact is thought to be the main method of sensitization, parthenolide dermatitis has also been shown to occur via airborne particles, occurring not only on the palmar surfaces of the hands but also on the upper eyelids, posterior ear, submandibular region, decolletage of neck, forearms, and chest. Other Compositae allergens, including ragweed, sunflower, and goldenrod, can also cause airborne contact dermatitis. In addition, patients with a past or present history of atopic dermatitis may become sensitized to parthenolide at any age, regardless of occupational exposures. Because of the purported anti-inflammatory effects of parthenolide, multiple studies have provided insight into possible mechanisms. One study demonstrated that parthenolide inhibited IkB kinase and nuclear factor kappa B activation in cystic fibrosis cell lines in mice. Another group studied the effect of parthenolide on human monocyteederived dendritic cells stimulated with LPS or TNF-a. Parthenolide inhibited the upregulation of costimulatory molecules (including CD 80, MHC class II, and CD 40) on dendritic cells induced by LPS but not by TNF-a, and parthenolide also prevented TNF-a and IL-12 secretion by LPS-stimulated dendritic cells. Parthenolide prevented nuclear factor kappa B nuclear translocation and IkB degradation in human dendritic cells induced by both LPS and TNF-a. Because of these potential effects, parthenolide is being used in various herbal remedies, including herbal teas, tinctures, tablets, and supplements. Topical products containing parthenolide have been shown to produce positive patch testing reactions in parthenolide-sensitive patients.

Incidence of allergic contact sensitization in central Chinese subjects with chronic urticaria.

BACKGROUNDChronic urticaria (CU) can be provoked by a wide variety of causes. Some studies suggest contact sensitization may play a role in the disease.OBJECTIVETo investigate the incidence and distribution characteristics of allergic contact sensitization in central Chinese subjects with CU, and assess contact allergen avoidance measures in managing CU.METHODSPatch tests were performed, following the recommended standard procedure, with 20 selected allergens, in line with the European baseline series. All subjects with positive results were prescribed appropriate avoidance measures for the sensitizing substances, while subjects with negative results served as the control group. CU severity was assessed daily from week1 to week4 and for each subject, applying the Urticaria Activity Score.RESULTS42.9% (233/543) of subjects with CU showed positive reactions to one or more contact allergen(s). Potassium dichromate, benzene mix and carba mix were more common in male patients, while nickel sulfate was more frequent in females. The positive rates for different allergens varied with age and occupation. The median (interquartile range) severity scores at week 1 were 20 (14-21) and 15 (14-27) for the allergen avoidance group and control group, respectively (P>0.05); and 12 (7-15) and 14 (12-17) at week 4 (P<0.001).CONCLUSIONThe incidence of allergic contact sensitization in CU patients was high, and appropriate contact allergen avoidance measures benefitted CU management. Contact allergens may play a role in the pathogenic mechanism of CU and patch tests are an option for CU patients.

"Parabenoia" Debunked, or "Who's Afraid of Parabens?".

Parabens have been used as preservatives in foods, injectables, and topical preparations for nearly 10 decades. Present in nature, rapidly metabolized by skin and liver enzymes, they have an excellent safety record. However, in the past 15 years, they have been under scrutiny for their alleged estrogenic and antiandrogenic effects, as well as their putative role in promoting cancerogenesis through endocrine disruption. Scientific articles supporting these assertions have led the European Community to ban or restrict the use of some parabens. Despite that methylparaben and ethylparaben have negligible endocrine disruption activity, the food, pharmaceutical, and cosmetic industries are under pressure from scare campaigns in the media and are responding by replacing parabens with other biocides that cause multiple cases, and even worldwide epidemics, of allergic contact sensitization. In the present review, we present a balanced account of the published literature about the metabolism and potential toxicology of parabens.

English

BACKGROUND: Eczema of the hands and feet is one of the commonest conditions encountered in dermatologic practice affecting 1% of adults. The patch test is the only scientific proof of contact allergy, a positive reaction to a correctly prepared and applied patch test confirms the person has allergic contact sensitivity. There are not much studies done on the patterns of lower leg and foot eczema's especially from India. Hence this study tries to determine the patterns of lower leg and foot eczema and also to evaluate the common allergens by patch testing. The aim of this study is: To determine the pattern of lower leg and foot eczema. Confirm the common allergens responsible by patch testing using Indian Standard Series. METHODS: A prospective clinical study was done comprising of 50 clinically suspected cases of lower leg and foot eczema for a period of 2 years from September 2008 to September 2010. The study included 32 males and 18 females. An informed consent was obtained from all the patients and detailed history with particular emphasis on age of onset, site of initial lesion, extent of dermatitis, seasonal variation, aggravating factors and association with atopy were noted. RESULTS: Mean age of 50 patients in this study was 44.52 years with a standard deviation of 15.8 (range 7 - 70 years). The most common age group affected was 46- 60 years (40%), followed by 31-45 years (30%). 32 cases (64%) were males and 18 cases (36%) were females with a male to female ratio of 1.78: 1.0. Out of 50 cases, 23 patients (46%) showed positive patch test result to at least a single allergen. To the 26 allergens in Indian standard series tested, around 19 allergens were found to be positive. Some were having positivity to multiple allergens, giving a total of 51 positive results. Out of which 46 were relevant (90.20%) against which only 5 cases were non-relevant (9.80%) according to the history.

Copper hypersensitivity.

The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.

An ITAM-Syk-CARD9 signalling axis triggers contact hypersensitivity by stimulating IL-1 production in dendritic cells.

A variety of reactive organic compounds, called haptens, can cause allergic contact dermatitis. However, the innate immune mechanisms by which haptens stimulate dendritic cells (DCs) to sensitize T cells remain unclear. Here we show that the coupling of ITAM-Syk-CARD9 signalling to interleukin-1 (IL-1) secretion in DCs is crucial for allergic sensitization to haptens. Both MyD88 and Caspase recruitment domain-containing protein 9 (CARD9) signalling are required for contact hypersensitivity (CHS). Naïve T cells require signals received through IL-1R1-MyD88 for effector differentiation, whereas DCs require CARD9 and spleen tyrosine kinase (Syk) signalling for hapten-induced IL-1α/β secretion and their ability to prime T cells. DC-specific deletion of CARD9, DAP12, Syk or NLRP3, but not MyD88, is sufficient to abolish CHS. All tested haptens, but not irritants, can induce Syk activation, leading to both the CARD9/BCL10-dependent pro-IL-1 synthesis (signal1) and reactive oxygen species-mediated NLRP3 inflammasome activation (signal2), required for IL-1 secretion. These data unveil an innate immune mechanism crucial for allergic contact sensitization to chemical compounds.

Disruption of the Complement Anaphylatoxin Receptor C5L2 Exacerbates Inflammation in Allergic Contact Dermatitis

The complement anaphylatoxin C5a is a critical mediator of allergic contact dermatitis, bridging essential aspects of innate and adaptive immunity. This anaphylatoxin functions by interacting with two 7-transmembrane segment receptors, the C5aR and C5L2. The C5aR is a classical G protein coupled receptor, whereas C5L2 is deficient in coupling to G proteins because of variations in the sequence. Our previous work in human neutrophils revealed a unique role for C5L2 in negatively modulating anaphylatoxin receptor mediated cellular activation through interactions with β-arrestin. When C5L2 is deficient, C5aR-mediated β-arrestin signaling is greatly enhanced. The work described in this study was undertaken first to determine the effect of C5L2 deficiency in a murine model of contact sensitivity, and second to determine whether the resultant exacerbation of inflammatory parameters reflects a negative modulatory function of C5L2 on the C5aR. First, we find dramatic increases in inflammation in C5L2(-/-) animals compared with wild type mice. Second, these increases are completely reversed following administration of mAb against the C5aR. Thus, in allergic contact sensitivity, as in isolated human neutrophils, C5L2 functions to suppress C5a-C5aR-mediated responses, further underscoring its role as a negative regulator of anaphylatoxin activity.

Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity

T-cell tolerance of allergic cutaneous contact sensitivity (CS) induced in mice by high doses of reactive hapten is mediated by suppressor cells that release antigen-specific suppressive nanovesicles. We sought to determine the mechanism or mechanisms of immune suppression mediated by the nanovesicles. T-cell tolerance was induced by means of intravenous injection of hapten conjugated to self-antigens of syngeneic erythrocytes and subsequent contact immunization with the same hapten. Lymph node and spleen cells from tolerized or control donors were harvested and cultured to produce a supernatant containing suppressive nanovesicles that were isolated from the tolerized mice for testing in active and adoptive cell-transfer models of CS. Tolerance was shown due to exosome-like nanovesicles in the supernatants of CD8(+) suppressor T cells that were not regulatory T cells. Antigen specificity of the suppressive nanovesicles was conferred by a surface coat of antibody light chains or possibly whole antibody, allowing targeted delivery of selected inhibitory microRNA (miRNA)-150 to CS effector T cells. Nanovesicles also inhibited CS in actively sensitized mice after systemic injection at the peak of the responses. The role of antibody and miRNA-150 was established by tolerizing either panimmunoglobulin-deficient JH(-/-) or miRNA-150(-/-) mice that produced nonsuppressive nanovesicles. These nanovesicles could be made suppressive by adding antigen-specific antibody light chains or miRNA-150, respectively. This is the first example of T-cell regulation through systemic transit of exosome-like nanovesicles delivering a chosen inhibitory miRNA to target effector T cells in an antigen-specific manner by a surface coating of antibody light chains.

Pattern of patch test reactivity among patients with clinical diagnosis of contact dermatitis: a hospital-based study

BACKGROUND AND OBJECTIVESContact allergy is associated with a significant morbidity all over the world. This study was performed to investigate the pattern of sensitization by contact allergens in the local population.DESIGN AND SETTINGRetrospective study to investigate patch test reactivity among patients with clinical diagnosis of contact dermatitis who were referred to the allergy clinic at the King Khalid University Hospital, Riyadh, between April 2008 and March 2010.PATIENTS AND METHODSOf the 196 patients referred to the allergy clinic over the 2-year period, 91 (46.4%) patients reacted to one or more patch test allergens, and these patients were included in this study. The study group included 82 (91.1%) of Saudi nationality and 9 (8.9%) patients of other nationalities. The patch test was performed using the T.R.U.E TEST, containing 24 allergens/allergen mixes.RESULTSOf the 91 cases who reacted positively to one or more allergens, 67 (73.6%) were females with a mean age of 37 (8.3 years) and 24 (26.4%) were males with a mean age of 34 (11.6 years). Thirty-three (36.2%) patients reacted to nickel sulfate, 14 (15.3%) to p-phenylenediamine, 13 (14.2%) to p-tert-butylphenol-formaldehyde resin, 13 (14.2%) to thimerosal, and 9 (9.8%) to colophony. Reactivity against the rest of the allergens was not remarkable. A significantly higher percentage of females reacted to nickel sulfate (84.8% vs 15.2% in males; P=.0001), p-tert-butylphenol-formaldehyde resin (92.3% vs 7.7%; P=.0001), and thimerosal (76.9% vs 23.1%; P=.03).CONCLUSIONSPatch test reactivity to nickel sulfate was high. The pattern of contact allergy observed in this study indicates the need for large-scale investigations to identify local allergens responsible for contact allergy and for formulation of policies directed towards avoidance of exposure.

Studies of cell signaling in a reconstructed human epidermis exposed to sensitizers: IL-8 synthesis and release depend on EGFR activation

Models of reconstructed human epidermis (RHE) holding proliferating and fully differentiated cultured keratinocytes allow in vitro investigation of early molecular and cellular epidermal events during the complex response of keratinocytes at the onset of allergic contact dermatitis (ACD) or sensitization. In this study, data collected on RHE exposed to well-characterized sensitizing chemicals, such as dinitrofluorobenzene, oxazolone, cinnamaldehyde and isoeugenol, revealed a transient expression of IL-8 mRNA in association with abundant IL-8 cell release. Investigations of keratinocyte signaling illustrate transient activation by tissue exposure to sensitizing chemicals of the epidermal growth factor receptor (EGFR). This activation of EGFR tyrosine kinase is involved in the expression and release of IL-8. The IL-8 release appears also to be partially dependent on p38 and ERK 1/2 MAPK activation. Moreover, data suggest that heparin-binding EGF-like growth factor (HB-EGF) expression and release induced after exposure of RHE to sensitizing chemicals are also under the control of EGFR tyrosine kinase activity, independently of the IL-8 expression and release. Mechanistic approach of keratinocyte responses in the context of RHE underlying regulation of expression and release of epidermal cytokines and growth factors after topical application of sensitizing chemicals is proposed to identify biomarkers which could then be analysed for in vitro toxicological screening of new or undefined compounds.

Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis.

Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of in vitro methods to assess chemical sensitivity. In this paper, we examine existing approaches including in silico models, cell and tissue based assays for distinguishing between sensitizers and irritants. The in silico approaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and co-culture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals.

Airborne contact dermatitis to tetrazepam in geriatric nurses – a report of 10 cases

Tetrazepam, a benzodiazepine, is a frequently used muscle relaxant. The most common adverse reactions are neurological and gastrointestinal. Cutaneous reactions to tetrazepam are rare and occur predominantly after systemic administration. To present 10 health care professionals who developed airborne contact dermatitis to tetrazepam due to occupational exposure to tetrazepam dusts. We report a series of 10 cases observed in our department between January 2006 and March 2011 where tetrazepam was identified to cause allergic airborne contact dermatitis. Affected individuals were employed as (geriatric) nursing staff, exposed to tetrazepam on a regular occupational basis when crushing tablets for their patients. Upon investigation, patients were patch tested with commercial and customized allergens. This included tetrazepam and in five cases diazepam. Tetrazepam revealed strong positive reactions in all patients. Additional diazepam sensitization was observed in three subjects. Following local treatment and occupational preventive action, patients recovered from their skin symptoms. Allergic contact sensitization to tetrazepam and cross-sensitization to diazepam seems to be underestimated and not appropriately diagnosed in patch test clinics, as it is so far insufficiently patch tested. They should be considered when allergic contact dermatitis is suspected, particularly in professionally exposed staff, and tested as supplemental allergens.