Approaches to the Management of Women with Psoriasis at Different Life Stages

During women’s childbearing years, it is important to consider that pregnancies often occur unplanned. Consequently, healthcare providers should avoid treatments that have known risks of teratogenic effects during this life stage, such as psoralen UVA, methotrexate, and acitretin. However, it is equally important not to undertreat this patient population, as psoriasis can significantly affect women’s personal, social, and sexual lives.⁸ Many women with psoriasis experience feelings of shame and social stigma, making effective treatment essential. Treatment strategies for women should be optimized during this time to help minimize flares if they choose to pursue pregnancy.⁹

Fortunately, studies show that approximately 40-60% of patients experience a natural improvement in their psoriasis during pregnancy.¹⁰ This positive change is thought to be linked to substantial increases in levels of estrogen and progesterone, promoting a state of immune tolerance. Estrogen has immunosuppressive and immunostimulatory properties, whereas progesterone is primarily immunosuppressive. It is believed that elevated progesterone levels may help downregulate T-cell proliferation and reduce inflammatory responses during pregnancy.⁹ For the 10-20% of women who flare during pregnancy, topical therapies and narrowband UVB are generally considered safe options. Of note, cumulative NB-UVB doses can induce folate photodegradation and decrease serum folate levels in a dose-dependent manner. Therefore, it is recommended to supplement folic acid in pregnant women on phototherapy.^11,12  

For psoriasis patients who are recalcitrant to topicals or light or those with moderate to severe psoriasis needing a systemic agent during pregnancy, cyclosporine can be cautiously utilized with attention to blood pressure due to risks of eclampsia. Additionally, certolizumab pegol (CZP), an Fc-free anti-tumor necrosis factor (anti-TNF) drug, may be appropriate. This medication has minimal to no active placental transfer, and limited studies have shown no increased risks to the fetus. In the CRIB study, a prospective postmarketing pharmacokinetic study involving 14 pregnancies exposed to CZP, there was minimal placental transfer of CZP from mothers to infants.¹³ Further, the CRADLE study measured CZP levels in the breastmilk of 17 persons and found very low or undetectable levels, suggesting it is also safe for breastfeeding women.¹⁴ Also, a follow-up analysis of a pharmacovigilance safety database encompassing 1,137 prospectively reported pregnancies with maternal exposure to CZP revealed no teratogenic effect and no increased risk of fetal death compared to the general population.¹⁵

The improvement of psoriasis during pregnancy is often short-lived, as many women experience flares in the postpartum period coinciding with hormonal changes and increased stress. Murase et al. studied 57 pregnant women with psoriasis compared with 27 non-pregnant women with psoriasis and found that 65% reported a worsening of their disease in the postpartum period.¹⁶ The study also noted that the body surface area (BSA) affected by psoriasis in the postpartum group doubled between 30 weeks gestation and 6 weeks postpartum.¹⁵ During the postpartum period, treatment options will vary depending on various factors, such as whether women are breastfeeding or not. For those who are not breastfeeding, patients can typically resume their previous treatment regimens before pregnancy.

Another major life stage for women is the perimenopausal and post-menopausal period, during which hormonal fluctuations again may contribute to psoriasis flares and late-onset psoriasis. During menopause, levels of estrogen and progesterone decline, leading to a stage of eventual overall hypogonadism. This decrease in estrogen is thought to be a key factor in the exacerbation of psoriasis, with studies showing that approximately 48% of women experience worsening symptoms during this time.¹⁸ Kanda and Watanabe et al. demonstrated that β17 estradiol (E2) inhibits the production of IL-12 and TNF-alpha by reducing dendritic cells’ ability to present antigens. This, in turn, stimulates T cells to synthesize the anti-inflammatory cytokine IL-10 by T lymphocytes, exerting an inhibitory effect on the Th1 immune response.¹⁸ Thus, high estrogen levels are believed to regulate and inhibit the immune system. In contrast, low levels of estrogen may promote a stimulatory or inflammatory effect.