Ana Poljanac

Brankica Ilić

Dragana Ljubojević Grgec

Sandra Marinović Kulišić

Suzana Ljubojević Hadžavdić

English

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ACTA DERMATOVENEROLOGICA CROATICA276Autoimmune Progesterone Dermatitis Diagnosed by Lymphocyte Transformation Test and Progesterone Provocation TestAutoimmune progesterone dermatitis (APD) is rare autoimmune response to endogenous proges-terone or to earlier exposure to exogenous progester-one (1). Skin lesions typically occur due to increases in progesterone during the luteal phase of the men-strual cycle (2). A-31-year-old mother of two children presented to our Department with a 5-year history of pruritic and painful erythematosus macules, papules, and patches on her neck, pectoral region, and face, which appeared 2-3 days before the onset of menses and gradually resolved 7-10 days later (Figure 1). The le-sions first appeared 10 months after her second preg-nancy and a few months after she had started using oral contraceptive pills (OCP) containing gestodene combined with ethinyloestradiol. A few months be-fore presenting to us, the lesions had started spread-ing on her forearms, elbows, and pretibial areas. Since one year prior to our visit she had complained of occasional urticaria with angioedema one week prior to menses, which resolved after menses. The le-sions were accompanied by malaise, headache, and fatigue. The patient was asymptomatic between the outbreaks. She reported that she had been using vari-ous local corticosteroids, peroral antihistamines, and prednisone for the treatment of her skin lesions, but this treatment had not improved her symptoms. She suffered from mild seasonal rhinoconjunctivitis.We performed multiple laboratory tests that were unremarkable. Histopathological examination of a biopsy taken from a lesion on the neck showed epi-dermal hyperplasia and nonspecific mild dermal in-flammation. Since progesterone was not available in aqueous solution in our country, we did not perform an intradermal test, but we performed a lymphocyte transformation test (LTT) to medroxyprogesterone and estradiol. The patient’s lymphocytes showed markedly enhanced proliferation to medroxypro-gesterone in vitro, while being negative to estradiol. We had performed control LTT in 10 healthy controls and 10 patients with atopy, and such hyperactivity was not observed in any of them. We performed an oral provocation test with OCP containing gestodene combined with ethinyloestradiol. Two days after commencing treatment, the patient developed wide-spread dermatitis (Figure 2) with nausea, malaise, and angioedema. The patient was informed about treat-ment options and possible side-effects. She started Figure 2. Papular and urticarial patches on the arms a few days after oral provocation test with oral contraceptive pills (OCP) containing gestodene combined with ethi-nyloestradiol.Figure 1. Erythematous, indurated patchy skin eruptions on the face.Acta Dermatovenerol Croat                              2018;26(3):276-277                               LETTER TO THE EDITORACTA DERMATOVENEROLOGICA CROATICALetter to the editor Acta Dermatovenerol Croat2018;26(3):276-277277with OCP with the lowest amount of progesterone, containing ethinyloestradiol and dropirenone for treatment of APD, but terminated treatment after the second cycle due to a worsening of the skin lesions and urticaria accompanied with angioedema. At the time of writing, our patient continues to have pre-menstrual flares. The typical symptoms of APD are skin lesions such as eczema, erythema multiforme, prurigo, sto-matitis, papulopustular lesions, folliculitis, urticaria, angioedema, and rarely anaphylaxis (2) that develop 3-10 days before and subside 1-2 days after menses, with recurrent cyclic aggravation (1,3,4). Frequently, patients have a history of exogenous progesterone intake (1,5,6), as in our patient, which could have re-sulted in antibody formation. The diagnosis of APD is established by an appropriate clinical history (pre-menstrual flare of skin lesions), a progesterone intra-dermal test, an intramuscular (7), oral (8), or intravagi-nal (1, 6) progesterone challenge test, and circulating antibodies to progesterone. Progesterone testing has not been standardized. Most of the sex hormones are not suitable for testing since they contain an oily component that can produce an irritant test reaction. Gestodene, which was used for the oral provocation test in our patient, is a potent progesterone (9). The LTT shows reactions to circulating lymphocytes and reflects immune reactions within the body. The goal of treatment is suppression of ovulation. Currently, the first-line choice of therapy is a combination oral contraceptive (3). We believe that OCP have a limited effect because all of them contain a progesterone component. If this treatment is ineffective, patients have been treated with danazol, gonadotropin releas-ing hormone analogs (3,4,6), conjugated estrogens (7), tamoxifen, oophorectomy (8), and progestogen desensitization (10) with varying success.References:1. Le K, Wood G. A case of autoimmune progeste-rone dermatitis diagnosed by progesterone pes-sary. Australas J Dermatol. 2011;52(2):139-41.2. Snyder JL, Krishnaswamy G. Autoimmune proges-terone dermatitis and its manifestation as anap-hylaxis: a case report and literature review. Ann Allergy Asthma Immunol. 2003;90(5):469-77.3. Baptist AP, Baldwin JL. Autoimmune progeste-rone dermatitis in a patient with endometriosis: case report and review of the literature. Clin Mol Allergy. 2004;2(1):10.4. Wingate-Saul L, Rymer J, Greaves MW. Chronic ur-ticaria due to autoreactivity to progesterone. Clin Exp Dermatol. 2015;40(6):644-6.5. Herzberg AJ, Strohmeyer CR, Cirillo-Hyland VA. Autoimmune progesterone dermatitis. J Am Acad Dermatol. 1995;32:333-8.6. Németh H, Kovács E, Gödény S, Simics E, Pfliegler G. Autoimmune progesterone dermatitis diagno-sed by intravaginal progesterone provocation in a hysterectomised woman. Gynecol Endocrinol. 2009;25(6):410-2.7. Oskay T, Kutluay L, Kaptanoğlu A, Karabacak O. Autoimmune progesterone dermatitis. Eur J Der-matol. 2002;12(6):589-91. 8. Shelley Wb, Preucel Rw, Spoont SS. Autoimmune progesterone dermatitis. Cure by oophorectomy. JAMA. 1964;190:35-8.9. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH. Clas-sification and pharmacology of progestins. Matu-ritas 2003;46 (Suppl 1):S7-S16.10. Foer D, Buchheit KM, Gargiulo AR, Lynch DM, Cas-tells M, Wickner PG. Progestogen Hypersensitivity in 24 Cases: Diagnosis, Management, and Propo-sed Renaming and Classification. J Allergy Clin Im-munol Pract. 2016;4(4):723-9. Suzana Ljubojević Hadžavdić1, Sandra Marinović Kulišić1, Dragana Ljubojević Grgec2, Ana Poljanac3, Brankica Ilić11Department of Dermatology and Venereology, University Hospital Center Zagreb, School of Medicine University of Zagreb, Croatia 2GinoDerma polyclinic for gynecology and obstet-rics, dermatology, and venerology, Zagreb, Croatia3Department of Dermatology and Venereology, County General Hospital Požega, CroatiaCorresponding author:Assoc. Prof. Suzana Ljubojević Hadžavdić, MD, PhDDepartment of Dermatology and VenereologyUniversity Hospital Center ZagrebSchool of Medicine University of ZagrebŠalata 410000 ZagrebCroatiasuzana.ljubojevic@gmail.comReceived: August 1, 2017Accepted: July 11, 2018

Autoimmune Progesterone Dermatitis Diagnosed by Lymphocyte Transformation Test and Progesterone Provocation Test

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