COMMENTARY

Review: Mast Cell-Mediated Disorders in Pregnancy

Gary J. Stadtmauer, MD

Disclosures

October 13, 2014

Mast Cell-Mediated and Associated Disorders in Pregnancy: A Risky Game With an Uncertain Outcome?

Woidacki K, Zenclussen AC, Siebenhaar F
Front Immunol. 2014;5:231

Introduction

Much of the literature about the pregnant allergic patient is focused on the safety of medications for the fetus[1] in allergic respiratory disease, especially asthma. Mast cell disorders in pregnancy do not garner the same degree of attention but merit a closer look in no small way, because mast cells appear to play a critical role in pregnancy.[2]

Recent research has shown that the uterus has an abundance of mast cells in the gravid state and that and mast cell density is significantly higher in the uterus of pregnant compared with nonpregnant women. The authors discuss the role of mast cells in pregnancy in both healthy and disease states in a review article published in May.[3]

Summary

Mast cells participate in "implantation, placentation, and fetal growth," according to the authors, and also have a vital role in the fetomaternal interface. These cells have both an immunologic and a nonimmunologic role in pregnancy. In early pregnancy, mast cells modulate "tissue remodeling, angiogenesis and spiral artery modifications." Yet later, mast cells have the potential to disrupt pregnancy, because mast cell-mediator release is associated with preterm delivery.

In the pregnant uterus, mast cell numbers increase in the myometrium and shift from both tryptase and chymase mast cells to the tryptase-only phenotype.[4] The contractility of the myometrium is also modulated by various mast cell mediators, including histamine, prostaglandins, and proteases; the latter in particular affect postpartum uterine remodeling. Given the importance of mast cells in normal pregnancy, the question arises of the degree to which diseases that trigger mast cell degranulation, and diseases of mast cells themselves, influence pregnancy.

Mast Cell Disorders and Pregnancy

Urticaria. As with asthma, chronic idiopathic urticaria may be influenced by the hormonal changes of pregnancy,[5] for either better or worse. The safety of higher-dose antihistamines (beyond the level of US Food and Drug Administration approval) has not been studied in pregnancy, and because mast cells mediators, including histamine, participate in uterine adaptation, there is reason for caution. One type of urticaria in pregnancy—pruritic urticaria papules and plaques of pregnancy—has not yet clearly been linked to mast cells, but antihistamines are effective in this condition.

Mastocytosis. The article references a review by the Spanish Network on Mastocytosis[6] that followed 45 pregnant patients with the disease and found that "in most cases mastocytosis-related symptoms remained unchanged throughout pregnancy and after delivery compared to the pregestational clinical profile." Pruritus, flushing, and gastrointestinal symptoms presented or worsened in only a minority of cases. Idiopathic anaphylaxis was less common. Patients with cutaneous mastocytosis experienced more mast cell-mediated symptoms than did those with indolent mastocytosis.

Overall, mastocytosis worsens in up to one third of women during pregnancy, and yet about the same percentage improve clinically during the first trimester, similar to what is typically seen with asthma during pregnancy. Worsening of symptoms in some patients might be due to the reduction in antihistamine dosing chosen for fetal safety.

Summary

Physicians treating mast cell diseases in pregnancy should remember that mast cells and their mediators are clinically relevant not only in disease, but also in the uterus of the healthy patient. Other than anaphylaxis, however, it is not clear what other manifestations of mast cell disorders post a risk for the fetus. As with asthma, hormonal changes of pregnancy have an unpredictable influence on the underlying mast cell condition.

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