Vasculitis is more often a disease of women beyond their reproductive years, leaving the challenges of pregnancy management difficult to study. Pregnancy complications, including pregnancy loss and preterm birth, are higher among women with all forms of vasculitis. It seems that controlling the disease before pregnancy may improve the chances of pregnancy success. Many medications used for vasculitis are considered low risk in pregnancy, including prednisone, colchicine, azathioprine, and tumor necrosis factor inhibitors. Cyclophosphamide, methotrexate, and mycophenolate mofetil should be avoided in pregnancy. Controlling disease with low-risk medications may allow women with vasculitis to have the pregnancies they desire.
Key points
- •
There are limited data to guide the management of vasculitis during pregnancy.
- •
Pregnancies that occur when vasculitis is well controlled and on medications considered low risk will result in the best opportunity for success.
- •
Although cyclophosphamide, methotrexate, and mycophenolate mofetil are known to cause pregnancy loss and congenital anomalies, the other medications that are typically used for vasculitis are largely considered low risk.
Introduction
Vasculitis is more often a disease affecting women beyond their reproductive years, making the challenges of pregnancy management difficult to study. Improved diagnostic capabilities and treatment options have both prolonged patient survival and led to earlier age of diagnosis, which in turn has increased the number of pregnancies in this population. Because of the earlier median age of onset in Behçet disease (BD) and Takayasu arteritis (TA), most of the literature focuses on pregnancies in women with these diseases; however, cases of pregnancy during antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis have also been reported in the literature. The various physiologic changes of pregnancy may have both positive and negative impacts on maternal vasculitis. Hormonal and endocrine changes during pregnancy may alter cytokines favoring the Th2-cytokine polarization, allowing a worsening of Th2-cytokine–mediated diseases, such as ANCA-associated vasculitis, and improving Th1-cytokine–mediated disorders, such as BD and TA. However, when carefully timed and managed, most pregnancies in patients with systemic vasculitis can be successful with minimal antepartum complications and minimal impact on disease process.
Introduction
Vasculitis is more often a disease affecting women beyond their reproductive years, making the challenges of pregnancy management difficult to study. Improved diagnostic capabilities and treatment options have both prolonged patient survival and led to earlier age of diagnosis, which in turn has increased the number of pregnancies in this population. Because of the earlier median age of onset in Behçet disease (BD) and Takayasu arteritis (TA), most of the literature focuses on pregnancies in women with these diseases; however, cases of pregnancy during antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis have also been reported in the literature. The various physiologic changes of pregnancy may have both positive and negative impacts on maternal vasculitis. Hormonal and endocrine changes during pregnancy may alter cytokines favoring the Th2-cytokine polarization, allowing a worsening of Th2-cytokine–mediated diseases, such as ANCA-associated vasculitis, and improving Th1-cytokine–mediated disorders, such as BD and TA. However, when carefully timed and managed, most pregnancies in patients with systemic vasculitis can be successful with minimal antepartum complications and minimal impact on disease process.
Antineutrophil cytoplasmic antibody–associated vasculitis, including granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis
ANCA-associated vasculitis includes granulomatosis with polyangiitis (GPA, formerly Wegener granulomatosis), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg Strauss). Although the prevalence of these diseases is relatively low in women of childbearing age because the mean age of onset is later in life, there are documented cases of pregnancies for each of these forms of ANCA-associated vasculitis.
Effect of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis on Pregnancy
GPA is a necrotizing vasculitis that typically affects the upper respiratory tract, lungs, and kidney with a peak age of onset after 40 years. MPA is a small vessel, necrotizing, pauci-immune vasculitis with complications, including severe renal disease and pulmonary hemorrhage. Preterm delivery is a common complication of GPA with rates as high as 35%, particularly when the disease is active during pregnancy. Preeclampsia, premature rupture of membranes, spontaneous abortion, prepartum hemorrhage, and retroplacental hematoma have all been reported. Poorer outcomes are associated with women who conceived with active disease or who had onset of GPA during pregnancy. There are limited data on the effects of MPA on pregnancy and vice versa, primarily consisting of case reports. In the few cases that have been reported, complications included maternal death, low birth weight, prematurity, and the occurrence of an MPA-like syndrome in the newborn.
EGPA is characterized by extravascular necrotizing granulomas rich in eosinophils, peripheral blood eosinophilia, and pulmonary and small vessel vasculitis occurring in patients with asthma and allergic rhinitis. The mean age of disease onset is approximately 48 years. As with GPA, preterm birth was the most common complication of pregnancy; however, fetal loss, intrauterine growth restriction (IUGR), and cesarean delivery were also observed.
Effect of Pregnancy on Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
With all forms of systemic vasculitis, complications are most severe and outcomes most devastating if pregnancy occurs during a disease flare. This point holds true for ANCA-associated vasculitis: high levels of disease activity persisted throughout pregnancy in most women who became pregnant with active disease; however, only 40% of those who conceived while in remission developed a disease flare. GPA flares during pregnancy mostly consisted of respiratory complications, subglottic stenosis, skin lesions, arthritis, and renal deterioration. However, it can be difficult to differentiate renal impairment from GPA flare or preeclampsia.
Vasculitis complications were also seen in cases of EGPA with complications as severe as maternal death. Complications were reported in patients with MPA also, with most symptoms involving rash, joint swelling, pain, and fever. The frequency of these complications is difficult to extrapolate to the general population considering the scarce data available.
Although the numbers are limited, ANCA-associated vasculitis seems to be more frequently reported to start during pregnancy than most other rheumatic diseases. Based on the available data, it is not possible to assess whether established ANCA-associated vasculitis flares more often during pregnancy than other autoimmune disorders. In a patient-reported retrospective study, only 20% of patients reported a vasculitis flare during pregnancy. In small prospective cohorts followed in university centers, however, vasculitis flare during pregnancy seems to be more common ( Table 1 ).
| Study | Number of Pregnancies | Pregnancy Loss | Preterm Birth | Vasculitis Activity During Pregnancy |
|---|---|---|---|---|
| Gatto et al, 2012 | 48 | 4 (8%) | 17 (35%) | 15 (45%) |
| Pagnoux et al, 2011 | 22 | 6 (27%) | 8 (36%) | 2 (Major flare) a |
| Fredi et al, 2015 | 17 | 1 (5%) | 4 (23%) | 6 (35%) |
a One patient with acute cardiac decompensation and another with rupture of pancreatic microaneurysm.
Polyarteritis nodosa
Polyarteritis nodosa (PAN) is a disorder characterized by necrotizing inflammation of medium size or small arteries, with prevalent features of musculoskeletal, gastrointestinal (GI), and neuropathic involvement. Pregnancy outcomes are generally favorable with rare disease relapse and the birth of healthy babies when patients conceive during disease remission. Reported complications include preterm delivery and IUGR. However, consequences of conceiving during active PAN, and particularly development of a new diagnosis during pregnancy, can be devastating. In 2 reports from the 1980s, 7 out of 8 patients with onset of PAN during pregnancy died during gestation or within the first 2 months of delivery; in many of these cases, the diagnosis was made post mortem.
Takayasu arteritis
TA is a granulomatous vasculitis that affects large vessels including the aorta and its branches. TA frequently presents in the second or third decade of life and is more commonly observed in pregnancy than other forms of vasculitis because of the earlier age of onset.
Effect of Takayasu Arteritis on Pregnancy
Most pregnancies in patients with TA are successful; however, women with TA are predisposed to complications, particularly during the peripartum period. Severe HTN and preeclampsia are the most frequent complications of pregnancy in women with TA, with a prevalence of approximately 40% in patients with TA compared with 8% in the general population. Intrauterine fetal death may also be more common in TA. In a recent systematic review of more than 200 pregnancies in women with TA, up to 20% of pregnancies were complicated by either IUGR or low birth weight ( Table 2 ). Other complications included preterm delivery and fetal loss, with risk of maternal and fetal complications greater in patients with more severe maternal disease. Patients with renal artery and abdominal aorta involvement experienced more frequent complications of preeclampsia and IUGR.
| Study | Number of Pregnancies | Pregnancy Loss a | Preterm Delivery | TA Complications b | Treatment Information |
|---|---|---|---|---|---|
| Gatto et al, 2012 | 214 | 40 (18.6%) | 35 (16%) | 25 (11.6%) | Recommends treatment with corticosteroids for disease relapse during pregnancy and azathioprine for refractory cases |
| Assad et al, 2015 | 156 | 20 (12.8%) | 28 (17.9%) | 9 (5.8%) | Showed no association between maternal/fetal outcomes with steroid use |
| Comarmond et al, 2015 | 98 | 12 (12.2%) | 8 (8.2%) | 38 (38.8%) | No significant difference in maternal complications with anti–IL-6 therapy or corticosteroids but noted a trend implying patients receiving therapy have fewer complications |
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
