Autoimmune Inflammatory Myopathy in Pregnancy

Abstract

Autoimmune diseases such as systemic sclerosis, Wegner's granulomatosis, and polyarteritis nodosa are rarely seen in pregnancy, unlike systemic lupus erythematosus, whose association with pregnancy is well studied. Dermatomyositis is a protean disease that affects women in reproductive age. There are only a few case reports documenting the outcome of pregnancy in patients with dermatomyositis/polymyositis. The disease is usually considered to have an adverse effect on pregnancy. Fetal prognosis is guided by the severity of maternal disease and is usually good when the disease remains inactive during pregnancy.

Introduction

Patients with autoimmune diseases face several pregnancy-related problems as well as disease flares during and after pregnancy. Dermatomyositis/polymyositis (DM/PM) is an uncommon medical disorder complicating pregnancy. It may start before, during, or even after pregnancy.[1,2] Optimal outcome can be anticipated when the pregnancy is undertaken with the disease in remission.[3] Pregnancy outcome is especially poor with disease onset or flare early in the gestation compared with an exacerbation in the second or third trimester, when the fetal prognosis is usually good.[4]

Unlike systemic lupus erythematosus (SLE), for which pregnancy has been well studied and reported, there are only a few case reports in the literature detailing this physiologic event in patients with DM/PM. We report on the outcome of 3 pregnancies in 2 women with DM/PM.

Case 1

Mrs. SB, a 28-year-old primigravida with a diagnosed case of dermatomyositis for the past 6 years, was supervised in our antenatal clinic. She had a history of intermittent painless swelling over the extremities, along with alopecia and photosensitivity at 12 years of age, for which she did not seek any medical advice. She was first seen in the rheumatology clinic of our institution at 22 years of age. At this time she had muscle pain, weakness, and facial rash. Investigations revealed a raised erythrocyte sedimentation rate (ESR) and creatine phosphokinase (CPK); antinuclear antibodies (ANA) were diffuse positive on immunofluorescence; and the muscle biopsy confirmed the diagnosis of DM. The disease did not show adequate improvement with steroids alone but responded well to the addition of methotrexate. Treatment was continued for the next 3 years.

At the time of conception, the disease had been in remission, and she was not on medication for her medical disorder for a period of over 6 months. Her disease remained quiescent throughout the pregnancy. Maternal and fetal surveillance was uneventful until late in the third trimester when she developed hypertension. Labor was induced with oxytocin at 37⁺⁵ weeks for gestational hypertension. She delivered vaginally a live-born female child weighing 2815 g and with normal Apgar score. Both the mother and the child were discharged in a satisfactory condition. There was no postpartum exacerbation of the disease.

With the disease in remission, she conceived spontaneously for the second time after 3 years and received antenatal care in our clinic. Unlike her first pregnancy, her blood pressure remained normal, but the fetus had intrauterine growth restriction (IUGR) at 32 weeks on ultrasonography, which incidentally revealed low-lying placenta as well, and therefore she was admitted for safe confinement. She delivered a live-born, small-for-date baby girl weighing 2170 g by emergency cesarean section for antepartum hemorrhage at 36 weeks. The intraoperative as well as postoperative period was uneventful.

Case 2

Mrs. S, a 25-year-old primigravida, was diagnosed with PM (after muscle biopsy) and lichen planus pigmentosus in the rheumatology clinic of our institution at 20 years of age when she had presented with increased patchy skin pigmentation and proximal muscle weakness, as well as a raised ESR and CPK. Her symptoms improved on steroids and methotrexate. The drugs were stopped after 4 years in the preconceptional period, and low-dose steroids were restarted after conception.

She received antenatal care in our clinic. Maternal follow-up was uneventful, with the disease in remission on steroids until late in the third trimester when she developed hypertension. Fetal surveillance revealed IUGR. In view of maternal hypertension and fetal growth restriction, labor was induced with oxytocin at 36 weeks' gestation. A live-born, small-for-date baby boy weighing 1540 g and with normal Apgar score was delivered by emergency lower segment cesarean section for fetal distress. She had an uneventful postoperative period and both the mother and the baby were discharged in a satisfactory condition.

Discussion

PM and DM are uncommon, acute, subacute, or chronic inflammatory diseases characterized by muscle weakness and inflammation. The exact etiology is not known, but a role for endomysial autoaggressive CD8 (+) T cells in PM and for perivascular B cells in DM is the suspected immune pathology.[5] In the general population, prevalence is 2.4–10.7/100,000, with females being affected more often than males.[4] There is a bimodal age distribution, with peaks between 10–25 years and 30–60 years.[3,4]

Fertility rates before and after the onset of disease vary in different populations. The exact incidence is not known because of use of contraception and late age of disease onset in some patients, but is comparable to their respective population. Although it is rare, a successful pregnancy outcome can be anticipated when the disease is in remission before conception.[3,4,6–11] This occurred in our first case patient, Mrs. SB. A 50% fetal loss was reported by King and Chow[3] when the disease appeared, or flared up, during pregnancy. In a retrospective analysis of pregnancy outcome in 4 patients who had active disease during pregnancy, only 1 ended in normal delivery; 2 delivered prematurely and 4 spontaneous abortions occurred.[12] Gutierrez and colleagues[7] reported outcome of 10 pregnancies in 7 patients, 4 of whom had a diagnosis of DM/PM made during pregnancy, while 3 had exacerbation after conception. The disease was in active stage in 5 of the 10 pregnancies and resulted in a fetal loss of 60% (1 spontaneous abortion, 1 stillbirth, and 1 neonatal death) and 2 live preterm neonates. With inactive disease in pregnancy, 2 spontaneous abortions, 1 preterm delivery, and 2 term deliveries occurred. In a case report, acute onset of DM in the second trimester, causing maternal rhabdomyolysis and myoglobinuria, resulted in spontaneous abortion.[13]

As reported by Wolfberg and colleagues,[14] women with rheumatologic diseases have a nearly 4-fold increase in the incidence of preeclampsia than women without rheumatologic disease (8.8% vs 2.3%). Women with rheumatologic diseases also have 2-fold greater risk for adverse pregnancy outcomes, including preterm delivery (15.2% vs 7.8%), SGA (small for gestational age), and IUGR (8.0% vs 3.1%) compared with women without rheumatologic disease. The reason for the association of IUGR and SGA with rheumatologic disease is not very clear. A possible explanation can be a common autoimmune process linking the pregnancy (a process of autoimmune tolerance), rheumatologic disease, and preeclampsia, and therefore leading to uteroplacental insufficiency. This requires further research. In our study, hypertension and IUGR were seen in both patients, supporting findings of the aforementioned study.[14]

Fetal prognosis is a reflection of maternal disease status. Fetal growth restriction, even with maternal disease in remission during pregnancy, has also been reported.[3,8] This was seen in the second pregnancy of our first case patient as well as our second case patient. Perinatal morbidity and mortality is stated to be up to 55%,[7] even when pregnancy is undertaken with disease in inactive stage. According to the Gutierrez and colleagues,[7] in PM/DM, the fetal loss is almost the same in active vs inactive disease; therefore, vigilant care is needed to detect complications. Silva and coworkers[8] reviewed pregnancy outcome in 47 patients with immune-inflammatory myopathy in the literature; they described fetal outcome associated with active disease during pregnancy compared with inactive disease as evidenced by rates of intrauterine fetal death (43% vs 13.6%, respectively) and IUGR/premature delivery (33% vs 13.6%, respectively).

The use of steroids as first-line therapy is indicated for maternal disease exacerbation during pregnancy, as in the nonpregnant state.[3,4,8] Other chemotherapeutic agents, such as intravenous immunoglobulins[1,15] and antineoplastic agents, can be used as second-line drugs to control disease activity and to maintain pregnancy.[3,4]

Recurrence in subsequent pregnancies is not always seen,[3,7] as was also shown in a case report of 3 pregnancies in the same woman with disease relapse during 1 pregnancy only.[11] Variable pregnancy outcome in 2 pregnancies in the same patient in terms of effect on the mother and fetus, as seen in case 1, suggests autoimmune pathology and consequently uteroplacental involvement, even when disease is in remission, as suggested in the study by Wolfberg and colleagues.[14]

The management of this rare medical disorder during pregnancy entails careful monitoring for signs and symptoms of disease exacerbation and reflects the need for heightened clinical vigilance and further research into the common pathophysiologic correlates from the viewpoint of a high-risk pregnancy. With availability of drugs for control of maternal disease, a good fetal outcome can be expected if the maternal disease remains inactive during pregnancy.