Medroxyprogesterone acetate is a highly effective contraceptive drug with low rates of failure.12 It is a weak androgenic progestin that is administered as a single 150-mg intramuscular injection every 3 months and inhibits gonadotropins. Common side effects include local injection-site reactions, unscheduled bleeding, amenorrhea, weight gain, headache, and mood changes. However, FDE has not been reported as an adverse effect to medroxyprogesterone acetate, both in official US Food and Drug Administration information and in the current literature.12
Autoimmune progesterone dermatitis (also known as progestin hypersensitivity) is a well-characterized cyclic hypersensitivity reaction to the hormone progesterone that occurs during the luteal phase of the menstrual cycle. It is known to have a variable clinical presentation including urticaria, erythema multiforme, eczema, and angioedema.13 Autoimmune progesterone dermatitis also has been reported to present as an FDE.14-16 The onset of the cutaneous manifestation often starts a few days before the onset of menses, with spontaneous resolution occurring after the onset of menstruation. The mechanism by which endogenous progesterone or other secretory products become antigenic is unknown. It has been suggested that there is an alteration in the properties of the hormone that would predispose it to be antigenic as it would not be considered self. In 2001, Warin17 proposed the following diagnostic criteria for autoimmune progesterone dermatitis: (1) skin lesions associated with menstrual cycle (premenstrual flare); (2) a positive response to the progesterone intradermal or intramuscular test; and (3) symptomatic improvement after inhibiting progesterone secretion by suppressing ovulation.17 The treatment includes antiallergy medications, progesterone desensitization, omalizumab injection, and leuprolide acetate injection.
Our case represents FDE from medroxyprogesterone acetate. Although we did not formally investigate the antigenicity of the exogenous progesterone, we postulate that the pathophysiology likely is similar to an FDE associated with endogenous progesterone. This reasoning is supported by the time course of the patient’s lesion as well as the worsening of symptoms in the days following the administration of the medication. Additionally, the patient had no history of skin lesions prior to the initiation of medroxyprogesterone acetate or similar lesions associated with her menstrual cycles.
A careful and detailed review of medication history is necessary to evaluate FDEs. Our case emphasizes that not only endogenous but also exogenous forms of progesterone may cause hypersensitivity, leading to an FDE. With more than 2 million prescriptions of medroxyprogesterone acetate written every year, dermatologists should be aware of the rare but potential risk for an FDE in patients using this medication.18