001476 - Hypersensitivity to endogenous progesterone manifested as fixed drug eruption: a case report

Dermatitis caused by progesterone hypersensitivity (PH) is a rare disorder characterized by skin lesions that appear concerning progesterone spikes during the menstrual cycle. It has been associated with various skin manifestations, such as urticaria, eczema, angioedema, ulcers, fixed drug eruptions, and even anaphylaxis making its diagnosis quite challenging. Treatment options include oral contraceptives, management with systemic corticosteroids, oophorectomy, or rapid drug desensitization.

A 28-year-old nulliparous woman, with no relevant medical history except intolerance to oral contraceptives 4 years prior due to weight gain, mood changes, and headaches.  Referred to our service from Dermatology due to erythematous-violet, scaly, pruritic, and burning skin plaques located on the lower lip and the palm of the right hand over the last 10 months. The patient does not report taking any medication before the onset of symptoms.

The lesions appear on the first day of menses, with no response to antihistamine treatment and partial management of symptoms (itching and pain) with high doses of corticosteroids (1mg/kg).

Skin tests were performed with progesterone, prick test with 150mg/ml, intradermal test with 0.1-0.2mg/ml, and an epicutaneous test with 5% dilution in vaseline, all on healthy skin. Lesions could not be subject to patch testing due to location.

Pharmacists in our hospital elaborated a 7-step desensitization plan with progesterone starting with 1mcg up to 100mcg, totaling 180mcg on the first day, consumed orally with a high-fat vehicle (whole-milk) to improve absorption. Afterward, the patient continued with 150mcg of progesterone daily, uninterruptedly. 

Cutaneous tests were all negative, despite this, the suggestive history of cycles of acute inflammation with persistent hyperpigmented lesions, combined with clinical exacerbations related to the menstrual cycle and no medication history, led to the diagnosis of hypersensitivity to endogenous progesterone manifested as fixed drug eruption.

Oral desensitization to progesterone was performed in 7 steps. The patient experienced self-limiting generalized itching at step 2 (2mcg), ultimately, she tolerated 180mcg in total, continuing with 150mcg without incidents. 

Fixed drug eruption due to PH is a rarely described entity. Although the pathogenesis is unclear, it suggests a delayed hypersensitivity (Type IV reaction) to high progesterone levels. 

Patch testing was not possible initially due to the location of lesions. On recent flares, the patient has presented recurrence in other areas (posterior thighs) that are easily tested and will be added to the results. 

Rapid oral drug desensitization was proposed for this patient as a treatment instead of other options due to previous intolerance to oral contraceptives, the high doses of corticosteroids needed for partial symptomatic management, and the significant impact on an oophorectomy. 

Follow-up is required to assess the reappearance of lesions at the onset of future menses.