Corticosteroid or steroid allergy?

The aim of this study was to elucidate the role of the C11-OH substituent of the corticosteroid molecule in relation to contact allergy to corticosteroids. This group, which is essential for glucocorticoid activity, is not present in other steroid molecules, such as deoxycortisol, progestagens, testosterone, and estrogen. Skin tests with these substances in hydrocortisone-allergic patients revealed a division between patients for whom the C11-OH group was essential to induce the allergic reaction and patients for whom this group did not seem to be essential. Some of the patients of the latter group also reacted to 17-alpha-OH-progesterone. This may indicate cross-sensitivity between hydrocortisone and 17-alpha-OH-progesterone, which might play an etiological role in autoimmune progesterone dermatitis.     

Sulfite contact allergy

In the last 2 years, 2,894 consecutive eczematous patients were patch tested with sodium metabisulfite 1% pet. Positive reactions were elicited in 50 subjects (1.7%). All 50 patients were also positive to potassium metabisulfite 1% pet. and sodium bisulfite 1% and 5% pet., while only 2 of them were positive to sodium sulfite 1% pet. Prick tests and intradermal tests with a sodium metabisulfite solution (10 mg/ml) were negative. No flare-ups of dermatitis or patch test were provoked by oral challenge with 30 mg and 50 mg of sodium metabisulfite. The dermatitis was taken to be occupational in 7 cases. In only 5 out of 43 non-occupational cases was the positive reaction considered relevant.     

Occupational allergic contact dermatitis in beauticians

We patch tested 13 beauticians with hand dermatitis between 1982 and 1986. They were all young female novice beauticians or those in training. The onset of their allergic dermatitis was noticed within 1 month to 1 year of their starting this occupation. Definite positive reactions to products were seen from hair dyes (as is, open test) (6/12), cold permanent wave primary solutions (as is, open test) (7/13) and a shampoo (1% aq., closed test) (1/13). Positive reactions to allergens were seen with para-phenylenediamine (1% pet) (12/13), ammonium thioglycolate (5% aq., open test) (3/7), para-toluylenediamine (1% pet) (7/9), para-aminophenol (1% pet) (1/4), ortho-aminophenol (1% pet) (1/4), Quinoline yellow SS (0.5% pet) (1/4), nickel sulfate (2.5% pet) (1/12), cobalt sulfate (2.3% pet) (1/12), thimerosal (0.05% pet) (1/12) and procaine hydrochloride (1% pet) (1/12). Study of the prognosis showed that 5 out of 12 cases could continue their occupation, but 4 cases had persistent hand dermatitis despite protecting their hands from hair dyes with gloves, 7 cases quitted their jobs, and in 5 their hands healed while 2 cases continued to have atopic hand dermatitis. A personal or family history of atopy was frequent among the cases, so we recommend that those who have such a history should not become beauticians.     

Autoimmune progesterone dermatitis presenting as recurrent,marked angioedema-like lip changes: An unusual presentation of an uncommon problem

Autoimmune progesterone dermatitis is a rare condition with varying clinical presentations. We present a case of autoimmune progesterone dermatitis presenting as recurrent, marked angioedema-like lip swelling without any other skin changes.     

The menstrual cycle and the skin

Perimenstrual exacerbations of dermatoses are commonly recognized, yet our knowledge of the underlying pathophysiological mechanisms remains imperfect. Research into the effects of oestrogen on the skin has provided evidence to suggest that oestrogen is associated with increases in skin thickness and dermal water content, improved barrier function, and enhanced wound healing. Research into the effects of progesterone suggests that the presence of various dermatoses correlates with peak levels of progesterone. Dermatoses that are exacerbated perimenstrually include acne, psoriasis, atopic eczema and irritant dermatitis, and possibly also erythema multiforme. Exacerbations occur at the peak levels of progesterone in the menstrual cycle. Underlying mechanisms include reduced immune and barrier functions as a result of cyclical fluctuations in oestrogen and/or progesterone. Autoimmune progesterone and oestrogen dermatitis are the best‐characterized examples of perimenstrual cutaneous reactions to hormones produced during the menstrual cycle. In this review, we describe the current understanding of the menstrual cycle, and its effect on the skin and cutaneous disorders.     

Occupational allergic contact dermatitis caused by nitroglycerin

Irritant contact dermatitis caused by occupational contact with nitroglycerin has been known since the end of the last century. Nitroglycerin is an allergen, and the transdermal drug delivery systems for nitroglycerin recently used to treat angina pectoris have sensitized. 4 patients with allergic contact dermatitis caused by nitroglycerin from explosives are described, and 1 patient who was sensitized by transdermal nitroplaster. On patch testing, dynamite and/or the explosive components nitroglycerin, ethylene glycol dinitrate and dinitrotoluene gave allergic reactions. The following concentrations and vehicles are suggested for patch testing: nitroglycerin 0.5-2% pet., dinitrotoluene and ethylene glycol dinitrate 0.1-0.5% pet. Persons exposed to nitroglycerin at work should try to avoid skin contact by using protective gloves. It is advisable that those who have become allergic to nitroglycerin should wear disposable protective gloves when handling explosives.     

Autoimmune progesterone dermatitis: effective prophylactic treatment with danazol

Background Autoimmune progesterone dermatitis is a rare condition appearing during the perimenstrual period or following progesterone treatment. Various treatment modalities have been suggested, but most have proved to be ineffective. Methods We used the anabolic androgen danazol as a preventive treatment for recurrent episodes of autoimmune progesterone dermatitis in two young women. The treatment regimen consisted of 200 mg danazol twice daily, starting 1–2 days before the expected date of each menses and continuing for 3 days thereafter. Results This treatment regimen proved to be highly effective in preventing the eruptions in these two patients. Conclusions Patients with autoimmune progesterone dermatitis may benefit from prophylactic treatment with danazol.     

Autoimmune progesterone dermatitis responding to Tamoxifen

A case of autoimmune progesterone dermatitis is described. Exacerbation occurred premenstrually and after intramuscular and oral challenge with synthetic progesterone. The condition failed to respond to oestrogen, but there has been a marked improvement with the anti-oestrogen drug Tamoxifen.     

Allergic contact dermatitis to topical corticosteroids: clobetasol propionate and clobetasone butyrate

2 case reports are given of patients with positive patch test reactions to clobetasol propionate. One of the patients also reacted to clobetasone butyrate. 30 other steroids that were chemically very closely related to these two 2l-chloro-9-α-fluoro-corticosteroids, were patch test negative. The literature on contact dermatitis reactions to corticosteroids is reviewed.     

Mercury allergy in a contact dermatitis clinic in Northern Ireland

441 consecutive patients (294 female, 147 male) with suspected contact dermatitis were patch tested to the European standard series, mercury metal (1% pet.). ammoniated mercury (1% pet.), and mercuric chloride (0.1% aq.), 14 patients (3.2%), 12 of whom were female, showed a positive response to 1 or more mercury compounds: none reacted to mercuric chloride alone. Primary sensitization was most likely due to either inoculation with vaccines containing merthiolate preservatives or amalgam dental restorations. Mercury allergy was of historical clinical relevance in only 2 pa I rents, both women who developed gingivostomatitis following insertion of amalgam dental fillings. 1 of these women subsequently developed allergic contact dermatitis from contact lens solutions, shampoos and cosmetics which contained mercury preservatives. On the basis of these findings, we recommend patch testing with both metallic mercury and ammoniated mercury in patients with suspected mercury allergy.     

Is benzoquinone the prohapten in cross-sensitivity among aminobenzene compounds?

Cross-sensitivity in allergic contact dermatitis is a simultaneous allergy to 2 or more contact substances which have in common an antigenic determinant or a metabolic derivative. One of the most notable examples is the cross-sensitivity among aromatic compounds which may be oxidized in vivo to benzoquinone (BQ). However, it has also been hypothesized that the allergenicity and cross-sensitization are modulated by the chemical reactivity of the substituents in the para position. A serial dilution of BQ (from 1% to 0.1% in pet.) and three 1,4-substituted benzene derivatives ( p -aminophenol, hydroquinone, metol), theoretically capable of conversion to BQ by oxidation, were patch tested in 22 p -phenylenediamine (PPD) positive patients and in 20 controls. The patients and a further 116 subjects with a positive history of sensitivity to 1 or more aminoaromatic compounds were also tested with some haptens of the para group (PPD, p -aminobenzoic acid, p -aminodiphenylamine, benzocaine, procaine chloride, p -toluenediamine sulfate). The results show that (i) the optimal patch test concentration for BQ was 0.2%, (ii) only 4 of the 22 patients allergic to PPD gave a clearly positive allergic reaction to BQ, and (iii) the number of positive reactions to the aromatic compounds was correlated with the presence of activating (-NH₂, -OH, -CH₃) and deactivating (-COOH) groups in the para position or, perhaps, with their effect on percutaneous penetration. The data suggest that BQ is not the only intermediate in the cross-sensitization of para group haptens. This is probably conditioned by other oxidation products and/or the chemical structure of the substituents in position 4 of the benzene ring.     

A study of cross-reactions between mango contact allergens and urushiol

The allergens causing mango dermatitis have long been suspected to be alk(en)yl catechols and/or alk(en)yl resorcinols on the basis of observed cross-sensitivity reactions to mango in patients known to be sensitive to poison ivy and oak (Toxicodendron spp.). Earlier, we reported the 3 resorcinol derivatives: heptadecadienylresorcinol (I), heptadecenylresorcinol (II) and pentadecylresorcinol (III); collectively named 'mangol', as mango allergens. In this study, we extracted the 1st 2 components (I and II) from the Philippine mango, adjusted them to 0.05% concentration in petrolatum and patch tested the components on 2 subjects with mango dermatitis. Both subjects reacted to I. 1 subject also elicited a weaker positive reaction to II. To investigate the cross-reaction between mangol and urushiol, we also patch tested the same subjects with urushiol. The subject sensitive to II reacted to urushiol. 6 subjects with a history of lacquer contact dermatitis and positive reactions to urushiol were similarly patch tested. 5 persons reacted to I. 2 subjects also exhibited a slower but positive reaction to II. This is the 1st report in which heptadec(adi)enyl resorcinols known to be present in mango have been shown to elicit positive patch test reactions in mango-sensitive patients.     

A case of autoimmune progesterone dermatitis diagnosed by progesterone pessary

Autoimmune progesterone dermatitis is a rare, cyclical eruption that occurs in the luteal phase of the menstrual cycle and during pregnancy. Many manifestations have been reported including cyclical eczema, urticaria, erythema multiforme, stomatitis and even anaphylaxis. The condition spontaneously resolves after menopause. As histopathology is non-specific, the diagnosis rests on history with precipitation of the eruption by a progesterone challenge, usually by the intradermal, intramuscular or oral route. We present the case of a 34-year-old woman with a premenstrual papular and eczematous eruption that was exacerbated after pregnancy. Biopsy showed subacute spongiotic dermatitis. To confirm the diagnosis, we used an intravaginal progesterone pessary as a provocation challenge. There was recurrence of the rash 12 h after insertion of the pessary with spontaneous resolution thereafter. We propose that use of a progesterone pessary is an effective tool in the diagnosis of autoimmune progesterone dermatitis.     

Sensitization to patch test acrylates

Data on allergic contact dermatitis from acrylates and 4 patients sensitized during routine patch testing are reported. During 1982-1985, we used 7 different acrylates for tests. 1 patient out of 22 (= 4.5%) was sensitized to ethyl acrylate and butyl acrylate (1% pet.). Since September 1985, we have used a commercial (meth)acrylate series containing 28 substances. 3 of 24 patients tested became sensitized to ethyl acrylate, 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate (0.5% pet.). Because active sensitization with acrylates can be very harmful, it may be necessary to use lower concentrations than recommended. Currently, we test ethyl acrylate, 2-hydroxyethyl acrylate and 2-hydroxypropyl acrylate at 0.167% pet.     

Cytokine gene polymorphisms and susceptibility to chronic irritant contact dermatitis

Background:  Cytokines play an important role in skin inflammation.
Objectives:  We determined whether polymorphisms in cytokine genes contribute to the occurrence of occupational chronic irritant contact dermatitis (CICD).
Methods:  In a case–control study, 9 polymorphisms in the genes coding for interleukin (IL)-1α, IL-1β, IL-8, IL-10, and tumour necrosis factor (TNF)-α were determined in 197 patients with CICD. 217 apprentices in vocational training for high-risk occupations for CICD served as controls.
Results:  For all polymorphisms, no differences in genotype distributions were found between patients and controls. However, in patients with self-reported low levels of wet work and irritant exposure, more TNFA −308 variant genotypes (G/A and A/A) were present compared with those exposed to higher levels or controls, which indicates a TNFA -induced increase of susceptibility. In patients with TNFA −308 variant genotypes, the prevalence of flexural eczema was higher (48% and 57%) compared with that in patients presented with wild-type genotype (30%). Regarding IL1A −889, prevalence of symptoms of dermatitis was lower in apprentices with T/T or C/T genotype (32% and 36%) compared with wild-type genotype (54%, C/C). This indicates a protective effect of these variant alleles in acquiring hand dermatitis.
Conclusions:  This study provides evidence that some genetic variations alter susceptibility to (chronic) dermatitis. Knowledge of the impact of genetic differences on the risk of CICD is essential in predictive testing of individuals at risk.     

Recommendation to include fragrance mix 2 and hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) in the European baseline patch test series

Background:  The currently used fragrance mix in the European baseline patch test series (baseline series) fails to detect a substantial number of clinically relevant fragrance allergies.
Objective:  To investigate whether it is justified to include hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral^®) and fragrance mix 2 containing hydroxyisohexyl 3-cyclohexene carboxaldehyde, citral, farnesol, coumarin, citronellol, and α-hexyl cinnamal in the European baseline patch test series.
Methods:  Survey of the literature on reported frequencies of contact allergy and allergic contact dermatitis from fragrance mix 2 and hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) as well as reported results of experimental provocation test.
Results:  Fragrance mix 2 has been demonstrated to be a useful additional marker of fragrance allergy with contact allergy rates up to 5% when included in various national baseline patch test series. Of the fragrance substances present in fragrance mix 2, hydroxyisohexyl 3-cyclohexene carboxaldehyde is the most common sensitizer. Contact allergy rates between 1.5% and 3% have been reported for hydroxyisohexyl 3-cyclohexene carboxaldehyde in petrolatum (pet.) at 5% from various European centres when tested in consecutive dermatitis patients.
Conclusions:  From 2008, pet. preparations of fragrance mix 2 at 14% w/w (5.6 mg/cm²) and hydroxyisohexyl 3-cyclohexene carboxaldehyde at 5% w/w (2.0 mg/cm²) are recommended for inclusion in the baseline series. With the Finn Chamber^® technique, a dose of 20 mg pet. preparation is recommended. Whenever there is a positive reaction to fragrance mix 2, additional patch testing with the 6 ingredients, 5 if there are simultaneous positive reactions to hydroxyisohexyl 3-cyclohexene carboxaldehyde and fragrance mix 2, is recommended.     

Pre-employment screening for contact dermatitis among the pupils of a metal industry school

79 male pupils of a metal industry school were investigated, none of whom had yet been occupationally exposed to metals or to cutting oils. In 1 or 2 years, depending on their grade and age, they would all be employees in the metal industry. Each was patch tested with nickel sulfate 5% pet., cobalt chloride 1% pet., and potassium dichromate 0.5% pet., and 28 had a positive reaction to 1 or more of the metals tested. This finding indicates the necessity not only for pre-employment patch testing in industries where contact dermatitis is likely to occur, but that patch testing should be done even earlier in school children, before they decide to enter certain occupations.     

Autoimmune progesterone dermatitis with persistent amenorrhoea

A case of autoimmune progesterone dermatitis is reported. The patient developed a recurrent eruption, primarily on the extremities, after receiving oral progesterone for the treatment of persistent amenorrhoea. Intradermal injection of 17 alpha-hydroxyprogesterone produced a positive skin reaction after 30 min, but no delayed onset reaction was observed. A patch test with progesterone in petrolatum was negative. The lymphocyte transformation test was normal. Histamine release from passively sensitized peripheral blood leukocytes was increased by progesterone preincubated in normal serum as a stimulating antigen. Conjugated oestrogen therapy suppressed the rash. Cyclical eruptions with elevated basal body temperature persisted for more than 20 months without menstruation.     

The possible relevance of sex hormones on irritant and allergic responses: their importance for skin testing

Dermatological responses are affected by the menstrual cycle phase in female patients, an unsurprising observation as oestrogen and progesterone affect the skin and immunological function, with oestrogen suppression of cellular immunity in particular. Exacerbation of dermatological symptoms is typically observed in either the latter phase of the menstrual cycle or during menstruation. The allergic response is diminished in the ovulatory phase and heightened in the progestinic phase. Definitive conclusions with regard to the effect of reproductive hormones on skin disorders have been somewhat hampered by a body of research that has employed diverse research parameters, such as dosage, testing sites, concentration, vehicle of irritant delivery, and method of assessment, however, individual patient sensitivity varies widely. Standardization of measurement techniques is necessary to provide reproducible results as much as individual patient variation and technique will allow.