Recommendation to include methyldibromo glutaronitrile in the European standard patch test series

The preservative methyldibromo glutaronitrilc (MDBGN) is used non-occupationally and occupationally. High contact allergy rates have been reported when tested in consecutive dermatitis patients as well as clinical cases with allergic contact dermatitis. Up till now there has been no agreement on which patch test preparation to use to trace contact allergy to MDBGN. From the year 2005 on, MDBGN at 0.5% w/w in petrolatum is recommended for the European standard patch test series. The choice of 0.5% is based on consideration of rates of contact allergy, doubtful and irritant reactions, as well as on information on clinical relevance represented by results of a repeated open application test, and patch test concentrations to diagnose allergic contact dermatitis from MDBGN in individual cases.     

Detection of contact hypersensitivity to topical corticosteroids with hydrocortisone-17-butyrate

We showed earlier that most patients with contact dermatitis due to corticosteroids show cross-reactions when patch tested with hydrocortisone-17-butyrate (H-17-B). To test whether H-17-B could be used for detecting topical corticosteroid allergy, we screened patients undergoing routine patch testing with H-17-B. Patients with clearly allergic or doubtful/mildly irritant patch test reactions to H-17-B, and with a history suggesting topical corticosteroid allergy, were further tested with a large panel of steroid preparations. 20 out of 4039 patients (0.5%) showed definite allergic test reactions to corticosteroids. A further 165 patients with clinically suspected corticosteroid allergy were directly tested with a panel of steroid preparations; 14 patients showed positive patch test reactions. Altogether, 33 out of 34 patients with corticosteroid allergy had positive test reactions to H-17-B. Inclusion of 1.0% H-17-B in ethanol in the standard patch test series improves the diagnosis of topical corticosteroid hypersensitivity.     

Patch testing with methyldibromo glutaronitrile, a multicentre study within the EECDRG

Contact allergy to and allergic contact dermatitis from methyldibromo glutaronitrile (MDBGN) have frequently been reported. As there has been no agreement on which MDBGN test preparation to use, a study was initiated to help determine the optimal patch test preparation for MDBGN. 2661 consecutively patch tested patients at 11 test clinics representing 9 European countries participated. Petrolatum preparations with MDBGN at 1.0%, 0.5%, 0.3% and 0.1% were inserted in the standard series. Contact allergy rates were noted in the range 4.4-1.1% following decreasing test concentrations. Reactions not fulfilling all criteria to be classified as allergic reactions could represent either weak allergic or irritant reactions, and such reactions were noted in the range 8.2-0.5% with decreasing concentrations. A significant number of these reactions represented weak allergic reactions, as allergic reactions were obtained to higher patch test concentrations in the same individual. Morphologically irritant reactions were noted only for the highest test concentrations. In summary, the contact allergy rates and frequencies of doubtful and irritant reactions vary with the patch test concentration. The final decision on patch test concentration for MDBGN should not only rely on these factors but also include information on patch test concentrations required to diagnose individual cases with allergic contact dermatitis from MDBGN as well as results of repeated open application tests.     

Epidemiological significance of bufexamac as a frequent and relevant contact sensitizer

Bufexumae-containing ointments and creams are widely used by many patients with eczematous disorders as an alternative to topical corticosteroids. Recent studies provide evidence of is notable prevalence of contact sensitization in patch test populations. The aim of this study was to assess the frequency of use of this topically-applied drug by eczema patients in general, and to evaluate its potential to cause allergic contact reactions. 500 routinely patch tested patients (f:m=377:123) were tested with bufexamac 5% and Parfenac® ointment (the only commercial product available in Austria I in addition lo the standard and other series of the German Contact Dermatitis Group. The packaging of the commercial product was shown to the entire study population, to decide whether or not they had ever used this product. In addition, their general practitioner was contacted to verify the anamnestic data. A total of 30 patients agreed (hut they had definitely used bufexamac. 5 others having probably applied it. The indication for and the duration of treatment were noted. Positive and relevant patch test reactions to bufexamac, as well as the bufexamc-containing ointment, ointment, were seen in 2(1 out of these 35 patients (57%). and sensitization occurred even alter short-term application. Our study demonstrates that bufexamac has to be assumed lo be a topical drug with a very high sensitization rate in an unselected patch test population (4% of 500 patients), and should therefore be added to the standard series.     

Comparative frequency of patch test reactions to topical antibiotics

BACKGROUND: Neomycin, clioquinol and fusidic acid are all topical antibiotics widely used in dermatological practice in the U.K., either as a single agent or in combination with topical corticosteroids. However, an adverse effect of topical antibiotics is contact sensitization. OBJECTIVES: To examine the frequency of positive patch test reactions to fusidic acid, clioquinol and neomycin. METHODS: To compare the frequency of allergic patch test reactions over 1 year, we patch tested all patients attending the St John's Institute of Dermatology contact dermatitis clinic for one calendar year with fusidic acid, neomycin and clioquinol. RESULTS: We patch tested 1119 patients. Positive patch test reactions to neomycin were noted in 40 patients (3.6%), compared with eight patients (0.7%) to clioquinol and three patients (0.3%) to fusidic acid. The frequency of medicament allergy to neomycin was thus five times more common than to clioquinol and ten times more common than to fusidic acid. Although fusidic acid is not part of our extended standard series, it is in our medicaments series. Therefore, in the second part of our study, we reviewed all cases of positive patch test reactions to fusidic acid over the last 20 years. We found that the frequency of hypersensitivity has decreased since the early 1980s despite increasing usage; the current average frequency being 1.62 patch-tested patients per year (1.45%) of those patch tested to the medicaments series). The most common diagnosis in such patients was stasis dermatitis (54.2%). CONCLUSIONS: The frequency of fusidic acid allergy in an eczema population is low and is comparable with published data from over 10 years ago.     

Contact allergy to bufexamac

Thirteen cases of contact allergy to bufexamac have been seen since 1976 at the Department of Dermatology of the University of Heidelberg. Most of the patients were women (69%). Nine patients suffered from chronic eczema and four had stasis dermatitis. Four patients had used bufexamac for less than 2 weeks. Based on the case histories, about half of the patients were suspected of having contact allergy to bufexamac. The clinical picture was consistent with that of allergic contact dermatitis; a generalized eruption was observed in two cases. Eight patients had additional sensitizations; three patients were allergic to benzyl alcohol, which is used as a preservative in the bufexamac cream available commercially. Contact allergy to bufexamac seems to be rare; however, it should be considered as a cause of sensitization in patients with chronic eczema, even after short-term application.     

Prevalence of benzocaine and lidocaine patch test sensitivity in Denmark: temporal trends and relevance

Background. Allergens included in the European baseline series should result in positive patch test reactions in at least 1% of a patch test population. Inclusion of local anaesthetics other than benzocaine in the baseline series has previously been debated. Objectives. To investigate temporal trends of benzocaine and lidocaine allergy in dermatitis patients who underwent routine patch testing in a tertiary referral patch test centre, and to clarify and discuss whether lidocaine and benzocaine should be included in routine series. Methods. Dermatitis patients who underwent routine patch testing with benzocaine as a part of the European baseline series between 1985 and 2010 (n = 19 347) and dermatitis patients who underwent routine patch testing with lidocaine between 1994 and 2001 (n = 6265) and between 2007 and 2009 (n = 1360) were included. Results. The overall prevalences of contact allergy were 0.5% (benzocaine), 0.3% (lidocaine for the period 1994–2001), and 0.14% (lidocaine for the period 2007–2009). Current relevance was observed in 10% of those with benzocaine allergy and in 5% of those with lidocaine allergy. Conclusions. Benzocaine and lidocaine allergy is infrequent in Danish dermatitis patients. Lidocaine should only be used for aimed testing, and benzocaine should be removed from the baseline series used in Denmark.     

Retrospective survey of patch testing at department of dermatology and venerology, zagreb university hospital center in zagreb, croatia

Epicutaneous (patch) test is a standard test to confirm contact allergy. During a six-year period (1998-2003), contact allergic dermatitis was diagnosed in 4132 (65%) of 6341 patients using standard patch test with a Croatian series of allergens according to the International Contact Dermatitis Research Group (ICDRG). The most common clinical diagnoses related to contact allergy (male; female) were contact allergic dermatitis (65.4%; 72.2%); atopic dermatitis (15.9%; 11.7%); contact irritant dermatitis (7.0%; 6.6%) and nummular eczematoid dermatitis (4.2%; 2.4%). According to occupation, positive patch test reaction was most commonly observed in workers, whereas 65% of patients showed positive reactions to one or more substances. There was an increased frequency of positive patch test reactions to potassium dichromate, nickel sulfate, thimerosal and neomycine sulfate, along with a significant decrease in the frequency of positive patch test reactions to cobalt chloride, carba mix, wood tars, detergents, parabens mixture, urushiol and rubber mixture. We strongly recommend keeping up-to-date with the epidemiology of contact allergy in Croatia.     

Contact allergy in chronic eczematous lip dermatitis

Chronic eczematous cheilitis comprises a heterogeneous group of disorders, the cause of which often remains obscure. Our object was to investigate the frequency of contact allergy in a cohort of patients with chronic eczematous cheilitis attending a tertiary referral clinic. Patients (106 females and 23 males) with chronic eczematous cheilitis were analyzed retrospectively. All patients were tested with a standard patch test series and a fraction with a dedicated patch test series. Children were also tested with atopy patch tests. Moreover, all patients were investigated for past or current presence of atopic diseases. Patch-test reactions of possible or probable relevance were detected in 84 patients (65.1%; 72 females; median age 40), of uncertain or not relevant significance in 26 (20.1%) and negative in 19 (14.7%). An extended series was necessary to reveal hapten hypersensitivity in 42 patients. The most frequent causes of allergic cheilitis were nickel, fragrances, balsam of Peru, chromium salts and manganese salts, present primarily in cosmetics, dental materials and oral hygiene products. Twenty four patients (18 females; median age 21; 18.6%) were diagnosed as having atopic dermatitis of the lips. Four children had allergic contact cheilitis to haptens or food allergens, whereas six had atopic cheilitis. Twenty one cases (16.3%) were considered irritant contact cheilitis. Allergic contact cheilitis is common in adult patients, with the haptens responsible varying with age. Patients with chronic eczematous cheilitis should undergo extended patch testing.     

Contact allergy to gold in dental patients

Summary Gold sodium thiosulphate (GSTS) In patch test series commonly yields positive reactions. In this study of dental patients, the clinical relevance of these positive reactions, the suitability of gold compounds as patch test materials, and value of the lymphocyte proliferation test in gold contact allergy, were evaluated. The frequency of positive patch test reactions to GSTS was 12·4% in the dental series. Fifty-two patients, only two of whom were male, were studied. Thirteen (25%) had had symptoms from jewellery or dental restorations. However, in most cases gold allergy was subclinical. A 10% aqueous solution of gold sodium thiomalate (GSTM) was almost as good as 0·5% GSTS in petrolatum as a marker of gold contact allergy, but 0·001% potassium dicyanoaurate (PDCA) yielded a high percentage of false-negative results. Seventy-three per cent of the subjects with positive patch tests to GSTS responded to gold compounds in vitro in the lymphocyte proliferation test, whereas 13 controls without gold contact sensitivity were negative. Consistent results in skin and lymphocyte proliferation tests provide support for the concept that gold salt-induced'allergic-like' reactions are truly allergic in nature.     

A clinically relevant contact allergy to methyldibromo glutaronitrile at 1% (0.32 mg/cm) detected by a patch test

Recently, the preservative methyldibromo glutaronitrile (MDBGN) at 0.5% w/w in petrolatum was included in the European standard patch test series based on the studies on chemical stability and consideration of rates of contact allergy, doubtful and irritant reactions as well as information on clinical relevance represented by results of a repeated open application test (ROAT) and patch test concentrations required to diagnose allergic contact dermatitis from MDBGN in individual cases. In this report, a case with a clinically relevant contact allergy to MDBGN, which on the mandatory reading occasion on D3 only was traced by a patch test with MDBGN at 1.0% (0.32 mg/cm2), is presented. The patient suffered from a chronic hand dermatitis, and when the patient stopped using a liquid soap containing MDBGN, the hand dermatitis substantially improved. A ROAT performed in a blinded and controlled way with applications twice daily on the hands with 2 moisturizers with and without MDBGN resulted in a deterioration of the hand dermatitis on the hand to which the MDBGN-preserved moisturizer had been applied.     

Analysis of patients with allergic patch test reactions to a plastics and glues series

839 patients were patch tested with a series of 31 plastics and glues allergens at a dermatologic clinic over a period of 7 years. 52 (6%) had a positive patch test reaction to 1 or more such allergens. Clinic charts of 47 patients (out of 52) were available for the study. All but 3 patients had dermatitis on their hands: 17 had only hand dermatitis. 25 (53%) patients' test results were of present or past relevance to their skin diseases. 11 patients (68%) with occupational allergic contact dermatitis (ACD) and 14 (45%) with non-occupational dermatitis had relevant reactions. p -tertiary-butylphenol-formaldehyde resin was the most common allergen (9 cases). 7 patients reacted to diaminodiphenylmethane. 5 patients, who had colophony allergy, reacted to abietic acid and 4 to abitol. There was no reaction to 14 test substances. Special series, such as this plastics and glues series, reveal the cause of ACD less frequently than standard series. However, there is no other way to confirm allergy to these usually industrial allergens, which can also sensitize through non-occupational exposure during hobby working or through unpolymerized monomer left in the finished plastic product.     

Anogenitaldermatosen – allergische und irritative Auslösefaktoren Analyse von Daten des IVDK1 und Literaturübersicht

Background: Anogenital dermatoses (AGD) are common and often very distressing. Clinically it is often unclear if allergic contact dermatitis or irritant dermatitis is involved. In order to optimize therapy and prophylaxis, it is essential to identify relevant allergens or irritants. Patients and Methods: Data of the Information Network of Departments of Dermatology (IVDK, data center in Göttingen) collected between 1999 and 2003 were analyzed. The anogenital area was involved in 1 168 patients with suspected allergic contact dermatitis. Clinical variables and patch test results were statistically compared with the remaining IVDK patch test population, the latter standardized for age and sex. Results: Allergic contact dermatitis had been suspected prior to patch testing in 39.5 %, while in 24.6 % this diagnosis was eventually confirmed. Irritant contact dermatitis was diagnosed in 11.8 %. Other diagnoses, included balanitis, lichen sclerosus et atrophicus and herpes genitalis. Positive reactions to cinchocaine (6.6 %), bufexamac (3.5 %) and benzocaine (2.4 %) were observed significantly more often among patients with anogenital dermatitis. Among those in whom co‐factors were considered important (n = 422), wetness (38.4 %), occlusion (30.3 %), mechanical strain (4.7 %) and heat (3.6 %) were mentioned as irritation factors. Conclusion: Because of the significantly higher frequency of sensitization to cinchocaine, benzocaine and bufexamac in patients with anogenital dermatitis, these ingredients should be used only with caution. According to the literature, ingredients of toiletries, cosmetics and contraceptives of any kind seem to cause allergic contact dermatitis rarely although there are several case reports. Comprehensive patch test including the standard series plus major sensitizers such as cinchocaine, benzocaine and bufexamac, and in particular patients' own skin care products, is recommended.     

Contact allergy to glucocorticosteroids in patients with chronic venous leg ulcers, atopic dermatitis and contact allergy

The aim of the study was to assess the prevalence of contact allergy to glucocorticosteroids in patients with chronic venous leg ulcers (CVLU), atopic dermatitis (AD) and contact dermatitis (CD), and in a group of healthy individuals; and to estimate differences among these patient groups. Patch tests with the European standard series, antibiotics, glucocorticosteroid contact allergy screening markers and ointment vehicles were performed in a population of 140 patients. Positive patch tests results were recorded in 80% and contact allergy to glucocorticosteroids in 40% of CVLU patients. In the group of AD patients, the respective figures were 30% and 3%. In the group of CD patients, allergic type of disease was detected in 80% and positive patch tests for glucocorticosteroids in 20% of patients. In healthy individuals, allergic contact reaction was observed in 17% of cases. Statistically significant differences among patient groups were found according to the prevalence of contact allergy, polyvalent allergy and contact allergy to glucocorticosteroids. We suggest that glucocorticosteroid contact allergy should be considered as a crucial clinical problem in patients with inflammatory dermatoses like CVLU, AD and CD.     

Allergic contact dermatitis to topical preparations of bufexamac

In Australia bufexamac is mainly used for pharmacist-initiated local treatment of various dermatoses. The European Medicines Agency's Committee for Medicinal Products for Human Use recently recommended that marketing authorisation for bufexamac-containing preparations be revoked throughout the European Union because of the risk of severe allergic contact dermatitis. We retrospectively reviewed the patch test database at the Skin and Cancer Foundation Inc. and identified 19 cases of positive reactions to bufexamac (5% petrolatum) from 451 people patch tested. The bufexamac reaction was deemed relevant to the presenting dermatitis in 13 of 19 (68%) patients. Bufexamac allergic contact dermatitis is under-reported in the English literature. We wish to emphasise the severity and the unusually polymorphic eruptions observed in some of the cases. Clinicians should consider the possibility of allergic contact dermatitis to bufexamac-containing preparations in all patients where there is a history of exposure, even if used for only a short time.     

Adding sorbitan sesquioleate to the European baseline series: Necessary,reasonable, or unavoidable?

Positive reactions to fragrance mix I (FM I) are frequent in consecutively patch tested patients suspected of having allergic contact dermatitis. However, the FM I test preparations contain 5% of the emulsifier sorbitan sesquioleate (SSO), and it is well known that SSO can cause contact allergic reactions in its own right. Indeed, the available data show that some patients with contact allergy to SSO react to FM I but are not allergic to fragrances. When SSO is not tested, this situation may go unnoticed, a wrong diagnosis of fragrance allergy may be given to the patient, and unjustified advice to avoid fragrances and fragranced products will be given in such cases. To avoid such suboptimal patient care, we postulate that testing with SSO in all patch tested individuals is mandatory. As it is well known that only a minority of FM I‐reactive patients will undergo a breakdown test with the ingredients and SSO, testing with SSO in all patients can only be achieved by adding it to the European baseline series. Not testing with SSO may also result in misinterpretation of patch test reactions to Myroxylon pereirae resin and 2‐hydroxyethyl methacrylate in the baseline series, as both (may) contain SSO, and, for the same reason, of reactions to several other hapten test materials.     

Multicenter study of preservative sensitivity in patients with suspected cosmetic contact dermatitis in Korea

As many new cosmetic products are introduced into the market, attention must be given to contact dermatitis, which is commonly caused by cosmetics. We investigate the prevalence of preservative allergy in 584 patients with suspected cosmetic contact dermatitis at 11 different hospitals. From January 2010 to March 2011, 584 patients at 11 hospital dermatology departments presented with cosmetic contact dermatitis symptoms. These patients were patch-tested for preservative allergens. An irritancy patch test performed on 30 control subjects using allergens of various concentrations showed high irritancy rates. Preservative hypersensitivity was detected in 41.1% of patients. Allergens with the highest positive test rates were benzalkonium chloride (12.1%), thimerosal (9.9%) and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (5.5%). Benzalkonium chloride and chlorphenesin had the highest irritancy rate based on an irritancy patch test performed using various concentrations. Seven of 30 normal subjects had a positive irritant patch reading with 0.1% benzalkonium chloride and eight of 30 normal subjects had a positive irritant patch reading at 4 days with 0.5% chlorphenesin in petrolatum. Although benzalkonium chloride was highly positive for skin reactions in our study, most reactions were probably irritation. MCI/MI and thimerosal showed highly positive allergy reactions in our study. The optimum concentration of chlorphenesin to avoid skin reactions is less than 0.5%.     

High frequency of contact allergy to gold sodium thiosulfate

When gold sodium thiosulfate was added to the patch test standard series, positive reactions were obtained in 8.6% of 823 consecutive patients with suspect contact allergy. The test reactions were clinically of an allergic type and, in several cases, long-lasting. There was no correlation with other allergens in the standard series. In a special study on 38 patients with contact allergy to gold sodium thiosulfate, the following principal findings were obtained: positive patch tests to the compound itself in dilute concentration; positive patch tests to potassium dicyanoaurate; negative patch tests to gold sodium thiomalate, sodium thiosulfate, and metallic gold; positive intradermal tests to gold sodium thiomalate. Our findings make gold sodium thiosulfate the 2nd most common contact allergen after nickel sulfate. It is suggested that a positive skin test to gold sodium thiosulfate represents gold allergy.     

Contact allergy in patients with chronic venous leg ulcers-- possible role of chronic venous insufficiency

The purpose of this study was to evaluate frequency of contact allergy in patients with chronic venous leg ulcers (CVLU) and to estimate possible relationships between allergic contact reactions and characteristics of both chronic venous insufficiency (CVI) and CVLU. We performed patch tests with the European standard series, antibiotics, glucocorticosteroids and ointment vehicles in 50 patients with CVLU. Patients underwent detailed CVI diagnostics using colour flow duplex ultrasound examination, ankle brachial pressure index determination and leg ulcers area measurement. Positive patch tests results were found in 80% and polyvalent allergy in 56% of patients. Statistically significant correlations were recorded between CVI and CVLU duration, CVLU duration and CVLU area and between CVI duration and polyvalent allergy frequency. Statistically significant differences were observed between coexistence of superficial and deep system insufficiency and CVLU duration, characteristics of contact allergic reactions and CVI duration, frequency of allergic contact reaction and presence or absence of long saphenous vein insufficiency, incidences of vein thrombosis and characteristics of contact allergic reactions as well as between characteristics of contact allergic reactions and both CVLU duration and area. Complex pathophysiological processes, including inflammatory reactions, in course of CVI may influence development of allergic contact reaction in CVLU patients.     

Delayed and immediate allergy caused by methylhexahydrophthalic anhydride

Epoxy resin compounds (ERC) include a large number of chemicals. Such as epoxy resins (ER), reactive diluents and hardeners. Many hardeners. e.g., aliphatic polyamines. are well-known sensitizers. Another type of ER hardeners are the phthalic anhydrides, such as methylhexahydrophthalic anhydride (MHHPA) and mathyltetrahydrophthalic anhydride (MTHPA). which have been reported as causing immunologically-mediated respiratory diseases and contact urticaria. but not allergic contact dermatitis. Here, we present a horizontal boring-machine worker who developed allergic contact dermatitis. as Well as allergic rhinitis and and immediate contact skin reaction from MHHPA. patch testing with a dilution series of MHHPA in pet. elicited the following results: 2%. 1% and 0.5. ++: 0.25%+ and 0.125%. + (3- to 6-day readings) An immunohistochemical and electron microscopic study also indicated that the patch lest reactions were conventional-delayed allergic reactions, Interleukin 8 was observed in the epidermal cells, whereas interleukin 4 immunoreactivity was detected in the dermal cell Immunoreactivity to interleukin 5. granulocyte/macrophage-colophony Stimulating factor (GM-CSF) or eosinophil cationic protein was not seen. In conclusion, the patient developed both Type I und Type IV allergy to MHHPA. The clinical data. patch lest results, immunohistochemical and electron microscopic observations indicated that the MHHPA allergy detected by the patch test reaction was a conventional delayed-type hypersensitivity reaction. The patient also had an allergic patch test reaction to para-phenylenediamine and diaminodiphenylmethane. possibly representing occupational sensitization.