Contact sensitivity to calcium hypochlorite

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Contact sensitivity to calcium hypochlorite

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Pankaj S. Salphale and Shrutakirthi D. Shenoi Department of Dermatology, Kasturba Medical College, Manipal, India

Key words: Eusol; calcium hypochlorite; contact allergy; medicaments.

Eusol (an abbreviation for Edinburgh University solution), consisting of aqueous boric acid and calcium hypochlorite, is widely used in the management of open wounds left to heal by secondary intention (1).

Case Report A 13-year-old boy with type II hereditary sensory autonomic neuropathy had been using Eusol soaks for recurrent trophic ulcers since the age of 4 years. He presented with itchy papulovesicular lesions on the dorsa of both feet for 1 month. He had applied neomycin cream on and off for the ulcers and wore cotton socks and rubber footwear with leather straps throughout the day. He was patch tested with a standard series of allergens obtained from Systopic Laboratories, New Delhi, India (Indian standard series), selected allergens of a rubber additives series (mercaptobenzothiazole, thiuram mix, carba mix, mercapto mix and diphenylguanidine), and selected allergens of a textiles series (dimethylol dihydroxyethylene urea, Disperse Blue 106/124, ureaformaldehyde resin and melamineformaldehyde resin), along with leather and foam of footwear, samples of coloured socks, and Eusol (containing 125 g each of boric acid and calcium hypochloritc in 100 mL of water). The following were positive on day (D) 2 and D3:

diphenylguanidine –/þ; neomycm þþ/þþ; gentamicin þþ/þþ; lanolin alcohol þ/þþ; Eusol þþ/þþ.

He was later tested with the individual components of Eusol and reacted to calcium hypochlorite (5% aqueous), which was negative in 10 controls. A scratch-patch test with calcium hypochlorite wias negative at 20 min, though a delayed reading at D2 and D3 was þ/þþ. Although Eusol was discontinued, the eruptions persisted.

Discussion Calcium hypochlorite is used in the preparation of disinfectants like surgical chlorinated soda solution and Eusol. Hypochlorites are also used in disinfecting public water supplies, where they release hypochlorous acid and hypochlorite ions on reacting with water (2). Exposure to hypochlorites occurs occupationally in dye factory workers, who use it to remove dye stains from the skin (3), in domestic settings from bleaches and detergents (4) and recreationally, in chlorinated swimming pool water (5). Hypochlorite is also used in endodontic treatment for irrigation of the root canal system (6). There are no reports of contact sensitivity to calcium hypochlorite, though sensitivity to sodium hypochlorite has been reported (4–6). Our patient had multiple sensitivities to various topical medicaments. It was difficult to establish the exact cause of the dermatitis as it persisted despite stopping all suspected allergens.

References 1. Leaper D J, Eusol. Br Med J 1992: 304: 930–931. 2. Parfitt K, eds. Disinfectants and preservatives. In: The Complete Drug Reference, 3rd edn. London: Pharmaceutical Press, 1999. 3. Schwartz L, Tulipan L, Birmingham D J. Occupational Diseases of Skin, 3rd edn. Philadelphia: Lea & Febiger, 1957.


4. Habets J M W, Geursen-Reltsma A M, Stolz E, Van Joost T. Sensitization to sodium hypochlorite causing hand dermatitis. Contact Dermatitis 1986: 15: 140–142. 5. Sasseville D, Geoffrion C T, Lowry R N. Allergic contact dermatitis from chlorinated swimming pool water. Contact Dermatitis 1999: 41: 347–348. 6. Kaufman. A Y, Keila S. Hypersensitivity to sodium hypochlorite. J Endod 1989: 15: 224–226.

Address: Dr Shrutakirthi D Shenoi Department of Dermatology Kasturba Medical College and Hospital Manipal 576,119 India Tel: þ 91 825 571200 (19 lines) Fax: þ 91 825 570062 e-mail: [email protected]

Drug intolerance reaction to insulin therapy caused by metacresol V. Clerx, C. Van Den Keybus, A. Kochuyt1 and A. Goossens Department of Dermatology,1Department of Internal Medicine, K.U. Leuven, University Hospital St. Rafael, 1Gasthuisberg, Leuven, Belgium

Key words: drug eruption; injection; insulin; metacresol; preservative; patch testing.

Drug intolerance reactions to insulin therapy are rarely caused by metacresol. These may, however, cause much discomfort when not recognized, as almost all commercially available types of human insulin contain metacresol as a preservative.

Case Report A 76-year-old woman with Type I diabetes had been treated since 1996 with various human insulins with no adverse reactions. In 1999, however,


she began to develop erythematous, burning lesions at the injection sites on the day after each injection. The lesions lasted for 1–2 weeks and were independent of the type of human insulin used or the site of the injection. On referral, clinical examination showed erythematous lesions at injection sites over the abdomen. A biopsy showed significant, non-specific inflammation compatible with a toxic drug reaction: there was no clear evidence of either a Type III or a Type IV hypersensitivity reaction. We performed intradermal tests with histamine, which were positive, and with media containing human insulin, parahydroxybenzoate esters, phenol, metacresol, zinc insulin, isofane insulin and protamine, which were all negative. Subcutaneous injections with a blank solution (sodium chloride), a medium containing metacresol, insulin and glycerol were also negative after 20 min, as well as later. Patch testing was positive to nickel sulphate 5% petrolatum, and to the various media containing human, pork and isofane insulin. A positive patch test was also seen to the metacresol medium, which was present in all the insulins tested. This medium contained metacresol (3 mg/mL) and glycerol (16 mg/mL), the latter being negative when patch tested alone. The patient is now being treated with a metacresol-free human insulin and is free from lesions. She also reports fewer headaches and less gastric pain.

Discussion Local reactions to insulin injections can be caused by true or false insulin allergy. 3 different types of true insulin allergy have been described. The 1st is a Type I, IgE-mediated reaction causing localized or generalized urticaria, angioedema and, rarely, anaphylaxis. The 2nd is a Type III, IgG-mediated reaction that can cause localized (Arthus phenomenon) or generalized (serum sickness type) reactions. And, 3rd, there is a Type IV reaction that manifests as a local skin reaction. False insulin allergy may be due to local disinfectants, nickel, zinc, protamine, preservatives and solvents, such as metacresol, glycerol, phenol and sodium phosphate (1). Our patient had Type IV hypersensitivity to metacresol (and nickel). Allergic reactions to metacresol are known to cause erythematous, burning lesions at the injection sites on the

day after the subcutaneous administration of insulin (1). Between January 1999 and June 2002, 2 other cases of allergic reaction to metacresol were reported to Novo Nordisk A/S, Bagsvaerd, Denmark, one of the producers of human insulin: these patients experienced not only local reactions at the insulin injection sites but also systemic reactions, such as nausea, headache, sweating and diarrhoea, some of which were also reported by our patient. As almost all commercially available human insulins contain metacresol, only the few with other pre-servative agents (Monotard, Ultratard, also from Novo Nordisk A/S, Denmark) can be used in diabetic patients with metacresol allergy. In addition, the short-acting insulin preparations also contain metacresol. When Novo Nordisk became aware of the possibility of such reactions, they produced a short-acting insulin containing methylparaben as a preservative instead. This metacresol-free insulin is not commercially available, but can be obtained from Novo Nordisk once allergy to metacresol has been demonstrated.

References 1. Plantin P, Sassolas B, Guillet M-H. Accidents cutane´s allergiques aux insulines. Ann Dermatol Venereol 1988: 115: 813–817.

Address: A. Goossens Department of Dermatology K.U. Leuven University Hospital St. Rafae¨l B-3000 Leuven Belgium

Acute irritation followed by primary sensitization to 2-cyclohexen-1-one in a chemistry student A. Goossens and A. Deschutter Department of Dermatology, Katholieke Universiteit Leuven, Leuven, Belgium

Key words: allergic contact dermatitis; cyclohexenone; chemist, laboratory; CAS 930-68-7.


Case Report A 22-year-old chemistry student presented on 4 April 2002 with a large bulla on the dorsal aspect of the left wrist (exactly where he wore a watch) and 2 smaller bullae on the dorsum of the left hand. 2 weeks previously, he had had a chemical burn due to accidental contact with 2-cyclohexene1-one, a hydrocarbon that he was using to produce its hydrogenated derivative. He had been wearing vinyl gloves but some of the product had entered under the glove and laboratory jacket and had collected under his watchband, where the eruption had first started. At a hospital emergency room, he was treated with amoxicillin and clavulanic acid 875 mg 3/day and topical application of a silver sulfadiazine and iodine-PVP preparation. He continued this treatment for 2 weeks, but the skin eruption got worse: the left arm began to become erythematous and swollen, and a palpable adenopathy developed in the axillary region. He consulted a general practitioner, who prescribed oral corticosteroids (methylprednisolone starting at 64 mg/day). When he consulted us 2 days later, dermatologic examination showed a very tense, organized (fibrotic), erythematous blister about 6 cm in diameter with a yellowish exudate on the dorsal aspect of the left wrist (Fig. 1). Around the blister was a poorly demarcated erythema. On the lateral and medial aspects of the dorsum of his hand, we noted 2 maculopapular lesions about 2 cm in diameter, which, according to the patient, had only recently appeared. The patient was otherwise in good health and was not taking any medication. He had no history of contact allergy or personal atopy (his brother had hayfever). A blood test showed a normal CRP, normal ESR, raised leucocytosis (14, 200), raised neutrophils (941%), lowered lymphocytes (5%) (perhaps an effect of the oral corticosteroids), and negative ASLO. A bacterial culture was sterile. We diagnosed a primary sensitization following a severe acute irritant reaction to 2-cyclohexene-1-one. We prescribed local treatment consisting of water paste and compresses with saline solution, followed later by topical application of betamethasone dipropionate. The dosage of peroral methylprednisolone was gradually



cyclohexanone resin in paints (3), has been reported in the literature. However, we found no reports on cyclohexenone, which, according to Jean-Pierre Lepoittevin (personal communication), may be a stronger sensitizer than cyclohexanone. Chemical intermediates are generally chemically very reactive agents and may be both irritants and sensitizers. We describe a primary sensitization reaction following an acute irritant contact dermatitis caused by 2-cyclohexen-1-one.

References 1. Occupational contact dermatitis from cyclohexanone as a PVC adhesive. Contact Dermatitis 1992: 27: 189–190. 2. Sensitivity to 2-chlorocyclohexanone and its derivatives. Contact Dermatitis 1977: 3: 195–197. 3. Contact allergy to a cyclohexanone resin in humans and guinea pigs. Contact Dermatitis 1988: 18: 46–49.

Fig. 1. Clinical picture of the severe primary sensitization reaction to 2-cyclohexen1-one.

decreased over a period of 4 weeks. It had to be increased again from 4 to 16 mg 2 weeks later because of a flare-up at the previous sites and the appearance of small erythematous papules, which had spread over both arms. Systemic corticosteroid therapy was stopped after another 2 weeks and, by the middle of May, the dermatitis was clear, leaving only a hyperpigmented lesion on his wrist, which was still visible in October 2002. Patch testing was proposed but the patient refused. He avoided all further contact with this product during his laboratory work and always wore gloves when handling solvents and other chemical products. He has developed no lesions since.

Discussion 2-Cyclohexene-1-one is a derivative of cyclohexene (Fig. 2) and is manufactured by dehydration (e.g. with sulfuric acid) of cyclohexanol at high temperatures over various catalysts. It can also be made by the

distillation of cyclohexanol over silica gel or alumina. It is a clear light-yellow-to-yellow water-soluble liquid and is frequently used as a chemical intermediate. According to the material safety data sheet, its purity is 97%, and it may cause harmful effects when inhaled or swallowed or may be toxic in contact with the skin. Occupational contact dermatitis from cyclohexanone (1) and some of its derivatives (2), as well as from


Address: A. Goossens Department of Dermatology Katholieke Universiteit Leuven B-3000 Leuven Belgium

Glucosides as unexpected allergens in cosmetics A. Goossens, T. Decraene, N. Platteaux, A. Nardelli and V. Rasschaert Department of Dermatology, University Hospital, Katholieke Universiteit Leuven. Leuven, Belgium

Key words: allergic contact dermatitis; cleansing agent; cetearyl glucoside; coco-glucoside; lauryl glucoside (CAS 27836-64-2); cosmetics; surfactants.

Fig. 2. Chemical formula of 2-cyclohexen-1-one (CAS 930-68-7) (CAS 93068-7).

Glucosides are the condensation products of fatty alcohols with glucose. They are widely used as surfactants, emulsifiers, and cleansing agents in skin care, cleansing and fragrance products, as well as in hair dyes and tanning products (1). They are considered mild irritants and are often


mixed with other surfactants, their irritant potential depending on total surfactant concentration, application mode, thermodynamic activity and chemical structure (2).

Case Reports

Case no. 1 A 55-year-old man, with no atopic history, presented in December 2000 after 8 months of recurrent papular and erythematosquamous lesions on the face (sometimes plus oedema), neck, forearms, wrists and dorsa of the hands. This was associated with his work, where he came into contact with epoxy-coated fibreglass. Patch testing in January 2001 with the European standard series, an epoxy-resin series and the patient’s own materials was positive to epoxy resin 1% pet. (þ þ on day (D) 2 and D4) and to a semi-open test (3) with his own shampoo (þ on D2). In addition, he alone, among 30 subjects predictively tested with 6 different shower gels (semi-open, to determine their irritant potential), reacted positively to all products tested (þ þ on D2 and D4). The common ingredient in all 6 was coco-glucoside, and in 5 out of 6 lauryl glucoside as well. In March 2002, the patient was tested with all the ingredients. Positive reactions were obtained only to coco-glucoside and lauryl glucoside (Table 1). The ingredients of his own shampoo were negative, hence the previous patch-test reaction was probably irritant. The positive epoxy resin was considered relevant and confirmed the occupational cause of his partly airborne dermatitis. However, he was found by chance also to be allergic to glucosides. We did not obtain the

composition of the soap he used at work, but it gave a negative semiopen test (3). In July 2002, the patient reported that he had not had any dermatitis since he had changed to a new job as a warehouse man, except once when he had again come into contact with waste material containing epoxy resin. He had only been using cleansing products without glucosides, as we had advised him (4).

Case no. 2 A 46-year-old nurse with atopic eczema (total IgE 447 k/L) presented in September 2001 with chronic hand dermatitis, which had been present since 1981 and was related at the time to her occupation. She had been transferred in 1990 to a medical technical department (stock management in the hospital pharmacy) to avoid further contact with antiseptics, disinfectants and detergents. She had been free of dermatitis until 1997. Clinical examination showed severe erythema, scaling and fissuring of the tips and sides of digits 1, 2, and 3, and the palmar and dorsal aspects sides of the right hand, accompanied by paronychia; on the left hand there were similar but less severe lesions on digits 2, 3, and 4. She arranged flowers as a hobby and wore rubber gloves over cotton gloves (dermatitis had occurred when using latex gloves alone). However, she did not always wear gloves while doing housework, even though handling certain fruits caused a burning sensation. She was intolerant to nickel jewellery. Prick testing with latex was negative, and no latex-specific IgE was detected. Patch testing with the European standard series, a rubber


series, a cosmetics series, and the patient’s own cosmetic products was positive to nickel sulphate 5% petrolatum (þ on D2 and D4). She also reacted to 2 sun sprays out of 13 sun products predictively tested (as is) on her as well as on 29 other subjects, all of which were negative. The only ingredients common to both products were octyl palmitate, cetearyl glucoside and galactorabinan. Since neither cetearyl glucoside nor the other compounds were available, we tested her with coco-glucoside (5% pet.) and lauryl glucoside (5% pet.), with the positive results shown in Table 1. We repeated the history and found that she had been cleaning her hands with a lotion that contained both coco- and lauryl glucosides. She later informed us of contact with 2 other glucoside-containing products: a body lotion and a sun cream that she had applied to her child’s skin. This might account for the localization of the more severe lesions on the right hand rather than the left. In July 2002, we examined the patient again. After applying potent topical corticosteroids daily in combination with a moisturizing cream and complete avoidance of glucosidecontaining cosmetics (4), her dermatitis had cleared almost completely. We diagnosed her dermatitis as a hybrid eczema (5), i.e. a combination of atopic, irritant, and allergic contact dermatitis, the latter having played a major role in the recurrence of hand dermatitis over the last 4 years.

Discussion Glucosides have, to the best of our knowledge, not been described as contact allergens, and are regarded

Table 1. Positive patch test results to the glucosides tested Test materials*

Lauryl glucoside 53% aq. (semi-open) Lauryl glucoside 12% aq. Lauryl glucoside 10% pet. Lauryl glucoside 5% pet. Coco-glucoside 35% aq. Coco-glucoside 10% pet. Coco-glucoside 5% pet.

Case no. 1

Case no. 2









þþ þþ þþ þþ þþ þþ

þþ þþ þþ þþ þþ þþ


NT NT þþ NT NT þ

*The preparation of lauryl glucoside was prepared from Plantacare 1200 (Henkel, Du¨sseldorf, Germany), which contains 53% water. The preparation of coco-glucoside was prepared from Lamesoft PO-65 containing 35% coco-glucoside, 30% glyceryl oleate, and 35% water (Henkel).



as mild irritants (5 control subjects were tested with both coco- and lauryl glucoside, 5% pet., and did not show any reaction). We here unexpectedly identified glucosides as contact allergens in cosmetic preparations, and established relevance to the recurrence of eczema on the hands in 1 of the 2 subjects found to be allergic to these compounds.

References 1. Anonymous. International Cosmetic Ingredient Dictionary and Handbook, 8th edn., Vol. 1. Washington, DC: The Cosmetic, Toiletry, and Fragrance Association, 2000: 242, 342, 777. 2. Turkoglu M, Pekmezci E. Evaluation of irritant potential of surfactant mixtures. Int J Cosmet Sci 1999: 21: 371–382. 3. Dooms-Goossens A. Patch testing without a kit. In: Guin J D, ed. Practical Contact Dermatitis. A Handbook for the Practitioner. New York: McGraw-Hill, 1995: 63–74. 4. Goossens A, Drieghe J. Computer applications in contact allergy. Contact Dermatitis 1998: 38: 52. 5. Malten K E, Nater J P, Van Ketel W G. Patch Testing Guidelines. Nijmegen: Dekker & van de Vegt, 1976: 5–9.

Address: A. Goossens Department of Dermatology University Hospital K.U. Leuven Kapucijnenvoer 33 B-3000 Leuven, Belgium

Case Report A 42-year-old woman presented with a history of a severe rash following the use of hair dye. For 2 years prior to presentation, she had been using hair rinses every 6–8 weeks. 1 month prior to the severe reaction, she had dyed her hair and noted mild transient scalp itching. She subsequently used the same hair dye and within 2 h of application her scalp was red and weeping. Shortly afterwards, she developed an eczematous rash involving the periorbital area, forehead, ears, cheeks and sides of the neck. This progressed to involvement of the trunk and buttocks. She required intramuscular and topical corticosteroids and the rash eventually cleared after 4 months. There was no personal or family history of atopy. She was known to be nickel-allergic. A 20-min occluded patch test with para-phenylenediamine (PPD) base 1% petrolatum resulted in an immediate urticarial reaction at the test site (right ventral forearm). 48 h later, an eczematous reaction developed at this site. Patch tests were performed with an extended British standard series, a hairdressing series and a textile dye series, excluding PPD, isopropyl PPD and nickel. At D4 she had the following reactions: quaternium 15 þ þ, methyldibromo glutaronitrile þ þ, Disperse Orange 3 þ þ, Disperse Orange 1 þ þ þ, Bismarck Brown þ þ and Reactive Black þ þ.


Immediate-type hypersensitivity and allergic contact dermatitis due to paraphenylenediamine in hair dye G. A. E. Wong and C. M. King Department of Dermatology, Royal Liverpool University Hospital, Prescot St., Liverpool L7 8XP, UK

Key words: allergic contact dermatitis; immediate-type hypersensitivity; immediatetype contact allergy; contact urticaria; paraphenylenediamine; hair dye.

PPD is an organic aromatic amine present in hair dyes and well known to cause allergic contact dermatitis. More rarely, Type 1 hypersensitivity reactions, including contact urticaria and anaphylaxis, can occur (1, 2). Fatal anaphylaxis from hair dye has also been reported (3). Combined immediate and delayed hypersensitivity to PPD occurring in the same patient, as in this case, has been reported previously but is rare (4). In a review of the contact urticaria syndrome (5), a number of cases with combined immediate and delayed hypersensitivity to various substances, including 1 to PPD, are described and the authors suggest the term ‘contact dermatitis of immediate and delayed type’ for these patients.

Azo and anthraquinone dyes are known to cross-react with PPD (6). This explains the reactions to clothing dyes in this patient. The prognosis of PPD-induced dermatitis appears to be good. There was clearance of dermatitis in 17 of 20 patients with positive patch test reactions to PPD of ‘present relevance’ after avoiding PPD-containing hair dyes (7). Investigation of hair dye allergy, particularly where immediate hypersensitivity is suspected, should be undertaken with caution and with resuscitation facilities available.

References 1. Temesvari E. Contact urticaria from paraphenylenediamine. Contact Dermatitis 1984: 11: 125. 2. Fukunaga T, Kawagoe R, Hozumi H, Kanzaki T. Contact anaphylaxis due to para-phenylenediamine. Contact Dermatitis 1996: 35: 185–186. 3. Belton A L, Chira T. Fatal anaphylactic reaction to hair dye. Am J Forensic Med Pathol 1997: 18: 290–292. 4. Edwards E K, JrEdwards E K. Contact urticaria and allergic contact dermatitis caused by paraphenylenediamine. Cutis 1984: 34: 87–88. 5. Von Krogh G, Maibach H I. The contact urticaria syndrome-an updated review. J Am Acad Dermatol 1981: 5: 328–341. 6. Rietschel R L, Fowler J F. Fisher’s Contact Dermatitis, 4th edn. Baltimore: Williams & Wilkins, 1995. 7. Chan Y C, Ng S K, Goh C L. Positive patch-test reactions to para-phenylenediamine, their clinical relevance and the concept of clinical tolerance. Contact Dermatitis 2001: 45: 217–220.

Address: Gavin Wong Department of Dermatology Royal Liverpool University Hospital Prescot St. Liverpool L7 8XP UK Tel: þ 44 151706 2000 Fax: þ 44 151706 5897 e-mail: [email protected]


Delayed hypersensitivity reaction to the non-ionic X-ray contrast medium Visipaque1 (iodixanol) Javier Sa´nchez-Pe´rez, Marı´a Garcı´a F-Villalta, Sara Alvarez Ruı´z and Amaro Garcı´a Diez Department of Dermatology, Hospital Universitario de la Princesa, Universidad Auto´noma de Madrid, Spain

Key words: X-ray contrast medium; Visipaque1; iodixanol; delayed cutaneous reactions; positive patch test.

Adverse reactions to iodinated X-ray contrast medium (CM) have been divided into immediate and late. Late reactions occur in between 05% and 2% of patients exposed to non-ionic iodinated X-ray contrast medium (1, 2), cutaneous involvement being their most frequent manifestation (3). A maculopapular exanthema, erythema multiforme, erythema, urticaria and angioedema are the most common types, fixed drug eruption, cutaneous vasculitis, Stevens–Johnson syndrome and toxic epidermal necrolysis being less common forms (4). Visipaque1 (iodixanol, iodine, trometamol) is a water-soluble, low-osmolar, non-ionic, dimeric, hexa-iodinated CM for general vascular use (5).

Case Report A 76-year-old man with hypercholesterolemia, hypertension, angina pectoris, prostatic hypertrophy and trigeminal neuralgia was on treatment with Zocor1, Enalapril1, Emconcor1, Omnic1, and Tegretol1. In March 1999, he was admitted to hospital to undergo cerebral arteriography, for which he received 150 mL of a CM i.v. (Visipaque1, 320 mg/mL, Nycomed Amersham, Madrid, Spain). Some hours after administration of the CM, itchy, erythematous, scaly plaques appeared on the back and chest, spreading to the abdomen and limbs. Histopathological examination showed psoriasiform hyperplasia, parakeratosis with focal plasma accumulation, spongiosis, oedema in the papillary dermis and a mixed perivascular infiltrate, composed mainly of lymphocytes and eosinophils. The cutaneous lesions disappeared in

20 days after treatment with oral corticosteroids and antihistamines. After this episode he was asymptomatic until September 2001, when he again received an arterial infusion of Visipaque1 for coronary arteriography. This time, he was pretreated with corticosteroids and antihistamines. 2 days later, non-itchy erythematoedematous lesions appeared on the back and chest, spreading to the limbs. These lesions disappeared in 10 days after treatment with oral corticosteroids and antihistamines. Patch tests were performed with the Spanish standard series, Visipaque1 and its individual components (iodixanol, iodine, trometamol). There was a positive reaction at day (D)2 and D4 to Visipaque1 and to 1 of its components, iodixanol, at 01%, 2% and 5% aqueous. 35 controls tested with iodixanol at 5% aq. were negative.

Discussion We have found no previous report of a patient with a positive patch test to iodixanol, as described in this report. The risk factors for late cutaneous reactions to CM have not been elucidated, though the history of a previous late cutaneous reaction has been proposed as the most frequent factor (6). In a recent review (4), patch tests and intradermal tests have been used in isolated cases when a late cutaneous reaction to other contrast media has been suspected. Akiyama et al. (7) studied 58 patients who presented clinically with erythemamultiforme-like lesions after the administration of non-ionic contrast media. In this study, positive results were more common with intradermal tests than with patch tests. However, the vehicle, the reading time and the location of the patches may influence such results. Non-ionic X-ray CM molecules are non-reactive and unable to bind covalently to protein. They may, however, bind to the major histocompatibility complex and the T-cell receptor, stimulating these, without covalent linkage to the peptide (8). References 1. Pedersen S H, Svaland M G, Reiss A-L, Andrew E. Late allergy-like reactions following vascular administration of radiography contrast media. Acta Radiol 1998: 39: 344–348.

167 2. Rydberg J, Charles J, Aspelin P. Frequency of late allergy-like adverse reactions following injection of intravascular non-ionic contrast media. A retrospective study comparing a non-ionic monomeric contrast medium with a non-ionic dimeric contrast medium. Acta Radiol 1998: 39: 219–222. 3. Yasuda R, Munechika H. Delayed adverse reactions to nonionic monomeric contrast-enhanced media. Invest Radiol 1998: 33: 1–5. 4. Christiansen C, Pichler W J, Skotland T. Delayed allergy-like reactions to X-ray contrast media: mechanistic considerations. Eur Radiol 2000: 10: 1965–1975. 5. Almen T. Visipaque: a step forward. A historical review. Acta Radiol 1996: 36: 2–18. 6. Bettmann M A, Heeren T, Greenfield A, Goudey C. Adverse events with radiographic contrast agents. results of the SCVIR Contrast Agent Registry. Radiology 1997: 203: 611–620. 7. Akiyama M, Nakada T, Sueki H, Fujisawa R, Iijima M. Drug eruption caused by non-ionic iodinated X-ray contrast media. Acad Radiol 1998: 5: s159–s161. 8. Zanni M P, von Greyerz S, Schnyder B et al. HLA-restricted, processing- and metabolism-independent pathway of drug recognition by human T lymphocytes. J Clin Invest 1998: 102: 1591–1598.

Address: Javier Sa´nchez-Pe´rez Servicio de Dermatologı´a Hospital Universitario de la Princesa C) Diego de Leo´n 62, 28006 Madrid Spain Fax: þ 34 91 5202435

Allergic contact dermatitis due to DL-atocopheryl nicotinate Haruko Oshima, Kaori Tsuji, Tsunao Oh-I and Michiyuki Koda Department of Dermatology, Tokyo Medical University, Tokyo, Japan

Key words: DL-a-tocopheryl nicotinate; vitamin E; allergic contact dermatitis; medicaments; cosmetics; lack of crosssensitivity.

Currently, many commercially available and prescribed drugs contain vitamin F, although this is not always mentioned on the label.



Fig. 1. Structures of patch test reagents.

Case Report A 32-year-old woman, with a past history of seasonal allergy to cedar pollen, and contact dermatitis from various topical agents and cosmetics, applied Medicated Cream for Hands and Fingers N1 (Kanebo Co. Ltd, Tokyo, Japan) to her trunk and extremities after swimming. On the following day, she presented with itchy eruptions where the cream had been applied. There was a welldefined oedematous erythema at these sites. We performed patch tests with Finn Chambers readings at 2 and 3 days according to the guidelines of the ICDRG. She was positive to the applied cream, as is. Thereafter, patch tests were performed with the Japanese standard series (Japanese Society for Contact Dermatitis) and the components of Medicated Cream for Hands and Fingers N1 cream. These were positive to nickel sulphate (25% petrolatum) (þ), potassium dichromate (05% pet.) (þ), Myroxylon Pereirae resin (25% pet.) (þ), colophonium (20% pet.) (þ), fragrance mix (8% pet.) (þ), and PPD (1% pet.) (þ) and DL-a-tocopheryl nicotinate (DLa-TN) (0.1% pet.) (þ), but negative to the other components of the cream. Patch tests with naturally occurring vitamin E D-a-tocopherol (1% pet.), its optical isomer, synthetic vitamin E DL-a-tocopherol (1% pet.), Nicotinell TTS1 (Nicotine) (Novartis Pharma Co. Ltd, Tokyo, Japan) (as is) and nico-

tinamide (1% pet.) (Fig. 1) were all negative. Patch tests performed with DL-a-TN (01% pet.) in 3 healthy volunteers were all negative.

Comment Nicotinic acid ester of vitamin E (DLa-TN), which has the additive effects of vitamin E and nicotinic acid, was developed as an ethical drug in 1967, and its use has since extended to cosmetics. A stable prolonged peripheral-blood flow-facilitating effect (1, 2), lipid metabolism-improving effect (3), vessel-reinforcing effect (4), antiplatelet-aggregation effect (5) and plasma partial oxygen pressure-elevating effect of DL-a-TN orally have been demonstrated. When applied locally, DL-a-TN can be absorbed through the skin (6). Vogel (7) applied 2 creams, one containing DL-a-TN and the other containing methyl nicotinate (vasodilator) at 05%, to human skin to compare elevation in skin temperature. Although DL-a-TN contains 25% or less nicotinate than methyl nicotinate, it showed a comparable effect. Drug eruptions due to DL-a-TN have been reported, but this is the first case of allergic contact dermatitis to be reported, to our knowledge. Since other forms of vitamin E were negative on patch testing, such antigenicity would seem to be specific to DL-a-TN.

Acknowledgements Our thanks to Eisai Co. Ltd. (Tokyo, Japan) for providing DL-a-tocopherol and D-a-tocopherol. References 1. Kaminura M. Am J Clin Nutr 1974: 27: 1110. 2. Asano M, Ohkubo C, Sawanobori K, Yonekaw K. Biochem Exp Biol 1980: 16: 341. 3. Takiuchi N. Tocopherol. Oxygen and Biomembranes. Amsterdam: Elsevier, 1978: 257. 4. Saitou Y, Shinomiya M, Kumagai A. Ann New York Acad Sci 1982: 393: 183. 5. Hamerin S S W, Chan A C. Lipids 1983: 18: 267. 6. Kaminura M, Matsuzaka T. J Vitaminol 1968: 14: 150. 7. Vogel F G M. Parfumerie Kosmet 1971: 21: 674. 8. Huruyano T, Taniguchi Y, Taniguchi A. A case of drug eruption due to Juvera N1 with. Sjogren syndrome [in Japanese]. Nishinihon J Dermatol 1994: 56: 625.

Address: Haruko Oshima Department of Dermatology Tokyo Medical University 6-7-1 Nishi-shinnjuku Shinnjuku-ku Tokyo, 160–0023 Japan Tel: þ 81 33342 6111 ext 5824 Fax: þ 81 33342 2055 e-mail: [email protected]


Clindamycin-associated acute generalized exanthematous pustulosis Maria Valois2, Elizabeth J. Phillips1,2, Neil H. Shear1,3 and Sandra R. Knowles1,4 1

Division of Clinical Pharmacology, 2Division of Infectious Disease, 3Division of Dermatology, 4 Department of Pharmacy, Sunnybrook & Women’s College Health Sciences Centre, Drug Safety Clinic, Toronto, Ontario, Canada

Key words: clindamycin; cutaneous adverse drug reaction; positive patch test; antibiotics.

distal left ring finger unresponsive to 3 weeks of oral cephalexin in January 2002. He was admitted to hospital and given intravenous prostaglandin E1 for 3 days. He was discharged on oral levofloxacin 500 mg 1 daily and oral clindamycin 300 mg 4 daily. Within 36 h of starting these antibiotics he developed a mildly pruritic generalized erythematous rash. He immediately stopped both antibiotics. The rash took approximately 1 week to resolve. Patch testing was performed 6 weeks later with 1% pet. clindamycin. A pustular patch reaction was demonstrated at D2 and D4. Intradermal testing to fluoroquinolones and oral challenge with levofloxacin 3 months later were negative.

169 6. Barbaud A, Reichert-Penetrat S, Trechot P et al. The use of skin testing in the investigation of cutaneous adverse drug reactions. Br J Dermatol 1998: 139: 49–58. 7. Schwab R A, Vogel P S, Warschaw K E. Clindamycin-induced acute generalized. exanthematous pustulosis. Cutis 2000: 65: 391–393.

Address: Elizabeth J. Phillips, MD, FRCPC Sunnybrook & Women’s College Health Sciences Centre 2075 Bayview Avenue, Room E240 Toronto, Ontario M4N 3M5 Canada Tel: þ 1 416 480 5162 Fax: þ 1 416 480 4326 e-mail: [email protected]

Case Reports

Case no. 1 A 69-year-old man presented with a mouth abscess 2 weeks after oral biopsy in May 2001. He was started on oral clindamycin 300 mg 4 daily. On day (D) 3 he developed a pruritic truncal rash. On D4 his temperature rose to 394 ˚ C and the rash spread distally. Clindamycin was replaced with penicillin and metronidazole. The following day he re-attended as an emergency with fever and a generalized exanthema. Penicillin and metronidazole were stopped. Laboratory tests showed a neutrophilic leukocytosis (WBC 337  109/L; neutrophils 314  109/L). A skin biopsy from the forearm showed spongiosis and exocytosis of lymphocytes and some neutrophils with dermal oedema and an interstitial mixed infiltrate of lymphocytes, neutrophils and eosinophils compatible with a pustular drug reaction. The rash resolved within 2 weeks. Patch testing was performed 6 weeks later with 5% in petrolatum of ampicillin and 1% pet. of clindamycin, both being positive at D2 and D3. Intradermal testing was positive to ampicillin at D1, but negative to penicillin G, cloxacillin, cefazolin and cefuroxime. An oral challenge with a single dose of penicillin V (300 mg) was negative. Metronidazole intradermal testing and oral challenge were both negative.

Case no. 2 A 76-year-old man had presented as an emergency with a necrotic ulcer on his

Discussion The cases described presented with clinical pictures compatible with clindamycin-associated AGEP, which was confirmed by positive clindamycin patch testing. Reviews of AGEP describe a pustular rash, leukocytosis and fever, occurring as early as the first 24 h of drug therapy (1). Antibiotics are commonly implicated, the most common being beta-lactams and the macrolides (2). Patch testing to the associated drug has been positive, often with a pustular reaction, in 50% of those with AGEP (3–6). In the only previously published case report linking AGEP to clindamycin, patch testing was not reported (7).

References 1. Beylot C, Doutre M S, Beylot-Barry M. Acute generalized exanthematous pustulosis. Semin Cutan Med Surg 1996: 15: 244–249. 2. Roujeau X, Bioulac-Sage P, Bourseau C et al. Acute generalized exanthematous pustulosis. Arch Dermatol 1991: 127: 1333–1338. 3. Whittam L R, Wakelin S H, Barker J N W N. Generalized pustular psoriasis or drug-induced toxic pustuloderma. The use of patch testing. Clin Exp Dermatol 2000: 25: 122–124. 4. Moreau A, Dompmartin A, Castel B et al. Drug-induced acute generalized exanthematous pustulosis with positive patch tests. Int J Dermatol 1995: 34: 263–266. 5. Vincente-Calleja J M, Aguirre A, Landa N. Acute generalized exanthematous pustulosis due to diltiazern: confirmation by patch testing. Br J Dermatol 1997: 137: 837–839.

‘Buffalo-hump’ dermatitis: a hat trick of antiretroviral sideeffects John R. Sullivan1,2,4, Anita Rachlis3 and Elizabeth Phillips1,3 Divisions of 1Clinical Pharmacology, 2 Dermatology and 3Infectious Diseases, Department of Medicine, Department of Pharmacology, Sunnybrook & Woman’s College Health Sciences Center, University of Toronto Medical School, Ontario, Canada, 4 Skin and Cancer Foundation of Australia, Australia

Key words: dermatitis; contact lipodystrophy; HIV; indinavir; AIDS; skin diseases; eczematous drug eruptions.

Case Report A 49-year-old man with HIV presented with a pruritic back. His medical history included allergic rhinitis, HIV, and a past history of rash associated with sulfamethoxazoletrimethoprim. He had been on antiviral medications for 7 years, including AZT (4 years), ddC (1 years), ddI, d4T, 3TC, indinavir, and saquinavir (all 2 years). He had had no AIDS-defining illnesses. Abnormal blood results following a ‘drug holiday’ just prior to presentation were viral load 254,103 (log 541), CD4 count 360  109/L, cholesterol 648 mmol/L (< 52), HDL 068 mmol/1 (077–168), triglycerides


403 mmol/L (< 23), and lactic acid 35 mmol/1 (05–20). The patient had developed a protuberant ‘buffalo hump’ over several years, with marked fat accumulation over the cervical and thoracic vertebral and paravertebral regions, accompanied by loss of facial and distal limb adipose tissue and increased abdominal girth. He reported that his skin had become dry and more easily irritated by fragranced products, wool, heat and sweating, after commencing combined antiviral therapy including indinavir. Epidermal changes confined to his prominent ‘hump’ occurred in a rhomboidal distribution and had a micropapular, shiny, smooth appearance, consistent with a frictional contact dermatitis (Fig. 1). His antiretrovirals were changed because of drug resistance demonstrated by increasing viral load and mutation analysis. After a ‘drug holiday’ he started nevirapine, nelfinavir, abacavir and lopinavir. 10 days later he complained his skin was hot, and sunburn-like. He had a symmetrical, generalized exanthematic


eruption with white dermographism probably due to nevirapine or lopinavir. The eruption was associated with pruritus, worse over his ‘buffalo hump’, with excoriation and eczematization limited to the ‘hump’. We continued his antiviral combination unchanged, and the exanthematic eruption settled over a week. His symptoms resolved with emulsifiable bath oil, moisturizer, 1% hydrocortisone ointment, diphenhydramine hydrochloride, wearing soft, smooth cotton tops, and not wearing a backpack. Since his most recent change in antiviral therapy the patient’s ‘buffalo hump’ has slowly become less prominent.

Discussion Several different side-effects of antiretroviral drugs contributed to this presentation with ‘buffalo-hump’ dermatitis: ‘lipodystrophy’, asteatotic ‘sensitive’ skin, plus a ‘hot’ pruritic exanthematic drug eruption. These led to a long-standing frictional contact dermatitis and superimposed

subacute eczema. 3 factors are thought important in causing frictional dermatitis: intrinsic skin factors, intensity of frictional trauma and the skin’s surface architecture (1, 2). Our patient exhibited evidence that all 3 had played a role. Antiretroviral therapy and HIV infection is associated with alterations in cholesterol, other lipids and fat redistribution. The development of a ‘buffalo hump’ can be part of this fat redistribution or ‘lipodystrophy’ syndrome (3). The patient’s altered body habitus and abnormal serum lipid profile were consistent with this syndrome. Cholesterol and other lipids are important to skin barrier function and skin desquamation (4). Many patients on antiretroviral therapy notice their skin becomes dry and develop asteatotic eczema, and/or irritable ‘sensitive’ skin (5). His abnormal upper body shape and irritable skin placed him at increased susceptibility to ‘normal’ frictional stimuli. Once recognized, this was correctable by simple measures to reduce friction and restore barrier function.

References 1. Freeman S. Repeated low-grade frictional trauma. In: Kanerva L, Elsner P, Wahlberg J E, Maibach H I, eds. Handbook of Occupational Dermatology. Berlin: Springer, 2000: 111– 115. 2. Menne´ T, Hjorth N. Frictional contact dermatitis. Am J Ind Med 1985: 8: 401– 402. 3. Carr A, Cooper D A. Adverse effects of antiretroviral therapy. Lancet 2000: 356: 1423–1430. 4. di Nardo A, Sugino K, Wertz P, Ademola J, Maibach H I. Sodium lauryl sulfate (SLS) induced irritant contact dermatitis. a correlation study between ceramides and in vivo parameters of irritation. Contact Dermatitis 1996: 35: 86–91. 5. Calista D, Boschini A. Cutaneous side effects induced by indinavir. Eur J Dermatol 2000: 10: 292–296.

Fig. 1. Frictional contact dermatitis over ‘buffalo hump’.

Address: Dr Elizabeth Phillips Department of Clinical Pharmacology, E-240 Sunnybrook & Women’s College Health Science Centre 2075 Bayview Ave. Toronto, Ontario M4N 3M5 Canada Tel: þ 1 416 480 5162 Fax: þ 1 416 480 4326 e-mail: [email protected]


Occupational airborne allergic contact dermatitis from mesna Marta Kiec-Swierczynska and Beata Krecisz Nofer Institute of Occupational Medicine, Lodz, Poland

Key words: airborne allergic contact dermatitis; medicaments; mesna; nurse; occupational; healthcare workers.

Mesna, a local mucolytic and also an antidote to acrolein  a metabolite formed during biotransformation of cyclophosphamide and iphosphamide, showing irritant activity to bladder mucosa  has caused cutaneous reactions in individual patients receiving the drug orally or by intravenous injection (1–4). Two distinct types of drug eruption have been observed: one, an extensive maculopapular rash on the face and trunk together with conjunctivitis, periorbital oedema and fever; the other, a widespread fixed drug eruption.

Case Report A 38-year-old atopic nurse, hypersensitive to house dust mite and with known bronchial asthma, had been employed for 17 years on an infant surgery ward. For around 7 years she had experienced recurrent itchy erythematous papulovesicular lesions on exposed parts of the body (face, neck, forearms, dorsum of the hand). She had noted that lesions occurred after assisting in sessions during which small children inhaled Mistabron1 (mesna) (Pliva, Cracow, Poland)., Patch tests with a standard series (Chemotechnique Diagnostics, Malmo¨, Sweden) were positive to nickel (þ þ þ) and chromate (þ þ þ). Patch tests with the antiseptics 01% benzalkonium chloride, 05% chlorhexidine digluconate, 05% chloramine, 02% glutaraldehyde and 2% glyoxal were all negative. A patch test with Mistabron1 1% aq. was þ þ at D2 and þ þ þ at D4, while at 01% aqeous it was negative at D2 and þ þ at D4. Open skin test and prick test with Mistabron1 1% aq. were negative. After inhalatory provocation with Mistabron1 10% aq. no

specific allergic respiratory reaction was recorded; however, after 24 h, cutaneous lesions, on the face and neck in particular, became more intense. Diagnostics for latex allergy comprising RAST (Allergopharma, Joachim Ganzer KG: Reinbek, Germany) and prick tests (Allergopharma, Joachim Ganzer KG: Reinbek, Germany) were negative.

Discussion Contact allergy from mesna has rarely been reported. Only 1 case of contact dermatitis on the hands in a nurse using mesna in an intensive care ward could be found (5). To our knowledge, the case of contact allergy to mesna reported above is the first description of occupational airborne allergic contact dermatitis from mesna.

References 1. Lang E, Goss M. Hypersensitivity to mesna. Lancet 1985: ii: 329. 2. Lakhi S A, Bais E M, Rutgers E J, Beijnen J H. Hypersensitivity after iphosphamide administration. J Oncol Pharm Practice 1996: 2: 113–116. 3. Zonzits E, Aberer W, Toppeiner G. Drug eruptions from mesna. Arch Dermatol 1992: 128: 80–82. 4. D’Cruz D, Haga H J, Hughes G R. Allergic reactions to mesna. Lancet 1991: 338: 705–706. 5. Benyoussef K, Bottlaender A, Pfister H R, Caussade P, Heid E, Grosshans E. Allergic contact dermatitis from mesna. Contact Dermatitis 1996: 34: 228–229.

Address: M. Kiec-Swierczynska Nofer Institute of Occupational Medicine 8, Sw. Teresy St. 90–950 Lodz Poland e-mail: [email protected]

Allergic contact dermatitis from formaldehyde with initially negative repeated open application test Chuchai Tanglertsampan Division of Dermatology, Pramonkutklao Hospital, Bangkok, Thailand

171 Key words: formaldehyde; DMDM hydantoin; 1,3-bis(hydroxymethyl)-5, 5-dimethylimidazolidine-2,4-dione; allergic contact dermatitis; repeated open application test; use test.

A 32-year-old housewife was referred with a 2-year history of recurrent dermatitis primarily on the extremities and buttocks. There was no history of atopy. Physical examination showed excoriated erythematous patches on both arms, legs, and buttocks. Patch testing was performed on her back to the European standard series, selected preservative, vehicle, corticosteroid, textile allergens (Chemotechnique), and her moisturizing lotion. Results are shown in Table 1 (session 1). Her lotion, which she used only on eczematous skin, was found to contain the formaldehyde donor DMDM hydantoin. A 7-day repeated open application test (ROAT) to her lotion was negative in the antecubital fossa. When she applied it on eczematous skin, however, she felt an itchy and stinging sensation. But when she applied a new lotion (no formaldehyde or formaldehyde donors) on eczematous skin it felt normal. She was advised to avoid formaldehyde, formaldehyde donors and formaldehyde resins. Three months later, retesting was performed with the allergens in Table 1 on the outer aspect of the upper arm. She again developed erythematous patches on legs. Results are shown in Table 1 (session 2). Again, a 7-day ROAT was negative. She has had no recurrence of dermatitis for 6 months since the 1st patch testing session.

Discussion 1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione (DMDM hydantoin) is a formaldehyde donor used as a preservative in cosmetics (1). ROAT is used to define the clinical relevance of exposure to an allergen identified by patch testing (2, 3). There are few documented examples of negative results of use tests on normal skin becoming positive on diseased skin (3). In our patient, ROAT on normal skin gave a negative reaction. But when she applied the lotion on eczematous skin, she felt an itchy and stinging sensation. Her normal skin could



Table 1. Patch test results

Formaldehyde (1% aq.) DMDM hydantoin (2% aq.) Ethylenurea-melaminemaldehyde resin (5% pet.) Urea-formaldehyde resin (10% pet.) Melamine-formaldehyde resin (7% pet.) Moisturizing lotion (as is)

tolerate exposure to small concentrations of formaldehyde, whereas dermatitic skin had a reduced threshold or barrier to it. Further studies of reaction differences between normal and compromised skin are required. Dermatologists often recommend moisturizers on eczematous skin. We usually asked patients to perform ROAT on normal skin only. We may need to recommend them do it on eczematous skin as well.

References 1. de Groot A C, van Joost T, Bos J D, van der Meeren H L M, Weyland J W. Patch test reactivity to DMDM hydantoin. Relationship to formaldehyde allergy. Contact Dermatitis 1988: 18: 197–201. 2. Hannuksela M, Salo H. The repeated open application test (ROAT). Contact Dermatitis 1986: 14: 221–227. 3. Nakada T, Hostynek J J, Maibach H I. Use tests. ROAT (repeated open application test)/PUT (provocative use test): an overview. Contact Dermatitis 2000: 43: 1–3.

Address: Chuchai Tanglertsampan, M.D. Bumrungrad Hospital 33 Sukhumvit 3 (Soi Nana Nua) Wattana, Bangkok 10110 Thailand Tel: þ 66 2667 1360/þ 66 2667 2280 Fax: þ 66 2667 1362 e-mail: [email protected]

Co-sensitivity between cobalt and other transition metals

Session 1

Session 2

?þ ?þ ?þ

þ ?þ ?þ

?þ ?þ –

þ þ –

Key words: cobalt; transition metals; nickel contamination; periodic table of elements; patch testing; co-sensitivity.

Cobalt (Co), a transition metal widely distributed in the earth’s crust, has been found to be a potent contact sensitizer in the human (1) and guinea pig (2) maximization tests (grade 3 and 5, respectively), but isolated positive patch test reactions to Co are rarely recorded and their relevance often remains unexplained. Contact sensitivity to Co, nickel (Ni) sulfate and/or potassium dichromate is usually found (3–5). This study was done to investigate whether (i) simultaneous reactivity to Co and Ni is due to Ni impurity in Co patch test preparations, and (ii) co-sensitivity among Co and other transition metals is correlated with their distribution in the periodic table. It has previously been reported that cross-reactivity among transition metals in guinea pigs may be restricted to groups, but not to periods, of the table (6).


Group A Erythema, papules and vesicles were observed on the test site of 0005% Ni sulfate in 6 of the 46 patients studied (130%).

Group B Materials and Methods

Group A The role of Ni contamination was investigated in 46 contact dermatitis patients (42 females and 4 males, aged between 12 and 77 years; mean age 354) with positive reactions to Co chloride (1% pet.) and Ni sulfate (5% pet.). As chemical analysis (mass spectrometry) of the Co chloride preparation sold by FIRMA (Florence, Italy) revealed traces of Ni sulfate (0005%), patients were retested with Ni sulfate 0005% pet.

Paolo Lisi, Laura Brunelli and Luca Stingeni Unit of Allergologic and Environmental Dermatology, Department of Medical and Surgical Specialities, University of Perugia, Italy

and 9 males, aged between 15 and 77 years; mean age 369). They were patch tested with rhodium (Rh) chloride (1% aq.), iridium (Ir) chloride (1% aq.), titanium (Ti) dioxide (1% pet.), potassium dichromate (Cr) (05% pet.), manganese (Mn) dioxide (10% pet.), iron (Fe) chloride (2% aq.), Ni sulfate (5% pet.), copper (Cu) sulfate (1% aq.), zinc (Zn) sulfate (25% pet.), and palladium (Pd) chloride (1% pet.). The first 2 allergens are transition metals of the same group as Co (the 9th), while the last belongs to the same group as Ni (the 10th) and the others to the same period as Co (the 4th). In all patients, patch testing was performed on the upper back using van der Bend square chambers (van der Bend B.V., Brielle, the Netherlands) on Scanpor tape (Norgesplaster, Kristiansand, Norway). The patches were left on for 2 days and the readings were carried out 30 min after removal (D2) and 2 days later (D4), according to ICDRG criteria. Only þ þ and þ þ þ reactions were accepted as positive. ‘Porotic’, follicular, pustular and/or purpuric reactions were excluded from the analysis.

Group B The co-sensitivity among transition metals was studied in 60 consecutive subjects sensitized to Co (51 females

Of the 60 patients sensitized to Co, 56 (933%) showed 1 or more positive reactions to the transition metals tested (Table 1). Ni sulfate, Pd chloride and potassium dichromate were the most frequently positive, while sensitivity to Rh chloride and Cu sulfate was rare. All patch tests with Ir chloride, Fe chloride, Mn dioxide, Ti dioxide, and Zn sulfate were negative. The positive reaction associations are shown in Table 2.

Discussion Co chloride is still a difficult substance with which to patch test, even though its concentration and vehicle have been refined (3, 7). ‘Porotic’ (8) and/or petechial reactions (9) were excluded from this analysis but false-positive reactions to Co can

CONTACT POINTS Table 1. Positive patch test reactions (þ þ/þ þ þ) to some transition metals at D2 and D4 in 60 consecutive contact dermatitis patients sensitized to cobalt chloride Transition metals

Rhodium chloride Iridium chloride Titanium dioxide Potassium dichromate Manganese dioxide Iron chloride Nickel sulfate Copper sulfate Zinc sulfate Palladium chloride


1% aq. 1% aq. 1% pet. 05% pet. 10% pet. 2% aq. 5% pet. 1% aq. 25% pet. 1% pet.

Positive patch test reactions n


2 – – 21 – – 50 1 – 24

33 – – 350 – – 833 17 – 400

Table 2. Concomitant positive reactions (þ þ/þ þ þ) observed in 56 of 60 consecutive cobalt-positive patients patch tested with transition metals Transition metals

Positive patch test reactions %

n Cobalt Cobalt Cobalt Cobalt Cobalt Cobalt Cobalt Cobalt

þ þ þ þ þ þ þ þ

nickel 19 palladium þ nickel 14 nickel þ dichromate 7 nickel þ dichromate us; palladium 7 dichromate 6 nickel þ palladium þ rhodium 1 nickel þ palladium þ copper 1 nickel þ palladium þ rhodium þ dichromate 1

also be caused by Ni contamination of patch test preparations, as shown by our data. Concomitant sensitivity to different transition metals was present in 933% of our Group B patients, as previously reported (10). Co–Ni and Co–Cr positive reactions were the most frequent, while those between Co and Pd in 24 subjects were always associated with sensitivity to Ni. In the 2 patients sensitized to Co and Rh, concomitant positive reactions to Ni and Pd were found in both and to Cr in one. Analysis of our patch test results showed that in Co-positive patients concomitant reactions among metals are not due to their distribution in the periodic table. In fact, sensitivity to metals of the same group (Rh, Ir) is negligible, while that to the metals of the same period (Ti, Cr, Mn, Fe, Ni. Cu, Zn) is frequent but only for Ni and Cr. Concomitant reactions between Co and Pd we believe to be correlated with sensitivity to Ni. Simultaneous patch test reactions to transition metals have been inter-

339 250 125 125 107 18 18 18

preted as indicative of cross-sensitivity, but our results and those of others (3, 11–13) suggest instead co-sensitivity due to combined exposure. Guinea pigs sensitized to Co do not react to systemic challenge with Ni or other metal salts (Cr, Pd, Rh) (6), and T-lymphocyte clones of Ni-sensitive subjects are able to cross-react with other metals, mainly Cu and Pd, but less frequently with Co (14). In conclusion, we believe it is still useful to include Co in standard patch testing, even though traces of Ni may sometimes elicit false-positive reactions.

References 1. Kligman A M. The identification of contact allergens by human assay. III. The maximization test, a procedure for screening and rating contact sensitizers. J Invest Dermatol 1966: 47: 393–409. 2. Wahlberg J E, Boman A. Sensitization and testing of guinea pigs with cobalt chloride. Contact Dermatitis 1978: 4: 128–132.

173 3. Fregert S, Rorsman H. Allergy to chromium, nickel and cobalt. Acta Derm Venereol 1966: 46: 144–148. 4. Rystedt I. Evaluation and relevance of isolated test reactions to cobalt. Contact Dermatitis 1979: 5: 233–238. 5. Filotico R, Grandolfo M, Foti C, Vena G A, Angelini G. Rilievi epidemiologici sull’allergia da contatto al cobalto. Boll Dermat Allergol Profess 1992: 1: 43–56. 6. Lide´n C, Wahlberg J E. Cross-reactivity to metal compounds studied in guinea pigs induced with chromate or cobalt. Acta Derm Venereol 1994: 74: 341–343. 7. Bonnevie P. Aetiologie und Pathogenese der Ekzemkrankheiten. Copenhagen: Nyt Nordisk Forlag, 1939: 305–307. 8. Fisher T, Rystedt I. False positive, follicular and irritant patch test reactions to metal salts. Contact Dermatitis 1985: 12: 93–98. 9. Schmidt H, Larsen F S, Larsen P O, Søgaard H. Petechial reaction following path testing with cobalt. Contact Dermatitis 1980: 6: 91–94. 10. Santucci B, Cannistraci C, Cristaudo A, Picardo M. Multiple sensitivities to transition metals: the nickel palladium reactions. Contact Dermatitis 1996: 35: 283–286. 11. Burrows D, Adams R M, Flint G N. Metals. In: Adams R M, ed. Occupational Skin Disease, 3rd edn. Philadelphia: Saunders, 1999: 395–433. 12. Kanerva L, Jolanki R, Estlander T, Alanko K, Savela A. Incidence rates of occupational allergic contact dermatitis caused by metals. Am J Contact Dermatitis 2000: 11: 155–160. 13. Lide´n C, Bruze M et al. Metals. In: Rycroft R J G, Menne´ T, Frosch P J, Lepoittevin J-P, eds. Textbook of Contact Dermatitis, 3rd edn. Berlin: Springer, 2001: 933–977. 14. Pistoor F H M, Kapsenberg M L, Bos J D, Minardi M M H M, von Blonberg B M E, Scheper R J. Cross-reactivity of human nickel-reactive T lymphocyte clones with copper and palladium. J Invest Dermatol 1995: 105: 92–95.

Address: Paolo Lisi Unit of Allergologic and Environmental Dermatology Department of Medical and Surgical Specialities Policlinico Monteluce Via Brunamonti 06100 Perugia Italy Tel: þ 39 0755731388 Fax: þ 39 0755731388 e-mail: [email protected]



Unusual widespread vesicular eruption related to dental composite resin sensitization S. Menni, A. Lodi, A. Coassini, D. Boccardi, P. Rossini and C. Crosti Clinica Dermatologica IV-Universita` degli Studi di Milano-Ospedale S. Paolo, Milan, Italy

Key words: dental composite resins; sensitization; cutaneous manifestations.

Hypersensitivity reactions to dental composite resins are rarely reported in dental patients (1, 2). Extra-oral manifestations of such hypersensitivity are still more rarely described (3).

have been described in dental personnel (dentists, dental nurses, technicians) (4, 5), but less frequently in dental patients. Stomatitis and perioral dermatitis caused by epoxy diacrylates (1), oedema and vesiculation of the lips and perioral skin from acrylic compounds (triethylene glycol dimethacrylate [TEGDMA] and BIS-GMA) (6), aphthous ulcerations from TEGMDA (7) and oedema and ulceration of the lips from 2-HEMA and TEGDMA (2) have all been described. We have found only 1 previous report of extra-oral manifestations of delayed hypersensitivity ascribed to BIS-GMA (3). The patient developed a measles-like rash, itching, open blisters and mild respiratory distress, but not stomatitis. Complete recovery occurred 6 months after removal of the allergen.

References Case Report A 12-year-old boy was complaining for about 1 year of an itchy relapsing dermatitis on the limbs, trunk and face. Pruritic clear vesicles, with slight erythematous halo, crusts and punctate hyperpigmentation constituted the lesions. After some initial doubt as to the diagnosis, the patient returned, a few days after remodelling of the connections of his orthodontic prosthesis, with a new, more severe vesicular eruption. He had worn this appliance for over 1 year without any changes on the oral mucosa. He was then patch tested with a standard series plus a dental series and showed a þ þ þ reaction to BISGMA(2,2-bis(4-[2-hydroxy-3-methacryloxypropoxy]phenyl)propane) 2% pet. and a þ þ þ reaction to paratertiary-butylphenol-formaldehyde resin 1% pet. One month later he patch tested positively to Ortho-OneTM (Bisco Inc, Schaumburg, IL, USA), the bonding paste used in our patient and containing BIS-GMA. After the removal of the orthodontic prosthesis, lesions cleared within 2 months, leaving only some hyperpigmentation.

Comment Manifestations of hypersensitivity to materials of dental composite resins

1. Kanerva L, Alanko K. Stomatitis and perioral dermatitis caused by epoxy diacrylates in dental composite resins. J Am Acad Dermatol 1998: 38: 116–120. 2. Agner T, Menne´ T. Sensitization to acrylates in a dental patient. Contact Dermatitis 1994: 30: 249–250. 3. Nathanson D, Lockhart P. Delayed extraoral hypersensitivity to dental composite material. Oral Surg Oral Med Oral Pathol 1979: 47: 329–333. 4. Geukens S, Goossens A. Occupational contact allergy to (meth) acrylates. Contact Dermatitis 2001: 44: 153–159. 5. Wrangsjo¨ K, Swartling C, Meding B. Occupational dermatitis in dental personnel: contact dermatitis with special reference to (meth)acrylates in 174 patients. Contact Dermatitis 2001: 45: 158–163. 6. Niinima¨ki A, Rosberg J, Saari S. Allergic stomatitis from acrylic compounds. Contact Dermatitis 1983: 9: 148. 7. Guerra L, Vincenzi C, Peluso A M, Tosti A. Role of contact sensitizer in the burning mouth sindrome. Am J Contact Dermatitis 1993: 4: 154–157.

Trends in allergic contact dermatitis and preventive measures among cement workers (1985–1999) A. Katsarou-Katsari, E. Bankovska, K. Lambrinopoulou, E. Davou, A. Bolbasis and A. Papakonstantinou Center for Occupational Skin Diseases, Department of Dermatology, University of Athens, ‘A. Syggros’ Hospital, 5, I. Dragoumi Street, 161 21 Athens, Greece

Key words: allergic contact dermatitis; cement; chromate; construction industry; prevention.

Prevention of occupational dermatitis from cement depends on many factors (1–4). Addition of ferrous sulphate to cement, a measure not applied in Greece, is believed to result in significant decrease in allergic contact dermatitis from chromate in some countries (5, 6). Nevertheless, such a decrease has also been noted recently in countries where this measure was not applied (4). The objective of this study was to determine the frequency of allergic contact dermatitis among patients working with cement, to identify the most common allergens involved and to examine the preventive measures that such workers used during the period 1985–1999.

Patients and Methods 904 cement workers with a history of eczema were patch tested during the period 1985–1999 with the European standard series supplied by Hermal (Trolab, Reinbek, Germany), according to ICDRG guidelines. The age of the patients, the duration and distribution of their skin disease and the preventive measures taken during work were the main parameters recorded.

Results and Discussion Address: S. Menni, M.D. Clinica Dermatologica IV Universita` degli Studi di Milano Ospedale S.Paolo Via A. di Rudinı` n ˚ 8 20142, Milan Italy e-mail: [email protected]

The number of cement workers patch tested each year (1985–1999), the frequency of patients with positive patch tests and the 8 most common allergens identified are summarized in Table 1. 678 (75%) cement workers demonstrated 1 or more patch test reactions. There was no statistically significant difference between the



Table 1. Number and percentage of cement workers patch tested each year and the 8 most common allergens identified Year Patients Patients Potassium Cobalt Nickel Thiuram tested (n) positive [n (%)] dichromate 05% chloride 1% sulfate 5% mix 1% 1985 93 1986 95 1987 80 1988 101 1989 48 1990 61 1991 57 1992 55 1993 43 1994 65 1995 37 1996 45 1997 46 1998 39 1999 39 Total 904

65 80 55 83 33 49 44 46 31 45 28 34 30 25 30 678

(699) (842) (688) (822) (688) (803) (772) (836) (721) (692) (757) (756) (652) (641) (769) (75)

51 65 40 79 32 48 37 42 30 28 19 26 28 20 23 568 (84%)

25 33 10 42 12 20 17 10 14 13 10 13 12 10 16 257 (38%)

5 5 5 7 2 1 3 1 6 6 3 2 2 3 3 54 (8%)

Epoxy Carba resin 1% mix 3%

6 2 34 1 24 2 29 4 14 1 19 2 18 1 13 2 12 – 12 2 9 – 18 1 15 – 12 – 16 1 251 (37%) 19 (3%)

Mercapto MBT mix 2% 2%

3 4 13 7 19 2 22 1 5 – 16 – 3 1 9 4 NT 1 NT 2 NT 1 NT 3 NT 2 NT 1 NT 3 90 (13%) 32 (5%)

1 8 – 1 2 2 – 2 1 2 2 1 2 2 1 27 (4%)

NT ¼ not tested. Table 2. Patients’ preventive measures during the periods 1985–1987 and 1997–1999 Questions

Use of Gloves during work Barrier cream Washing facilities Mild washing Emollients at home

1985–1987 (n ¼ 268)

1997–1999 (n ¼ 124)








32 16 129 64 48

70 21 80 48 102

166 231 59 156 118

35 20 56 37 31

27 15 52 27 53

62 89 16 60 40

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