Luigi Rigano

3-Dimethylaminopropylamine: a key substance in contact allergy to cocamidopropylbetaine?

In the past year, 1200 consecutive eczematous patients were tested with cocamidopropylbetaine 1% aq. Contact allergy was evinced in 46 subjects (3.8%), while irritant reactions (slight erythema only) were observed in 15 cases (1.25%). 30 out of 46 patients with allergic reactions were subsequently tested with the substances used in the synthesis of cocamidopropylbetaine, together with a sample of cocamidopropylbetaine declared by the supplier to possess a greater purity. In all 30 subjects, positive reactions were obtained to 3‐dimethylaminopropylamine (DMPA) 1% aq., while the cocamidopropylbetaine denned of purer grade, at 0.5% and 1% aq., gave positive reactions in 10% and 53% of cases, respectively. These results suggest that the DMPA present at various levels as an impurity in the commercial product is responsible for cocamidopropylbetaine allergy. Owing to the inconsistency of positive reactions to cocamidopropylbetaine of variable purity, and to the consistency of positive reactions to DMPA, it seems likely that these reactions may also be connected with the presence in the product, defined of purer grade, of unknown amounts of DMPA as impurity. Structural similarities between the 2 molecules cannot be considered in this case, because the DMPA structure is radically changed in its transformation to the betaine structure, Further experiments with other molecules related to the above structures are in hand.

Occupational sensitization to epoxy resin and reactive diluents in marble workers

10 out of 22 marble workers handling a bicomponent resin, based on epoxy resin and ortho‐cresyl glycidyl ether (CGE), developed Contact dermatitis and airborne contact dermatitis within 20 days to 2 months of exposure. All 22 subjects were patch tested with epoxy resin, bisphenol A, epichlorohydrin and a series of reactive diluents. The 10 symptomatic subjects were all positive to the reactive diluent CGE, and 4 of them also to epoxy resin. The other reactive diluents that gave positive reactions were phenyl glycidyl ether (7 cases), cyclohexanedimethanol glycidyl ether (2 cases), 1,6‐hexanediol diglycidyl ether (2 cases) and allyl glycidyl ether (1 case). The findings of our Study suggest that allergic potential is directly proportional to the electronic charge available, for all electron‐rich molecules (solvents, high and low polymers, reagents) that interact with the glycidyl ether group. Lesser, but still noticeable, effects are detected when activation of the glycidyl group is related to the possible formation of intramolecular hydrogen bonds. In practice, the occupational problem was partly solved by changing the type of glycidyl ether.

The role of 3-dimethylaminopropylamine and amidoamine in contact allergy to cocamidopropylbetaine

Since it has been found that all subjects with contact allergy to cocamidopropylbetaine (CAPB) have positive reactions to 3‐dimethylaminopropylamine (DMAPA), and reports have appeared in literature of the sensitizing action of amidoamine in products containing CAPB, we aimed to verify the possibility that pure amidoamine may have a sensitizing role in subjects with positive reactions to CAPB. To this end, in 10 patients with contact allergy to a commercial CAPB, we tested DMAPA 1% aq. and a pure amidoamine in concentrations ranging from 0·5% aq. to 0·1% aq. The study showed that all patients with positive reactions to DMAPA reacted to amidoamine at 0·5% and 0·25% aq., while 4 of the 10 also had positive reactions to amidoamine at 0·1% aq. We consider that simultaneous allergic reaction to DMAPA and amidoamine represents cross‐reactivity and hypothesize that DMAPA is in fact the true sensitizing substance, while amidoamine, which may in any case release DMAPA in vivo as a result of enzymatic hydrolysis, may favour the transepidermal penetration of the sensitizing agent. In addition, we advise that testing of CAPB be suspended, because, as suggested by chemico‐structural analyses and demonstrated in vivo, when thoroughly purified, it no longer has a sensitizing action.

Allergic and Photoallergic Contact Dermatitis from Ketoprofen: Evaluation of Cross-Reactivities by a Combination of Photopatch Testing and Computerized Conformational Analysis

Allergic contact dermatitis (ACD) and photo-ACD are cell-mediated delayed hypersensitivity reactions of the skin caused by a wide range of substances. Topical ketoprofen (KP), a nonsteroidal anti-inflammatory drug (NSAID), can induce ACD and photo-ACD. Patients with ACD and/or photo-ACD to KP frequently show concomitant sensitization to other substances. The aim of this study was to identify the substances most frequently associated with sensitization to KP, and to evaluate, by means of computerized conformational analysis, whether this association could be due to cross-allergy. 15 subjects with ACD and photo-ACD to KP were tested with the SIDAPA (Società Italiana di Dermatologia Allergologica Professionale ed Ambientale) patch test standard series, including fragrance mix and its components (eugenol, isoeugenol, oak moss, geraniol, hydroxycitronellal, amylcinnamaldehyde, cinnamyl alcohol and cinnamaldehyde) and with the SIDAPA photopatch test series. Allergic reactions to cinnamyl alcohol were noted in all patients, whereas some patients also showed positive reactions to fenticlor, octocrylene and benzophenone-10. Computerized conformational analysis demonstrated that the structure of cinnamyl alcohol is similar to that of KP, whereas the structures of benzophenone-10, octocrylene and fenticlor are completely different. These results suggest that in patients with contact allergy to KP, concomitant positive reactions to cinnamyl alcohol are due to cross-sensitization, whereas simultaneous allergic reactions to fenticlor, octocrylene and benzophenone-10 should be regarded as co-sensitizations.

Contact allergy to impurities in surfactants : amount, chemical structure and carrier effect in reactions to 3-dimethylaminopropylamine

Since finding that all Subject with contact allergy to cocamidopropylbetaine give positive reactions to 3‐dimethylaminopropylamine (DMPA), we wished to verify whether sensitization to other industrially‐used tensioactives might also be due to contact of DMPA as an impurity. We also investigated the possible “carrier action” that tensioactives might exert on minimal quantities of DMPA. Finally, we analyzed the relationship between the structure of DMPA and other chemically‐correlated molecules and their sensitizing potential, with particular reference to the structure of alkylam‐idopropylbetaines. For this purpose, in 34 patients with contact allergy to DMPA, we tested: (i) DMPA in concentrations below the threshold limit in water and in different tensioactives: (ii) substances that employ DMPA as a reagent in their synthesis: (iii) substances similar to DMPA as regards chemically reactive groups. The study showed that: (i) DMPA remains as a quantitatively detectable impurity in all tensioactives employing it in their synthesis: (ii) some common anionic (SLES) and non‐ionic (polysorbate 20) tensioactives enhance the risk of sensitization from very low doses of DMPA, presumably due to a “carrier effect:” (iii) the sensitizing chemical structures in DMPA and related molecules are the primary amine and the tertiary (dimethyl‐substituted) amine groups, when separated by either 2 or 3 carbon atoms:(iv) no sensitizing action can be attributed to the functional groups present in alkylamidopropylbetaine molecules.

Photoallergic contact dermatitis to 8-methoxypsoralen in Ficus carica

Background: Photocontact dermatitis to Ficus carica is induced by furocoumarins present in sap. These substances are generally considered to cause phototoxic reactions.

Pure cocamidopropylbetaine is not the allergen in patients with positive reactions to commercial cocamidopropylbetaine

Discussion Allergic contact dermatitis from antimycotic imidazoles is uncommon when compared to their widespread use. The high concentration of tioconazole (28%) in the nail solution, the presence of undecylenic acid and of ethyl acetate in the vehicle, as well as its application to periungual folds, are all factors favouring sensitization. Cross-reactions between phenethyl imidazoles and phenmethyl imidazoles have previously been described (1, 2, 5, 6), the common structure, 2-(2,4-dichlorophenyl)ethyl imidazole, appearing to be the antigenic determinant.

Contact allergy to oleamidopropyl dimethylamine and related substances

Contact allergy to oleamidopropyl dimethylamine and related substances CATERINA FoTI , LuiGI RIGAN0, GrNo A. VENA , MAURO GRANDOLFo 1, GIOVANNI LIGuoRr 1 AND GIANNI ANGELINI 1 Department of Dermatology, University of Bari, Policlinico, 70124 Bari, Italy Institute of Skin and Product Evaluation (ISPE), 20150 Milano, Italy

Aminoethylethanolamine: a new allergen in cosmetics?

Amphoacetates are organic compounds used in many industrial applications and in cosmetic formulations for the skin, hair and mucosa, as surfactants, mild foaming and cleansing agents in concentrations ranging from 0.1% to 50%. Despite the fact that they have been in use for many years, cases of contact allergy to them are extremely rare. We describe 4 patients who developed an eczematous reaction after use of detergents containing amphoacetates. Patch testing showed positive reactions to sodium lauroamphoacetate (Miranol® HM Special, Rhodia, England) as is or diluted at decreasing concentration (10%, 5% and 1%) in water and to aminoethylethanolamine (AEE) at the concentration of 1% in various vehicles (ethanol, acetone, and sodium laurylethersulfate 1% aqueous solution) and at decreasing concentrations ranging from 1% to 0.005% in water. AEE is one of the reagents used in the synthesis of amphoacetates. This molecule, that is structurally an ethylenediamine derivative, has sensitizing power and is reported as a cause of occupational contact allergy in cable jointers. Combined eczematous reactions to AEE and sodium lauroamphoacetate can be consequent to the presence of the former substance as an impurity in amphoacetates‐containing products, as demonstrated by ion chromatography‐mass spectrometry analysis.

Contact dermatitis from organophosphorus pesticides

Keywords: allergic contact dermatitis; organophosphorus pesticides; chlorpyriphos-methyl; fenthion; methidathion; parathion-methyl; malathion; cross-sensitivity; occupational; agriculture