In 2009, a 51-year-old Caucasian woman was diagnosed with SLE, secondary Sjögren’s syndrome and hypothyroidism. In the preceding months, she had pleuritis, polyarthritis, photosensitivity, alopecia, oral ulcers, xerophthalmia and xerostomia. Laboratory findings on admission demonstrated the presence of antinuclear antibodies (HEp-2 ANA, in a titer of 1/320 with speckled and nucleolar patterns), lupus anticoagulant, anti-cardiolipin, and anti-SSA autoantibodies. Hypocomplementemia (low C3 and C4), lymphopenia, thrombocytopenia and hypothyroidism (TSH > 100 mU/L) were also documented. She was admitted to the hospital for progressive dyspnea and anasarca. Cardiac ultrasound showed a normal left ventricular ejection fraction, no pericardial effusion but elevated systolic pulmonary artery pressure (49 mmHg). Pericardial calcifications and thickening were detected by computed tomography. On cardiac catheterization, mean pulmonary artery pressure was 28 mmHg and wedge was 13 mmHg. Diuretic therapy led to a weight loss of 12 kg and normalisation of the pulmonary arterial hypertension on repeat cardiac catheterization. A diagnosis of constrictive pericarditis was made. Thyroid hormone supplementation was initiated. SLE manifestations responded to low-dose corticosteroids and hydroxychloroquine 200 mg twice daily.
In 2016, she experienced new-onset Raynaud’s phenomenon, mild proximal muscle weakness, and progressive exertional dyspnea. The patient’s exam demonstrated moderate symmetric muscle weakness in axial, hip and shoulder girdle muscles. Weakness was graded at 4− to 4+ out of 5 on the MRC scale for neck extensors, shoulder abductors, internal and external rotation of the shoulders, flexion and extension of the elbows and movements of the hip (flexion, abduction, adduction, extension). There was also some mild weakness (4+ out of 5) for finger extension and finger abduction. Serial pulmonary function testing revealed a progressive restrictive ventilatory defect (Fig. 1). On March 2018, while on oral hydroxychloroquine alone, pulmonary function testing showed a marked restrictive pattern: total lung capacity was 2.90 L (65% of the predicted normal value), forced expiratory volume in 1 second (FEV1) was 1.36 L (60%), and forced vital capacity (FVC) was 1.70 L (58%). Diffusing capacity of the lung for carbon monoxide (DLCO) was 63% of the predicted value. In the supine position, FEV1 and FVC both declined by 10%. Maximal inspiratory pressure was 109% of predicted. Chest radiograms revealed chronic elevation of the right hemidiaphragm. Chest computed tomography showed no evidence of interstitial lung disease, and cardiac ultrasound and ventilation-perfusion scans were normal.
Diaphragmatic ultrasound was performed in July 2018 to assess diaphragmatic contractility. Right and left diaphragm thickening fractions (TFdi) were respectively of only 38% and 45% (mean normal TFdi values in the healthy population are approximately 80%, with TFdi values < 20% being indicative of significant diaphragmatic weakness) [4] (Fig. 2). In the combined presence of unexplained dyspnea, an extrapulmonary restrictive lung disease, a positional decrease in FVC and TFdi values that were judged to be on the lower end of the normality spectrum (although no previous examination was available for comparison), a diagnosis of SLS was made [14].
Since the patient had a two-year history of Raynaud’s phenomenon with proximal and neck flexor muscle weakness on physical examination, additional investigations were undertaken. Serological markers of lupus showed normal dsDNA, but low complement levels. Nailfold capillaroscopy as well as serum creatine kinase (CK) and aldolase levels were normal. Serology demonstrated the presence of anti-Ro-52/TRIM21 (high positive), but no myositis-specific, SSc-specific or SSc-overlap autoantibodies were found on line immunoassays (Euroimmun AG, Luebeck, Germany) or on Protein A-assisted immunoprecipitation using radiolabeled K562 cell extracts (Fig. 3). A muscle MRI of the lower limbs was unremarkable.
Electromyography revealed fibrillation potentials in the biceps, iliopsoas, cervical and thoracic paraspinal muscles, and complex repetitive discharges in cervical paraspinal muscles. In addition, myopathic units (small amplitude, polyphasic motor unit potentials) in triceps, first dorsal interosseous and vastus lateralis were observed. Biceps muscle biopsy revealed dense endomysial lymphocytic aggregates rich in CD20+ B cells, perimysial fragmentation with plasma cell-rich perivascular infiltrates, diffuse sarcolemmal upregulation of class I MHC, perifascicular upregulation of class II MHC (Fig. 4), and focal sarcolemmal deposition of C5b-9 (not shown), meeting the diagnostic criteria of polymyositis by the 119th ENMC classification criteria [15].
Treatment with prednisone 15 mg/day and mycophenolate mofetil 2 g/day was initiated, and shortness of breath and proximal muscle weakness improved. In March 2019, diaphragmatic ultrasonography revealed marked improvement in diaphragmatic function: right TFdi was 51% and left TFdi 128%. Pulmonary function testing also showed improvement of the restrictive ventilatory defect: total lung capacity was 3.13 L (70% predicted), FEV1 was 1.41 L (63% predicted), FVC was 1.61 L (60% predicted) and DLCO was stable.