Potential classification of chemical immunologic response based on gene expression profiles.

Occupational immune diseases are a serious public health burden and are often a result of exposure to low molecular weight (LMW) chemicals. The complete immunological mechanisms driving these responses are not fully understood which has made the classification of chemical allergens difficult. Antimicrobials are a large group of immunologically-diverse LMW agents. In these studies, mice were dermally exposed to representative antimicrobial chemicals (sensitizers: didecyldimethylammonium chloride (DDAC), ortho-phthalaldehyde (OPA), irritants: benzal-konium chloride (BAC), and adjuvant: triclosan (TCS)) and the mRNA expression of cytokines and cellular mediators was evaluated using real-time qPCR in various tissues over a 7-days period. All antimicrobials caused increases in the mRNA expression of the danger signals Tslp (skin), and S100a8 (skin, blood, lung). Expression of the TH2 cytokine Il4 peaked at different timepoints for the chemicals based on exposure duration. Unique expression profiles were identified for OPA (Il10 in lymph node, Il4 and Il13 in lung) and TCS (Tlr4 in skin). Additionally, all chemicals except OPA induced decreased expression of the cellular adhesion molecule Ecad. Overall, the results from these studies suggest that unique gene expression profiles are implicated following dermal exposure to various antimicrobial agents, warranting the need for additional studies. In order to advance the development of preventative and therapeutic strategies to combat immunological disease, underlying mechanisms of antimicrobial-induced immunomodulation must be fully understood. This understanding will aid in the development of more effective methods to screen for chemical toxicity, and may potentially lead to more effective treatment strategies for those suffering from immune diseases.

Mechanism and diagnosis of protein contact dermatitis.

PURPOSE OF REVIEW: Protein contact dermatitis (PCD) is a chronic eczema because of immediate hypersensitivity to protein and not related to haptens. As it has to be diagnosed by prick tests, it is probably under-recorded and under-estimated that is why it is important for dermatologists, allergists and occupational physicians to better know this peculiar contact dermatitis. RECENT FINDINGS: Some recent series have emphasized that PCD is mainly an occupational dermatosis, mainly observed in food handlers. SUMMARY: PCD is a chronic eczematous dermatitis, possibly exacerbated by work, suggested if associated with inflammatory perionyxis (paronychial inflammation) and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have in most of the cases negative results. Prick-by-prick tests with fresh material are recommended. The product has to be 'pricked', for instance the food, and immediately after the forearm is pricked. In case of multisensitization revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. History of atopy found in 56--68% of the patients has to be checked for. Most of the cases are observed among food-handlers but PCD can also be because of nonedible plants, latex, hydrolyzed proteins or animal proteins.

Skin reactions to latex in dental professionals - first Croatian data.

Purpose. To determine the prevalence of undesirable skin reactions to latex in dental professionals and students of the School of Dental Medicine in Zagreb, Croatia. Methods. Our research included 444 participants, of which 200 agreed to undergo a skin prick test (SPT). All participants answered a questionnaire in which we asked about incidence of skin lesions, duration of occupational exposure to latex, localization of skin lesions and symptoms. Statistical analysis of the questionnaire and test results was then carried out. Results. Of the total 444 participants surveyed, 249 (56.1%) reported lesions on their skin (professionals 64.8%, students 6.1-58.5%). From the questionnaire, 239 (96.0%) respondents reported lesions on the hands and fingers, mostly in the form of erythema (37.0%) and occasional dryness of skin (29.0%). Positive SPT results were found in 14 (7.0%) out of the 200 respondents who underwent the test. Conclusions. While a large number of subjects (56.1%) reported skin lesions when using latex products at their workplace, the SPT test was positive only in 7.0%. The results show that the prevalence of self-reported skin lesions was significantly related to the length of occupational exposure, with a substantial effect size (p < 0.001; V = 0.334).

An Analysis of Skin Prick Tests to Latex and Patch Tests to Rubber Additives and other Causative Factors among Dental Professionals and Students with Contact Dermatoses.

BACKGROUND: Dental workers often experience unwanted allergic and nonallergic skin reactions resulting in different contact dermatoses (e.g., contact urticaria, irritant and allergic contact dermatitis) that are often attributed to rubber gloves. OBJECTIVE: To examine allergic and nonallergic contact dermatoses by different methods amongst dental professionals and dental students, more specifically, reactions to natural rubber latex (NRL), rubber additives, and other causative factors. METHODS: In this cross-sectional study we surveyed a total of 444 subjects (dentists, assistants, technicians, and students); 200 agreed to be tested to latex by the standard skin prick test (SPT) and prick-by-prick test, of whom 107 were patch tested to rubber additives (mercapto mix, thiuram mix, carba mix, and N-isopropyl-N-phenyl-4-phenylenediamine [IPPD]). RESULTS: Skin lesions appeared significantly more frequently with longer work experience (p = 0.002; V = 0.181), frequent glove changes (p < 0.001; V = 0.310), and hand washing (p < 0.001; V = 0.263), and in subjects with a history of allergies (atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and others) (p < 0.001; V = 0.183). Positive SPTs to latex occurred in 14/200 subjects (7%), of whom 5/14 subjects (35.7%) were also positive in prick-by-prick tests. Patch tests were positive in 5/104 subjects (4.8%) (mercapto mix 1%, thiuram mix 1.9%, and carba mix 1.9%). CONCLUSION: Only a small number of our subjects were allergic to latex (7%) or rubber additives (4.8%). Thus, self-reported contact dermatoses (during NRL product use) in dental professionals and students are not commonly caused by allergies to latex and rubber additives, as is often assumed, but by other factors.

Occupational allergic contact dermatitis caused by antibiotics in healthcare workers - relationship with non-immediate drug eruptions.

BACKGROUND: Occupational allergic contact dermatitis (ACD) in healthcare workers (HCWs) is common, but systemic antibiotics are rarely reported as the cause. OBJECTIVES: Characterize occupational ACD by handling systemic antibiotics. METHOD: A retrospective analysis was performed of ACD caused by systemic antibiotics among HCWs patch tested between 2010 and 2016 with a series of systemic antibiotics. RESULTS: We studied 4 female nurses aged 28-47 years who developed ACD while working in surgical departments. They had eczema of the hands, and forearms or face, and 1 patient, who previously had exanthema caused by flucloxacillin, also developed a generalized rash following airborne exposure to systemic antibiotics. Patch tests showed positive reactions to ampicillin and cefazolin in 1 patient, to cefotaxime and ceftriaxone in 2 patients, and to several penicillins in another patient. Three patients also reacted to rubber allergens, fragrances, and/or preservatives. All patients admitted having direct and sporadic exposure to systemic antibiotic solutions. Avoidance resulted in a significant improvement of ACD, but 1 patient had to change job. CONCLUSIONS: Occupational ACD caused by ß-lactam antibiotics, particularly cephalosporins, is significant in HCWs. Cross-reactions between ß-lactams are similar to those described in non-immediate drug eruptions. A relationship between systemic delayed drug hypersensitivity and ACD, as observed in one case, suggests that patients should avoid future use of the antibiotic to which they are sensitized.

Contact allergy: an update.

Contact allergies are common cause of eczema in all age groups and are one of the most common causes of occupational disability. Contact dermatitis (CD) can be divided into irritant and allergic contact dermatitis. Distinguishing between irritant and allergic triggers of CD by clinical and histologic examinations can be challenging. The approach to patients with CD should consist of a detailed (work and leisure) history, skin examination, patch tests with allergens based on history, physical examination, education on materials that contain the allergen and adequate therapy and prevention.

Occupational asthma to detergent protease associated with a late-phase neutrophilic cutaneous response

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Inflamed skin predisposes to sensitization to less potent allergens.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Association cannot prove causation. CONCLUSIONS: 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.

Benzalkonium Chloride: A Known Irritant and Novel Allergen.

BACKGROUND: Benzalkonium chloride (BAK), a detergent and preservative found in health care and household products, is an established irritant, yet BAK is seldom considered to cause allergic contact dermatitis. We have, however, observed positive patch test reactions more often than is typically reported. From 2001 through 2005 and 2006 through 2010, BAK was among the top 10 most frequent allergens in our standard series. OBJECTIVE: The aim of this study was to review the Mayo Clinic experience from 2000 to 2012 with patch testing to BAK. METHODS: An electronic patch test database was used to acquire results of patients who underwent patch testing for BAK 0.1% aqueous after it was introduced to the standard series in 2000 until 2012. Previous reports (1998-2000, 2001-2005, 2006-2010) from our institution were also reviewed. CONCLUSIONS: Our study showed BAK to be an allergen of increasing importance. From 1998 through 2000, 2001 through 2005, and 2006 through 2010, the rate of allergic patch test results to BAK increased. More than half of the reactions in each period studied were graded as macular erythema, with at least one third of all reactions deemed to be relevant. Irritancy rates were consistently low.

Sensitization to Formaldehyde in Northeastern Italy, 1996 to 2012.

BACKGROUND: Formaldehyde is a widely used organic compound, used in several applications (hard thermoset resins, adhesives, disinfectants, tissue fixatives, etc), in its free form or released by formaldehyde releaser products. Its use is under control due to its toxic, carcinogenic, and allergenic properties. OBJECTIVE: The aim of this study was to investigate the frequency of formaldehyde sensitization, time trend, and correlation to occupations. METHODS: This study is a cross-sectional study on a population of 23,774 patients tested from 1996 to 2012 in Northeastern Italy. RESULTS: Frequency of sensitization was 3.3%, without any significant time trend. Hands (39.8% overall) and face (25.6% females, 15.5% males) were mainly involved. We found a trend toward decrease by age in females (3.11% in first quintile [14-26 years], 2.29% in fifth quintile [59-97 years], P < 0.01). On a logistic regression analysis (control group: white-collar workers), we found associations in health care (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.04-1.81), wood (OR, 2.14; 95% CI, 1.30-3.51), and textile (OR, 1.79; 95% CI, 1.14-2.79) sectors and professional drivers (OR, 1.94; 95% CI, 1.05-3.60). We found a high rate of cosensitization to formaldehyde in patients with positive patch test reactions to quaternium-15 (OR, 18.7; 95% CI, 12.6-27.7). CONCLUSIONS: Sensitization to formaldehyde is relevant in our population, especially in the health care sector, wood and textile industries, and professional drivers. No significant time trend was found.

Comparison of IgG against plastic resin in workers with and without chemical dermatitis.

BACKGROUND: There are many chemical sensitizers which cause allergy in the surrounding environment. However, the identification of substances causing allergy is difficult. We developed a new method to detect IgG which reacts against many kinds of chemical-human serum albumin (HSA) adducts at the same time. In this study, the diagnostic significance of the IgG was studied among workers of a company where a mass outbreak of chemical dermatitis had occurred after changing a plastic resin to a new one. METHODS: Eleven workers who handled the new plastic resin and suffered from dermatitis (case) and 9 workers who also handled the same resin in the same company but were free from dermatitis (control) were the subjects. Immunological dot blotting was carried out to detect serum IgG using originally prepared diagnostic antigens, comprising a mixture of HSA and the plastic resin or its components under various conditions. RESULTS: IgG against the plastic resin in use was detected in all workers who suffered from dermatitis. The prevalence of the IgG against the plastic resin was significantly higher in workers with than in those without dermatitis. On the other hand, IgG against its components (bisphenol A diglycidyl ether, m-xylylenediamine and butyl 2,3-epoxypropyl ether) was detected in a few workers with dermatitis. DISCUSSION: This suggests that IgG against chemical-HSA adduct reflects not only exposure but also causative chemicals of dermatitis. Our method to use a material itself as a hapten is practical and useful in the occupational field. CONCLUSION: It is suggested that IgG against chemicals is a useful marker of chemicals inducing dermatitis.

Occupational protein contact dermatitis.

Occupational contact dermatitis is generally caused by haptens but can also be induced by proteins causing mainly immunological contact urticaria (ICU); chronic hand eczema in the context of protein contact dermatitis (PCD). In a monocentric retrospective study, from our database, only 31 (0.41%) of patients with contact dermatitis had positive skin tests with proteins: 22 had occupational PCD, 3 had non-occupational PCD, 5 occupational ICU and 1 cook had a neutrophilic fixed food eruption (NFFE) due to fish. From these results and analysis of literature, the characteristics of PCD can be summarized as follows. It is a chronic eczematous dermatitis, possibly exacerbated by work, suggestive if associated with inflammatory perionyxix and immediate erythema with pruritis, to be investigated when the patient resumes work after a period of interruption. Prick tests with the suspected protein-containing material are essential, as patch tests have negative results. In case of multisensitisation revealed by prick tests, it is advisable to analyse IgE against recombinant allergens. A history of atopy, found in 56 to 68% of the patients, has to be checked for. Most of the cases are observed among food-handlers but PCD can also be due to non-edible plants, latex, hydrolysed proteins or animal proteins. Occupational exposure to proteins can thus lead to the development of ICU. Reflecting hypersensitivity to very low concentrations of allergens, investigating ICU therefore requires caution and prick tests should be performed with a diluted form of the causative protein-containing product. Causes are food, especially fruit peel, non-edible plants, cosmetic products, latex, animals.

[Not Available]. / Kontaktallergien im Kindesalter.

Allergic contact eczema in children is frequent. If clinically suspected, a patch test should be performed. In the present study, data obtained from 116,742 patients who had undergone a patch test from 2005-2014 were analysed. The children group (range 0-12 years) included 925 patients. If at least 700 tested individuals were considered, the most frequent sensitizations in this group were nickel sulfate (8.5 %), fragrance mix I (5.5 %), and colophony (3.4 %), whereby sensitisation in adults was higher for nickel sulfate (15.5 %) and fragrance mix 1 (8.4 %), while being similar for colophony (3.7 %). In adolescents with and without a profession, nickel sulfate (11.1 and 13.6 %, respectively) and cobalt (II) chloride (3.9 and 3.4 %, respectively) were the most frequent positively tested contact allergens. Sensitisations toward fragrance mix I was low (3.9 and 3.4 %, respectively) in comparison to the adult group (8.4 %). In both children and adolescents, toluene diamine and paraphenylenediamine sensitizations were not infrequent, but it must be considered that these allergens were only tested if suspected. The data show that the sensitisation profile among children and adolescents display patterns similar to those in adults. Sensitisations in childhood and adolescence towards dyes like paraphenylendiamine may be associated with increased use of tattooing in these groups.