Causal relationship between humidifier disinfectant exposure and Th17-mediated airway inflammation and hyperresponsiveness.

In this study, we investigated whether humidifier disinfectants (HDs) induce asthmatic airway inflammation in an animal model and compared the features of HD-induced inflammatory symptoms with ovalbumin (OVA)-induced allergic asthma. Mice were intratracheally instilled three times with either the control or 0.1, 0.3, or 0.5 mg/kg of polyhexamethylene guanidine phosphate (PHMG-P). To characterize asthmatic features, the following parameters were analyzed: (i) differential cell counts and cytokine expression in the bronchoalveolar lavage fluid (BALF); (ii) presence of mucus-producing goblet cells and pulmonary eosinophilic infiltration in the lungs; (iii) serum immunoglobulin levels; and (iv) airway hyperresponsiveness (AHR). RNA-Seq and bioinformatics tools were used to investigate whether PHMG-P altered asthma-related gene expression in lung tissues. The PHMG-P exposure groups showed higher peribronchial/perivascular inflammation, elevated goblet cell hyperplasia, and inhaled methacholine-induced airway resistance. Additionally, IL-13 and IL-17 in BALF were significantly increased in the PHMG-P exposure groups. However, there were no significant differences in total serum IgE and BALF IL-4 and IL-5 levels in the PHMG-P exposure groups compared to the control group. PHMG-P exposure modulated the expression of genes related to Th17 signaling pathways including the IL-17A, IL-23, and STAT3 signaling pathways, but not the Th2 signaling pathway. Altogether, our results suggest that repeated exposure to low does PHMG-P induces asthma-like symptoms and is thus a possible risk factor for developing asthma. The PHMG-P-induced asthmatic airway inflammation showed a different pattern from that found in typical allergic asthma and may be related to irritant-induced airway inflammation and hyperresponsiveness characterized by Th2-low, Th17-related, IgE-independent, and mixed granulocytic features.

A Case of Severe Anaphylaxis to Polyhexanide: Cross-Reactivity between Biguanide Antiseptics.

We present the case of a 77-year-old female patient who suffered from severe anaphylaxis during wound care. Allergologic evaluation yielded specific IgE antibodies to chlorhexidine, but anaphylaxis to chlorhexidine was not congruent with the patient history and dermal provocation tests. However, skin prick tests provided evidence for a sensitization to polyhexanide that was further supported by the detection of specific IgE antibodies to polyhexanide, the results of basophil activation tests and IgE inhibition analysis. We presume cross-reactive IgE antibodies binding to both biguanide antiseptics and identified polyhexanide as the likely cause of the anaphylactic reaction. We recognize polyhexanide as an emerging allergen that has to be considered as a cause of anaphylaxis.

Work-related asthma among professional cleaning women.

The job of cleaning has developed dynamically as a working service, and women constitute the majority of all professional cleaning workers. Cleaners are at an increased risk of work-related asthma (WRA). This study characterizes work-related respiratory symptoms reported by female cleaners, evaluates any associated factors of WRA, and shows diagnostic management of medical certification. The study group comprised 50 professional cleaning women referred to our Occupational Diseases Department due to suspicion of occupational asthma (OA). A questionnaire, skin prick tests, serum specific IgE antibodies, and specific inhalant challenge were performed in all of the participants. Work-related asthma was recognized in 46% of symptomatic cleaners, of whom 15 were considered as having work-exacerbated asthma (WEA) and 8 as having OA. Sensitization to latex and disinfectants played an important role as a causative agent in OA of cleaners.

Occupational contact sensitization in female geriatric nurses: Data of the Information Network of Departments of Dermatology (IVDK) 2005-2014.

BACKGROUND: Geriatric nurses (GN) have a high risk of occupational contact dermatitis (OCD), with chronic irritant contact dermatitis predominating. However, allergic contact dermatitis is an important issue as well. Little is known whether the relevant occupational allergen spectrum reported in the 1990s, including fragrances, preservatives, rubber chemicals and ingredients of surface disinfectants to be the most common sensitizers in GN, is still valid. OBJECTIVES: To monitor the current allergen spectrum in GN with OCD and verify the validity of the patch test recommendations (baseline-, preservative-, ointment base-, rubber-, disinfectant, series and fragrances) in GN with suspected OCD given by the German Contact Dermatitis Research Group (DKG). METHODS: Retrospective analysis of IVDK data (2005-2014) of 743 female GN with OCD, in comparison to 695 GN without OCD. RESULTS: GN with OCD reacted significantly more frequently to both fragrance mixes, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), thiuram mix, zinc diethyldithiocarbamate and mercaptobenzothiazole than GN without OCD. Reactions to MDBGN, methylchloroisothiazolinone/methylisothiazolinone and oil of turpentine occurred substantially, but not significantly more frequently among GN with OCD. The latter may be due to former use of a special alcoholic liniment in geriatric care. Among material from the patients' workplaces, tetrazepam was a frequent allergen, due to dust exposure from pill crushing. Furthermore, occupationally used protective gloves, body care products as well as surface disinfectants were often tested positively. CONCLUSIONS: The general allergen spectrum in GN with OCD is unchanged, so the DKG patch test recommendations are still valid. Prevention of occupational sensitization should focus on fragrance-free hygiene and body care products, usage of accelerator-free protective gloves and avoidance of drug dust exposure.

American Contact Dermatitis Society Contact Allergy Management Program: An Epidemiologic Tool to Quantify Ingredient Usage.

BACKGROUND: The usage prevalence of ingredients in topical products is important to dermatologists and industry. OBJECTIVE: To determine the prevalence of methylisothiazolinone (MI) in various types of consumer products METHODS: The Contact Allergy Management Program (CAMP) database was mapped and sorted in spreadsheet format to determine the prevalence of MI in various types of consumer products. RESULTS: Methylisothiazolinone was found in 13.2% of 4660 total products in CAMP. High usage of MI was seen in dishwashing products (64%), shampoos (53%), bathroom/kitchen/all-purpose cleaners (47%), hair conditioners (45%), hair dyes (43%), laundry additives/fresheners/softeners (30%), soaps/cleansers (29%), and surface cleaners/disinfectants (27%). Of the products containing MI, MI alone (without methylchloroisothiazolinone) was most common in makeup products (100%), cleaning/dish/laundry products (>99%), moisturizers (82%), shaving products (78%), sunscreens (71%), and antiaging products (67%). CONCLUSIONS: The American Contact Dermatitis Society's CAMP is a valuable tool to collect epidemiologic data on the incidence of specific ingredient usage in various types of topical products.

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.

Occupational contact allergy in nurses: results from the Information Network of Departments of Dermatology 2003-2012.

BACKGROUND: Healthcare workers are occupationally exposed to various allergens in protective gloves, surface or instrument disinfectants, drugs, and skin care products. An increased prevalence of sensitization to thiurams, glutaraldehyde, formaldehyde and glyoxal in nurses with occupational contact dermatitis (OCD) has been known since the 1990s. OBJECTIVES: To update the range of occupational allergens in healthcare professionals. METHODS: We retrospectively analysed patch test data from the Information Network of Departments of Dermatology (IVDK), 2003-2012. Patch test results from 2248 nurses with OCD were compared with those of 2138 nurses without OCD. RESULTS: Significantly increased sensitization rates were found for thiuram mix (6.7%), potassium dichromate (5.7%), methylchloroisothiazolinone/methylisothiazolinone (4.4%), colophonium (3.4%), 2-bromo-2-nitropropane-1,3-diol (1.7%), and zinc diethyldithiocarbamate (1.7%). Patch testing with products from the patients' workplaces gave additional clues to further allergens, for example tetrazepam. CONCLUSIONS: The known range of contact sensitization in nurses with OCD has been confirmed. Formaldehyde allergy seems to be less important today. Drugs such as tetrazepam are occupational sensitizers in nurses. The increase in chromium sensitization remains unexplained.

Work-related respiratory symptoms among health centres cleaners: a cross-sectional study.

OBJECTIVES: Several studies, mostly based on questionnaire-derived data, have shown an increased risk of allergic diseases, especially asthma, among cleaners. The risk factors and etiological mechanisms are still being investigated. Occupational exposure to various chemical and biological agents may induce specific sensitization and/or irritant effects. The aim of our study was to estimate the prevalence of work-related symptoms suggesting the presence of allergic disease reported by cleaners, and to relate them to the results of commercially available and standardized objective tests used for screening detection of occupational sensitization and chronic respiratory disorders. MATERIAL AND METHODS: A cross-sectional study was performed among 142 Polish workers of cleaning service in their workplaces. A detailed questionnaire, skin prick tests to common allergens and chemicals used by these workers for cleaning purposes (chloramine T, chlorhexidine, formaldehyde, glutaraldehyde, benzalconium chloride), total and specific serum IgE antibodies to disinfectants and rest spirometry were performed in all the subjects. RESULTS: Fifty nine percent of all the subjects declared occurrence of at least 1 symptom suggesting allergic ailment during cleaning activities at work. Skin prick tests and specific serum IgE antibodies to disinfectants were negative in all the subjects. In 8 cases wheezing was detected during auscultation, but only in 5 of them obstructive pattern in rest spirometry was found. CONCLUSIONS: Occupational allergic causation of symptoms among cleaners could be less likely than work-related symptoms associated with exacerbations of new-onset or pre-existing respiratory diseases. Therefore, in this group of workers, mainly the non-specific irritant impact of chemicals on airways should be taken into consideration.

Methylisothiazolinone: a case of perianal dermatitis caused by wet wipes and review of an emerging pediatric allergen.

Methylisothiazolinone (MI) is a preservative found in cosmetic, personal hygiene, and industrial products. It has been characterized as a moderate to strong sensitizer and is an emerging allergen in the pediatric population. We discuss a case of perianal dermatitis in a child caused by contact allergy to MI-containing wet wipes.

Contact dermatitis in the cleaning industry.

PURPOSE OF REVIEW: The review summarizes recent findings on contact dermatitis in the cleaning industry. RECENT FINDINGS: Contact dermatitis is still an important issue in cleaning. Recent studies identified cleaning work sites and tasks, as well as specific cleaning products, which incur a risk increase for occupational contact dermatitis in cleaning. Workers involved in cleaning outdoors prevalence ratio [PR 1.85, 95% confidence interval (CI) 1.16-2.96], cleaning common areas of residential buildings (PR 1.77, 95% CI 1.11-2.84), schools (PR 1.84, 95% CI 1.15-2.93) and cleaning building sites (PR 1.87, 95% CI 1.18-2.95) showed significantly higher rates of contact dermatitis. Relevant allergens in cleaning are rubber chemicals and disinfectants. Leading allergens are thiurams (11.6%, 95% CI 9.1-14.1) and formaldehyde (3.4%, 95% CI 2.0-4.7), but contact with metal allergens might also be important. The most likely allergen sources for sensitization against rubber chemicals are protective gloves. High sensitization rates for disinfectants might result from the fact that employees in cleaning often use single-use medical examination gloves while cleaning. These gloves are not resistant to chemicals, which may break through the gloves within a short period of time, depending on glove material and thickness. No differences in sensitization rates and sensitization profiles were seen in cleaners of younger (≤40 years) and older (>40 years) age. SUMMARY: Prevalence of occupational contact dermatitis is still high in cleaning. Irritant contact dermatitis is prevailing, but allergic contact dermatitis is quite frequent, too. Up to now, prevention strategies in cleaning seem to be insufficient.

Allergy to ortho-phthalaldehyde in the healthcare setting: advice for clinicians.

This study summarizes and reviews the available health information on ortho-phthalaldehyde (OPA), a recently introduced and widespread disinfectant for heat-sensitive medical equipment, particularly focusing on its possible immunological effects in the healthcare setting. OPA properties derived from laboratory and clinical studies, and in vivo and in vitro tests for the diagnosis of OPA allergy are described. The available evidence suggests the spreading of OPA as disinfectant in endoscopy units despite the little available scientific evidence on its safety. Indeed, some papers reported on serious adverse reactions to OPA in patients and, to a lesser extent, in exposed workers, and in vivo studies suggested that OPA is a dermal and respiratory sensitizer. Finally, until more definite safety data become available only suggestions on possible preventive measures can be provided.

Effectiveness and immunomodulation of chemotherapeutants against scuticociliate Philasterides dicentrarchi in olive flounder.

Philasterides dicentrarchi is a histophagous scuticociliate causes fatal scuticociliatosis in farmed olive flounder Paralichthys olivaceus. The average monthly prevalence of scuticociliatosis due to P. dicentrarchi infections was increased from May to July (40+/-3.1% to 79.4+/-1.7%) and it decreased from August to November (63+/-2.3% to 30+/-2.6%) in olive flounder farms at Jeju Island, South Korea during 2000-2006. The prevalence of mixed infection along with Vibrio spp. bacterial infection was 49+/-7.2% than that of other mixed infection. At present no effective control measure for P. dicentrarchi infection has been described and large production losses continue. In the present study, formalin, hydrogen peroxide and Jenoclean chemotheraputants were used for bath treatment. Among Jenoclean at a low concentration of 50ppm proved effective. The results were confirmed with in vitro motility assessments and morphological changes scoring system in P. dicentrarchi. On the other hand, similar trend was noted following hydrogen peroxide treatment at this concentration, but formalin was only moderately effective. Either hydrogen peroxide or Jenoclean are the promising compounds effective at low concentrations with short application time for P. dicentrarchi. Therefore, these substances were evaluated on day 10, 20 and 30 for their ability to enhance innate immune response and disease resistance against P. dicentrarchi in olive flounder after chemotheraputants bath treatment with 100ppm for 30min per day. All the tested immune parameters were enhanced by treatment with Jenoclean, but not formalin and hydrogen peroxide. These findings suggest that Jenoclean bath treatment can be used for ensuring the heath of cultured marine fish against internal parasites such as P. dicentrarchi.

Spa contact dermatitis.

Potassium monopersulfate (MPS) is widely used in spa and pool "shock" treatments, yet contact dermatitis associated with MPS has been rarely reported. A patient presented with a generalized scattered dermatitis from the neck down that worsened after spa use. Patch testing elicited a ++ reaction to ammonium persulfate. Contact with ammonium persulfate was ruled out; however, MPS, which can cross-react with ammonium persulfate, was found to be the active ingredient in the patient's spa shock treatments. The dermatitis cleared after the patient switched to a hydrogen peroxide-based shock treatment.

Different regulation of T helper 1- and T helper 2-promoting cytokine signalling factors in human dendritic cells after exposure to protein versus contact allergens.

Cytokine-dependent T helper 1 (Th1) differentiation versus T helper 2 (Th2) differentiation is controlled by distinct transcription factors. Previously, we have demonstrated that immature human dendritic cells (DC) from blood donors with allergies show rapid phosphorylation of the Th2-associated signal transducer and activator of transcription 6 (STAT6) upon contact with protein allergens. In the present study we investigated whether this process is regulated by the downstream molecules suppressor of cytokine signalling (SOCS) and/or by the factors T-bet and GATA3. Therefore, immature DC of grass or birch pollen-allergic donors were treated with the respective Th2-promoting protein allergens, and, for comparison, with the Th1-promoting contact allergen 5-chloro-2-methylisothiazolinone plus 2-methylisothiazolinone (MCI/MI) or with the antigen tetanus toxoid. Changes in the mRNA levels of SOCS1, SOCS3, T-bet and GATA3 were analysed by quantitative real-time polymerase chain reaction. Exposure of DC to protein allergens led to the up-regulation of the Th2-associated genes SOCS3 and GATA3, whereas the contact allergen MCI/MI preferentially enhanced the expression of the Th1-associated gene T-bet. Treatment of immature DC with the antigen tetanus toxoid increased both Th1- and Th2-associated genes. Our data indicate that polarization of type 1 versus type 2 immune responses takes place already at the level of antigen-presenting cells, involving molecules similar to those used in T-cell polarization.

IgE-mediated allergy to chlorhexidine.

BACKGROUND: Investigations at the Danish Anesthesia Allergy Centre have included testing for allergy to chlorhexidine since 1999. OBJECTIVE: To investigate whether measurement of IgE and histamine release confirm an IgE-mediated mechanism for chlorhexidine allergy. METHODS: Twenty-two patients with clinical history suggestive of chlorhexidine allergy were included. Skin tests with chlorhexidine and tryptase measurements were performed during initial investigations. Sera were analyzed retrospectively for IgE and histamine release (passive sensitization) to chlorhexidine. RESULTS: Twelve patients were skin test positive and 10 were skin test negative. Of the skin test-positive patients, 11 of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test. None of the skin test-negative patients had specific IgE or positive histamine release to chlorhexidine. Skin test-positive patients had higher median age (64 vs 49 y) and were mainly male (11/12 vs 6/10). In both groups, 8 patients had hypotension, but bronchospasm mainly appeared in skin test-negative patients (1/12 vs 6/10). Reactions occurred more often during urologic surgery in skin test-positive patients (5/12 vs 0/10). Baseline tryptase was higher in skin test-positive patients (median, 11.5 vs 3.7 microg/L), and 6 of 7 patients had elevated IgE to chlorhexidine in serum at the time of reaction. CONCLUSION: This study confirms that chlorhexidine allergy is IgE-mediated and that measurement of specific IgE and histamine release are good adjuncts to skin testing in patients with clinical history suggesting chlorhexidine allergy. CLINICAL IMPLICATIONS: IgE and histamine release can be used to support the diagnosis of allergy to chlorhexidine.

Three cases of ortho-phthalaldehyde-induced anaphylaxis after laryngoscopy: detection of specific IgE in serum.

BACKGROUND: Ortho-phthalaldehyde (OPA) has recently been used as a disinfectant for various medical apparatuses. OPA is not generally recognized as a potential allergen. CASE SUMMARY: Subsequent to our recent report describing a patient presenting with OPA-induced anaphylaxis following laryngoscopy, we experienced two more such cases. In all three cases, the basophil histamine release test was useful for identifying the allergen as OPA. OPA-specific IgE was successfully detected in the serum of the patients by ELISA. DISCUSSION: Physicians and co-medical workers need to be aware of potential allergens to which patients may be exposed during routine medical procedures.