Background

This rare skin rash is thought to be due to hypersensitivity to progesterone. For unknown reasons, some women develop antibodies against progesterone leading to a cyclical rash, often occurring with menstrual periods.

 

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE	Rare
AGE RANGE-MEDIAN	Usually reproductive age
SEX (M:F)	F

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
AMENORRHEA
Autoimmune progesterone dermatitis with persistent amenorrhoea. Katayama I, Nishioka K.	Br J Dermatol 1985 Apr;112(4):487-91 Abstract quote A case of autoimmune progesterone dermatitis is reported. The patient developed a recurrent eruption, primarily on the extremities, after receiving oral progesterone for the treatment of persistent amenorrhoea. Intradermal injection of 17 alpha-hydroxyprogesterone produced a positive skin reaction after 30 min, but no delayed onset reaction was observed. A patch test with progesterone in petrolatum was negative. The lymphocyte transformation test was normal. Histamine release from passively sensitized peripheral blood leukocytes was increased by progesterone preincubated in normal serum as a stimulating antigen. Conjugated oestrogen therapy suppressed the rash. Cyclical eruptions with elevated basal body temperature persisted for more than 20 months without menstruation.
ENDOMETRIOSIS
Autoimmune progesterone dermatitis in a patient with endometriosis: case report and review of the literature. Baptist AP, Baldwin JL. Division of Allergy/Immunology, Department of Internal Medicine, University of Michigan, 3918 Taubman Center, #0380, 1500 E Medical Center Drive, Ann Arbor, MI 48109-0380, USA.	Clin Mol Allergy. 2004 Aug 2;2(1):10. Abstract quote   Autoimmune progesterone dermatitis (APD) is a condition in which the menstrual cycle is associated with a number of skin findings such as urticaria, eczema, angioedema, and others. In affected women, it occurs 3-10 days prior to the onset of menstrual flow, and resolves 2 days into menses. Women with irregular menses may not have this clear correlation, and therefore may be missed. We present a case of APD in a woman with irregular menses and urticaria/angioedema for over 20 years, who had not been diagnosed or correctly treated due to the variable timing of skin manifestations and menses. In addition, we review the medical literature in regards to clinical features, pathogenesis, diagnosis, and treatment options.

 

PATHOGENESIS	CHARACTERIZATION
HYPERSENSITIVITY REACTION
Autoimmune progesterone dermatitis: absence of contact sensitivity to glucocorticoids, oestrogen and 17-alpha-OH-progesterone. Stephens CJ, McFadden JP, Black MM, Rycroft RJ. St. John's Institute of Dermatology, St. Thomas' Hospital, UK.	Contact Dermatitis 1994 Aug;31(2):108-10 Abstract quote Autoimmune progesterone dermatitis is a rare condition, characterized by recurrent premenstrual exacerbations of a dermatosis, in which sensitivity to progesterone can be demonstrated. The sensitizing mechanism is unknown. The aim of this study was to test the hypothesis that cross-sensitivity between steroid groups could induce allergy to endogenous progesterone in these patients. 5 patients with autoimmune progesterone dermatitis and 1 with oestrogen-sensitive dermatitis have been patch tested with a corticosteroid series, conjugated oestrogen 1% in petrolatum (pet.), and 17-alpha-OH-progesterone 2% pet. There were no immediate or delayed reactions at 2 and 4 days to any steroid group. We have therefore been unable to demonstrate steroid cross-sensitivity, or a use for 17-alpha-OH-progesterone in the investigation of oestrogen - and progesterone-sensitive dermatoses.

 

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
Two cases of autoimmune progesterone dermatitis. Immunohistochemical and serological studies. Miura T, Matsuda M, Yanbe H, Sugiyama S. Department of Dermatology, Sapporo Medical College, Japan.	Acta Derm Venereol 1989;69(4):308-10 Abstract quote Two cases of autoimmune progesterone dermatitis are reported. The patients developed recurrent pruritic erythematous and edematous eruptions on the extremities, trunk or face, with occasional vesicles on the palms and soles. The eruptions appeared 7 to 10 days prior to their menstruation and persisted for several days. They showed immediately positive skin tests with 0.1 mg/ml and 0.2 mg/ml of aqueous progesterone suspension, respectively. The patients had IgG serum factor which bound rat corpus luteum. Positive indirect basophil degranulation tests against progesterone were demonstrated in both patients. Circulating autoantibodies to patients' own progesterone may cause or modulate the intermittent eruptions of the disease.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Autoimmune progesterone dermatitis. Rasi A, Khatami A. Department of Dermatology, Hazrat-e-Rasul Hospital, Iran University of Medical Sciences and Health Services, Tehran.	: Int J Dermatol. 2004 Aug;43(8):588-90. Abstract quote   Autoimmune progesterone dermatitis is a rare cutaneous disorder characterized by recurrent cyclic eruptions with variable morphology occurring during the luteal phase of the menstrual cycle. We report a case of a 40-year-old woman with recurrent pruritic eruptions of 8 years' duration. The possibility of autoimmune progresterone dermatitis was raised because of the cyclic nature of the exacerbations. We used oral estrogen both to confirm the diagnosis and to treat the patient. A brief review of the clinical features of the disease is also presented.
Autoimmune progesterone dermatitis. Hart R.	Arch Dermatol 1977 Apr;113(4):426-30 Abstract quote Seven patients had autoimmune progesterone dermatitis. The morphological findings illustrate the polymorphous nature of the disease in which urticaria, erythema multiforme, and dyshidrosiform lesions were seen. Recurrence of the eruption five to ten days prior to the menses with spontaneous resolution following the menses was present in all cases. Intradermal skin testing to progesterone was done to confirm the diagnosis. Six of the seven patients has a history of use of artificial progestational hormones prior to the beginning of their eruption. It is postulated that the artificial progesterones may have been the trigger for the development of their autosensitivity. Treatment with conjugated estrogens resulted in remission of the disease in five of the seven cases reported.
Post-menopausal cyclic eruptions: autoimmune progesterone dermatitis. Bolaji II, O'Dwyer EM. Department of Obstetrics and Gynaecology, University College Hospital, Galway, Ireland.	Eur J Obstet Gynecol Reprod Biol 1992 Nov 19;47(2):169-71 Abstract quote Two cases of autoimmune progesterone dermatitis (AIPD) are reported. The patients developed a recurrent eruption, primarily on the extremities after receiving oral oestrogen/progesterone replacement for the treatment of climacteric symptoms. The diagnosis was confirmed in one of the cases who had intradermal progesterone injection producing an early positive reaction. One case required transient prednisolone therapy and both eventually resolved completely. Aetiological postulates are discussed.
Autoimmune progesterone dermatitis: onset in a women without previous exogenous progesterone exposure. Moody BR, Schatten S. Emory University School of Medicine, Atlanta, Ga, USA.	South Med J 1997 Aug;90(8):845-6 Abstract quote Autoimmune progesterone dermatitis is a rare clinical entity that may be seen by the family practitioner, gynecologist, or dermatologist. Recognition of the entity is paramount in the therapy of this easily treated condition. We report a case of a 36-year-old woman with a recurrent facial dermatitis of many months' duration. We found the cutaneous eruption to be temporally related to her menstrual cycle. The patient denied any changes in her diet, cosmetics, medications, or soaps that could account for the dermatitis. Despite no previous exposure to exogenous progesterone, the diagnosis of autoimmune progesterone dermatitis was made. The patient was cured by oophorectomy.
VARIANTS
GYRATE
Autoimmune progesterone dermatitis manifested as erythema annulare centrifugum: Confirmation of progesterone sensitivity by in vitro interferon-gamma release. Halevy S, Cohen AD, Lunenfeld E, Grossman N. Department of Dermatology, the Department of Obstetrics and Gynecology, and Investigative Dermatology Laboratory, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev.	J Am Acad Dermatol 2002 Aug;47(2 Pt 1):311-3 Abstract quote Autoimmune progesterone dermatitis was manifested as deep-type erythema annulare centrifugum. Sensitivity to progesterone was studied in vivo by means of intradermal and patch tests, which revealed immediate-type and delayed-type hypersensitivity, respectively. Sensitivity to progesterone was further confirmed in vitro by results of an interferon-gamma release test, which imply a possible role for T(H)1-type cytokines in autoimmune progesterone dermatitis.
URTICARIA
Autoimmune progesterone urticaria. Vasconcelos C, Xavier P, Vieira AP, Martinho M, Rodrigues J, Bodas A, Barros MA, Mesquita-Guimaraes J. Department of Dermatology and Venereology, University Hospital of Sao Joao, Porto, Portugal.	Gynecol Endocrinol 2000 Aug;14(4):245-7 Abstract quote Autoimmune progesterone dermatitis is a rare cutaneous disorder characterized by recurrent and cyclic skin eruption with variable morphology, occurring during the luteal phase. A case of autoimmune progesterone urticaria in a 47-year-old woman is reported. An intradermal progestin test revealed a strong reactivity against this hormone. Treatment with tamoxifen and leuprolide acetate induced only a partial remission of urticaria. Bilateral oophorectomy was performed with absolute clearing of cutaneous lesions.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT
DANAZOL
Autoimmune progesterone dermatitis: effective prophylactic treatment with danazol. Shahar E, Bergman R, Pollack S. Institute of Allergy, Clinical Immunology, and AIDS, Rambam Medical Center, Haifa, Israel.	Int J Dermatol 1997 Sep;36(9):708-11 Abstract quote BACKGROUND: Autoimmune progesterone dermatitis is a rare condition appearing during the perimenstrual period or following progesterone treatment. Various treatment modalities have been suggested, but most have proved to be ineffective. METHODS: We used the anabolic androgen danazol as a preventive treatment for recurrent episodes of autoimmune progesterone dermatitis in two young women. The treatment regimen consisted of 200 mg danazol twice daily, starting 1-2 days before the expected date of each menses and continuing for 3 days thereafter. RESULTS: This treatment regimen proved to be highly effective in preventing the eruptions in these two patients. CONCLUSIONS: Patients with autoimmune progesterone dermatitis may benefit from prophylactic treatment with danazol.
OOPHORECTOMY
Autoimmune progesterone dermatitis: treatment with oophorectomy. Rodenas JM, Herranz MT, Tercedor J. Department of Dermatology, Hospital General Universitario Morales Meseguer, Av. Marques de los Velez, 30008 Murcia, Spain.	Br J Dermatol 1998 Sep;139(3):508-11 Abstract quote Autoimmune progesterone dermatitis is a rare manifestation of hypersensitivity to endogenous hormones with polymorphic clinical manifestations. We report a 28-year-old woman with a 5-year history of mucocutaneous erythema multiforme occurring cyclically in the premenstrual period. Progesterone sensitivity was demonstrated by challenge test with medroxyprogesterone acetate. Treatments with oestrogens, tamoxifen and triptorelin had to be withdrawn because of intolerable adverse effects. Oophorectomy finally cured the disease.
TAMOXIFEN
Autoimmune progesterone dermatitis responding to Tamoxifen. Stephens CJ, Wojnarowska FT, Wilkinson JD. Wycombe General Hospital, U.K.	QBr J Dermatol 1989 Jul;121(1):135-7 Abstract quote A case of autoimmune progesterone dermatitis is described. Exacerbation occurred premenstrually and after intramuscular and oral challenge with synthetic progesterone. The condition failed to respond to oestrogen, but there has been a marked improvement with the anti-oestrogen drug Tamoxifen.

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Last Updated June 17, 2005

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