Contraception and Pregnancy in Patients with Rheumatic Disease

10. Myositis and Pregnancy

Stephen J. Di Martino¹

(1)

Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA

Stephen J. Di Martino

Email: dimartinoS@hss.edu

Introduction

The idiopathic inflammatory myopathies (IIM) are a group of rare autoimmune conditions that share the common theme of an immune-mediated attack on skeletal muscle with resulting clinical weakness. The group includes dermatomyositis (DM), polymyositis (PM), juvenile myositis (JM), inclusion body myositis (IBM), cancer-associated myositis, overlap myositis, and necrotizing autoimmune myopathy (NAM). Women are affected at three times the rate of men with the exceptions of overlap myositis (myositis patients that also meet criteria for or share features of other autoimmune conditions) in which the ratio is higher at 9:1, and IBM, which affects men more than women at a ratio of 3:1.

In general, studies performed in patients with inflammatory myopathy are subject to several challenges at the onset. First, the incidence of IIM is estimated to be between five and ten cases per million people; because these conditions are so rare, most reports only include small numbers of patients. Indeed, most of the therapeutic trials on which current treatment is based have included less than 30 patients, making it difficult to extrapolate findings to individual patients. Second, the differential diagnosis is broad for these entities and includes muscular dystrophies, metabolic myopathies and toxic myopathies, all of which can present with the same clinical features as IIM, and some of which may even exhibit inflammation on muscle biopsy. Therefore, it is impossible to be certain that a group of myositis patients in a given study does not include some patients with non-inflammatory myopathy. The presence of myositis-specific autoantibodies (MSA’s) can be helpful in establishing the diagnosis of a true inflammatory myopathy; however, because there are so many MSA’s, they also serve to further subdivide these rare entities, again making it difficult to extrapolate study results to individual patients.

It has been estimated that only 14 % of patients with inflammatory myopathy develop disease before or during childbearing years [1]. Therefore, because IIM’s are already rare, diverse, and have a broad differential, the challenges described above are amplified for investigators seeking to understand the association of pregnancy with inflammatory myopathy. The vast majority of literature concerning IIM and pregnancy are single cases or reports of two or three patients. Despite the limited numbers, there are several clinical scenarios that have been described in articles discussing myositis and pregnancy: (1) new onset of disease during pregnancy (2) pregnancy in a patient with preexisting disease (with or without flare), and (3) new disease onset after pregnancy.

In this chapter, we review 36 publications that, in total, describe 78 pregnancies of 59 women. Overall, there were 31 women with DM, 21 women with PM, 5 women with JM or JDM (juvenile dermatomyositis), and one woman with PM/DM. Six patients were known to be Jo-1 positive and one PL-7 positive; however, most were not tested. These cases include 27 pregnancies where there was no flare of preexisting disease, 21 cases in which preexisting disease flared during pregnancy, 20 cases of new onset disease during pregnancy, and 10 cases of new onset disease shortly after pregnancy. In these published cases, three women had three reported pregnancies each and 12 women had two reported pregnancies each. Many patients had pregnancies before the diagnosis of inflammatory myopathy, but there was no clear indication that there was a higher rate of complications before the onset of disease; however, this issue has not been examined in detail. There are no reported cases of malignancy-associated inflammatory myopathy during pregnancy. There are several important concerns when looking at this group of publications. First, it seems reasonable to suspect that pregnancies in women with preexisting inflammatory myopathy who had uneventful outcomes would be less likely to be reported, meaning that the existing literature may over-represent negative outcomes. Second, these conditions can be difficult to diagnose, therefore, cases of new onset during pregnancy, especially those with poor outcomes, may not be reported due to lack of a definitive diagnosis.

Fertility in Women with Inflammatory Myopathies

The issue of fertility in patients with inflammatory myopathy has been addressed in two publications [2, 3] to date. Both reports looked at very small groups of patients who developed IIM before or during their childbearing years. One concluded that there was an incidence of nulliparity comparable to the general population [2] while the other concluded that there was a reduction in the fertility rate [3]. The small sample sizes make it impossible to have confidence in either conclusion.

Pregnancy Outcome in Women with Inflammatory Myopathies

Pregnancy Outcome with Disease Onset During Pregnancy

Twenty cases of new onset inflammatory myopathy during pregnancy have been described; these are summarized in Table 10.1 [3–19]: eleven patients had DM, seven patients had PM, one had JDM, and one had PM/DM. Cases were reported with onset during each of the three trimesters: nine cases presented before 15 weeks, four cases presented at 18–24 weeks, and seven cases presented after 28 weeks. Ages of the patients at pregnancy ranged from 14 to 42 years old. It was the first pregnancy for 7 of the 20 patients. Eleven patients had previous pregnancies before the diagnosis of myositis. Three of those 11 previous pregnancies did not end with a live birth; reasons for this were not discussed.

Table 10.1

Treatment and outcome of pregnancy in inflammatory myopathy with onset during pregnancy

Reference	Diagnosis	Time of disease onset	Therapy	Fetal/neonatal outcome
Tsai et al. [4]	DM	10 weeks	Topical steroid	Neonatal death (39 weeks)
Bauer et al. [5]	PM	3 months	Prednisone 60–160 mg/day	IUFD (8 months)
Katz [6]	PM	3 months	None	Induced 36 weeks, healthy
Gutierrez et al. [3]	Pt 1: DM	First trimester	Prednisone	IUFD < 20 weeks
	Pt 2: DM	First trimester	Prednisone	IUFD > 21 weeks
	Pt 4: PM	First trimester	Prednisone	Neonatal death (premature birth)
England et al. [7]	DM	15 weeks	Corticosteroid	IUGR
Emy et al. [9]	DM/PM	30 weeks	Corticosteroid	IUGR (C/S 37 weeks)
Ishii et al. [12]	DM (first pregnancy)	32 weeks	None	Delivered 38 weeks, healthy
Pinheiro et al. [8]	JDM Age 14	35 weeks	Corticosteroid	Emergency C/S 37 weeks, healthy
Satoh et al. [14]	PM	23 weeks	Not stated	IUFD 24 weeks
Harris et al. [10]	DM	36 weeks	None	Induced 38 weeks, healthy
Solomon and D’Alton [11]	DM	29 weeks	Prednisone 80 mg/day	Induced 34 weeks, healthy
Kofteridis et al. [13]	DM	13 weeks	Prednisone 1 mg/kg	IUFD 14 weeks
Messina et al. [15]	Pt 1: PM	Third trimester	None	Healthy
	Pt 2: PM	6 month	Prednisone 60 mg/day, tapered	Healthy
Vancsa et al. [19]	Pt 7: DM	28 weeks	High-dose IV corticosteroid with po taper	37 weeks, healthy
Nozaki et al. [17]	DM	18 weeks	Prednisone 60 mg/day, tapered (IVIG after delivery)	IUGR, Emergency C/S 35 weeks
Okada et al. [16]	PM	20 weeks	None (Prednisone, tacrolimus, cyclophosphamide after TOP)	Elective termination pregnancy
Linardaki et al. [18]	DM	15 weeks	Methylprednisolone 24 mg/day, IVIG monthly	Planned C/S 37 weeks, healthy

DM dermatomyositis, PM polymyositis, JM juvenile myositis, JDM juvenile dermatomyositis, IUFD intrauterine fetal demise, IUGR intrauterine growth restriction, C/S Cesarean section, IVIG intravenous immunoglobulin, TOPtermination of pregnancy

Of the seven patients who presented with disease late in pregnancy (after 28 weeks), all pregnancies produced healthy babies, although one was small for gestational age (SGA). Four of those seven patients were treated with corticosteroids and three were untreated. One of the treated patients was induced at 34 weeks due to disease activity and was noted to respond better to therapy after delivery [11], and two patients had Cesarean sections at 37 weeks [9, 19]. In at least three of the cases, there was the suggestion of active disease as manifested by descriptions of proximal weakness and dysphagia. This suggests that healthy babies were born despite significant disease activity when disease onset was late in pregnancy.

There were four cases of disease onset between 18 and 24 weeks: two pregnancies resulted in healthy babies, one was an intrauterine death, and the other was an elective abortion. The two patients with successful pregnancies were treated with high-dose steroids (one of these patients also received monthly IVIG) and had Cesarean sections after 35 weeks: both babies were healthy, although one was SGA [15, 17]. The patient who had an intrauterine death presented with myositis at 23 weeks and lost the baby at 24 weeks [14]. The fourth patient, who was Jo-1 positive, had interstitial lung disease and chose to have an elective abortion [16]. Nine cases presented early in pregnancy, during the first trimester: six of those nine pregnancies ended in intrauterine or neonatal death. Seven of the nine pregnancies were treated with high-dose corticosteroids. One of the patients who was not treated had a history of tuberculosis and histoplasmosis [4] and although this patient had a live birth at 39 weeks, the infant died shortly thereafter; there were no noted placental abnormalities. The other patient who was not treated did not have inflammation observed on muscle biopsy: she went into rapid remission shortly after birth after delivering a healthy baby at 36 weeks following artificial rupture of membranes [6]. In the two other cases that resulted in a healthy baby, one was treated with high doses of corticosteroids starting at 15 weeks [7] and one was treated with both high doses of corticosteroids and monthly IVIG starting at 21 weeks [18].

While the interpretation of the above information is subject to concerns mentioned earlier, it seems reasonable to conclude that the earlier the disease presents during pregnancy, the greater the likelihood of a poor outcome. Whether or not this is a consequence of disease activity, therapy, or both is not clear. However, in 7 of the 12 successful pregnancies, the patients were treated with high-dose corticosteroids (four of these patients were started on corticosteroids in the first or second trimester). All of the losses occurred in pregnancies with disease onset prior to the third trimester: eight fetal or neonatal deaths in total of the 20 cases reported where disease onset occurred during pregnancy. However, it is important to note that five of these eight losses were reported in 1986 or earlier, two were reported in the 1990s, and the one published in 2012 was an elective abortion. Therefore, given advances in maternal–fetal medicine, one can question whether these numbers are applicable to modern-day pregnancies.

Pregnancy Outcome in Which Disease Was in Remission During Gestation

There have been 27 reported pregnancies in 22 women with preexisting inflammatory myopathy that remained quiescent during pregnancy [1–3, 12, 19–25]. Fourteen patients had DM, two had JDM, and six had PM. Ages at pregnancy ranged from 22 to 42 years. It was the first pregnancy for 4 of the 22 women. The duration of remission prior to the beginning of pregnancy was only reported in about one third of cases and ranged from less than 1 to 5 years. Nine patients were treated with low doses of steroids, ranging from a low of 5 mg prednisone (4 mg methylprednisone) to a high of 12 mg of methylprednisone, possibly suggesting that in these patients disease remission was medication-dependent. Seven of the nine pregnancies in which steroids were used resulted in healthy babies at term. In the other two pregnancies, one required an emergency Cesarean section at 32 weeks (the baby was healthy, and the placenta exhibited borderline massive fibrin deposition) [22], and the other was a spontaneous abortion in the second trimester reported in 1962 [20]. In the remaining 18 pregnancies that were not treated with steroids, two patients had elective abortions [19], there were two intrauterine deaths [3, 20] and one neonatal death in a twin pregnancy [3]. The two spontaneous abortions and neonatal death were all reported in 1984 or earlier. Three of the women had a flare of disease postpartum (mild in two of the three cases) [3, 24, 25].

As one might expect, the absence of disease activity during pregnancy appears to be associated with a higher percentage of favorable outcomes. This was the case whether or not steroids were employed to keep the disease under control. Because one cannot differentiate between a patient in complete, permanent remission and one who has the potential for disease activity, it may be that the group maintained on steroid to prevent disease activity may be the most instructive. The favorable outcomes seen in this group provide compelling information to suggest keeping a patient in remission on therapy into pregnancy.

Pregnancy Outcomes in Which Disease Flares During Pregnancy

There are reports of 21 pregnancies in 17 patients with known inflammatory myopathy that flared during pregnancy, with treatment and clinical outcomes summarized in Table 10.2 [1–3, 19–22, 26–32]. Ages of patients ranged from 20 to 40 years. Seven patients had DM, seven patients had PM, and three patients had juvenile myositis. This was the first pregnancy for 6 of the 17 patients. Four of the remaining eleven patients had previous unsuccessful pregnancies for unclear reasons. A number of the patients were in remission at the beginning of pregnancy, although this was often not commented upon. In the few reports where the information was available, time of remission before pregnancy ranged from less than 3 months to greater than 5 years.

Table 10.2

Treatment and outcome of pregnancy in inflammatory myopathy with flare during pregnancy

Reference	Diagnosis	Time of disease flare	Treatment	Fetal/neonatal outcome
Glickman [26]	DM	Duration of pregnancy	Prednisone 20 mg/day	Healthy, term
Massé [20]	DM (first pregnancy)	Unknown	Corticosteroid	Healthy
Gutierrez et al. [3]	Pt 3 (second pregnancy): JDM	Third trimester	Prednisone	Premature, C/S
	Pt 7 (first pregnancy): DM	Third trimester	Prednisone	Premature
King and Chow [2]	Pt 3: DM	18 weeks	Prednisone 60 mg/day taper	Healthy, term
Houck et al. [27]	JM (first pregnancy)	17 weeks	None	IUFD 22 weeks
	JM (second pregnancy)	Second trimester	Prednisone 20 mg/day	Induced 37 weeks, healthy
Le Thi Huong et al. [28]	PM	37 weeks	Corticosteroid	IUGR
Rosenweig et al. [29]	PM	26 weeks	Prednisone 60 mg/day	Emergency C/S 27 weeks
Papapetropoulos et al. [21]	PM (second pregnancy)	10 weeks	Prednisone 60 mg/day	Termination of pregnancy 16 weeks
Silva et al. [1]	PM	Unknown	None	IUFD 34 weeks
Park et al. [30]	DM	Time of conception	Unknown	Termination of pregnancy
Mosca et al. [31]	DM	Time of conception	Prednisone 40–60 mg/day, IVIG	C/S for PPROM 35 weeks, healthy
Williams et al. [32]		2 months prior to conception	IVIG	Healthy, term
Vancsa et al. [19]	Pt 1 (first pregnancy): PM	Prior to conception	Methylprednisolone high dose, taper	Premature at 35 weeks, healthy
	Pt 5 (first pregnancy): JM	Prior to conception	Corticosteroid	Spontaneous abortion, first trimester
	Pt 5 (second pregnancy): JM	Prior to conception	Corticosteroid	Spontaneous abortion, first trimester
	Pt 5 (third pregnancy): JM	Prior to conception	Prednisone high dose, taper	Healthy, term
	Pt 9 (first pregnancy): PM	Unknown	Corticosteroid	IUFD
	Pt 9 (second pregnancy): PM	Unknown	Corticosteroid	IUFD
Al-Adnani et al. [22]	PM (first pregnancy)	Unknown	None	IUFD, 34 weeks

DM dermatomyositis, PM polymyositis, JM juvenile myositis, JDM juvenile dermatomyositis, IUFD intrauterine fetal demise, IUGR intrauterine growth restriction, C/S Cesarean section, PPROM preterm premature rupture of membranes, IVIG intravenous immunoglobulin

Seven pregnancies have been reported in which the disease was active going into pregnancy; three of these cases were in a single patient who had a diagnosis of juvenile myositis at 10 years old and became pregnant in three successive years starting at age 25 [19]. Her disease was active going into all three pregnancies, although the severity of the symptoms was not discussed. The patient was treated with high doses of corticosteroids during each pregnancy and had a spontaneous abortion in the first trimester of both the first and second pregnancies. The third pregnancy resulted in a healthy baby at term; during this time, the patient was maintained on 12 mg methylprednisone. In the four remaining cases [19, 30–32], the onset of disease occurred just prior to pregnancy and the patients were flaring while entering pregnancy. One of these patients had an elective abortion and responded to IVIG after the termination of pregnancy (TOP) [30]. Two other cases were reported in 2005 [31] and 2007 [32]; each patient was treated with IVIG, although the case presented in Mosca et al. [31] was also treated with high doses of corticosteroid. Each mother delivered a healthy baby: the patient treated with steroids had a Cesarean section at 35 weeks, the other had a spontaneous vaginal delivery at term. The last case developed anti-synthetase syndrome 3 months before pregnancy and was on high doses of steroids going into pregnancy; remission was achieved by 6 months and a healthy premature baby was delivered [19].

Five pregnancies have been reported in which there was a myositis flare in the second trimester. One patient had an elective TOP with subsequent good response to therapy [21]. Another patient had an intrauterine death at 22 weeks gestation (this patient started the pregnancy on 10 mg of prednisone and was tapered off by the third month) [27]. Each of the three remaining patients was treated with high-dose corticosteroid and each delivered a healthy baby.

Three pregnancies (including one twin pregnancy) in which preexisting disease flared in the third trimester have been reported [3, 28]. Severity of disease was not discussed but all patients were treated with standard doses of corticosteroid. All three pregnancies produced healthy babies although two infants were premature and the twins were small for age.

In the remaining six reported cases with disease flare during pregnancy, it is unclear exactly when during the pregnancy the patient’s disease became active. Four of the six ended with intrauterine death or abortion, and two had healthy babies. In the two cases with healthy babies, both patients were treated with steroids and both were reported before 1965 [20, 26]. Two of the four pregnancy losses were in the same patient, who was treated with steroid during both pregnancies [19]. The other two losses were in patients who were not treated because they had high creatine kinase (CK) but no clinical weakness: these intrauterine deaths were in the third trimester and were associated with massive amounts of fibrin in the placentas [1, 22].

It is difficult to draw conclusions regarding several important questions because many of the reports are missing critical information including the time during pregnancy when the disease became active and the duration of disease remission prior to pregnancy. The three cases reported to have flared during the third trimester all resulted in healthy babies, giving some support to the idea that outcome may be more favorable if there is no disease activity early in the pregnancy. Corticosteroids were used in all 12 successful pregnancies. Also notable is that two patients were independently reported with high CK levels but no weakness followed by pregnancy losses in the third trimester [1, 22]. This finding suggests that elevated CK may be clinically significant even in the absence of weakness. Both patients had massive deposits of fibrin in the placenta.

Outcomes of Women with Multiple Pregnancies

The question of whether prior pregnancy outcome can be predictive of the outcome of a subsequent pregnancy in an individual patient is partially addressed in the current literature. Fifteen women with inflammatory myopathy and multiple pregnancies have been described [2, 3, 12, 19, 21–23, 25, 27] including three women with three documented pregnancies each. One of these women had spontaneous abortions in her first two pregnancies followed by a healthy baby [19]. One had a healthy baby followed by an elective TOP, which was subsequently followed by another healthy baby [21]. The third woman had onset of symptoms shortly after delivery of a healthy baby and had two subsequent normal births after diagnosis of disease [23].

Of the remaining 12 women (who each had two pregnancies), nine had established disease before both of their reported pregnancies. Four of these nine had a pregnancy loss during their first pregnancy and three of them went on to have a healthy baby during their second pregnancy, although two of these were premature births. Of the five women who had healthy babies during their first described pregnancy, two had elective TOP, one had a twin pregnancy where one of the twins died during the neonatal period and two women had healthy babies. While one must be cautious in drawing conclusions from such a limited amount of information, at this point there does not appear to be support for the idea that the outcome of one pregnancy is predictive of subsequent pregnancies in women with inflammatory myopathies.

Neonatal Outcome

In general, neonatal outcome is good and is complicated primarily by the sequelae associated with preterm delivery or small size for gestational age. The characteristic rash of dermatomyositis has not been described in any newborn of a mother with polymyositis or dermatomyositis to date. However, in one publication [15] the authors reported elevation of the CK level in two newborns, ages 2 and 4 months. This suggests the possibility of a passive transfer of autoimmunity from mother to child; however, the babies were not weak and it was unclear if the source of the CK was neonatal or maternal. This was the only article in which this potentially important issue was examined.

New Disease Onset After Pregnancy

There are ten reports of new onset inflammatory myopathy presenting shortly after pregnancy [3, 12, 23, 25, 33–36], ranging from 4 days to 3 months postpartum. Five of the cases developed DM, five developed PM; one patient was anti-RNP positive and had overlap features of systemic lupus erythematosus (SLE). At least two of the cases followed the patient’s first pregnancy, although this information was reported in only one-third of cases. Five cases followed the delivery of a healthy child. Two followed a spontaneous abortion (one of a 3-week-old embryo) and two followed fetal losses at 32 and 38 weeks. In the case of the 38-week pregnancy loss, massive amounts of perivillous fibrin were observed in the placenta: this patient was Jo-1 positive [36]. Three of the ten cases of new onset disease after pregnancy reviewed here were reported by Steiner et al. [23]: these authors examined their group of 22 female polymyositis patients and found that eight patients (36 %) developed PM during their childbearing years. Three of these eight patients (38 %) developed the disease within 3 months of delivery; the authors argue that this high percentage of patients who develop disease temporally close to pregnancy suggests that the association is not coincidental.

Treatment Options

The only therapies that have been described for active inflammatory myopathy during pregnancy are corticosteroids and IVIG. While corticosteroids are associated with numerous pregnancy complications, their use in patients with active inflammatory myopathy does not appear to be associated with pregnancy loss. Of 27 successful pregnancies in patients with either new onset of disease during pregnancy or a flare of existing disease, 20 (74 %) were treated with high doses of steroids. In contrast, in the 14 patients with disease activity who had pregnancy loss, only seven (50 %) were treated with steroids. When one looks at patients with preexisting disease who did not flare during pregnancy, one of nine (11 %) patients treated with low doses of steroids had a pregnancy loss, while 3 of 17 (18 %) patients not treated with steroids had a pregnancy loss.

There are three reports of IVIG (1g/kg/day over 2 days/per month) use during pregnancy in patients with active inflammatory myopathy [18, 31, 32]. All three patients had disease activity either going into pregnancy or in the first trimester and the IVIG was started in either the first or second trimester; two of the three were also treated with moderate-dose corticosteroids [18, 31]. In one report, the dose of 1 gram/kilogram/day (g/kg/day) for two consecutive days per month was used starting in the second trimester and the patient received a total of four doses [18]: a healthy baby was delivered by planned Cesarean section at 37 weeks. In a second report [31], the patient was treated with 1 g/kg/day for two consecutive days starting at 17 weeks and continued monthly: the baby was born healthy by Cesarean section at 34 weeks after premature rupture of membranes. In the third report [32], the patient was treated with 1 g/kg/day for two consecutive days monthly for 3 months starting in the first trimester and remission was achieved by 19 weeks. However, the patient flared again at 28 weeks and IVIG was resumed until a spontaneous vaginal delivery at term of a healthy baby. This patient received six monthly cycles of IVIG in total.

Fibrin Deposition and Massive Perivillous Fibrin Deposition in the Placenta

There are several reports of pregnancies in women with inflammatory myopathies associated with massive perivillous fibrin deposition (MPVFD) in the placenta [1, 14, 22, 36]. MPVFD is a rare and serious condition of unknown etiology, although autoimmune mechanisms have been suspected. Incidence is estimated between 0.028 and 0.5 % with risk factors including infection, autoimmune disease, and thrombophilia. Autoimmune conditions that have been associated with MPVFD include SLE, antiphospholipid antibody syndrome, systemic sclerosis, and inflammatory myopathy. The condition is characterized by diffuse fibrin deposition within the intervillous space and is associated with prematurity, intrauterine growth restriction (IUGR), and intrauterine fetal demise (IUFD) [22].

Four of the five pregnancies (in four patients) in which diffuse fibrin deposition was seen in the placenta ended with intrauterine death; none of the patients were taking medication at the time. One patient [22] had an IUFD and then a subsequent pregnancy that resulted in a live birth after emergent Cesarean section at 32 weeks due to abnormal findings on cardiotocography (fetal heart rate monitoring). This patient was maintained on low doses of steroids during that pregnancy. During her first unsuccessful pregnancy, she had isolated elevated CK without weakness and therefore was not treated. Similarly, the second patient [1] also had elevated CK without clinical weakness and was untreated during the pregnancy: outcome was an intrauterine death at 34 weeks. The third patient [36] reported with MPVFD was diagnosed with polymyositis within 3 months of a pregnancy loss at 38 weeks. Two of these three patients were known to be Jo-1 positive, while one was PL-7 positive [14, 22, 36]. These cases raise the possibility there may be a role for anticoagulation in patients with inflammatory myopathy, certainly in those patients who have experienced prior pregnancy loss associated with MPVFD, and highlight the importance of obtaining placental pathology in inflammatory myopathy patients who have had pregnancy loss. The fact that three of the four patients with MPVFD were anti-synthetase antibody positive (it is not clear whether the fourth patient was tested) raises the possibility of an association with anti-synthetase syndrome (although this is obviously a very small sample). Finally, two of four patients with MPVFD had isolated elevated CK without other symptoms and were untreated [1, 22], raising the question of whether elevated CK should be treated even in an asymptomatic pregnancy patient. The patient who had a second MPVFD pregnancy with a live birth at 32 weeks (albeit by emergent Cesarean section) was treated with prednisone during the pregnancy.

Maternal Outcome

Just over 60 % of the reported cases of inflammatory myositis in pregnancy have occurred in patients with preexisting myositis. Of these 48 cases, 21 (44 %) were complicated by flare during the pregnancy, with treatments detailed as above. Despite this significant rate of flare in cases reported in the literature, there is only a single reported case of maternal mortality, in 1986, which occurred postpartum after a successful delivery and was attributed to hypertension combined with a severe exacerbation of disease [7].

Conclusions

Pregnancy in myositis patients is rare and, as a result, incompletely understood. Confounding issues include reporting bias, accuracy of diagnosis, and the varied nature of specific details included in each report. These factors combine to make interpretation of the limited literature quite challenging. Systematic review of myositis pregnancy case reports and case series suggests that disease activity during pregnancy is associated with adverse pregnancy outcome, and that treatment during pregnancy may be associated with greater likelihood of live birth. In all, there are 41 reported pregnancies associated with disease activity, whether a flare of existing disease or new onset of disease. Fourteen of these ended in either intrauterine death or neonatal loss, including three elective terminations (34 %). In contrast, in the 27 reported pregnancies without disease activity, there were only five losses (18 %). Moreover, of the 27 pregnancies complicated by disease activity but resulting in a successful live birth, 22 were treated (81 %). Of the 14 cases with disease activity and fetal or neonatal death, only seven were treated (50 %). While few in number, overall review of these cases suggests that disease activity is associated with poor outcome (especially if early in the pregnancy) and that treatment of disease may be beneficial despite the potential negative side effects of corticosteroid use during pregnancy. The three cases in which IVIG was used successfully [18, 31, 32] make this agent an attractive alternative to corticosteroids. Azathioprine is another potential alternative to corticosteroid, but thus far there have not been any publications examining its use in pregnant patients with inflammatory myopathy.

The question of whether or not to treat a myositis patient during pregnancy may be more difficult in patients with mild disease activity such as rash, arthritis, mild weakness, or elevated CK without weakness. In general, most patients will shy away from medical therapy out of concern for the fetus if symptoms are not disabling. However, when one looks at pregnancies with successful outcomes where the patient did not have a flare of disease, 36 % (8/22) were treated with low-dose steroid, whereas only 20 % (1/5) pregnancies complicated by fetal or neonatal losses were treated with corticosteroids.

It seems likely that even subclinical disease activity may have a negative effect on pregnancy outcome. In two of the published cases, the patients had elevated muscle enzymes without other symptoms [1, 22], were not treated, and had pregnancy loss. Both cases were associated with massive deposition of fibrin in the placenta. In all, five pregnancies in four patients [1, 14, 22, 36] were described with MPVFD in the placentas of patients with pregnancy loss (one patient had a live birth following a loss). Three of these four patients had the anti-synthetase syndrome. The reported MPVFD cases underscore the importance of obtaining placental pathology following a pregnancy loss in a patient with inflammatory myopathy. Whether or not these patients would benefit from anticoagulation or treatment with immunosuppression (even during instances with minimal symptoms) is unknown, but clearly warrants further investigation.

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