Autoimmune Progesterone Dermatitis: Potential Role of Cutaneous Angiogenin Expression?

Based on the patient’s history and clinical features typical of an AIPD [3] , to demonstrate the presence of hypersensitivity to progesterone, we performed patch testing, prick and intradermoreactions with progesterone solubilized in sesame oil as described [2, 3] . All these investigations were performed during the follicular phase to avoid interference with endogenous progesterone. While patch and prick testing remained negative, intradermoreaction with micronized progesterone (at a concentration of 50 mg/ml diluted at 1/10 and 1/100 in sesame oil) elicited both an immediate and delayed reaction. The test at the 1/10 dilution triggered a very intense immediate reaction at the site of testing with a pruritic plaque of 6 cm in diameter associated with diffuse lesions (delayed reaction) on the trunk reproducing the usual relapsing dermatosis. The pruritic plaque persisted for 4 weeks. The obtained results were scored as positive provocation test. In contrast, testing with sesame oil alone triggered only a slight erythema consistent with a toxic reaction as previously described [2] . With the informed consent of the patient, we next performed cytokine arrays (Ray Bio Human Cytokine antibody array; C series 2000; panel 6.1, 7.1, 8.1; http://www.raybiotech.com/map_ all_m.asp#11) using tissue lysates prepared from normal and lesional skin specimens obtained from our patient. Among the 180 tested proteins, we found an increased expression of angiogenin, adiponectin, agouti-related protein, epidermal growth factor receptor (EGFR) and intercellular adhesion molecule 1 in lesional skin compared to uninvolved skin ( fig. 3 ). AIPD is a rare but characteristic entity, of which at least 70 cases have been described so far [1] . Its clinical presentation is extremely variable with erythematous, macular, papular and/or vesicular rashes [7–9] , palmoplantar dyshidrosis [2, 10] , erythemamultiforme-like lesion [2–4, 11, 12] , stomatitis [9] as well as urticaria [13, 14] , angioedema [6] and anaphylactic-like shock [7, 10, 15] . The lesions typically and constantly relapse during the luteal phase of the menstrual cycle. Besides cutaneous testing with progesterone as carried out in our case, other investigations useful for the diagnosis of AIPD include the intramuscular injection of medroxyprogesterone acetate [4, 8] , a vaginal progesterone provocation test [16] , search for circulating antibodies to progesterone [1, 2] , basophilic degranulation tests [4] , as well as the Elispot assay to identify progesterone-sensitive interferon -producing cells [11, 17] . The pathogenicity of AIPD is unclear. A model predicts an immune reaction to endogenous progesterone during the menstrual cycle [4] . This dermatosis, which is exclusively observed in women during child-bearing years, disappears completely with the menopause, an observation highlighting the importance of hormonal triggers. It has been suggested that previous progesterone