Progestogen Hypersensitivity in 24 Cases: Diagnosis, Management, and Proposed Renaming and Classification

Abstract

Background: Autoimmune progesterone dermatitis is a poorly recognized syndrome associated with a hypersensitivity to progestogens. Symptoms present heterogeneously, which may complicate diagnosis. Management has generally centered on symptomatic control with medication. Recently, an increasing number of cases have been reported with in vitro fertilization (IVF). Desensitization to progestogens is suggested as an approach to tolerate fertility treatments and provide symptom control.

Objectives: To describe the diagnosis and management of progestogen hypersensitivity (PH) and to detail the use of desensitization. We also propose a new terminology of progestogen hypersensitivity instead of autoimmune progesterone dermatitis, and a classification system based on exogenous and endogenous progestogen triggers to facilitate diagnosis and management.

Methods: Twenty-four cases of PH were evaluated retrospectively. Symptom presentation, diagnostic modalities, desensitization protocols, and outcomes were analyzed.

Results: Symptom onset was classified as a reaction to either endogenous progesterone (42%) or exogenous progestogens (58%). Symptoms were heterogeneous and included cyclical dermatitis, urticaria, angioedema, asthma, and anaphylaxis. Triggers were also heterogenous and included progesterone as well as progestins. Eleven patients underwent intramuscular (27%) or oral (73%) desensitization. Desensitization resulted in symptom control in 8 patients, IVF medication tolerance in 3 patients, and 2 pregnancies.

Conclusions: This is the largest case series of patients with PH with successful treatment outcomes. The new terminology progestogen hypersensitivity more accurately represents the diversity of presentations to endogenous or exogenous progestogens. We demonstrate that progestogen desensitization is successful in multiple patients and can result in symptom control and fertility. Women with cyclical allergic symptoms, including those undergoing IVF, should be evaluated for PH.

Keywords: Autoimmune progesterone dermatitis; Catamenial anaphylaxis; Desensitization; Infertility; Progesterone; Progestin; Progestogen.