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 1970.9–35
The cases in the literature are described in . Diagnosis can be difficult to establish and often relies on clinical findings and immunological testing. Management of this uncommon scenario can be challenging.
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 (). 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.
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.
- 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.