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Fixed drug eruptions caused by tonic water

2003; Elsevier BV; Volume: 111; Issue: 1 Linguagem: Inglês

10.1067/mai.2003.44

1097-6825

Riccardo Asero,

Chemotherapy-related skin toxicity

Fixed drug eruption (FDE) is a nummular skin lesion that recurs at a given site on re-exposure to a drug. The lesion begins with edema; this is followed by erythema, which darkens to a raised reddish purple color. The lesion or lesions resolve 2 to 3 weeks after drug withdrawal, but they can leave residual hyperpigmentation.1Yates AB deShazo RD Drug allergies and hypersensitivities.in: 2nd ed. Clinical immunology: principles and practice. Mosby, St Louis2001: 54.1-5415Google Scholar The most frequently responsible drug is cotrimoxazole,2Mahboob A Haroon TS Drugs causing fixed eruptions: a study of 450 causes.Int J Dermatol. 1998; 37: 833-838Crossref PubMed Scopus (226) Google Scholar, 3Hunziker T Kunzi UP Braunschweig S Zehnder D Hoigne R Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey.Allergy. 1997; 52: 388-393Crossref PubMed Scopus (187) Google Scholar but a number of different drugs, including tetracycline, pyrazolones, barbiturates, aspirin, paracetamol, and many others, have been reported to have induced FDE.2Mahboob A Haroon TS Drugs causing fixed eruptions: a study of 450 causes.Int J Dermatol. 1998; 37: 833-838Crossref PubMed Scopus (226) Google Scholar, 4Kauppinen K Stubb S Drug eruptions: causative agents and clinical types. A series of in-patients during a 10-year period.Acta Dermatol Venereol. 1984; 64: 320-324PubMed Google Scholar, 5Stubb S Heikkila H Kauppinen K Cutaneous reactions to drugs: a series of in-patients during a five-year period.Acta Dermatol Venereol. 1994; 74: 289-291PubMed Google Scholar The origin of FDE is still unclear. Although it is considered a probably immunologic (allergic) drug hypersensitivity reaction,6Adkinson NF Drug allergy.in: 5th ed. Allergy: principles and practice. Mosby, St Louis1998: 1212-1224Google Scholar pathogenic mechanisms underlying the appearance of recurrent skin lesions in the same limited areas after systemic administration of the offending drug are obscure. A case of FDE induced by tonic water is reported here. In January 2002, a 23-year-old woman presented at our allergy unit reporting 4 episodes of skin rash characterized by multiple, pruritic, fixed skin lesions during the previous year. The patient said that the acute lesions had lasted approximately 4 to 5 days and responded quite well to local corticosteroids. At the clinical examination, nummular hyperpigmented lesions were visible on her upper lip, left arm (2 close lesions), neck, back, and right breast. The woman was otherwise well and had not taken any drugs during the previous year. All results of laboratory investigations (including a large panel of immunologic tests) were normal. An independent dermatologist confirmed the diagnosis of probable FDE. At the end of February, the patient presented for a follow-up visit; she reported a relapse of her skin lesions approximately 1 hour after drinking half a can (approximately 150 mL) of tonic water. Moreover, she noted that the previous episode had also been preceded by ingestion of the same kind of tonic water, which she had started to consume occasionally during the previous year. The label on the beverage can reported “flavours” and “quinine bichlorhydrate” among the ingredients. After 3 weeks, an open challenge test with 50 mL of the same brand of tonic water was performed at the allergy center. Informed written consent was obtained before the procedure was begun. We planned to keep the patient under observation at the center for 2 hours after administration of the beverage. After 90 minutes, clear-cut erythema and edema appeared at the usual sites. Intolerance to tonic water was diagnosed. To exclude other possible causes for the skin lesions, the patient was asked to avoid tonic water but to otherwise maintain her alimentary habits during the following 3 months. At a mid-June follow-up visit, the patient reported that she had not had any further episodes of fixed eruption. A patch test with a 20% solution (both in water and alcohol) of quinine sulfate was tentatively carried out on both affected and normal skin. No reaction was observed at 48 hours or 72 hours. Finally, an open oral challenge with quinine sulfate was performed. (The patient gave an informed consent before this procedure was begun.) Approximately 40 minutes after the ingestion of 30 mg of the drug, pruritus, erythema, and edema appeared at the usual sites. Quinine hypersensitivity was diagnosed. This is probably one of the first reports of a fixed eruption induced by a drug present in a food rather than by a drug taken by itself. In fact, the woman had never taken quinine before the challenge test. This suggests that the small concentration of quinine contained in the commercial tonic water had been sufficient to sensitize her and to induce all of the reported episodes of fixed eruption. Although a photo patch test was not carried out, the negativity of patch tests with a quite high concentration of quinine (20%), both on affected and normal skin, in the presence of a rather rapid response on oral challenges (90 minutes with tonic water, 40 minutes with quinine 30 mg) raises some doubts about a delayed hypersensitivity reaction as a possible pathogenic mechanism of this kind of skin reaction. Quinine hypersensitivity reactions, including thrombocytopenia and hemolytic uremic syndrome,7Glynne P Salama A Chaudry A Swirsky D Lightstone L Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic syndrome.Am J Kidney Dis. 1999; 33: 133-137Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar lupuslike syndrome,8Rosa-Re D Garcia F Gascon J Angrill J Cerva R Quinine-induced lupus-like syndrome and cardiolipin antibodies.Ann Rheum Dis. 1996; 55: 559-560Crossref PubMed Scopus (14) Google Scholar photosensitivity,9Ljunggren B Hindsen M Isaksson M Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine.Contact Dermatitis. 1992; 26: 1-4Crossref PubMed Scopus (26) Google Scholar cutaneous vasculitis,10Price EJ Bevan JS Rees A Quinine-induced cutaneous vasculitis.Br J Clin Pract. 1992; 46: 138-139PubMed Google Scholar and anaphylactic shock,11Pin I Dor PJ Vervloet D Senft M Charpin J Immediate hypersensitivity to quinine.Presse Med. 1985; 14: 967-969PubMed Google Scholar have been described, and IgE-mediated urticaria from quinine in tonic water has recently been reported.12Gonzalez R Merchan R Crespo JF Rodriguez J Allergic urticaria from tonic water.Allergy. 2002; 57: 52Crossref PubMed Google Scholar Moreover, quinine was previously implicated in FDE.13Kuokkanen L Drug eruptions: a series of 464 cases in the Department of Dermatology, University of Turku, Finland during 1966-1970.Acta Allergol. 1972; 27: 407-410Crossref PubMed Scopus (26) Google Scholar, 14Van Arsdel PP Adverse drug reactions.in: 2nd ed. Allergy: principles and practice. Mosby, St Louis1983: 1389-1414Google Scholar Our study shows that the quinine contained in commercial tonic water (and in other soft drinks, as well as in alcoholic beverages) might elicit FDE as well. I thank Dr Adriana Gobbi, pharmacist at Bollate Hospital, for her kind cooperation in preparing quinine solutions for the patch tests and for providing the drug for the oral challenge.