Effects of pregnancy on chronic urticaria: Results of the PREG‐CU UCARE study

Abstract

KOCATÜRK eT Al. | INTRODUC TI ONChronic urticaria (CU) is an inflammatory disease characterized by the appearance of wheals, angioedema, or both for longer than 6 weeks. CU is classified into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), where signs and symptoms occur in response to definite triggering factors such as cold in cold urticaria and perspiration-inducing activities in cholinergic urticaria. 1 CSU is more common in females than males as confirmed by a recent systematic review and meta-analysis of the available epidemiological data, which showed that the point prevalence of CSU is 1.3% in women versus 0.8% in men. 2 CIndUs are also more common in females, with a female:male ratio of 2:1 to 3:1. 3 In a study from China, women, across all CindUs, accounted for 58% of patients, with higher rates in some CIndUs, cold urticaria for example, where 66% of patients were female. 4The reasons for this female preponderance in CU are currently unknown and subject of ongoing investigations, but several points are important in this context. First, it is well known that autoimmune diseases are more common in women, with female:male ratios of 3:1 for multiple sclerosis and 15:1 for autoimmune thyroiditis, for example. 5 It is now widely accepted that autoantibodies and their activating effects on skin mast cells play a role in the pathogenesis of CSU in a proportion of patients. In CSU, two types of underlying autoimmunity are postulated; type I autoimmunity (also called autoallergy) with IgE autoantibodies against autoallergens and type IIb autoimmunity with stimulatory IgG and IgM autoantibodies to receptors on mast cells; even some authors proposed two types of autoimmunity co-existing in some patients. 6,7 This is supported by the common association of CSU with autoimmune diseases, which has been reported in many studies. 8 Second, mast cells, the key drivers of CU pathogenesis, express hormone receptors, and sex hormones can influence mast cell functions including their activation and release of proinflammatory mediators. Estrogens increase histamine release in rat mast cells and sensitized human basophils upon stimulation

Urticaria

“…Even though the lesions are usually confined to areas of skin exposed to the trigger stimuli, systemic reactions including anaphylaxis may occur and adrenaline autoinjectors should be prescribed to highrisk patients 114 . During pregnancy, one-half of patients experience improvement of their CU, whereas exacerbation occurs in approximately one-third of patients 115 . In particular, patients with CIndU or both CSU and CIndU showed a twofold increase of disease exacerbation during pregnancy.…”

“…The use of sgAHs such as loratadine and cetirizine is also advised in breastfeeding women 4 , as nursing infants can develop sedation from first-generation antihistamines secreted into breast milk 194 . Omalizumab is reported safe in pregnancy 115,[195][196][197][198] and in younger children, although current licensing is for individuals aged 12 years and older 146 .…”

“…Risk-benefit profiles for immunosuppressive therapies, including corticosteroids and cyclosporine, need to be carefully considered given the increased toxic effects in all three of these patient populations. Detailed reviews of all aspects of CSU management in these groups are available 115,199,[201][202][203] .…”

Urticaria in Pregnancy and Lactation

“…Although CU is a very common and female-dominant disease that favors the reproductive age group, there is only one study that evaluates the effects of pregnancy on CU or the effects of CU on pregnancy outcomes, which is performed by the UCARE network ( 12 , 85 ). In this study, 288 pregnant patients with CU from 21 centers/13 countries were asked to answer an a-47-item questionnaire which included questions on the exacerbations, angioedema attacks, emergency referrals, the overall course of CU during pregnancy, the course of urticaria after giving birth as well treatments before and during pregnancy, outcomes of pregnancy, and treatments given during breastfeeding.…”

“…Robust data on this is scarce, but a recent multicenter study revealed that CU tends to improve during pregnancy in half of the patients and worsen in one third of them ( Figure 1 ). Worsening of urticaria was associated with having a mild disease before pregnancy and not being on treatment before pregnancy ( 12 ). These findings stress the importance of proper clinical and laboratory diagnosis as well as treatment of CU for patients willing to get pregnant and also a personalized follow-up during pregnancy.…”