British Journal of Dermatology 1995; 133: 792-794. Progesterone-induced urticaria—need it be autoimmune? S.M.WILKINSON, M.H.BECK AND T.P.KINGSTON The Skin Hospital. Chapel Street. Salford M60 9EP. U.K. Accepted for publication 22 December 1994 Summary A patient with persistent urticaria related to the premenstrual phase of the menstrual cycle is presented. Although systemic administration of progesterone provoked the eruption, we were unable to confirm that there was an immunological reaction to endogenous progesterone or oestrogen. Mechanisms whereby progesterone can augment subclinical types I and IV hypersensitivity reactions are discussed. Case report A 31-year-old woman presented with a 2^ year history of urticaria occurring every month, beginning mid- cycle and resolving within 3 days of menstruation. A diary of her symptoms confirmed the relationship to her menstrual cycle. She had taken the combined oral contraceptive pill from the age of 18 to 27 years, with a gap when she became pregnant for the first time. The eruption had started after the birth of her second child, with the onset of her periods, and lasted for 6 months until she again became pregnant. She remained free of disease during the third pregnancy but her urticaria recurred following delivery. She had a past history of atopic eczema and allergic rhinitis, and previously had been treated with danazol for endometriosis. Examination confirmed the diagnosis of urticaria. Previous treatment Included a salicylate-free diet and terfenadine, 120 mg daily, which had been without benefit. Treatment with Marvelon® (ethinyloestradiol, desogestrel) had exacerbated the urticaria. She was patch-tested to a modified standard battery, 18 corticosteroids (1% in ethanol), tixocortol pivalate (1% pet.) and five sex steroids (17-hydroxyprogesterone- 1% in ethanol; progesterone-1% in ethanol; medroxypro- gesterone-1% in acetone; oestradiol-1% in ethanol and testosterone-1% in ethanol. All tests were negative. Intradermal tests with 0-1 and lmg progesterone and 1 mg oestradiol, in 0-1 ml normal saline, at 30 min, 3 h and 48 h, were negative. At the time of testing the patient had not taken an antihistamine for 72 h. During an attack, complement levels were normal and immune complexes could not be detected. Oral challenge with medroxyprogesterone (Provera®), 10 mg daily in the first half of the menstrual cycle when the urticaria was quiescent, resulted in a fiare of the urticaria after 2 days. Discussion Our patient is similar to cases described in the literature as having autoimmune progesterone dermatitis. In some with negative skin tests, the eruption fiared within 1 h of a systemic hormonal challenge, suggest- ing an immunologically mediated reaction,^ but in others the eruption has taken 2^-4^ days to develop. Where there is a delay between systemic hormone administration and a fiare of the rash, repeated double-blind challenge would be a more stringent diagnostic test to confirm a temporal relationship. Autoimmune progesterone dermatitis is a term attached to cycfical menstrually related dermatoses. They are thought to be caused by an immune reaction to raised levels of endogenous progesterone in the premenstrual phase of the menstrual cycle. In some patients, the existence of positive intradermal tests,*'^ progesterone antibodies,'*'^ circulating immune com- plexes'' and positive basophil degranulation tests' sup- port this hypothesis. Urticaria,^ erythema multiforme'' and eczematous eruptions' have all been described. It is postulated that sensitization occurs as a result of previous exposure to oral contraceptives'' or as a cross-reaction in patients sensitized to topical corticosteroids.*'^ It is suggested that the latter mechan- ism does not occur in most patients.^" Cutaneous tests may be negative, as in our patient, and the dermatosis may only fiare fofiowing systemic chafienge.^'^ This may occur due to an immune reac- tion to a metabofite of progesterone. However, the skin has a limited capacity to metabolize progesterone^^ (the responsible enzymes being 20a-ol-dehydrogenase, 3a- 792 1995 British Association ofDermatologists