Pregnancy-related polymyositis and massive perivillous fibrin deposition in the placenta: Are they pathogenetically related?



Adult polymyositis is a rare, inflammatory, striated muscle disease of unknown etiology characterized by symmetric weakness of the limb girdles, neck, and pharynx in particular. Much research points to autoimmune cell–mediated muscle damage in the pathogenesis. Myositis-specific autoantibodies produced to aminoacyl-transfer RNA synthetase enzymes are characteristic, but the underlying stimulus to their production remains elusive.

Equally unusual in incidence is massive perivillous fibrin deposition (MPFD) in the placenta. In MPFD, the villous trophoblast syncytium is replaced by a mixture of fibrin and extracellular matrix that envelops the chorionic villi, obliterating large areas of the fetomaternal interface.

We present the case of a young woman who presented with the unusual conditions of polymyositis immediately following a pregnancy complicated by stillbirth and placental MPFD. We question whether these conditions could be pathogenically related.

Case report

Three months before presentation with features of myositis, a 20-year-old white woman delivered a stillborn, anatomically normal male fetus following spontaneous labor at 38 weeks' gestation. A tight nuchal cord indenting the neck of the fetus was presumed to have led to fetal asphyxia. Postmortem examination of the fetus revealed no myositic features in striated muscles of the thorax, neck, and cardiac muscle. The placenta was twice the normal weight (940 gm) with massive amounts of perivillous fibrin throughout the placental bed, most pronounced around the anchoring villi and maternal floor (Figure 1).

Figure 1.

A,Macroscopic photo of placenta on cut section showing massive amounts of perivillous fibrin; B,low-power photomicrograph of perivillous fibrin deposition and remaining uninvolved chorionic villi below; C,high-power photomicrograph showing vascularized chorionic villi largely devoid of a cytotrophoblast or syncytiotrophoblast layer and maternal space occupied by fibrin.

During the next 3 months, the patient reported morning stiffness predominantly affecting the large joints, fatigue, sweats, and anorexia. Muscle aches and weakness progressed to the point where she had to be helped from a chair and was unable to shower.

Physical examination revealed an overweight young woman who appeared fatigued. Her joints were cool, with squeeze tenderness of her proximal interphalangeal joints and metatarsophalangeal joints. There was marked weakness of shoulder elevation and the neck flexors could be overcome. The patient had symmetric weakness in 4+ proximal muscles and 4+ distal muscles in both the upper and lower limbs. She had difficulty rising from a chair, and was unable to sit up from a lying position. She had a waddling gait and was unable to squat.

Laboratory tests at this time revealed that the patient's creatine kinase (CK) level was 19,904 units/liter, and her troponin T was 0.916 μg/liter (normal <0.035 μg/liter). Electromyogram showed marked myopathic changes with fibrillation potentials consistent with inflammatory myopathy. Whole-body magnetic resonance imaging STIR scan showed muscle edema in multiple muscle groups, more marked proximally than distally. Muscle biopsy confirmed an inflammatory myopathy with scattered degenerate and regenerate fibers, mild perifascicular accentuation, and perivascular lymphocytic inflammation (Figure 2). The patient's antinuclear antibody titer was 1:80, and anti–Jo-1 antibodies were positive. Treatment consisted of intravenous methylprednisolone followed by 60 mg of oral prednisone with bisphosphonate cover. Because of the suspicion of myocardial involvement and a suggestion of dysphagia, she was also started on an oral, weekly dose of methotrexate. Three months following presentation, her weakness was improved and she was able to work 3 full days per week. Her CK was 1,060 units/liter.

Figure 2.

Degenerate and regenerate muscle fibers associated with a mononuclear cell infiltrate in a perifascicular distribution.


In this case, florid polymyositis closely followed the delivery of a dead fetus and damaged placenta. The patient and her mother were convinced that the events were linked. Is this possible?

Takei et al (1) described a similar case of postpartum polymyositis following the delivery of a dead fetus at 32 weeks' gestation. Steiner et al (2) reported 2 cases of polymyositis following live deliveries. Poor fetal outcome following a diagnosis of polymyositis/dermatomyositis was highlighted by Gutierrez et al (3) and Silva et al (4). The histopathologic findings in the placentas were not discussed in these reports; however, Satoh et al (5) did describe extensive areas of perivillous fibrin in the placenta after a spontaneous abortion at 23 weeks' gestation in which the patient developed severe relapsing myositis with onset during pregnancy. MPFD (and its related diagnosis of maternal floor infarction) has been reported in association with antiphospholipid antibody syndrome (6), dermatomyositis (7), and autoimmune disease (8).

Maternal floor infarction and MPFD are associated with lymphocyte-mediated villitis of unknown etiology (9). If this were the mechanism in the present case, what could link T cell recognition of antigens in the syncytiotrophoblast and immune-mediated attack on skeletal muscle? We point out that a common feature of the syncytiotrophoblast and skeletal muscle is the rare process of cell to syncytium fusion. So far, the molecular mechanisms involved in this cell fusion pathway are not well understood, but the system does appear to use many aspects of the apoptosis pathway (10).

We propose that an initial T cell–mediated response against the syncytiotrophoblast may have led to massive fibrin deposition in the placenta in this case. This may have triggered the subsequent myositis due to sharing of antigens between the syncytiotrophoblast and skeletal muscle, possibly through antigens associated with the process of cell to syncytium fusion, which is a common feature of these 2 tissues.

The placenta is an often unappreciated organ, and in this case, without the nuchal cord leading to fetal death, the placenta may never have been pathologically examined. We presented a case with 2 rare diagnoses, whose temporal relationship requires further consideration of the role of the placenta in immunologically-mediated disease.