Sensitization to thiourea derivatives among Finnish patients with suspected contact dermatitis

Background: Thiourea derivatives in rubber products may induce contact sensitization and allergic contact dermatitis. Sensitization is most often from neoprene rubber, but the multitude of possible sensitizing products has remained poorly characterized. Objective: The aim of this study was to collect information on the occurrence of thiourea‐related contact allergy and to show novel sources of sensitization. Patients and methods: A mixture of dibutyl‐, diethyl‐, and diphenylthiourea was included in patch test baseline series in five Finnish dermatology clinics during 2002–2007. In addition, an extended series of rubber chemicals was tested in patients with suspected rubber allergy. Sources of sensitization to thioureas were analysed in sensitized patients. Results: Thiourea mix yielded positive patch test reactions in 59 of 15 100 patients (0.39%); 33/59 patients were also tested with individual rubber chemicals. Diethylthiourea was positive in 24/33, diphenylthiourea in 5, and dibutylthiourea in 1 patient. The most common sources of sensitization included various neoprene‐containing orthopaedic braces, sports equipment, and foot wear. Conclusions: The sources of sensitization to thiourea chemicals were detected in most cases. These sources comprise a heterogenous group of products extending from orthopaedic materials to sports equipment.     

Allergic contact dermatitis to chlorhexidine

Chlorhexidine is a commonly used antiseptic agent in the health‐care setting. Although exposure to chlorhexidine is very common, allergic contact dermatitis (ACD) is rarely reported. We report a case series of ACD to chlorhexidine in health‐care workers and discuss our rates of allergy to chlorhexidine, from patch‐testing performed at the Skin and Cancer Foundation, Melbourne, Australia. Of 7890 patients patch‐tested, 840 patients were tested to 0.5% chlorhexidine diacetate with 28 (3%) positive reactions, 13 (2%) of which relevant to their presenting dermatitis. Altogether 1565 patients were tested to 0.5% chlorhexidine digluconate, with 47 (3%) positive reactions, 16 (1%) of which were relevant. We estimate our rate of relevant chlorhexidine ACD from our total clinic patients, non‐occupational and occupational, to be at least 19/7890 (0.24%). Our rate of relevant chlorhexidine ACD in health‐care workers is 10/541 (2%). Interestingly, our rates of chlorhexidine allergy are slightly higher than documented elsewhere. This raises the possibility that chlorhexidine is underestimated as an allergen worldwide, and should be tested for in health‐care workers where there is a history of exposure.     

Epidemiological data on consumer allergy to p‐phenylenediamine

Many women and men now dye their hair. p‐Phenylenediamine (PPD) is a frequent and important component of permanent hair dye products; exposure to it may cause allergic contact sensitization, acute dermatitis, and severe facial oedema. To increase our understanding of PPD allergy, we reviewed published literature containing PPD patch test data from dermatitis patients and individuals in the general population. This was performed to estimate the median prevalence and the weighted average of PPD sensitization and thereby assess the burden of PPD‐containing hair care products on health. Literature was examined using PubMed–MEDLINE, Biosis, and Science Citation Index. The median prevalence among dermatitis patients was 4.3% in Asia, 4% in Europe, and 6.2% in North America. A widespread increase in the prevalence of PPD sensitization was observed among Asian dermatitis patients. In Europe, a decrease in the 1970s was replaced by a plateau with steady, high prevalences ranging between 2% and 6%. The prevalence remained high in North America, although a decreasing tendency was observed. Contact allergy to PPD is an important health issue for both women and men. More stringent regulation and enforcement are required as public health measures to reduce the burden of disease that exposure to PPD has brought to populations.     

Allergic Urticaria: A Case Report of Rare Skin Allergy with a Common Mouthwash

Chlorhexidine is a widely used antiseptic and disinfectant in medical and non-medical environments. Compared to its ubiquitous use, allergic contact dermatitis from chlorhexidine has rarely been reported and so its sensitization rate seems to be low. Chlorhexidine has been used for more than 50 years but it was only in the last two decades, that reports of immediate- type reactions to chlorhexidine were seen. Reactions ranging from localized urticaria to anaphylactic shock and hypersensitivity reactions, including delayed hypersensitivity reactions such as contact dermatitis, fixed drug eruptions, and photosensitivity reactions, began to appear more frequently. However the prevalence of contact urticaria and anaphylaxis due to chlorhexidine remains to be unknown. In this case report we have reported a case of urticaria due to oral use of chlorhexidine. The adverse reaction was confirmed by a skin prick test.     

Positive patch test reactions to gentamicin show sensitization to aminoglycosides from topical therapies, bone cements, and from systemic medication

Background: A history of prolonged use of topical antimicrobials is common among patients with positive patch test reactions to gentamicin and to aminoglycosides. Objectives: The aim of this study was to show sources of gentamicin sensitization in patients with positive patch test reactions to gentamicin. Patients and methods: About 7814 patients were patch tested with a baseline patch test series and 620 of them were further tested with gentamicin. The clinical histories, concurrent contact sensitivities, and sources of sensitization are analysed among these patients. Results: Positive patch test reactions to gentamicin were seen in 29/620 patients, most of whom (18/29) also reacted to neomycin and to kanamycin (7/29). Mean age of the gentamicin‐positive patients was 62 years, but three young operating room nurses with hand dermatitis had a history of gentamicin exposure from bone cement. Among the 11/29 neomycin‐negative patients, a history of exposure to different aminoglycosides was apparent, and one patient had a history of systemic netilmicin‐medication‐associated exanthema. Conclusions: Positive patch test reactions to gentamicin reflect sensitization to different aminoglycosides for which gentamicin seems to represent a sensitive indicator. Gentamicin sensitization may result from occupational exposure to gentamicin containing bone cements or from systemic medication with aminoglycosides.     

Formaldehyde exposure and patterns of concomitant contact allergy to formaldehyde and formaldehyde‐releasers

Background: Formaldehyde and formaldehyde‐releasers are widely used in consumer products and may often cause contact allergy. Objective: To investigate the prevalence of concomitant contact allergy to formaldehyde and formaldehyde‐releasers in dermatitis patients, and to determine the sources of formaldehyde exposure based on personal and occupational products obtained from dermatitis patients. Methods: Patch test data from referred dermatitis patients with a positive patch test reaction to formaldehyde or formaldehyde‐releasers were analysed. For the period 2000–2008, the formaldehyde content in products obtained from formaldehyde‐allergic patients was analysed by chromotropic acid test and/or acetylacetone test. Results: Patients allergic to a formaldehyde‐releaser often had simultaneous contact allergy to formaldehyde. Other combinations were also prevalent. In patients who reacted to more than two formaldehyde‐releasers, nearly all reacted simultaneously to formaldehyde. Seventy‐five percent of the formaldehyde‐allergic patients used a product that contained formaldehyde. The main source of formaldehyde exposure was cosmetics (78%). Conclusions: Concomitant contact allergy to formaldehyde and formaldehyde‐releaser remains common. Furthermore, contact allergy to a formaldehyde‐releaser was nearly always concomitant with another formaldehyde‐releaser. Formaldehyde was commonly found in personal products used by formaldehyde‐allergic patients.     

Contact allergy to epoxy resin: risk occupations and consequences

Background. Epoxy resin monomers are strong skin sensitizers that are widely used in industrial sectors. In Denmark, the law stipulates that workers must undergo a course on safe handling of epoxy resins prior to occupational exposure, but the effectiveness of this initiative is largely unknown. Objectives. To evaluate the prevalence of contact allergy to epoxy resin monomer (diglycidyl ether of bisphenol A; MW 340) among patients with suspected contact dermatitis and relate this to occupation and work‐related consequences. Patients/methods. The dataset comprised 20 808 consecutive dermatitis patients patch tested during 2005–2009. All patients with an epoxy resin‐positive patch test were sent a questionnaire. Results. A positive patch test reaction to epoxy resin was found in 275 patients (1.3%), with a higher proportion in men (1.9%) than in women (1.0%). The prevalence of sensitization to epoxy resin remained stable over the study period. Of the patients with an epoxy resin‐positive patch test, 71% returned a questionnaire; 95 patients had worked with epoxy resin in the occupational setting, and, of these, one‐third did not use protective gloves and only 50.5% (48) had participated in an educational programme. Conclusion. The 1% prevalence of epoxy resin contact allergy is equivalent to reports from other countries. The high occurrence of epoxy resin exposure at work, and the limited use of protective measures, indicate that reinforcement of the law is required.     

Myroxylon pereirae resin (balsam of Peru) – A critical review of the literature and assessment of the significance of positive patch test reactions and the usefulness of restrictive diets

In this article, contact allergy to Myroxylon pereirae resin (MP) (balsam of Peru) is reviewed. The topics presented include the uses, the chemical composition, the frequency of sensitization, the relevance of positive reactions, the MP‐containing products causing allergic contact dermatitis, co‐reactivity with other fragrance and non‐fragrance materials, the sensitizers, the usefulness of MP as a “marker” of fragrance allergy, and the effectiveness of, and indications for, “balsam‐restrictive” diets. Sensitization to MP occurs in 4% to 8% of patients routinely tested for suspected contact dermatitis. There are few adequate data on relevance. Topical pharmaceuticals were formerly, but are not today, important sources of sensitization. Cosmetics and foods or drinks are hardly ever products responsible for sensitization to MP. Positive patch test reactions in the large majority probably result from previous sensitization to MP constituents because of their presence in fragrances and fragranced products, MP thereby acting as marker (or “indicator”) of fragrance allergy. However, fragrance mix I is a more sensitive marker, and the added diagnostic value of testing with MP is unknown. The allergenic ingredients of MP include isoeugenol, eugenol and cinnamyl alcohol, but there are other—largely unknown—chemicals that are responsible for contact allergy. Suggestions are given for further research to address questions thus far unanswered and to improve patient care.     

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.     

Occupational contact allergy to cocamidopropyl betaine and its impurities

Background. Contact allergy to cocamidopropyl betaine has been attributed to its impurities dimethylaminopropylamine and cocamidopropyl dimethylamine. Objectives. To describe patients with positive patch test reactions to cocamidopropyl betaine‐related compounds in an occupational dermatology clinic. Methods. We reviewed the 2002–2009 patch test records at the Finnish Institute of Occupational Health for allergic reactions to cocamidopropyl betaine, dimethylaminopropylamine, cocamidopropyl dimethylamine, and oleamidopropyl dimethylamine. Results. Irritant reactions to at least one of the test substances were seen in 39% of the 1092 patients tested. Fifteen (1.3%) patients showed allergic reactions: 13 to cocamidopropyl dimethylamine, 11 to dimethylaminopropylamine, 8 to oleamidopropyl dimethylamine, and 2 to cocamidopropyl betaine. Concomitant reactions to cocamidopropyl dimethylamine, dimethylaminopropylamine and oleamidopropyl dimethylamine were common. Ten of the 15 patients were diagnosed with occupational allergic contact dermatitis caused by cocamidopropyl betaine‐related compounds. The sources of occupational exposure included hair care products, hair colours, perm wave solutions, and liquid soaps. Multiple contact allergies and exposure to several irritant factors were common, and all patients had hand eczema. Conclusions. Patch test reactions to cocamidopropyl betaine‐related compounds are difficult to interpret, owing to extremely common irritant reactions. Cocamidopropyl betaine itself is probably not an allergen. Occupational allergic contact dermatitis caused by cocamidopropyl betaine‐related compounds is relatively rare and, unlike non‐occupational cocamidopropyl betaine‐related allergy, typically manifests as hand dermatitis.     

Allergic contact dermatitis to chlorhexidine-containing antiseptics and their excipients in children: A series of six cases

Contact allergy to skin disinfectants is not often recognized in children. We report the cases of six children (1–16.5 years old) with allergic contact dermatitis to ingredients commonly contained in commercial antiseptic and cosmetic products. Patch test responses to chlorhexidine, benzyl alcohol, and benzalkonium chloride varied from one child to another one, but most children were sensitized to at least two components. In several of the cases, exposure had initially occurred in the neonatal period, but diagnosis occurred only after multiple reactions of increasing severity.     

Allergic contact dermatitis to proparacaine with subsequent cross-sensitization to tetracaine from ophthalmic preparations.

We report 2 cases of allergic contact dermatitis (ACD) to proparacaine and tetracaine. Patient 1 is an ophthalmologist with chronic finger pad dermatitis sensitized to the topical anesthetic proparacaine. Despite discontinuance of proparacaine and substitution with a patch test negative agent, tetracaine, his hand dermatitis persisted. Follow up patch testing documented that acquisition of contact allergy to tetracaine as well as thiuram had taken place. Patient 2 had a periocular eczematous dermatitis with ACD to both proparacaine and tetracaine. Cross sensitization between related topical ophthalmologic anesthetics has been suggested to be a rare occurrence. We suggest that allergic sensitization and possible cross-reaction to topical anesthetics in ophthalmologists and ophthalmologic technicians is an occupational hazard. Chronically eczematized skin might result in increased exposure to contact allergens and result in concomitant allergic sensitization. ACD to topical anesthetic agents among ophthalmologists should be recognized as a potential hazard.     

Formaldehyde-releasers: relationship to formaldehyde contact allergy. Contact allergy to formaldehyde and inventory of formaldehyde-releasers

This is one of series of review articles on formaldehyde and formaldehyde-releasers (others: formaldehyde in cosmetics, in clothes and in metalworking fluids and miscellaneous). Thirty-five chemicals were identified as being formaldehyde-releasers. Although a further seven are listed in the literature as formaldehyde-releasers, data are inadequate to consider them as such beyond doubt. Several (nomenclature) mistakes and outdated information are discussed. Formaldehyde and formaldehyde allergy are reviewed: applications, exposure scenarios, legislation, patch testing problems, frequency of sensitization, relevance of positive patch test reactions, clinical pattern of allergic contact dermatitis from formaldehyde, prognosis, threshold for elicitation of allergic contact dermatitis, analytical tests to determine formaldehyde in products and frequency of exposure to formaldehyde and releasers. The frequency of contact allergy to formaldehyde is consistently higher in the USA (8–9%) than in Europe (2–3%). Patch testing with formaldehyde is problematic; the currently used 1% solution may result in both false-positive and false-negative (up to 40%) reactions. Determining the relevance of patch test reactions is often challenging. What concentration of formaldehyde is safe for sensitive patients remains unknown. Levels of 200–300 p.p.m. free formaldehyde in cosmetic products have been shown to induce dermatitis from short-term use on normal skin.     

Contact dermatitis from methylisothiazolinone in a paint factory

Introduction of new potential contact-sensitizing chemicals have in the past led to epidemics of contact dermatitis. A new preservative containing only methylisothiazolinone (MI) and not methylchloroisothiazolinone (MCI) has recently been introduced in the European Union for use in products, such as paint, glue and cosmetics. The objective of this article is to describe a factory outbreak of contact allergy to MI and MCI preservatives. This factory outbreak describes allergic contact dermatitis towards MI in 4 patients of 14 persons working at a paint manufacturer. Patch test results from all patients showed positive reactions for MI and MCI/MI. The reactions were stronger for MI than MCI/MI indicating a primary sensitization to MI. The combination of MCI/MI remains widely used, and therefore various patterns of exposure and sensitization could be seen in the future. Our data show that MI holds a potential for eliciting and propably inducing contact allergy in humans. Whether this preservative is safe to use in cosmetics where billions of consumers are exposed needs a care full monitoring.     

Contact allergy to oxidized d-limonene among dermatitis patients

d -Limonene. obtained as a by-product from the citrus juice industry was introduced on the market as a more environmentally friendly defatting and cleaning agent than the traditionally used organic solvents. Autoxidation of d -limonene readily occurs to give a variety of oxygenated monocyclic terpenes that are strong contact allergens. The aim of the present study was to investigate the prevalence of contact allergy to air exposed d-limonene among dermatitis patients. A fraction consisting of d-limonene hydroperoxides was also tested. Screening with oxidized d-limonene will detect cases of allergic contact dermatitis. Additional cases were detected when testing with the fraction of limonene hydroperoxides. The proportion of positive patch test reactions to oxidized d-limonene was comparable to that seen for several of the allergens within the standard series. An increased UAT of d-limonene containing allergenic oxidation products in industry where high concentrations are used, as well as in domestic exposure, might result in contact sensitization and dermatitis. Patients reacting to d-limonene often reacted to fragrance mix, balsam of Peru and colophony in the standard series.     

Deodorants: an experimental provocation study with isoeugenol

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.     

Occupational allergic contact dermatitis due to coconut diethanolamide (cocamide DEA)

Coconut diethanolamide (CDFA). manufactured from coconut oil, is widely used as a surface-active agent in hand gels. hand-washing liquids, shampoos, and dish-washing liquids. CD HA has rarely caused allergic contact dermatitis. During NS5 IW2, we investigated 6 patients with occupational allergic contact dermatitis caused by CDEA. 2 became sensitized from a barrier cream, 3 from a hand-washing liquid, and 1 had been exposed both to a hand-washing liquid and to a metalworking fluid containing CDEA. Leave-on products (hand-protection foams) caused sensitization much more rapidly (2 3 months) than rinse-off products (hand-washing liquids: 5–7 years). Due to the extensive use of CDEA and the lack of proper declaration of products, it is difficult to avoid CDEA exposure. No contact allergy to another coconut-oil-derived sensitizer (cocamidopropyl betaine) was found in the patients.     

Cobalt release from implants and consumer items and characteristics of cobalt sensitized patients with dermatitis

Background. Cobalt allergy is prevalent in dermatitis patients. Very little documentation exists about current sources of cobalt exposure. Objectives. To investigate and discuss putative sources of cobalt exposure and to present selected epidemiological data on cobalt allergy from patch‐tested dermatitis patients in an attempt to better understand cobalt allergy. Materials and methods. 19 780 dermatitis patients aged 4–99 years were patch tested with nickel, chromium or cobalt between 1985 and 2010. The cobalt spot test was used to test for cobalt ion release from mobile phones as well as cobalt‐containing dental alloys and revised hip implant components. Results. Six of eight dental alloys and 10 of 98 revised hip implant components released cobalt in the cobalt spot test, whereas none of 50 mobile phones gave positive reactions. The clinical relevance of positive cobalt test reactions was difficult to determine in the majority of patients. Isolated patch test reactivity to cobalt was less associated with occupational dermatitis and hand eczema than patch test reactivity to cobalt in combination with other contact allergies. Conclusions. It is often difficult to interpret the relevance of a positive patch test reaction to cobalt, and there is a need for further studies to determine sources of cobalt exposure.     

Allergic contact dermatitis from fragrance components in specific topical pharmaceutical products in Belgium

Objectives:  To determine which topical pharmaceutical products marketed in Belgium contain fragrances and to examine the nature of the fragrance allergens in specific pharmaceutical products having caused iatrogenic contact dermatitis.
Methods:  All topical pharmaceutical products marketed in Belgium, that is 3820 products, were examined as to their fragrance content as labelled. Data of 18 960 patients investigated for contact allergy between 1978 and 2008 were retrieved from our database, including information on the nature of the topical pharmaceutical products used, the results of patch tests, and the sensitization sources.
Results:  Three hundred and seventy (10%) of 3280 of the topical pharmaceutical products were found to contain a total of 66 fragrance substances. Among 3378 patients suffering from iatrogenic allergic contact dermatitis, 127 were found to react to 48 specific products, for which 38 different fragrance substances gave relevant positive reactions. Women were more affected than men, and legs, hands, and face were the most commonly affected body sites.
Conclusions:  Fragrances, the presence of which is in most cases unnecessary, do contribute to iatrogenic allergic contact dermatitis. Moreover, sensitized patients have difficulties in avoiding their specific allergens because standardized labelling of the ingredients in pharmaceutical products is lacking.     

Contact sensitization to 4,4'-diaminodiphenylmethane and to isocyanates among general dermatology patients

Background:  Diisocyanates and 4,4'-diaminodiphenylmethane (MDA) are industrial sensitizers. Occupational asthma is a risk among workers exposed to diisocyanates. Exposure may also lead to contact sensitization and allergic contact dermatitis.
Objective:  The aim of this study was to determine the occurrence of contact sensitization to MDA and to diisocyanates among general dermatology patients.
Patients and methods:  Patch testing with MDA was carried out in 1595 patients. Diphenylmethane-4,4'-diisocyanate (MDI) and toluene-2,4-diisocyanate (TDI) were tested in 1023 patients and isophorone diisocyanate (IPDI) and 1,6-hexamethylene diisocyanate (HDI) in 433 patients. The clinical data and sources of exposure are analysed.
Results:  MDA reactions were seen in 17 (1.1%) patients and MDI reactions in 4 patients. Six MDA-positive patients reacted to p -phenylenediamine and two to epoxy chemicals. 5/10 of the TDI reactions were seen concurrently with reactions to MDI, MDA, HDI, or to IPDI. IPDI reactions were seen in eight patients and HDI reactions in two patients. Possible sources of exposure were traced in most patients, although the association with the current dermatitis was not apparent in all cases.
Conclusion:  (Di)isocyanates may induce contact sensitization with or without allergic contact dermatitis.