2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis. Part 2. Cross- and co-sensitization, other skin reactions to HEMA, position of HEMA among (meth)acrylates, sensitivity as screening agent, presence of HEMA in commercial products and practical information on patch test procedures.

This is the second part of a literature review of the clinical aspects of contact allergy to and allergic contact dermatitis from 2-hydroxyethyl methacrylate (HEMA). Topics include cross- and co-sensitization, atypical manifestations of contact allergy, frequency of positive patch tests to HEMA compared with other (meth)acrylates, sensitivity of HEMA as a screening agent, the presence of HEMA in commercial products, and practical information on patch testing procedures. Primary sensitization to methacrylates including HEMA may result in methacrylate and acrylate cross-sensitization. There is a strong cross-allergy between HEMA, ethylene glycol dimethacrylate (EGDMA), and hydroxypropyl methacrylate; many reactions to EGDMA are cross-reactions to primary HEMA sensitization. Rare atypical manifestations of HEMA-allergy include lichen planus, lymphomatoid papulosis, systemic contact dermatitis, leukoderma after positive patch tests, and systemic side effects such as nausea, diarrhoea, malaise, and palpitations. The occurrence of respiratory disease caused by methacrylates such as asthma is not infrequent. HEMA is the most frequently patch test-positive methacrylate. It is a good screening agent for allergy to other (meth)acrylates. Patch test sensitization to HEMA 2% pet. is extremely rare. There are (some) indications that HEMA is frequently used in dental products and nail cosmetics.

2-Hydroxyethyl methacrylate (HEMA): A clinical review of contact allergy and allergic contact dermatitis-Part 1. Introduction, epidemiology, case series and case reports.

2-Hydroxyethyl methacrylate (HEMA) has been increasingly recognised as a contact allergen and was added to the European baseline series in 2019. In this article (2 parts), the results of an extensive literature review of the clinical aspects of contact allergy/allergic contact dermatitis to HEMA are presented. In part 1, the epidemiology of HEMA contact allergy is discussed and detailed information on published case series and case reports presented. HEMA is an important cause of contact allergy/allergic contact dermatitis in North America and Europe with recent prevalences of >3% in the USA + Canada and 1.5%-3.7% in Europe. Currently, most cases are caused by nail cosmetics, both in consumers and professional nail stylists. In our literature review, we have found 24 studies presenting case series of patients with allergic contact dermatitis attributed to HEMA and 168 case reports. However, the presence of HEMA in the products causing ACD was established in only a minority. Part 2 will discuss cross- and co-sensitisation, and other skin reactions to HEMA, will assess whether HEMA is the most frequent (meth)acrylate allergen and how sensitive HEMA as a screening agent is, investigate the presence of HEMA in commercial products and provide practical information on patch testing procedures.

Systemic allergic dermatitis (systemic contact dermatitis) from pharmaceutical drugs: A review.

The literature on systemic allergic dermatitis (SAD; also known as systemic contact dermatitis) is reviewed. Both topical drugs (from absorption through mucosae or skin) and systemic drugs (oral, parenteral, rectal) may be responsible for the disorder. The topical route appears to be rare with 41 culprit topical drugs found to cause SAD in 95 patients. Most reactions are caused by budesonide (especially from inhalation), bufexamac, and dibucaine. SAD from systemic drugs is infrequent with 95 culprit drugs found to cause SAD in 240 patients. The drugs most frequently implicated are mitomycin C, methylprednisolone (salt, ester), and hydrocortisone (salt). The largest group of culprit drugs consisted of corticosteroids (19%), being responsible for >30% of the reactions, of which nearly 40% were not caused by therapeutic drugs, but by drug provocation tests. The most frequent manifestations of SAD from drugs are eczematous eruptions (scattered, widespread, generalized, worsening, reactivation), maculopapular eruptions, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE [baboon syndrome]) and widespread erythema or erythroderma. Therapeutic systemic drugs hardly ever cause reactivation of previously positive patch tests and infrequently of previous allergic contact dermatitis. The pathophysiology of SAD has received very little attention. Explanations for the rarity of SAD are suggested.

Results of patch testing in acute generalized exanthematous pustulosis (AGEP): A literature review.

The literature on positive patch-test results in acute generalized exanthematous pustulosis (AGEP) is reviewed. Ninety-three drugs were identified that have together caused 259 positive patch tests in 248 patients with AGEP. The drug classes causing the highest number of reactions are beta-lactam antibiotics (25.9%), other antibiotics (20.8%), iodinated contrast media (7.3%), and corticosteroids (5.4%), together accounting for nearly 60% of all reactions. The highest number of reactions to individual drugs was to amoxicillin (n = 36), followed by pristinamycin (n = 25), diltiazem (n = 14), amoxicillin-clavulanic acid (n = 13), clindamycin (n = 11), and iomeprol (n = 8); 59 of the 93 drugs each caused a single case only. The "Top-10" drugs together caused over 50% of all reactions. The sensitivity of patch testing (percentage of positive reactions) in patients with AGEP is largely unknown, but may generally be ~50%, which also applies to pristinamycin. Patch testing in AGEP appears to be safe, although mild recurrence of AGEP skin symptoms or other rashes may occur occasionally. Clinical aspects of AGEP, including epidemiology, etiology and pathophysiology, clinical features, histology, treatment, and prognosis are briefly presented, as are diagnosing the disease and identifying the culprit drugs with patch tests, intradermal tests, in vitro tests, and challenge tests.

Patch testing in drug reaction with eosinophilia and systemic symptoms (DRESS): A literature review.

The literature on positive patch test results in drug reaction with eosinophilia and systemic symptoms (DRESS) is reviewed. One hundred and five drugs were identified that have together caused 536 positive patch tests in 437 DRESS patients. By far, the most reactions (n = 145) were caused by carbamazepine, followed by amoxicillin, isoniazid, phenytoin, ethambutol, fluindione, phenobarbital, rifampicin, and ceftriaxone; 43 drugs each caused a single case only. The drug classes causing the highest number of reactions were anticonvulsants (39%), beta-lactam antibiotics (20%), antituberculosis agents (11%), non-beta-lactam antibiotics (6%), and iodinated contrast media (5%). The sensitivity of patch testing (percentage of positive reactions) is high for anticonvulsants (notably carbamazepine), beta-lactam antibiotics (notably amoxicillin), and, possibly, iodinated contrast media. Allopurinol and sulfasalazine frequently cause DRESS but never give positive patch tests. Patch testing in DRESS appears to be safe, although mild recurrence of DRESS symptoms, mostly skin reactions, may not be rare. Multiple drug hypersensitivity was found to occur in 16% of all patients, but it is argued that the true frequency is higher. Clinical aspects of DRESS, including diagnosing the disease and identifying culprit drugs (patch tests, intradermal tests, in vitro tests, challenge tests) are also provided, emphasizing the role of patch testing.

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.

Tea tree oil: contact allergy and chemical composition.

In this article, contact allergy to, and the chemical composition of, tea tree oil (TTO) are reviewed. This essential oil is a popular remedy for many skin diseases, and may be used as neat oil or be present in cosmetics, topical pharmaceuticals and household products. Of all essential oils, TTO has caused most (published) allergic reactions since the first cases were reported in 1991. In routine testing, prevalences of positive patch test reactions have ranged from 0.1% to 3.5%. Nearly 100 allergic patients have been described in case reports and case series. The major constituents of commercial TTO are terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and α-pinene. Fresh TTO is a weak to moderate sensitizer, but oxidation increases its allergenic potency. The major sensitizers appear to be ascaridole, terpinolene, α-terpinene, 1,2,4-trihydroxymenthane, α-phellandrene, and limonene. The clinical picture of allergic contact dermatitis caused by TTO depends on the products used. Most reactions are caused by the application of pure oil; cosmetics are the culprits in a minority of cases. Patch testing may be performed with 5% oxidized TTO. Co-reactivity to turpentine oil is frequent, and there is an overrepresentation of reactions to fragrance mix I, Myroxylon pereirae, colophonium, and other essential oils.

Contact and photocontact allergy to octocrylene: a review.

Octocrylene is an ultraviolet (UV)B and UVAII absorber that was introduced some 15 years ago, and is now widely used in sunscreen agents and skin care cosmetics. Since 2003, several studies, notably from France, Belgium, Spain, and Italy, have reported an increasing number of patients with photocontact allergy to octocrylene. This reaction is seen mainly in adult patients who have previously used topical products containing the non-steroidal anti-inflammatory drug ketoprofen. Photosensitization to ketoprofen leads, in many cases, to photocontact allergy to octocrylene; the mechanism of this reaction is unknown. Contact allergy to octocrylene also occurs, but is far less frequent, and is seen, in most cases, in children, resulting from the use of octocrylene-containing sunscreen products. In this article, (photo)contact allergy to octocrylene is fully reviewed.

Side-effects of henna and semi-permanent 'black henna' tattoos: a full review.

Henna, the dried and powdered leaf of Lawsonia inermis, is widely used as a dye for the skin, hair, and nails, and as an expression of body art, especially in Islamic and Hindu cultures. As it stains the skin reddish-brown, it is also called red henna. Black henna is the combination of red henna with p-phenylenediamine (PPD), and is used for temporary 'black henna tattoos'. This article provides a full review of the side-effects of topical application of red and black henna, both cutaneous (allergic and non-allergic) and systemic. Red henna appears to be generally safe, with rare instances of contact allergy and type I hypersensitivity reactions. In children with glucose-6-phosphate dehydrogenase deficiency, topical application of henna may cause life-threatening haemolysis. Black henna tattoos will induce contact allergy to its ingredient PPD at an estimated frequency of 2.5%. Once sensitized, the patients may experience allergic contact dermatitis from the use of hair dyes containing PPD. There are often cross-reactions to other hair dyes, dyes used in textiles, local anaesthetics, and rubber chemicals. The sensitization of children to PPD may have important consequences for health and later career prospects. Systemic toxicity of black henna has been reported in certain African countries.

Patch Testing in Drug Eruptions: Practical Aspects and Literature Review of Eruptions and Culprit Drugs.

ABSTRACT: There is overwhelming evidence that many delayed cutaneous adverse drug reactions (beginning >6 hours after drug intake) are mediated by delayed-type (type IV) hypersensitivity, including maculopapular eruptions, erythroderma, symmetrical drug-related intertriginous and flexural exanthema/baboon syndrome, eczematous eruptions, fixed drug eruptions, acute generalized exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome. Therefore, after resolution of the reaction, patch tests should be performed as first diagnostic method to identify the culprit drug(s). This article provides tools to perform drug patch tests properly and safely, discussing clinical history, indications, procedure, drug patch test materials, sensitivity, the meaning of negative patch tests, and safety of the procedure. In addition, a literature review of eruptions and culprit drugs is provided in tabular format.

Determination of formaldehyde in formaldehyde-releaser patch test preparations.

BACKGROUND: Positive patch test reactions to formaldehyde-releasers in patients co-reacting to formaldehyde are often ascribed to formaldehyde allergy. However, the formaldehyde content of patch test materials has not been investigated. OBJECTIVES: To demonstrate and quantify free formaldehyde in commercial patch test materials and in prepared aqueous solutions of formaldehyde releasers. MATERIALS: Free formaldehyde was measured by (13)C NMR Spectroscopy in (i) all formaldehyde-releasers in water available from Chemotechnique and Brial, (ii) 5 releasers in petrolatum, (iii) 12 prepared aqueous solutions of formaldehyde-releasers and (iv) water that had been in contact with petrolatum test samples. RESULTS: In none of the five petrolatum test substances was free formaldehyde found. In all nine commercial aqueous patch test substances and 9 of the 12 prepared solutions, free formaldehyde was demonstrated with concentrations ranging from 0.019% to 0.37% (detection limit 0.01%). Contact of the petrolatum test samples with water resulted in the release of formaldehyde. CONCLUSIONS: Most aqueous solutions of formaldehyde-releasers contain free formaldehyde. Petrolatum-based patch test materials with formaldehyde-releasers do not contain free formaldehyde, but probably start releasing it upon contact with water. Therefore, in future studies, determination of free and releasable formaldehyde may be preferable.

Twenty-five years quaternium-15 in the European baseline series: does it deserve its place there?

For allergens to be included in the European baseline series, they should have allergy rates of at least 1%. In several studies quaternium-15 had lower scores. Also, many cases of sensitization are already detected by formaldehyde contact allergy. The aim of this study was to evaluate whether quaternium-15 deserves continued inclusion in the baseline series on the basis of current criteria: 1% positive reactions, common occurrence in the environment, many relevant reactions. We used the literature survey method in this study. Only the United Kingdom has rates consistently over 1%. The mean for all other countries together and for many individual nations is lower than 1%. At least half of the reactions are already detected by formaldehyde sensitivity, which lowers rates for allergy to quaternium-15 per se (i.e. not caused or at least detected by formaldehyde sensitivity) to less than 0.6% for all countries except the United Kingdom. Neither common occurrence in the environment nor a high percentage of relevant reactions has been ascertained. It may well be argued that quaternium-15 does not deserve its place in the European baseline series and could be incorporated in a cosmetic screening series or preservative series instead. In the United Kingdom, routine testing should be continued.

Does allergic contact dermatitis from formaldehyde in clothes treated with durable-press chemical finishes exist in the USA?

Recent US studies have presented case series of patient with allergic contact dermatitis (ACD) allegedly caused by formaldehyde in clothes treated with durable-press chemical finishes (DPCF), which are known formaldehyde releasers. However, the amounts of formaldehyde released by modern DPCF are thought to be well below the levels previously estimated to be able to elicit ACD. The objectives of this review are (i) to investigate whether clothes sold in the USA may contain enough free formaldehyde to elicit ACD in previously sensitized individuals and (ii) to assess the validity of US reports on ACD from formaldehyde in DPCF treated clothes. Literature was examined using various resources. The threshold level for formaldehyde in clothes that may cause ACD in sensitized individuals is unknown; we present data suggesting that levels < 200 ppm will be safe for most patients and that textiles will rarely contain higher amounts. All US studies presenting patients with ACD from formaldehyde in clothes had some weaknesses and in no report was the diagnosis proven beyond doubt. Currently, there is no definite proof that textile ACD from formaldehyde in DPCF in the USA exists. Future research should be directed at establishing the elicitation threshold and the amounts of formaldehyde present in textiles.

Formaldehyde-releasers in cosmetics in the USA and in Europe.

BACKGROUND: Frequencies of sensitization to formaldehyde among US patients patch tested for suspected contact dermatitis are higher than in Europe. Cosmetics are an important source of contact with formaldehyde. OBJECTIVES: To acquire data on the frequency of use of formaldehyde-releasers in cosmetics sold in the USA and Europe and their use concentrations. To assess whether any observed differences may contribute to the discrepancies in sensitization rates. METHODS: Enquiries with Food and Drug Administration (FDA), the European Cosmetics Association, and the Dutch Cosmetics Association. Reading the labels of skin care cosmetics in a local drugstore. RESULTS: The FDA provided data on the presence of formaldehyde and releasers. Nearly one fifth of all cosmetics contain a releaser. In 25% of 496 examined skin care products, releasers were present. In comparable FDA data categories, the percentage was 24. No data were found on use concentrations of the releasers in cosmetics in either the USA or Europe. CONCLUSIONS: The percentages of stay-on skin care products containing a formaldehyde-releaser are virtually identical in the USA (FDA data) and our local drugstore sample. However, this does not necessarily imply that cosmetics play no part in the differences in formaldehyde sensitization rates.

Frequency of sensitization to common allergens: comparison between Europe and the USA.

BACKGROUND: Previously, contact allergy to formaldehyde and quaternium-15 was found to be more prevalent in the United States than in Europe. No such data have been assessed for other contact allergens. OBJECTIVE: Determine any differences in frequencies of sensitization to contact allergens in the United States and Europe. METHODS: Literature study. Comparison of reported frequencies of sensitization to contact allergens routinely tested both in the United States and Europe in recent, large, multicentre studies. Because of the heterogeneity of studies and background parameters, statistical evaluation was not attempted. RESULTS: Major differences were found only for neomycin (USA 10.0-11.8%, mean 11.4%; Europe 1.2-5.4%, mean 2.6%). Most allergens had somewhat higher prevalence in the United States, with rates versus Europe ranging from 1.3 to 1.9. CONCLUSIONS: Contact allergy to neomycin is much more prevalent in the United States. Stricter selection of patients for patch testing in United States tertiary referral centres may result in 50% more positive reactions compared to European studies.

Relationship between formaldehyde and quaternium-15 contact allergy. Influence of strength of patch test reactions.

BACKGROUND: In groups of patients with formaldehyde allergy, many have positive patch tests to quaternium-15. Conversely, of patients allergic to quaternium-15, over half also react to formaldehyde. OBJECTIVES: To test our hypothesis that patients with stronger patch test reactions to formaldehyde are more likely to react to quaternium-15, attesting to the aetiological role for formaldehyde in such co-reactivity. METHODS: Retrospective analysis of all patients patch tested with formaldehyde and quaternium-15 in the European baseline series between 1994 and 2009 (TRUE test). RESULTS: In a group of 86 patients allergic to formaldehyde, 73% co-reacted to quaternium-15; in the subgroup of 70 women, the percentage was 83. In both groups, more reactions were observed to quaternium-15 in the patients with a ++ reaction compared to the patients with a + reaction to formaldehyde. Conversely, stronger reactions to quaternium-15 were significantly more often associated with formaldehyde sensitivity in a group of 107 patients reacting to quaternium-15 and a subgroup of 88 women. In men, such effects were not observed and only 5 of 16 (31%) men allergic to formaldehyde also reacted to quaternium-15. CONCLUSIONS: In women, but not in men, stronger reactions to formaldehyde lead to more positive quaternium-15 patch tests.

Formaldehyde-releasers in cosmetics: relationship to formaldehyde contact allergy. Part 1. Characterization, frequency and relevance of sensitization, and frequency of use in cosmetics.

In this part of a series of review articles on formaldehyde-releasers and their relationship to formaldehyde contact allergy, formaldehyde-releasers in cosmetics are discussed. In this first part of the article, key data are presented including frequency of sensitization and of their use in cosmetics. In Europe, low frequencies of sensitization have been observed to all releasers: 2-bromo-2-nitropropane-1,3-diol 0.4-1.2%, diazolidinyl urea 0.5-1.4%, imidazolidinyl urea 0.3-1.4%, quaternium-15 0.6-1.9% (for DMDM hydantoin no recent data are available). All releasers score (far) higher prevalences in the USA; the possible explanations for this are discussed. The relevance of positive patch test reactions has been insufficiently investigated. In the USA, approximately 20% of cosmetics and personal care products (stay-on products: 17%, rinse-off products 27%) contain a formaldehyde-releaser. The use of quaternium-15 is decreasing. For Europe, there are no comparable recent data available. In the second part of the article, the patch test relationship of the releasers in cosmetics to formaldehyde contact allergy will be reviewed and it will be assessed whether products preserved with formaldehyde-releasers may contain enough free formaldehyde to pose a threat to individuals who have contact allergy to formaldehyde.