Review
Pregnancy and vasculitis: A systematic review of the literature

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Abstract

Primary systemic vasculitis are uncommon diseases that may affect young women in their childbearing age. To date, patients affected with primary systemic vasculitis are often diagnosed and treated earlier than in the past, due to improvement in diagnostic skills and a larger availability of effective drugs. The progressive achievement of a longer life expectancy and a better quality of life have progressively led to an increased number of pregnancies observed during the course of such diseases. Here, we review 567 pregnancies among patients with primary systemic vasculitis, in order to define the relationship between pregnancy and these conditions and to suggest guidelines for their management. However, data on pregnancy outcomes are limited and knowledge about their gestational risk is mostly provided by single case reports or at best by retrospective studies which may result in intrinsic observational bias; unfortunately, long term prospective studies are still lacking. Analysis of the data highlighted a reciprocal influence between disease course and gestational outcome, although no definite effects can be outlined. Indeed, either improvement or worsening of the different vasculitis can occur, probably due to diverse genetic, clinical and immunological background of the patients. Since disease course may vary over time, careful management of systemic vasculitis during gestation is required. Furthermore, organ failure or damage must be carefully considered, since it can lead to adverse obstetrical and fetal outcomes.

Introduction

Primary systemic vasculitis are uncommon diseases characterized by a great variety of symptoms, ranging from mild to life threatening manifestations and encompassing different natural histories, from self-limiting to relapsing or chronic active disease.

Over the past years, the number of pregnancies among affected women greatly increased, due to improvement in survival as well as in quality of life of these patients. Frequency of pregnancy in different vasculitis depends on epidemiological factors: pregnancy is more frequent in vasculitis that have onset at younger age and affect the female gender, such as Takayasu's arteritis and Behçet disease.

During pregnancy, immune and endocrine systems undergo profound transformations concerning both hormonal assessment and cytokine microenvironment: cortisol, progesterone, estradiol and testosterone increase physiologically during gestation and seem to favor Th-2 cytokine polarization at the feto-maternal interface as well as at the systemic level [1], [2], [3]. Such immunological changes may suggest a natural improvement of primarily Th1-mediated vasculitis (mainly Takayasu arteritis and Behçet disease which are the most prevalent vasculitis during pregnancy) and a worsening of Th2-driven ones, such as Wegener granulomatosis or Churg–Strauss syndrome. The course of the different vasculitis in pregnancy appears to be affected by several factors and whether or not such changes are able to modify maternal and fetal outcomes in each specific vasculitis is still uncertain.

These conditions should be managed very carefully during pregnancy, since both disease complications and pharmacological treatment may have negative effects on maternal and fetal health. Furthermore, treatments mainly based on the use of cytotoxic and immunosuppressive drugs may have a detrimental effect on the fetus.

To date, variations in disease activity of the different vasculitis during pregnancy and their relationship with the modification of immunoendocrine environment have not been evaluated. Most of the studies have mainly investigated the effects of disease complications on maternal and fetal outcomes, thereby including organ failure or irreversible vascular lesions.

This systematic review is focused on the relationship between pregnancy and systemic primary vasculitis. Guidelines for the management of these conditions during pregnancy are also suggested.

Section snippets

Search strategy

We performed a systematic review of the literature to find out all the cases of pregnancy in women affected with different vasculitis reported from 1960 to 2011, using the PubMed, Cochrane and Embase databases. Moreover, we hand-searched for the relevant articles referenced in other publications and not available on the web database.

Every report in English and in English-written abstracts concerning pregnant women affected with the following vasculitis were included in the analysis: Takayasu's

Search results

As summarized in Fig. 1, the initial search, based on the search terms, led to the finding of 2319 titles. Among these, 242 titles were pertaining to the search. By reading the abstracts, 82 of them were excluded because they did not meet the inclusion criteria and 160 were selected. Furthermore, 8 case reports were excluded after discussion by the two blinded Authors because they did not find a full agreement on the description accuracy of the cases and two were excluded because they had been

Takayasu's arteritis

TA is a granulomatous vasculitis which affects large vessels such as aorta, its major branches, and the pulmonary arteries. TA typically occurs in women during their childbearing age, therefore it is more common to observe pregnancy in patients with TA than in those with other vasculitis [4].

We have been able to identify TA in the literature 214 pregnancies in 168 patients affected with [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23],

Polyarteritis nodosa

PAN is a disorder characterized by necrotizing inflammation of medium size or small arteries. In patients with PAN prevalent features are general symptoms, musculoskeletal, skin and gastrointestinal manifestations, and peripheral neuropathy, especially mononeuritis multiplex [4].

Nineteen case reports on pregnancy in PAN patients are available in the literature (Table 2) [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62].

Wegener's granulomatosis

WG is an uncommon, small-vessel, necrotizing vasculitis which usually affects upper respiratory tract, lungs, and kidney. The disease peaks after the age of 40, thus, pregnancies in women with WG are uncommonly observed [4]. To date 48 pregnancies in 38 patients are available in literature [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82], [83], [84], [85], [86], [87], [88], [89], [90], [91], [92]. Disease started during

Behçet's disease

BD is a chronic, relapsing, multisystemic, inflammatory process characterized by recurrent oral and genital ulcers, ocular, gastrointestinal, neurological manifestations, and thrombosis. It predominantly affects young women during childbearing age, therefore it is not rare to observe pregnancy in patients with BD [4].

Data regarding the reciprocal influence of BD and pregnancy derive from the analysis of 229 pregnancies in 131 patients diagnosed with BD, obtained from several case reports, five

Other vasculitis

So far, we have discussed the most common vasculitis that may affect gestational outcome. Although less frequently, other vasculitis have been reported in pregnant women.

Conclusions

The modulation of immune functions induced by pregnancy period may influence the course of vasculitis, which may in turn affect fetal or maternal outcome [4].

Unfortunately, no extensive data on pregnancy in patients with systemic vasculitis are available, due to the low incidence of such diseases, the low female-to-male ratio and disease onset, which often occurs after childbearing age. Most of the information we have derives from case reports and retrospective studies, since long term

References (170)

  • B. Sibai et al.

    Pre-eclampsia

    Lancet

    (2005)
  • D.A. Nagey et al.

    Pregnancy complicated by periarteritis nodosa: induced abortion as an alternative

    Am J Obstet Gynecol

    (1983)
  • J. Owen et al.

    Polyarteritis nodosa in pregnancy: a case report and brief literature review

    Am J Obstet Gynecol

    (1989)
  • A.G. Aya et al.

    Severe preeclampsia superimposed on polyarteritis nodosa

    Am J Obstet Gynecol

    (1996)
  • E.S. Dayoan et al.

    Successful treatment of Wegener's granulomatosis during pregnancy: a case report and review of the medical literature

    Chest

    (1998)
  • N. Bessias et al.

    Wegener's granulomatosis presenting during pregnancy with acute limb ischemia

    J Vasc Surg

    (2005)
  • S. M'Rad et al.

    Wegener's granulomatosis and pregnancy. A case

    Rev Med Interne

    (1989)
  • A. Doria et al.

    Steroid hormones and disease activity during pregnancy in systemic lupus erythematosus

    Arthritis Rheum

    (2002)
  • A. Doria et al.

    Pregnancy, cytokines and disease activity in systemic lupus erythematosus

    Arthritis Rheum

    (2004)
  • A. Doria et al.

    Pregnancy in rare autoimmune rheumatic diseases: UCTD, MCTD, myositis, systemic vasculitis and Behçet disease

    Lupus

    (2004)
  • A. Doria et al.

    Seltene autoimmune rheumatische erkrankungen in der schwangerschaft: systemische sklerose, dermato-polymyositis und vaskulitiden

    Z Rheumatol

    (2006)
  • A. Matsumura et al.

    Pregnancy in Takayasu arteritis from the view of internal medicine

    Heart Vessels Suppl

    (1992)
  • T. Aso et al.

    Clinical gynaecologic features of pregnancy in Takayasu arteritis

    Heart Vessels

    (1992)
  • G.S. Kerr et al.

    Takayasu arteritis

    Ann Intern Med

    (1994)
  • A. Ioscovich et al.

    Peripartum anesthetic management of patients with TA: case series and review

    Int J Obstet Anesth

    (2009)
  • V. Suri et al.

    Pregnancy in Takayasu arteritis: a single centre experience from North India

    J Obstet Gynaecol Res

    (2010)
  • L. Grcevska et al.

    Successful pregnancy and long-term follow-up (12 years) in a patient with Takayasu arteritis and renovascular hypertension as a first clinical sign

    Clin Nephrol

    (1997)
  • O. Gasch et al.

    Takayasu arteritis and pregnancy from the point of view of the internist

    J Rheumatol

    (2009)
  • N. Lakhi et al.

    Takayasu's arteritis in pregnancy complicated by peripartum aortic dissection

    Arch Gynecol Obstet

    (2010)
  • A. Manika et al.

    Pregnancy and Takayasu's arteritis with bilateral renal artery and abdominal aorta stents

    Aust N Z J Obstet Gynaecol

    (2010)
  • N.A. Shafi et al.

    Management of Takayasu arteritis during pregnancy

    J Clin Hypertens

    (2009)
  • E. Hauenstein et al.

    Takayasu's arteritis in pregnancy: review of literature and discussion

    J Perinat Med

    (2010)
  • C. Vayasse et al.

    Mort foetale in utero durant la gestation compliquant une maladie de Takayasu: à propos d'un cas et revue de la littérature

    J Gynecol Obstet Biol Reprod (Paris)

    (2009)
  • S. Adler et al.

    Combined Takayasu arteritis and hashimoto thyroiditis during 3 consecutive pregnancies

    J Rheumatol

    (2009)
  • B. Kraemer et al.

    A successful pregnancy in a patient with Takayasu's arteritis

    Hypertens Pregnancy

    (2008)
  • Y. Jacquemyn et al.

    Pregnancy and Takayasu's arteritis of the pulmonary artery

    J Obstet Gynaecol

    (2005)
  • Y. Umeda et al.

    Abdominal aortic aneurysm related to Takayasu arteritis during pregnancy

    Heart Vessels

    (2004)
  • A.A. Al-Ghamdi

    Successful pregnancy in a patient with Takayasu's arteritis

    Saudi Med J

    (2003)
  • P.M. Latthe et al.

    Pregnancy in Takayasu's arteritis with thrombophilia

    J Obstet Gynaecol

    (2002)
  • S. Kathirvel et al.

    Anesthetic management of patients with Takayasu's arteritis: a case series and review

    Anesth Analg

    (2001)
  • K. Henderson et al.

    Epidural anesthesia for caesarean section in a patient with severe Takayasu's disease

    Br J Anaesth

    (1999)
  • N. Tomioka et al.

    Indications for peripartum aortic pressure monitoring in Takayasu's diseases. A patient with past history of intrapartum cerebral hemorrhage

    Jpn Heart J

    (1998)
  • A.G. Clark et al.

    Anaesthesia for caesarean section in Takayasu's disease

    Can J Anaesth

    (1999)
  • T. Mahmood et al.

    Three successive pregnancies in a patient with Takayasu's arteritis

    J Obstet Gynaecol

    (1997)
  • A. Bassa et al.

    Takayasu's disease and pregnancy. Three case studies and a review of the literature

    S Afr Med J

    (1996)
  • Y. Beilin et al.

    Successful epidural anaesthesia for a patient with Takayasu's arteritis presenting for caesarean section

    Can J Anaesth

    (1993)
  • L. Del Corso et al.

    Takayasu's arteritis: low corticosteroid dosage and pregnancy — a case report

    Angiology

    (1993)
  • R.S.F. McKay et al.

    Management of epidural anaesthesia in a patient with Takayasu's disease

    Anesth Analg

    (1992)
  • S.L. Crofts et al.

    Epidural analgesia for labour in Takayasu's arteritis

    Br J Obstet Gynaecol

    (1991)
  • L.M. Graca et al.

    Takayasu arteritis and pregnancy: a case of deleterious association

    Eur J Obstet Gynecol Reprod Biol

    (1997)
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