Journal List > Ann Dermatol > v.29(4) > 1096535

You, Yun, Kim, Lee, Won, and Lee: Three Cases of Autoimmune Progesterone Dermatitis


Autoimmune progesterone dermatitis is a rare cyclic premenstrual reaction to progesterone produced during the luteal phase of the menstrual cycle. The clinical symptoms of autoimmune progesterone dermatitis overlap with other forms of dermatosis such as erythema multiforme, eczema, fixed drug eruption, urticaria, and angioedema. We experienced 3 cases of autoimmune progesterone dermatitis. All patients had a recurrent history of monthly skin eruptions. Skin lesions normally began a few days before menstruation and resolved a few days later. Patients were confirmed to have autoimmune progesterone dermatitis by the results of the progesterone intradermal test. All three patients had different clinical findings such as erythema annulare centrifugum, urticaria, contact dermatitis, and rosacea. Because patients presented with variable clinical manifestations, they could have been easily misdiagnosed. The patients were treated with oral contraceptive, antihistamine and steroids for symptom control. We propose that dermatologists should consider autoimmune progesterone dermatitis in cases of recurrent cyclic skin eruptions in female patients. Further, if this condition is suspected, thorough history taking including that on menstrual cycle and intradermal progesterone test should be performed.


Autoimmune progesterone dermatitis is a rare dermatosis characterized by recurrent skin eruptions during the luteal phase of the menstrual cycle1. The nature of eruption varies widely and is diverse, and thus, its diagnosis is challenging. Clinical history of recurrent cyclical skin lesions and symptomatic improvement after inhibition of progesterone, along with a positive result for intradermal progesterone test can confirm the diagnosis. The prevalence of autoimmune progesterone dermatitis is unclear, but about 80 cases have been reported in the literature thus far. Here, we present 3 cases of autoimmune progesterone dermatitis with a review of the related literature.


An 18-year-old girl with no significant medical history and no prior exogenous hormone use presented with a 4-month history of skin eruption. The lesions were localized to both cheeks and appeared as well demarcated erythematous patches with heating sense and edema (Fig. 1A, B). She had no history of contact, cosmetic changes or symptoms of arthritis, or photosensitivity. Allergic contact dermatitis, rosacea, or lupus erythematosus were considered as the clinical impressions. Routine laboratory findings including complete blood count, blood chemistry, and hormonal and immunological examinations were within the normal ranges.
The second patient, a 29-year-old woman had pruritic erythematous patches with edema on her chest and back (Fig. 2A, B). Based on her history of nickel allergy, skin lesions were noted on her bra lines, and histopathologic findings indicated dilated vessels and patchy infiltration of lymphocytes in the upper dermis (Fig. 2C), and contact dermatitis or urticarial dermatitis was considered as a clinical diagnosis.
The third patient was a 38-year-old woman who complained of pruritic and erythematous polycyclic patches on her trunk, arms, and face that caused a stinging sensation (Fig. 3A, B). Clinically, erythema annulare centrifugum or tinea corporis or urticaria was considered.
These three female patients were treated with oral antihistamines and topical steroids. However, the symptoms fluctuated. After further interviews with the patients, we found the fact that these skin lesions occurred or exacerbated 5~6 days before their onset of menstruation, when their progesterone levels were elevated. Further, these lesions were resolved or partially improved after cessation of menses. As these eruptions waxed and waned in accordance with progesterone levels, we considered the diagnosis of autoimmune progesterone dermatitis. Intradermal tests using 50 mg/ml progesterone were performed to confirm the diagnosis of autoimmune progesterone dermatitis, and all patients showed positive results (Fig. 1C, 2D, 3C). The first patient was treated with oral contraceptives, but the second and third patients were treated with antihistamine and systemic steroids to maintain their fertility. While two patients showed clinical improvement, one patient recovered after menopause.


Autoimmune progesterone dermatitis is a rare autoimmune response to endogenous or exogenous progesterone. The pathogenesis of this disease is unclear, but it is considered to be caused by a hypersensitivity reaction to endogenous progesterone1. Onset has been described at menarche, in the peripartum period, or apparently spontaneously.
The clinical features of autoimmune progesterone dermatitis dermatitis vary and thus far, about 80 cases have been reported in the literature. The most common clinical manifestations were urticaria2, angioedema and erythema multiforme23. In addition to these, eczema, Steven-Johnson syndrome, fixed drug eruption4 and erythema annulare centrifugum like lesions5 have also been observed. Initially, each of these patients was considered to have allergic contact dermatitis, rosacea, and erythema annulare centrifugum. Because of its polymorphic characteristics, physicians can easily misdiagnose and treat this condition incorrectly.
However, there are no definitive diagnostic laboratory tests or histopathological findings. Variable skin disorders such as acne, psoriasis, lupus erythematosus and so on can flare up before menstruation. Due to its rarity, the diagnosis for autoimmune progesterone dermatitis should be excluded.
The diagnostic criteria for autoimmune progesterone dermatitis proposed by Warin6 include 1) skin lesions associated with menstrual cycle (premenstrual flare); 2) a positive response to the progesterone intradermal test or reproducibility of the rash with the intramuscular test; and 3) symptomatic improvement after inhibiting progesterone secretion by suppressing ovulation. In particular, skin lesions of autoimmune progesterone dermatitis develop 3~10 days before menstruation and persist up to 1~2 days after cessation of menses, and correlate with serum progesterone levels7. Autoimmune estrogen dermatitis also presents as a cyclic skin disorder but the hallmark of estrogen dermatitis is the cyclic premenstrual flare. This hormone-induced dermatosis may appear as variable clinical manifestations. However, the lesions tend to involute during pregnancy and at menopause8.
The intradermal test can be used to confirm autoimmune progesterone dermatitis, and both immediate and late reactions may occur. If a wheal or erythema appears at the site of aqueous suspension of progesterone immediately, or within 48 hours, a positive test can be concurred. Some patients experience recurrence of skin lesions after an injection of progesterone19. Autoimmune progesterone dermatitis can be treated or controlled mainly by suppressing ovulation. The initial therapy is combined oral contraceptives. To control such simple cutaneous reaction of autoimmune progesterone dermatitis, an antihistamine combined with a systemic steroid may be helpful during exacerbations. Further, GnRH agonists, danazol and tamoxifen can be used, and in refractory cases, bilateral oophorectomy can also be considered10. Patient 1 had irregular menstrual cycles, and was unmarried, and she was treated with oral contraceptives. However, patients 2 and 3 had tried conception, and antihistamines with steroids were used. Since there is no preferable treatment, treatment options vary with individuals.
In conclusion, autoimmune progesterone dermatitis is a rare autoimmune response to endogenous or exogenous progesterone. Patients with autoimmune progesterone dermatitis may present with diverse unusual manifestations, resulting in a delayed diagnosis and misdiagnosis. Moreover, patients are not aware that their skin lesions are associated with their menstrual cycle before discussion with their clinicians. These cases emphasize that dermatologists should consider autoimmune progesterone dermatitis in the differential diagnosis when female patients complain of recurrent cyclic skin eruptions. Further, if this commotion is suspected, thorough history taking on the menstrual cycle and results of the intradermal progesterone test are mandatory.


CONFLICTS OF INTEREST The authors have nothing to disclose.


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