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Urticaria, progesterone and pregnancy


I was recently referred a patient for chronic urticaria (35 yo F). There is a strong history of physical urticaria since childhood (dermatographism, cold-induced, and delayed pressure). She was evaluated 2 years prior by another allergist. At that time, anti TPO was 221.0 and anti-thyroglobulin was 2.0. TSH level was slightly elevated at 4.64. Repeat level one year later was 2.99. There is a family history of Hashimoto’s disease. She has experienced recent trouble with conceiving and has established with an REI specialist. This specialist is re-evaluating her thyroid levels. In the meantime, she established with me to discuss her concern regarding localized urticaria (commonly around R hip) during her menstrual cycle for the last 2 years. Of note, she was on OCP management for 12 years and never experienced urticarial eruptions during her cycle. She stopped her OCP 5 years ago, and developed associated urticaria in the last 2 years. The patient does openly voice that her symptoms are not affecting her quality of life (self-reported mild urticaria), but she is concerned for progesterone hypersensitivity and implications during pregnancy. Her history does appear to be consistent with possible progesterone hypersensitivity. Her lack of symptoms while on OCP management further support this diagnosis, as modulation of the luteal phase of ovulation is the treatment approach. Can you please comment on the natural course of this condition during pregnancy? Do patients experience refractory urticaria during the second half of pregnancy when progesterone level rise, and what is the recommended management plan for these patients during pregnancy?

I am grateful to Dr Karen Hsu Blatman who provided the following response.

It would be important to obtain more information regarding the timing of her urticarial symptoms in relation to the phase of her menstrual cycle. Does she have regular menstrual cycles? In a normal menstrual cycle, progesterone is released from the corpus lutem during the luteal phase (the 2nd half of the menstrual cycle, from ovulation to menstruation). Progesterone levels start to rise about 24-48 hours prior to ovulation and reach its peak on day 20-21 of a 28-day cycle. If pregnancy does not happen, the corpus luteum starts to break down, causing progesterone levels to fall. Due to low progesterone, the period starts. So, if she reports hives around the time of her period, it is unlikely to be explained by progesterone hypersensitivity. In that case, I would be interested if she is takes any NSAIDs at the time of her menses. If hives appear around day 20-21 of her cycle, then one can consider the possibility of progesterone hypersensitivity.

If the patient has symptoms consistent with progesterone hypersensitivity, I still cannot predict how the patient will respond during pregnancy. There are reports of patients with a history of progesterone hypersensitivity with worsening of symptoms during pregnancy, when systemic progesterone levels rise (as you noted). However, there are also reports of patients who fare better during pregnancy, with the hypothesis that it may be due to autodesensitization to progesterone or an attenuation of maternal immune responses during pregnancy.

I would be interested in her re-evaluation of her thyroid function, as her symptoms seem to coincide of her urticarial history within the last 2 years.

The recommended management plan of chronic urticaria during pregnancy would be to use a combination of second generation H1 antihistamines, H2 antihistamines and possibly leukotriene receptor antagonist. Omalizumab has also been used safely in pregnant women for refractory urticaria.

I hope this helps you with your patient.

Jacqueline A. Pongracic, MD, FAAAAI