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.

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.

A laboratory test based on determination of cytokine profiles: a promising assay to identify exposition to contact allergens and predict the clinical outcome in occupational allergic contact dermatitis.

BACKGROUND: Para-phenylenediamine (PPD) is the main allergen causing adverse reactions to hair dyes and a frequent cause of occupational-related skin sensitization among hairdressers and beauticians. The immunologic mechanism of the disease relies on the production of inflammatory cytokines by allergen-specific T cells, while regulatory T cells are thought to down-modulate the allergic response. This study was aimed at investigating the expression of effector or regulatory cytokines in exposed subjects in order to verify whether different cytokine profiles might predict distinct clinical outcomes. Peripheral blood mononuclear cells (PBMC) from 21 subjects occupationally exposed or not (10) to PPD were kept in short term cultures in the presence of optimized concentrations of NiSO4 × 6H2O or PPD. The production of IFN-γ and IL-10 elicited by antigens were analyzed by the ELISpot assay. RESULTS: The presence of IFN-γ responses toward PPD was significantly correlated with a positive patch test (P = 0.002) and allergic symptoms, while IL10 responses were invariably found in PPD-exposed but clinically asymptomatic subjects with negative patch testing. We found concordance between the different cytokine profiles and patch test results. No false-positive results were found for the different cytokine profiles induced by PPD, resulting in 100% specificity. The sensitivity of the test was 87.5% (95% CI 65.9-100.0) with an overall test accuracy of 93.3%. Although larger prospective-retrospective studies are necessary to validate the predictive potential of the test, the negative and positive predicted values for PPD in this study were NPV = 87.5% and PPV = 100%, respectively. CONCLUSIONS: These data indicate that distinct cytokine profiles are associated with different clinical manifestations. The test, which is based on a simple and rapid profiling of cytokine responses by T lymphocytes against allergens, has proven to be a promising laboratory tool, useful for both the identification of previous contact with allergens and the etiologic diagnosis of contact allergies as well as capable of predicting the clinical outcome (development of an allergic or tolerant response).

Allergen Levels in the Hair of Different Cattle Breeds.

BACKGROUND: Cattle are well-known sources of respiratory allergens in agricultural environments. Breed-specific differences in Bos d 2 (a major bovine allergen) levels in cattle hair have been previously suggested but not fully characterized. Therefore, the aim of the current study was to determine whether hair from common cattle breeds differs in protein and allergen content. METHODS: In total, 80 hair samples from 16 different cattle breeds were analyzed. The protein concentration was determined using the Bradford assay. The allergen content was measured using a sandwich ELISA based on polyclonal antibodies against a bovine hair protein extract and a commercial immunoassay based on monoclonal antibodies against Bos d 2. Results are given in micrograms per gram of hair. Statistical analysis was performed using the Kruskal-Wallis test and Spearman's rank correlation. RESULTS: A wide variability in all 3 tested parameters was observed between the individual samples. The protein content differed by about 35-fold (0.3-12 mg/g), the bovine hair allergen content differed by about 500-fold (37-18,553 µg/g), and the Bos d 2 content differed by about 1,200-fold (5-6,323 µg/g). Protein, bovine hair allergen, and Bod d 2 values correlated strongly and significantly with one another. The median Bos d 2/bovine hair allergen ratio was 0.28. No significant differences were found between the most common breeds in Germany (Simmental, Holstein, and Braunvieh) and a group of rare breeds or between female and male animals. CONCLUSIONS: The results confirm a high variability in allergen levels between individual animals but also indicate that allergen production is related neither to the breed nor to gender.

Recent Trends in Occupational Contact Dermatitis.

Occupational contact dermatitis (OCD) remains prevalent among workers and impacts quality of life and workability. The purpose of this review is to summarize the recent advances in occupational contact dermatitis as well as potential hazardous agents in the workplaces causing OCD. The review covers new developments in the epidemiology, etiology, diagnosis, and management of occupational contact dermatitis. This article also provides updated information on the prevalence of work-related skin symptoms and on new contact allergens among working population. It is emphasized that in the context of prevention of OCD, special attention should be focused on the identified high-risk occupational groups, especially healthcare workers and hairdressers starting with the apprentices. Current approaches include working out the standards and guidelines to improve the education, knowledge, diagnosis, and management of OCD based on a multidisciplinary team of medical specialists and an employer.

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.

Decrease in the rate of sensitization and clinical allergy to natural rubber latex.

BACKGROUND: In the 1980s, a striking increase in natural rubber latex (NRL) allergy was seen. Since then, many measures have been taken to prevent NRL allergy. OBJECTIVES: To investigate changes in the prevalence of NRL sensitization/clinical NRL allergy over time from 2002 to 2013. METHODS: All patients prick tested for NRL at the Department of Dermatology and Allergy Centre, Odense University Hospital were included in this study (n = 8580). In NRL-sensitized patients, the clinical relevance was evaluated for NRL. Furthermore, concomitant positive prick test results for birch pollen were recorded, together with food-related symptoms and sensitization in a subgroup of patients. RESULTS: The prevalence of NRL sensitization declined from 6.1% in 2002-2005 to 1.9% in 2006-2009, and then to 1.2% in 2010-2013 (p < 0.0001). The prevalence of clinical NRL allergy declined from 1.3% in 2002-2005 to 0.5-0.6% in 2006-2013 (p < 0.004). Among the NRL-sensitized patients, 64% had a concomitant positive prick test reaction to birch pollen, and 52% had a history of reaction to oral intake of related fruits or vegetables. CONCLUSION: Our study showed a statistically significant decline in the number of patients sensitized/clinically allergic to NRL. Many of the NRL-sensitized patients without clinical allergy to NRL had concomitant birch pollen sensitization, and reported food-related symptoms.

[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.

[Anaphylactic reactions to low-molecular weight chemicals]. / Reakcje anafilaktyczne na substancje chemiczne o malej masie czasteczkowej

Low-molecular weight chemicals (haptens) include a large group of chemical compounds occurring in work environment, items of everyday use (cleaning products, clothing, footwear, gloves, furniture), jewelry (earrings, bracelets), drugs, especially in cosmetics. They cause type IV hypersensitive reactions. During the induction phase of delayed-type hypersensitivity, haptens form complexes with skin proteins. After internalization through antigen presenting cells, they are bound to MHC class II molecules. Next, they are exposed against specific T-lymphocytes, what triggers activation of Th1 cells mainly. After repeating exposition to that hapten, during effector phase, Th1 induce production of cytokines affecting non-specific inflammatory cells. Usually, it causes contact dermatitis. However, occasionally incidence of immediate generalized reactions after contact with some kinds of haptens is noticed. A question arises, how the hapten does induce symptoms which are typical for anaphylaxis, and what contributes to amplification of this mechanism. It seems that this phenomenon arises from pathomechanism occurring in contact urticaria syndrome in which an anaphylactic reaction may be caused either by contact of sensitized skin with protein antigens, high-molecular weight allergens, or haptens. One of the hypotheses indicates the leading role of basophiles in this process. Their contact with haptens, may cause to release mediators of immediate allergic reaction (histamine, eicosanoids) and to produce cytokines corresponding to Th2 cells profile. Furthermore, Th17 lymphocytes secreting pro-inflammatory interleukin-17 might be engaged into amplifying hypersensitivity into immediate reactions and regulatory T-cells may play role in the process, due to insufficient control of the activity of effector cells.

Occupational skin allergies: testing and treatment (the case of occupational allergic contact dermatitis).

Occupational contact dermatitis, including occupational allergic contact dermatitis, is one of the most common occupational diseases. Making a timely and accurate diagnosis is important to improving the outcome. Taking a work history and patch testing are essential elements in the diagnostic process. Management, based on an accurate diagnosis, must include both medical treatment to address the disease and workplace modifications as appropriate to reduce exposure the causative agents.

Reaction profile in patch testing with allergens formed during vulcanization of rubber.

BACKGROUND: Vulcanization of rubber changes its allergen pattern. OBJECTIVES: To estimate the contact allergic reactivity profile of users of finished rubber products. METHODS: Twenty-four patients with known contact allergy to rubber accelerators were patch tested with 21 compounds found in chemical analyses of vulcanized rubber products. No diphenylguanidine, p-phenylenediamine antioxidants or thioureas were included in the study. RESULTS: Thiuram monosulfides formed during vulcanization showed generally stronger test reactions than the corresponding thiuram disulfides. We also obtained more positive thiuram reactions to the monosulfides than to the disulfides. A positive reaction to a dithiocarbamate was accompanied by a positive reaction to the corresponding thiuram, except for 1 patient. The nitrogen substituents showed only minor differences between the methyl, ethyl and pentamethylene groups, but the butyl derivatives gave, in most cases, a negative response. Dialkylthiocarbamyl benzothiazole sulfides, formed between thiurams and mercaptobenzothiazoles during vulcanization, showed strong test reactions in almost all patients who were sensitive to dithiocarbamates, thiurams, or mercaptobenzothiazoles. CONCLUSIONS: We found thiuram monosulfides to be better markers of thiuram sensitivity than the corresponding disulfides or dithiocarbamates. Surprisingly, the dialkylthiocarbamyl benzothiazole sulfides were good markers of both thiuram and mercaptobenzothiazole sensitivity. This is an unexpected finding that needs to be confirmed in a larger study.

No remarkable differences in rates of sensitization to common type I and IV allergens between FLG loss-of-function mutation carriers and wild-type subjects.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) have been associated with reduced skin barrier function, possibly allowing increased penetration of irritants and allergens. OBJECTIVES: To study whether FLG loss-of-function mutation carriers show different rates of sensitization to common type I and IV allergens among patients referred for occupational contact dermatitis of the hands. MATERIALS AND METHODS: Four hundred and ninety-six Caucasian patients were genotyped for four FLG null mutations and patch tested with the European baseline series. In addition, 431 patients underwent prick testing with common type I allergens. RESULTS: Overall, 67 patients showed a heterozygous mutation in the FLG alleles R501X, R2447X, S3247X, and/or 2282del4. Sensitization rates for type I allergens from a European prick test series did not show significant differences between FLG loss-of-function mutation carriers and wild-type subjects. For type IV allergens, significantly more FLG loss-of-function carriers were found to be sensitized to lanolin and p-tert-butylphenol-formaldehyde resin. CONCLUSIONS: Probably a variety of immunological mechanisms other than that resulting from the filaggrin system have an impact on allergic sensitization to a greater degree. Larger cohorts may be necessary to increase the statistical power of the findings presented regarding type I and IV sensitization.

Japanese Guideline for Occupational Allergic Diseases 2014.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Peptide-binding motifs and characteristics for HLA -B*13:01 molecule.

Trichloroethylene (TCE)-induced hypersensitivity dermatitis is one of the critical occupational diseases among workers in China. Our previous studies have identified a strong linkage between the disease and the HLA-B*13:01 allele. In this study, we searched for peptides bound to the HLA-B*13:01 molecule; 57 HLA-B*13:01-bound peptides in total were identified and 54 peptides were used to calculate frequency of amino acid residues to obtain binding motifs of HLA-B*13:01 molecule. The results showed P2, P3, and P9 were the primary binding anchor positions with the dominant anchor motifs of L, Q at P2, L at P9, D at P3. HLA-B*13:01-bound peptides were identified for the first time in our research, the results of which could contribute to the human leukocyte antigen (HLA)-binding peptides database.

Risk factors of polysensitization to contact allergens.

BACKGROUND: 'Polysensitization' (PS) is usually defined as contact sensitization to three or more unrelated haptens of the baseline patch test series. Despite PS being an important clinical phenotype indicating increased susceptibility to contact allergy, statistical approaches to analyse PS have hitherto been preliminary. OBJECTIVES: To apply an appropriate regression model for count data, namely, negative binomial hurdle regression, to a large set of clinical patch test data with the aim of estimating PS risk in more detail than previously achieved. METHODS: The detailed information provided by the hurdle model includes a separate estimation of an 'increment factor' quantifying the likelihood of further positive reactions, i.e. PS. Clinical data of 126 878 patients patch tested by departments comprising the IVDK (Information Network of Departments of Dermatology) network (www.ivdk.org) between 1995 and 2010 were included. RESULTS: Regarding anatomical sites as exposure (surrogate), the axillae and the feet were found to be strong PS risk factors. Moreover, age was a strong PS risk factor, and less so, female sex. In comparison, atopic eczema and occupational dermatitis were less important risk factors. Single allergens contributed to PS to a varying extent. CONCLUSIONS: The data presented point to some, very likely exposure-related, risk factors which need to be considered in future PS research, e.g. addressing the genetic basis for PS.