Morniflumate-induced urticaria-angioedema

June 19, 2017 | Autor: Zita Sierra | Categoria: Immunology, Allergy
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ALLERGY 1998: 53: 812-820

COPYRIGHT ® MUNKSGAARO 199B

Momiflumate-induced urticariaangioedema

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ORNiFLUMATE is the morpholinoethyl ester of niflumic acid, a nonsteroidal anti-inflammatory drug (NSAID) in the antranihc acid group, derived from nicotinic acid. Morniflumate is almost equal to the parent compound in anti-inflammatory, analgesic, and antipyretic activity with less toxic and ulcerogenic effects than niflumic acid (1). Fenamates have been shown to inhibit the 5lipoxygenase pathway of the arachidonic acid cascade as well as the synthesis of cyclooxygenase products. This dual inhibitory property has represented an improvement in anti-inflammatory therapy. Morniflumate can reduce arachidonic acid metabolism by acting both on cyclooxygenase and 5-lipoxygenase (2). Morniflumate has been used in inflammatory conditions and can be given twice daily as rectal suppositories in children (3). Drug eruption caused by morniflumate has been described (4), but not immediate hypersensitivity reactions. We report a child patient with urticariaangioedema induced by morniflumate. A 4-year-old girl suffered discomfort, sick feeling with erythematous lesions, and swelling on the eyelids within 30 min after administration of oral amoxicillin and rectal morniflumate (400 mg). These drugs were stopped and the lesions resolved in 48 h with no treatment. Subsequently, she underwent treatments with paracetamol, azytromicine, trimethoprim sulfamethoxazole, and ibuprofen without problems. Her previous clinical history was anodyne. After a washout period and previous written consent had been obtained from the parents, the skin prick test and intradermal test with PPL, MDM, and amoxicillin were done with negative result. Specific IgE to penicillins G and V and amoxicillin (CAP-System Pharmacia) was negative. The oral challenge test with amoxicillin to therapeutic doses was performed, and no adverse effects appeared. Morniflumate as suppositories was then given. Within 35 min after a dose of 200 mg, the patient developed disseminated erythema and some wheals on her forehead and neck with no other symptoms. Dexchlorpheniramine was administered but the lesions persisted for 1 h. After a 812

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second washout, the patient was challenged with isonixine and acetylsalicylic acid, which were well tolerated. Adverse reactions to NSAIDs have been widely reported. Associated with fenemates also, these reactions include acute hepatitis, acute kidney failure, osteomalacia, osteofluorosis, agranulocytosis, cytopenia, oral aphthoid toxic dermatoses, and other disorders. However, only a few cases of drug eruptions have been described, de Suremain et al. reported one case of toxidermia induced by niflumic acid (5), and Raymond et al. reported toxic epidermal necrolysis (Lyell's syndrome), after administration of erythromycine sulfafurazole, in which morniflumate was implicated (4). Recently, Laguna et al. (6) reported a case of urticaria, angioedema, and dyspnea after niflumic acid with tolerance of other NSAIDs. We present a case of urticaria-angioedema induced by morniflumate with positive challenge test. In view of the fact that the symptoms had disappeared by 1 h after A case of non-IgEdexchlorpheniramine mediated urticaria to a administration, the central role that histaNSAID with aspirin mine plays, in this tolerance. momiflumate-indu^———^—————^ ced skin reaction, must be considered; an IgE-mediated mechanism could be possible. To some extent, this hypothesis is supported by the good tolerance of four NSAIDs in this case. Fmally, in the literature reviewed, it may be observed that morniflumate has good tolerance and does not often cause drug eruption. Keywords: angioedema; morniflumate; NSAID; urticaria, V, MATHEU*, Z . SIERRA, M . I GRACIA, M , CALOTO, M . M. ALCAZAR, M , I, MARTINEZ, L, ZAPATERO

*Secci6n de Alergia Infantil Hospital General Universitario Gregorio Maranon C/Dr, Castelo, No 49 28009 Madrid Spain Tel, 34-1-5868731 Fax: 34-1-5868018

Accepted for publication 6 February 1998 Copyright © Muntisgaartj 1998 ALLERGY 1998:53:812-813 REFERENCES 1, Schlantareili P, Cadel S, Acerbi D, A gastroprotectiva antiinflammatory agent: the beta-morpholinoethyl ester of niflumic acid (morniflumate). Agents Actions 1984;14(2):247-56,

ALLERGYKS3 2. Civelli M, Vigano T, Acerbi D, et al. Modulation of arachidonic acid metabolism by orally administered morniflumate in man. Agents Actions 1991;33(3-4):233-9. 3. Manach Y, Ditisheim A. Double-blind placebo-controlled multicentre trial of the efficacy and tolerance of morniflumate suppositories in the treatment of tonsillitis in children (used with phenoxymethylpenicillin). J Int Med Res 1990,18:30-6. 4. Raymond f, Paillat A, Gambert C, Gamier R Syndrome de Lyell apres administration d'erytromycine-sulfafurazole et de morniflumate [Letter]. Arch Pediatr 1995;2:494-5. 5. de Suremain N, Le Roux P, Smith-Xiberras 1^ Briquet MX Le Luyer B. Toxidermie medicamenteuse avec I'acide niflumique [Letter]. Arch Pediatr 1995;2(7):698. 6. Laguna J, Trampal A. Paz S, Santaolalla M, Minguez A, Rodriguez M. Reaccion adversa al acido niflumico [Abstract]. Rev Esp Alergol Inmunol Clin 1997;12(2S):60.

Fixed drug eruption caused by cyproterone acetate YPROTERONE acetate (CPA) is an antiandrogen C drug that inhibits the action of endogenous and exogenous androgens in all androgen target organs. The indications are prostate cancer, androgeninduced disorders of the skin (acne, seborrhea, hirsutism, alopecia), precocious puberty, and sexual disorders in men (1). To our knowledge, this is the first fixed drug eruption (FDE) due to CPA reported in the literature. • A 21-year-old woman, 2 months after taking Diane® (CPA plus ethinyloestradiol) and Androcur® (CPA) to treat hirsutism, showed large, brown, pruriginous, macular lesions on both flanks of the abdomen and on the chest. The macules disappeared spontaneously 1 month after the withdrawn of the drugs, with a mild superficial desquamation without hyperpigmentation. Six months later, the patient again took both drugs, and the same lesions reappeared on the same sites after 10 days of treatment. The drugs were withdrawn, and the lesions clarified, but residual brown hyperpigmentation remained for 6 months. Because of her hirsutism, she started treatment with flutamide (a nonsteroidal antiandrogen). This drug was not tolerated, because headache and nausea appeared. Patch tests performed on affected and unaffected skin with Androcur, Diane, and CPA at 5% in petrolatum and water were negative. A single-blind oral challenge with the excipients of Androcur, kindly supplied by Schering Espafia SA (manufacturer of Androcur), was performed. The patient received a daily dose on days 5-14 of her menstrual cycle without adverse effects. In the next menstrual cycle, a daily pill of Androcur was administered on days 5-14. Two days after she had

finished that treatment, the pruriginous FDE flared up again on the same sites. • CPA is effective in treatment of hirsutism. It is generally well tolerated and adverse effects are mild and transient. Ttredness, lack of drive, listlessness, depressive moods, and gynecomastia have been reported (1). To the best of our knowledge, no case report of FDE from this drug has been published. The term "FDE" denotes a lesion of the skin or mucous membranes that occurs with administration of a drug, subsides when the drug is withdrawn, and recurs at the same location when the drug is reintroduced. As the lesion resolves, residual hyperpigmentation remains (2). Our patient had classic FDE while taking CPA, which resolved with residual hyperpigmentation when the drug was withdrawn and recurred in the same location when it was readministered. Androcur excipients are excluded as causative agents because the patient took them with good tolerance. For diagnosis of FDE, patch tests on previously affected skin have given variable results, while no reaction appeared on unaffected skin. Topical provocation at the site of '~~'~~~"~~"~~~~"^~'~~~ old lesions achieves A case of oral good results. Never. . theless, in several provocation-posittve causative drug it has but patch test-negative been necessary to perform an oral FDE. ~~~~"^~——————— provocation test with the suspected drugs (3). In our patient, patch tests with Androcur, Diane, and CPA in affected and unaffected skin were negative. The diagnosis of FDE due to CPA was confirmed after oral intake of the drug. Key words: androgen antagonists; cyproterone acetate; drug allergy; fixed drug eruption. R A. GALINDO*, J . BORJA, R FEO, E. G6MEZ, R. CHAMORRO, C. ENCINAS, R. GARCIA

*C/ Azucena, 10. 3°-B. 13.003- Ciudad Real Spain Tel. 34-26-227911 Fax: 34-26-225154 Accepted for publicatior} 23 February 1998 Copyright © Munksgaard 1998 ALLERGY 1998:53:813

REFERENCES 1. Neumann F; Kalmus J. Cyproterone acetate in the treatment of sexual disorders: pharmacological base and clinical experience. Exp Clin Endocrinol 1991;98:71-80. 2. Sehgal VN, Gangwani OR Fixed drug eruption. Int J Dermatol 1987;26:67-74. 3. Alanko K. Topical provocation of fixed drug eruption. A study of 30 patients. Contact Dermatitis 1994;31:25-7

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