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BMJ Case Rep. 2010; 2010: bcr09.2009.2296.
Published online 2010 January 13. doi:  10.1136/bcr.09.2009.2296
PMCID: PMC3029874
Rare disease

Wegener’s granulomatosis in pregnancy: a case report and review of the medical literature

Abstract

A Caucasian woman in the third trimester of her sixth pregnancy was diagnosed with Wegener’s granulomatosis (WG) following investigation for recurrent ear infections and a persistent dry cough. Chest radiograph showed granulomatous lesions and the c-ANCA (antineutrophil cytoplasmic antibody) was strongly positive. She required pulsed methylprednisolone and cyclophosphamide followed by oral prednisolone and azathioprine to control the disease process during and after pregnancy. Neither the disease nor aggressive treatment adversely affected the pregnancy and she delivered a healthy baby girl by elective induction at 37 weeks. A review of the literature on Wegener’s granulomatosis in pregnancy is presented.

Background

Wegener’s granulomatosis (WG) is a rare systemic vasculitis of unknown aetiology. It is characterised by necrotising granulomata of the upper and lower respiratory tracts, focal glomerulonephritis and necrotising systemic vasculitis.1

Prognosis has been vastly improved with the use of steroids and cyclophosphamide. The National Institute of Health cohort study in 1992 reported an 80% survival for a mean of 8 years in 158 patients with WG.2

We describe the case of a woman who developed WG during her third trimester and delivered a healthy baby while on cyclophosphamide. The use of cyclophosphamide in pregnancy has never been formally investigated. There have been case reports suggesting an increased incidence of spontaneous abortions and birth deformities especially when used in the first trimester.3,4 Other studies have shown more success, particularly when initiated after the first trimester.5,6 However, there have only ever been a few cases reported of the successful use of cyclophosphamide in WG during pregnancy. We have also reviewed the literature of the management of WG in pregnancy.

Case report

A 39-year-old Caucasian woman with a 6 month history of recurrent ear infections with middle ear effusions, despite bilateral myringotomies, presented with breathlessness on exertion. She had a dry cough and a recent onset of bloodstained postnasal discharge.

She was 33 weeks pregnant with her sixth child, having had five normal vaginal deliveries previously. The only past medical history was hypothyroidism for which she was on replacement therapy. She denied alcohol or tobacco use and had been immunised with BCG.

She was breathless and unwell at this stage, but fetal monitoring was normal. A differential diagnosis of an atypical chest infection, vasculitic illness or a form of acute alveolitis was considered.

Investigations

Initial investigations revealed a marked inflammatory picture with an elevated erythrocyte sedimentation rate (ESR) at 99 mm/h and C reactive protein (CRP) at 52 mg/l. A blood film revealed no eosinophilia, urea and electrolytes were normal, urinalysis clear and a 24 h urine collection contained 0.21g of protein. A chest radiograph revealed multiple parenchymal opacities with ill defined margins (fig 1).

Figure 1
Chest radiograph showing pulmonary infiltrates.

Blood cultures and viral serology were normal and ultrasound imaging of the abdomen and heart showed no abnormalities. The positive c-ANCA (antineutrophil cytoplasmic antibody) with anti-proteinase-3 titre of 23.4 ELISA units (normal range <1.5 units), confirmed a clinical suspicion of WG.

Treatment

The patient was commenced on pulsed intravenous methylprednisolone, 500 mg daily for 3 days, and a single dose of 1g of cyclophosphamide. Oral prednisolone was started at 30 mg daily. She began to improve clinically after a second dose of cyclophosphamide 10 days later and a repeat chest radiograph showed improvement of the pulmonary infiltrates (fig 2). During this time fetal monitoring was normal with both regular cardiotocography (CTG) and ultrasound scanning.

Figure 2
Chest radiograph 10 days after commencing treatment with steroids and cyclophosphamide showing resolution of pulmonary infiltrates

At 37 weeks before her third dose of cyclophosphamide she underwent an elective induction of pregnancy and had a normal delivery of a healthy baby girl. Her postpartum care was uneventful and she was subsequently discharged home.

She continued to have pulsed intravenous cyclophosphamide every 10–14 days as an outpatient for a further 5 months. She also had intermittent pulsed methylprednisolone. The dose of oral prednisolone was slowly reduced according to clinical response.

Clinically the patient continued to improve and her inflammatory markers showed steady improvement. At 6 months she was commenced on oral azathioprine as maintenance therapy. She suffered a relapse at week 45 requiring a further 10 doses of two-weekly intravenous cyclophosphamide following which oral azathioprine was reintroduced.

Outcome and follow-up

The patient remained stable on azathioprine for a further 9 months during which time she had an episode of uveitis treated with increased oral steroids and topical cyclopentolate eye drops. She then had a flare affecting predominantly her joints and was restarted on cylophosphamide and methylprednisolone. Following this she failed to attend further appointments and her current clinical condition is not known.

Discussion

The incidence of WG is 5–10 per million with approximately equal sex distribution.1 According to the Chapel Hill nomenclature7 the diagnosis of WG requires the demonstration of granulomatous inflammation of the respiratory tract, and necrotising vasculitis affecting small to medium sized vessels. In practice it is often difficult to obtain representative biopsies because of the segmentary and dynamic nature of the vasculitis process or the circumstances of the clinical scenario as in this case. Sørensen et al8 acknowledged this and proposed the following diagnostic criteria for WG:

  • Biopsy or surrogate parameter for granulomatous inflammation in the respiratory system, and
  • Biopsy verified necrotising vasculitis in small to medium sized vessels or biopsy/surrogate parameter for glomerulonephritis or positive PR3-ANCA test, and
  • Lack of eosinophilia in blood and biopsy samples.

Management involves immunosuppression with steroids and cyclophosphamide, and remission is often maintained with the use of azathioprine.

WG is rare in pregnancy; to date 42 pregnancies have been reported in 33 patients (including this present case) since first described in 1970.935 The cases in the literature are described in table 1. Diagnosis can be difficult to establish and often relies on clinical findings and immunological testing. Management of this uncommon scenario can be challenging.

Table 1
Descriptive data on patients with Wegener’s granulomatosis during pregnancy in order of disease appearance

The established cases in the literature include newly diagnosed patients in pregnancy (n=16), flares of existing disease during pregnancy (n=14), and pregnancy while disease in remission with no disease flares (n=11). The management and prognosis of these patients has been variable with two maternal deaths, eight fetal deaths and 35 healthy live births including two sets of twins. For one case no information was available.

The influence of pregnancy on WG is unpredictable (fig 3). Disease onset or a flare may occur at any time during the pregnancy, but the trimester in which they occur appears to influence the outcome. From the literature, all three cases where relapse or disease onset occurred within the first trimester resulted in fetal deaths despite treatment.15,17,22 In contrast, there were 16 healthy births and three fetal deaths in the 18 cases who suffered a disease flare or onset during second or third trimesters. Eleven patients remained in remission throughout pregnancy, most of them managed with steroids alone, with only one leading to fetal death. Predictably, those mothers that suffered a flare of WG postpartum survived with healthy children.

Figure 3
Fetal death in various stages of pregnancy in Wegener’s granulomatosis.

In keeping with most connective tissue diseases and/or vasculitides, WG activity at conception appears to adversely affect maternal and fetal prognosis. Two patients clearly had active disease before becoming pregnant and only one of them went on to have a successful fetal outcome.18,28 Of the 12 patients in remission before pregnancy who suffered a relapse, nine went on to have successful deliveries with three fetal deaths. It has been suggested that in order to improve the chances of a successful outcome, patients should plan pregnancy during a quiescent period of their disease, ideally on the minimum of treatment. Maternal outcomes were generally good; the two deaths in the literature were in patients with active disease.

The management of WG during pregnancy has to be on an individual basis. With the potential life threatening consequences of WG, an aggressive approach to the treatment of the disease in pregnancy should be adopted. There are no controlled trials as to the safety of many drugs in pregnancy and the experience of WG in pregnancy comes from anecdotal case reports.

The choice of drugs will depend on the stage of pregnancy and the severity of the disease flare. The teratogenic effects of cyclophosphamide have been reported previously3,4 and it should be used with caution particularly early in pregnancy. However, there is evidence that it can be safely used with steroids in the second and third trimesters of pregnancy.22 Three reports have shown good success with the use of intravenous immunoglobulin in maintaining remission of disease during pregnancy28,33 and for the management of newly diagnosed WG in the first trimester.25

In our patient the diagnosis of WG was made on the basis of characteristic clinical, immunological, and radiographic findings in the absence of biopsy findings. She responded well to treatment and had a relatively straightforward pregnancy following initiation of immunosuppressive regime.

In conclusion, WG in pregnancy should be managed by a multidisciplinary team and with aggressive treatment of the active disease to maximise the successful outcome of pregnancy for both mother and baby.18,22 Conventional treatments, including steroids and immunosuppressive agents, should be used depending on the timing of the disease onset or flare in relation to the gestation period and on the severity of the clinical picture.

Learning points

  • Wegener’s granulomatosis is rare in pregnancy but needs to be considered as a differential diagnosis in patients presenting with otolaryngological and respiratory symptoms and raised inflammatory markers.
  • Steroids and immunosuppressive agents can be administered safely depending on the disease severity and gestation period.
  • Aggressive treatment with a multidisciplinary approach can improve the outcome for both mother and fetus.

Footnotes

Competing interests: None.

Patient consent: Patient/guardian consent was obtained for publication.

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