Autoimmune progesterone dermatitis

Management Strategy

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 after 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. However, concomitant administration of osteoprotective agents may partly mitigate this risk and may allow longer treatment in carefully selected cases. 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 APD. However, in patients naive to exogenous progesterone, inducing anovulation with oral contraceptive pills may be successful.

Mild cases of APD may be controlled with short courses of systemic corticosteroids before 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 1–2 days before 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 APD. Intradermal testing that is positive to estrone and negative to progesterone clarifies the diagnosis. Autoimmune estrogen dermatitis responds to tamoxifen, progesterone, and oophorectomy.

The only alternative approach to the inhibition of endogenous progesterone production by suppressing ovulation is progesterone desensitization. This represents the only treatment option that preserves a patient’s fertility, and it may be especially useful for patients undergoing in vitro fertilization (IVF) treatment, who are required to take high doses of exogenous progesterone.

There is wide variation between desensitization protocols. There is also a theoretical concern that desensitization treatment could aggravate latent autoimmunity in genetically predisposed women.

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 mcg/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 APD.