Q:

5/23/2012
I am seeing an 18 y.o. young woman for a second opinion on allergy to progesterone. She has PCO syndrome and develops urticaria and vomiting mid cycle every month. Her symptoms resolve when she starts menstruating. Her GYN treated her with Lupron which successfully suppressed the allergic problem but made her menopausal. She was seen by another allergist and had a positive skin test to progesterone. The history and testing are fairly convincing for IgE-mediated allergy to progesterone. The question was raised as to whether she can be desensitized to progesterone and I could not find a protocol that would fit this situation. I would appreciate any help you can offer.

A:

Thank you for your inquiry.

There are a number of references to attempts to desensitize to progesterone in the older literature as discussed in a review of this condition published in 1995 (1). These attempts have met with various success, producing, according to this reference, temporary improvement, complete improvement, and failing to induce improvement.

More recently, however, two publications have dealt with the issue of progesterone desensitization, and you will find a protocol for this procedure within these publications. The abstracts are copied below.

I might mention parenthetically that there are other options for treatment that you might consider. The principle behind such therapy is suppression of menses as has been previously tried in your patient using Lupron. Alternatively, one can treat with birth control pills, but there have been anecdotal reports of a reaction to the progesterone contained in such pills. You can review a discussion in this regard on our Academy "Ask the Expert" website by typing "progesterone" into the search box. The entries which might be of interest to you in this regard are noted below. Of particular note in terms of the use of birth control pills to suppress menses is an entry on 6/22/2011.

Entered 11/07/2011 - "Progesterone dermatitis"

Entered 06/22/2011 - "Possible progesterone-related anaphylaxis"

Entered 09/27/2010 - "Recurrent severe anaphylaxis possibly related to progesterone"

Also, danazol has been used successfully (see abstract below).

Thank you again for your inquiry and we hope this response is helpful to you.

Reference:
1. Herzberg AJ, et al. Autoimmune progesterone dermatitis. Journal of American Academy of Dermatology 1995; 32(2) Part 2:333-338.

Fertil Steril. 2011 Mar 1;95(3):1121.e9-13. Epub 2010 Nov 18.
Autoimmune progesterone dermatitis: clinical presentation and management with progesterone desensitization for successful in vitro fertilization.
Prieto-Garcia A, Sloane DE, Gargiulo AR, Feldweg AM, Castells M.
Source
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract
Objective: To report clinical cases of autoimmune progesterone (P) dermatitis, its relationship to IVF, and the potential for P desensitization to treat these cases to achieve viable pregnancies.
Design: Clinical description.
Setting: Institutional hospitalary practice - Allergy Division.
Patient(s): Six patients from the Allergy Clinic consulting for cyclic rashes or anaphylaxis related to the luteal phase of the menstrual cycle. Three of the conditions were related to IVF.
Intervention(s): Skin tests were performed with P. For IVF, rapid 8- and 10-step P desensitization protocols were performed, with increasing doses administered every 20 minutes via intravaginal suppositories. A rapid oral desensitization protocol was performed in one patient who required an oral contraceptive for uterine bleeding.
Main Outcome Measure(s): Progesterone skin test results. Tolerance to P desensitization. Achievement of viable pregnancies.
Result(s): Skin tests were positive in all patients and negative in 10 controls. Desensitization was successful in four patients: three patients for IVF, resulting in viable pregnancies. Another patient achieved tolerance to oral contraceptives.
Conclusion(s): Women with autoimmune P dermatitis can be desensitized successfully to P. We provide the first evidence of successful P desensitization in patients requiring IVF culminating in successful pregnancies.

Fertil Steril. 2011 Jun 30;95(8):2571-3. Epub 2011 Jun 8.
Steroid hormone hypersensitivity: clinical presentation and management.
Itsekson AM, Seidman DS, Zolti M, Alesker M, Carp HJ.
Source
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Israel.
Abstract
Hypersensitivity to estrogens and progestogens is often undiagnosed. The condition has many manifestations, including premenstrual syndrome, dysmenorrhea, and impaired fertility. Diagnosis is confirmed by skin testing for inflammatory responses to small doses of the hormone, and desensitization with small doses of the hormone is the most appropriate form of management.

Int J Dermatol. 1997 Sep;36(9):708-11.
Autoimmune progesterone dermatitis: effective prophylactic treatment with danazol.
Shahar E, Bergman R, Pollack S.
Source
Institute of Allergy, Clinical Immunology, and AIDS, Rambam Medical Center, Haifa, Israel.
Abstract
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.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology