Progesterone Hypersensitivity

Question 1

Symptoms are more prominent during what phase of the menstrual cycle?

Answer 1

• Luteal phase of the menstrual cycle for the endogenous form and after exposure to progestins for exogenous PH

Question 2

Progestogen

Answer 2

• Class of steroid hormones that bind to the progesterone receptor.
• Umbrella term that encompasses both progesterone and progestins.

Question 3

Pathogenesis

Answer 3

• Estrogen promotes the differentiation of DCs and the production of Th2 cytokines.
• Estrogen inhibits B cell apoptosis and tolerance induction of naive B cells
• These mechanisms drive a Th2 prone environment in women of reproductive age, which may contribute to progestogen sensitization and progestogen-specific IgE production.

Question 4

In 58% of women with PH, the initial symptoms are triggered by an ___________ progestogen.

Answer 4

• Exogenous

Question 5

Symptoms of PH:

Answer 5

• maculopapular rash
• cutaneous plaques
• asthma
• anaphylaxis
• urticaria
• eczematous dermatitis
• annular targeted plaques
• nummular eczematous dermatitis
• pustules and plaques

SYMPTOMS ARE TYPICALLY CYCLICAL, THESE MAY BE EITHER IMMEDIATE OR DELAYED

Question 6

Onset of symptoms in patients with PH triggered by endogenous, ovarian progesterone

Answer 6

• Clinical symptoms present during the lethal phase of the menstrual cycle, usually 3-10 days before the start of menses

Question 7

Proposed criteria for diagnosis of PH (3):

Answer 7

1.Symptoms are compatible with PH: cutaneous symptoms (ie, dermatitis, urticaria, vesiculobullous disease, fixed drug eruption) and/or bronchospasm and/or anaphylaxis.
a. Alternative etiologies for symptoms are ruled out (ie,
chronic idiopathic urticaria, uncontrolled atopic dermatitis,
medication allergy).
2. Timing is consistent with the luteal phase of menstrual cycle
or in the setting of exogenous progestin exposure.
3. There is a response to inhibitors of ovulation.

Question 8

Skin testing

Answer 8

• Progesterone requires a nonaqueous diluent for
  skin testing preparation. Benzyl alcohol, sesame, olive, and peanut oil have been used (keep in mind that diluents may contribute to a false positive result)
• A negative result cannot rule out PH in the context of a convincing history, and a positive result should not be used to justify intervention.
• Based on this, progesterone skin testing should no longer be used to make the diagnosis of PH.
• Progestogen challenge should be considered in all patients when the confirmation of a suspected diagnosis is necessary and safe.

Question 9

Other diagnostic options:

Answer 9

• Empiric suppression of ovulation with low-dose combined oral contraceptives can be considered a diagnostic tool for endogenous PH in patients who are not actively planning for pregnancy.
• Alternative options lacking progestins include analogs of gonadotropin-releasing hormone (GnRH) or GnRH
  receptor blockade.

Question 10

Treatment of PH

Answer 10

• In some patients who do not respond to standard-of-care allergy treatment, a trial of an oral contraceptive with a constant dose of progesterone administered continuously can ameliorate symptoms