D3.66 - When dermatitis follows the menstrual cycle: two cases of endogenous progestogen hypersensitivity

Introduction:

Progestogen hypersensitivity (PH) is a rare immune-mediated reaction to endogenous progesterone and/or synthetic progestins. Clinical manifestations are heterogeneous and may arise at any point during reproductive life, with cutaneous involvement being the most common. Frequently reported skin presentations include eczematous dermatitis (ED), urticaria, and maculopapular rash.

Case reports:

The first patient reported a long-standing history of recurrent ED localized to the décolletage, occurring 7–10 days before menstruation and resolving with menstrual bleeding. Skin lesions persisted throughout both pregnancies. She had never been exposed to progesterone-based therapies or hormonal contraception. An in vivo progesterone provocation test (PPT) was performed on day 10 of the menstrual cycle (follicular phase). No immediate reaction occurred. However, 72 hours after the PPT, lesions developed on the upper chest, reproducing her typical cyclic eruptions.

The second patient had recurrent, localized ED on the right upper arm and genital area since 2013, appearing around ovulation, with spontaneous resolution. She had never been pregnant and had no exposure to exogenous progestogens. The PPT performed in the follicular phase was negative, with no immediate or delayed reactions.

Results:

Both patients showed recurrent ED with a consistent temporal association with the menstrual cycle and no prior exposure to progesterone-containing medications. The timing and spontaneous resolution of lesions correlated with endogenous hormonal fluctuations, supporting a diagnosis of endogenous PH. In the first patient, delayed exacerbation after PPT was interpreted as a flare of endogenous disease, indicating that exogenous progesterone may reproduce cutaneous manifestations without implying an exogenous or mixed phenotype. The delayed onset and eczematous morphology were suggestive of a delayed, non-IgE-mediated hypersensitivity pattern. A negative PPT in the second patient did not exclude endogenous PH, as the diagnosis is primarily clinical and based on a consistent temporal relationship between symptoms and the menstrual cycle. Interindividual variability and the inability of exogenous progesterone to fully replicate endogenous hormonal fluctuations may explain false-negative test results.

Conclusion:

Cyclic ED temporally associated with the menstrual cycle represents a key diagnostic clue for endogenous PH. Increased clinician awareness of this pattern is essential to prevent misdiagnosis and delays in recognition.