Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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Arif M. Aslam and Ian Coulson
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Autoimmune progesterone dermatitis is an uncommon cyclical pruritic dermatosis affecting women of childbearing age. The diagnosis is suggested by premenstrual flares and improvement during pregnancy. It can present in a variety of morphologies including eczematous, vesicular, and papulovesicular, with urticarial and erythema multiforme-like lesions the commonest. Angioedema or anaphylaxis may accompany the skin eruptions. Hypersensitivity following exposure to exogenous progesterone, usually in the form of an oral contraceptive pill, has been implicated in some cases of autoimmune progesterone dermatitis. Endogenous progesterone may also serve as a trigger for autoimmune progesterone dermatitis in cases arising during menarche or pregnancy. The diagnosis is one of exclusion and is based upon the occurrence of cyclical premenstrual flares, the response to inhibition of ovulation, and the results of intradermal testing and hormone challenge.
The mainstay of treatment is to inhibit endogenous progesterone secretion by suppressing ovulation. Classically, conjugated estrogens 0.625–1.25 mg daily in a 21-day cycle was a mainstay of therapy, but recently this treatment has been supplanted by gonadotropin-releasing hormone (GnRH) agonists. A transient worsening of the skin eruption is expected following initial treatment with GnRH agonists, with improvement thereafter. A major side effect of GnRH agonists is loss of bone density, which generally limits their use to 6 months of therapy. Patients frequently require estrogen replacement while on GnRH agonist therapy.
The antiestrogen tamoxifen, 20 mg daily or 10 mg twice a day, exerts its effect by interfering with clinical estrogen sensitivity, possibly by competitive binding of the estrogen receptors.
Oral contraceptive pills have been implicated in triggering some cases of autoimmune progesterone dermatitis. However, in patients naïve to exogenous progesterone, inducing anovulation with oral contraceptive pills may be successful.
Mild cases of autoimmune progesterone dermatitis may be controlled with short courses of systemic corticosteroids prior to the luteal phase of the menstrual cycle. Very limited disease may respond to potent topical corticosteroids and oral antihistamines.
Danazol 200 mg twice daily for 1 to 2 days prior to menses and continued for 3 days thereafter may prevent the skin eruptions by inhibiting pituitary gonadotropins.
For severe, intractable cases, bilateral oophorectomy is curative.
Autoimmune estrogen dermatitis is a separate entity that can be difficult to distinguish clinically from autoimmune progesterone dermatitis. Intradermal testing that is positive to estrone and negative to progesterone clarifies the diagnosis. Autoimmune estrogen dermatitis responds to tamoxifen, progesterone, and oophorectomy.
Intradermal testing with progesterone
Progesterone challenge
ELISA and ELISpot testing
Different authors have advocated intradermal testing with progesterone in varying amounts and dilutions. One common method of intradermal testing is with 0.1 mL of aqueous progesterone suspension at 100 mg/mL diluted with normal saline to 0.1 mg/mL, 0.01 mg/mL, and 0.001 mg/mL, with normal saline serving as the control. There may be an immediate urticarial reaction within 30 minutes, or a delayed-type hypersensitivity reaction at 24–48 hours.
Progesterone challenge may also be attempted intramuscularly (medroxyprogesterone 10–20 mg) or orally (10 mg) in the first half of the menstrual cycle. Intramuscular skin testing with the depot form of medroxyprogesterone acetate is not advised because of the risk of severe systemic reactions.
ELISA and ELISpot testing can detect elevated levels of IFN-γ-producing peripheral blood mononuclear cells in response to progesterone.
If progesterone testing is negative, consider estrogen sensitivity. Intradermal testing with either estrone (0.1 mL at 1 mg/mL) or conjugated estrogen (0.1 mL of 1, 10, and 100 µg/mL) can be attempted. A positive reaction may be immediate or delayed for several hours, and should persist for more than 24 hours.
The use of a progesterone pessary has recently been proposed as an effective tool in the diagnosis of autoimmune progesterone dermatitis.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
