Pregnancy outcome in adult-onset idiopathic inflammatory myopathy

C. A. Silva1, S. M. Sultan1 and D. A. Isenberg

Department of Medicine, University College Hospital, London W1P 9PG, UK. 1Joint first authors.

Correspondence to: D. A. Isenberg. E-mail: d.isenberg{at}ucl.ac.uk


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
Objectives. To assess the prevalence of pregnancy in 28 females with dermatomyositis (DM) and polymyositis (PM), assess the outcome in those who became pregnant after the onset of the disease and review the literature of all published cases.

Method. Fifty-four patients with myositis have been under long-term follow-up from 1976–2001 (28 female, nine male).

Results. Twenty-eight female patients were divided into 15 with pure DM/PM (seven PM, eight DM) and 13 with an overlap syndrome. The majority of patients had the onset of the disease after childbearing years (mean age of 32 yr for the overlap group and 41 for the DM/PM group). Only four of our patients (14.3%) have been pregnant after the onset of the disease. One patient had a spontaneous abortion, but was on methotrexate and had active disease; one had a late pregnancy loss, but had active disease; and the other two had uneventful pregnancies during a time when the disease was in remission.

Conclusion. Fetal prognosis in the main reflects the level of maternal disease. The more active the myositis during the pregnancy, the greater the chance of fetal loss.

KEY WORDS: Idiopathic myositis, Pregnancy, Outcome, Review.


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
Polymyositis (PM) and dermatomyositis (DM) are the most common forms of idiopathic inflammatory myopathy, with an incidence of 1–9 cases per million per year and prevalence from 2.4–10.7 cases per 100 000 persons [1]. The female to male ratio is 2:1, but lower in myositis associated with malignancy and higher in patients with associated autoimmune rheumatic diseases (ARDs) [e.g. 10:1 in systemic lupus erythematosus (SLE)/myositis patients] [2]. There are two incidence peaks in the age groups 10–15 yr and 40–60 yr, with only 14% of patients estimated to present during childbearing years (15–30 yr) [3]. Pregnancies in this last group are uncommon. Little is known about the effects of pregnancy on myositis, whether these patients find it harder to conceive or if the outcome of pregnancy is adversely affected by the myositis.

We have reviewed the prevalence of pregnancy in 28 females with DM and PM followed up at our ARD clinic for the past 25 yr and looked at the outcome in those who became pregnant after the onset of disease to examine our experience of these problems. We provide a review of the literature of all cases published with the association of DM/PM in pregnancy.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
Fifty-four patients with PM or DM have been under long-term follow-up between 1976 and 2001 in the autoimmune rheumatic diseases clinic at the Centre for Rheumatology, University College London Hospitals and 37 patients (28 female and nine male) currently attend the out-patient clinic. A prospective record of all such patients had been kept by one of us (D.A.I.). All patients met the Bohan and Peter criteria for DM and PM [4]. The presence of other autoimmune diseases was noted. Twenty-eight patients were interviewed by one of the authors (C.A.S.) using a questionnaire that recorded information such as basic demographic data, age at onset, treatment, number of pregnancies before and after the onset of the disease, activity of the disease during pregnancy and outcome of pregnancy.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
Twenty-eight patients were examined by one of us (C.A.S.) (the nine male patients under long-term follow-up were obviously not reviewed in this study). Six patients had died, nine were lost to follow-up and two were contacted but did not attend the out-patient clinic. The female patients were in two groups: 15 with pure DM/PM (seven PM, eight DM) and 13 who had an overlap syndrome [seven patients with SLE, two with rheumatoid arthritis (RA), two with Sjögren’s syndrome and two with scleroderma]. None of these women had an underlying malignancy. Serological data showed that, out of 28 patients, 19 were ANA positive (by Hep 2), five were anti-Jo-1 positive, four were anti-RNP positive and four were anti-SSA positive (by ELISA, Shield Diagnostics, Dundee). Anticardiolipin antibodies were negative in the patients who became pregnant. The median age at onset was 44 yr (range 16–67). The majority of patients had the onset of the disease after childbearing years (mean age of 32 yr for the overlap group and 41 yr for the DM/PM group). No definition of disease activity in patients with myositis has yet been internationally agreed. However, for the purposes of this study we considered both the clinical assessment and a creatinine kinase (CK) level at twice the upper limit of normal before concluding that the patient’s disease was active.

Only four of our patients (14.3%) have been pregnant after the onset of the disease.


    Case 1
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
A woman of African origin was diagnosed at the age of 22 yr with DM. She was commenced on steroids and azathioprine, and later methotrexate, but was not compliant. At the age of 26 she became pregnant while on therapy and while her disease was active. A spontaneous abortion occurred at 12 weeks, with no apparent change in the disease activity.


    Case 2
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 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
A Caucasian woman at the age of 27 had an uneventful pregnancy, which resulted in a normal delivery at 38 weeks. At the age of 28 she developed DM and her CK level was 5000 IU/l. She was treated with steroids and azathioprine with good results. In April 1991 (age 31) when reviewed in clinic she was 9 weeks pregnant. She had felt well and had stopped the azathioprine. The prednisolone dose was reduced to 5 mg during the pregnancy, which was uneventful (CK in the third trimester was 56 IU/l). The disease was inactive during pregnancy and has remained in remission subsequently.


    Case 3
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
A woman of African origin had an uneventful pregnancy at the age of 18. At the age of 31 she developed features suggestive of SLE. In April 1993 (age 32) she developed proximal muscle weakness involving her shoulder and pelvic girdle, without other systemic features. Her CK level was 500 IU/l (normal <173) and the electromyograph (EMG) and muscle biopsy confirmed the diagnosis of PM. She was treated with prednisolone and azathioprine with good results. She became pregnant at the age of 33 whereupon the azathioprine and hydroxychloroquine were discontinued and she was maintained on 7.5/10 mg of prednisolone on alternate days. She had an uneventful term delivery. Her disease, too, was inactive during pregnancy and has remained in remission subsequently.


    Case 4
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
A Caucasian woman was diagnosed with PM aged 38. Her CK level was over 2000 IU/l, her EMG was myopathic and the muscle biopsy showed a typical inflammatory response with muscle fibre necrosis and phagocytosis. After a short period on corticosteroids she stopped the medication and aged 39 became pregnant for the first time. During the pregnancy her CK increased from 397 IU/l at 4 months to 1579 IU/l at 7 months, but there was no increase in her muscle weakness. Sadly, at 34 weeks she lost the baby. The summary of the post-mortem report described ‘intrauterine growth retardation and death due to massive intervillous fibrin deposition’. (This patient did not have anticardiolipin or antinuclear antibodies.)


    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
Pregnancies in ARDs are problematic. Pregnancy has been implicated in disease flares of SLE [5, 6] and with poor outcome in patients with active diffuse scleroderma [7]. Several other immune disorders such as myasthenia gravis [8] and multiple sclerosis [9] have been reported to present or relapse post-partum.

In patients with myositis, pregnancy outcome and disease activity are not well defined, with only a few case reports [2, 1032] and one retrospective series [33] being published. Our review of the literature identified 35 cases. We have considered only 33 patients with a total of 43 pregnancies, because two of the cases are very similar and seem to show the same patient [18, 22]. The disease may be present before the onset of pregnancy, occur during pregnancy or develop post-partum. In the case reports, 21 patients (48.8%) had established myositis before becoming pregnant, 15 patients (34.9%) developed the disease during pregnancy (nine DM and six PM patients) and seven (16.3%) developed the disease post-partum.

The outcome of 37 patients and 47 pregnancies (29 DM, 18 PM), including our own four cases and three twin pregnancies, is shown in Table 1 and 2. We have not considered the outcome of pregnancies occurring prior to the diagnosis of PM/DM.


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TABLE 1. Dermatomyositis and pregnancy—a review of published cases

 

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TABLE 2. Polymyositis and pregnancy—a review of published cases

 
Does DM/PM affect fertility? It has been suggested that fertility rates are significantly different before and after the onset of PM/DM [33]. However, the late age of onset and the use of contraceptives precludes an accurate evaluation of the influence of the disease on fertility. Different follow-up periods, absence of information on the use of contraception and few cases also make this analysis difficult. A reduction of parity might be expected because of the chronic character of the disease, leading to a possible reduction in sexual activity and the use of immunosuppressive drugs. However, King and Chow [17] reported a nulliparity incidence of 12% among 78 patients with DM/PM, which was reported to be similar to that found in the general population. Gutiérrez et al. [33] report a fertility rate of 4.5 pregnancies/patient before the beginning of the disease, and again this was considered to be comparable with the healthy population.

Does pregnancy increase disease activity of DM/PM? In our patients, no increase in activity of the disease was found and the two patients in whom the disease was under control decreased their treatment. A similar outcome was also described by King and Chow [17] in a retrospective review of 78 adult patients with dermatomyositis. Only three patients had the onset of the disease before pregnancy; two of these patients were in remission and all four pregnancies were normal. One of the patients had a flare at 18 weeks and needed prednisolone, but had a healthy term baby.

Does DM/PM affect pregnancy outcome? Many cases reported as starting during pregnancy had a very poor outcome [33]. However, more recent cases [2, 10, 19, 22, 27, 28] had a good outcome, probably because treatment with steroids was introduced. There are also seven cases that started after pregnancy (1 to 3 months), suggesting that the post-partum period may be a trigger to the development of myositis [24]. However, although these cases were diagnosed post-partum, it is difficult to ascertain the exact time of onset as initial symptoms can be vague.

In our patients who had inactive disease there were good fetal outcomes. Two of the patients decreased their dose of prednisolone and immunosuppression during pregnancy, with no disease flare. Case 1 had a spontaneous abortion, but had active disease and the concomitant use of methotrexate, which even at low dose could have contributed to the abortion. Outcome in the 37 cases (46 pregnancies including our three patients and three pairs of twins) is summarized in Table 3. Of the 28 pregnancies with active disease, 43% (12 pregnancies) were complicated by fetal death, either in utero or immediately after delivery, and 33% (nine pregnancies) were associated with intrauterine growth retardation (IUGR)/premature delivery compared with 13.6 and 13.6%, respectively, in those with inactive disease. In pregnancies complicated by SLE these rates are approximately 20 and 24%, respectively [34].


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TABLE 3. Fetal outcome during pregnancies with active and inactive myositis—a review of the literature from 1966–2000 (including three current cases)

 
In general it appears that the fetal prognosis parallels activity of the maternal disease. In patients with pre-existing quiescent disease, little apparent risk to the mother or fetus is observed. This is in contrast to new onset of disease during pregnancy or exacerbation during pregnancy, for which a significantly worse outcome is noted [2, 23, 27, 29]. Poor fetal outcome occurs in patients who have disease onset during pregnancy, being worse if it flared during the first trimester (five pregnancies with 100% fetal loss) [17]. These cases suggest that although patients with myositis who get pregnant must be considered as having a relatively high risk of developing complications, the outcome is better when the disease is inactive.

Autoimmune disease may be induced as a result of maternal hormonal changes, alteration of immune function during pregnancy or as a consequence of exposure of the mother to fetal antigens [35], which may explain the onset of PM/DM in the post-partum period.

The risk to the fetus from steroid administration appears very low. Thus the criteria for the initiation and discontinuation of steroids should be identical during pregnancy and the non-pregnant state. Placental enzymes inactivate prednisolone, and hence decrease the steroid concentration in the fetal blood to 10% [36]. Those patients on steroids at the time of delivery require additional hydrocortisone to prevent acute adrenal insufficiency. Fulminant and potentially life-threatening cases of PM/DM are probably the only indication for the use of chemotherapeutic agents for the treatment of disease during pregnancy because of the potential teratogenic effects.

Pregnancy complicating myositis is a rare event. Pregnancy in these women should be regarded as high risk, with a close monitoring of activity of the disease from rheumatologists and obstetricians. Optimal pregnancy success can be anticipated when pregnancy is undertaken while the disease is in remission.


    Conflict of interest
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 
The authors have declared no conflicts of interest.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Case 1
 Case 2
 Case 3
 Case 4
 Discussion
 Conflict of interest
 References
 

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Submitted 13 August 2002; Accepted 12 February 2003





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