Myositis with prominent B-cell aggregates causing shrinking lung syndrome in systemic lupus erythematosus: a case report

Abstract

Background: Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE) characterized by decreased lung volumes and diaphragmatic weakness in a dyspneic patient. Chest wall dysfunction secondary to pleuritis is the most commonly proposed cause. In this case report, we highlight a new potential mechanism of SLS in SLE, namely diaphragmatic weakness associated with myositis with CD20 positive B-cell aggregates.

Case presentation: A 51-year-old Caucasian woman was diagnosed with SLE and secondary Sjögren's syndrome based on a history of pleuritis, constrictive pericarditis, polyarthritis, photosensitivity, alopecia, oral ulcers, xerophthalmia and xerostomia. Serologies were significant for positive antinuclear antibodies, anti-SSA, lupus anticoagulant and anti-cardiolopin. Blood work revealed a low C3 and C4, lymphopenia and thrombocytopenia. She was treated with with low-dose prednisone and remained in remission with oral hydroxychloroquine. Seven years later, she developed mild proximal muscle weakness and exertional dyspnea. Pulmonary function testing revealed a restrictive pattern with small lung volumes. Pulmonary imaging showed elevation of the right hemidiaphragm without evidence of interstitial lung disease. Diaphragmatic ultrasound was suggestive of profound diaphragmatic weakness and dysfunction. Based on these findings, a diagnosis of SLS was made. Her proximal muscle weakness was investigated, and creatine kinase (CK) levels were normal. Electromyography revealed fibrillation potentials in the biceps, iliopsoas, cervical and thoracic paraspinal muscles, and complex repetitive discharges in cervical paraspinal muscles. Biceps muscle biopsy revealed dense endomysial lymphocytic aggregates rich in CD20 positive B cells, perimysial fragmentation with plasma cell-rich perivascular infiltrates, diffuse sarcolemmal upregulation of class I MHC, perifascicular upregulation of class II MHC, and focal sarcolemmal deposition of C5b-9. Treatment with prednisone 15 mg/day and oral mycophenolate mofetil 2 g/day was initiated. Shortness of breath and proximal muscle weakness improved significantly.

Conclusion: Diaphragmatic weakness was the inaugural manifestation of myositis in this patient with SLE. The spectrum of myologic manifestations of myositis with prominent CD20 positive B-cell aggregates in SLE now includes normal CK levels and diaphragmatic involvement, in association with SLS.

Keywords: B cell; CD20 antigen; Case report; Dyspnea; Respiratory diaphragm; Systemic lupus erythematosus; Ultrasound.

Fig. 1

Course of pulmonary function tests over time. Course of pulmonary function tests over time, showing improvement with onset of prednisone and mycophenolate mofetil (arrow). TLC total lung capacity, FVC forced vital capacity, DLCO Diffusing capacity of the lung for carbon monoxide, FEV1 forced expiratory volume in 1 second

Fig. 2

B-mode ultrasound of the right hemidiaphragm. A ultrasound performed during end-expiration. B Ultrasound performed during maximal inspiration. The diaphragm is visible between two-hyperechoic lines representing the pleural and peritoneal membranes, respectively. At the end of maximal inspiration, lung tissue is visible in B, end-expiration diaphragm thickness was 1.90 mm. Di diaphragm, S subcutaneous tissue, Li liver, Lu lung

Fig. 3

Immunoprecipitation using radiolabeled K562 cell extracts. ³⁵S-methionine labeled human K562 cell lysates were immunoprecipitated by patients’ IgG and resolved by electrophoresis on 8% and 12.5% gels as previously described [25]. The 12.5% gels are used to provide better resolution of lower molecular mass proteins. The case report patient (Pt) is shown with comparator human sera bearing autoantibodies to U1RNP and survival of motor neuron (SMN) complex (lane 1), or anti-Ro60 (lane 2), and a negative human serum that did not immunoprecipitate any protein (lane 3)

Fig. 4

Muscle biopsy findings. A, B Hematoxylin & eosin staining showing dense endomysial lymphocytic aggregates (A), and perimysial fragmentation with plasma cell-rich perivascular infiltrates (B). C–F Immunohistochemical stains showing endomysial aggregates composed of predominant CD20 + B cells (C) and accompanying CD3 + T cells (D); diffuse upregulation of MHC class I (E); and perifascicular upregulation of MHC class II (F). Bar, A–D 50 μm (× 20 objective); E–F 100 μm (× 10 objective). Method for picture acquisition: Olympus BX46 microscope, with UPlanFL objectives with CellSens software (Olympus). The six images were placed in photoshop, in a 600dpi canvas, without further processing, to organize them and include lettering and bars. The final panel was exported as a jpg with 80% quality setting