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A 26-Year-Old Woman With Systemic Lupus Erythematosus Presenting With Orthopnea and Restrictive Lung Impairment FREE TO VIEW

Tanmay S. Panchabhai, MD, FCCP; Debabrata Bandyopadhyay, MD; Kristin B. Highland, MD, FCCP; Neal F. Chaisson, MD; Loutfi S. Aboussouan, MD, FCCP
Author and Funding Information

CORRESPONDENCE TO: Loutfi S. Aboussouan, MD, FCCP, Cleveland Clinic, Department of Pulmonary Medicine, Respiratory Institute, 9500 Euclid Avenue /A90, Cleveland, OH, 44195


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(1):e29-e33. doi:10.1016/j.chest.2015.10.053
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A 26-year-old white woman diagnosed with systemic lupus erythematosus (SLE) presented with left shoulder pain and a three-pillow orthopnea. Lupus was diagnosed at age 21 years when she developed arthritis, and she has been maintained on prednisone (2.5 mg) and mycophenolate (500 mg bid). In the course of evaluating her new symptoms, imaging revealed a small left pleural effusion with exudative characteristics on a diagnostic thoracentesis, but there was no evidence of infection. Her immunosuppression treatment was increased to 1,000 mg bid of mycophenolate and 20 mg of prednisone. Three months later, she presented to our clinic with worsening six-pillow orthopnea, such that she usually slept with 45° truncal elevation on a recliner at night. She was unable to lie flat. Her dyspnea was worse in the mornings, and she described having to “gasp” for air.

Figures in this Article

The patient was afebrile, tachypneic (respiratory rate, 26 breaths/min), and anxious, with an oxygen saturation of 94% on room air. Chest auscultation was clear, with slightly diminished breath sounds at the bases. In the supine position, severe abdominal paradox was noted during inspiration.

Laboratory evaluation showed anemia (hemoglobin, 7.8 g/dL), leukopenia (WBC count, 2,580 k/μL), and microscopic hematuria and proteinuria. Inflammatory markers were elevated, with erythrocyte sedimentation rate of 85 mm/h and C-reactive protein level of 6.3 mg/dL. Serology showed a strongly positive antinuclear antibody of 12.7 (normal < 1.5 optical density ratio) and a markedly elevated anti-dsDNA (365 IU/mL). Antibodies against extractable nuclear antigens and myositis-specific antibodies were negative. Complement levels were normal (C3, 99 mg/dL; C4, 10 mg/dL). The chest radiograph and CT scan of the chest (Figs 1, 2) showed a small left pleural effusion and small lung volumes, with otherwise normal lung parenchyma. Pulmonary function tests (PFTs) (Table 1) revealed a restrictive ventilatory defect, with an FVC of 1.17 L in the sitting position (23% predicted), which decreased by 27% to 0.85 L in the supine position. The maximal inspiratory pressure and maximal expiratory pressure were 57% and 40% predicted, respectively. Evaluation of the diaphragms under fluoroscopy showed reduced downward excursion of both diaphragms, with the right diaphragm being the most impaired.

Figure 1
Figure Jump LinkFigure 1 Chest radiograph, posteroanterior (A) and lateral (B) views, revealing a small left pleural effusion.Grahic Jump Location
Figure 2
Figure Jump LinkFigure 2 CT scan of the chest showing a small left pleural effusion (A) with low lung volumes (B).Grahic Jump Location
Table Graphic Jump Location
Table 1 Pulmonary Function Tests

Dlco = diffusing capacity of the lung for carbon monoxide; DL/VA = diffusing capacity per unit alveolar volume; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; PFT = pulmonary function test.

What is the diagnosis?

Diagnosis: Shrinking lung syndrome

Pleurisy with or without pleural effusions is the most common pulmonary manifestation of SLE. Other pulmonary presentations include diffuse alveolar hemorrhage, acute lupus pneumonitis, pulmonary arterial hypertension, interstitial lung disease, and thromboembolic disease. SLS is a very rare presentation of SLE, occurring in 0.5% of patients with SLE. In 1965, Hoffbrand and Beck described this disease entity characterized by restrictive impairment on PFTs with progressive loss of lung volume and coined the term “shrinking lung syndrome.” Presenting symptoms include progressive dyspnea, orthopnea, and pleuritic chest pain. Dyspnea is generally worse in the supine position, with abdominal paradox noted in some cases. The time to symptom onset varies from being a presenting manifestation of SLE to 2 to 3 decades after the original diagnosis of SLE.

Many theories have been proposed for the mechanism behind shrinking lung syndrome. Initially, excessive surface tension from failure of surfactant production was proposed to result in microatelectasis and a consequent decrease in lung volume. Subsequently, reduced transdiaphragmatic pressure was seen in these patients, supporting a diagnosis of diaphragmatic dysfunction. Several other reports of SLS have also suggested that diaphragm weakness may be an important contributor. Although some authors have suggested that diaphragmatic myopathy occurs from corticosteroid use, the stabilization in lung function with augmented immunosuppression seen in some patients contradicts this. Phrenic neuropathy has also been implicated. Another hypothesis is that persistently low lung volumes may be the consequence of impaired inspiration as a result of pleural inflammation, which subsequently results in reduced lung compliance. However, autopsy studies have failed to show pleural fibrosis or adhesions to support this claim. Overall, the cause of SLS seems to be interplay between diaphragmatic dysfunction and pleural inflammation.

Treatment of SLS has focused on antiinflammatory therapy for lupus with incremental doses of prednisone with azathioprine, mycophenolate, or cyclophosphamide. There are also case reports using rituximab. Anecdotally, theophylline has been used because of its effect in supporting diaphragmatic contractility. Most patients respond to antiinflammatory therapies with improvement or stabilization in pulmonary function.

Since diaphragmatic dysfunction is believed to play a pivotal role in the pathophysiology of SLS, supporting the diaphragm with nocturnal noninvasive positive pressure ventilation (NIPPV) until diaphragmatic recovery occurs, as done in other neuromuscular diseases, makes intuitive sense.

Clinical Course

Given clinical and laboratory evidence for active SLE, the patient’s immunosuppression treatment was intensified to 1,000 mg bid of mycophenolate and 80 mg of prednisone. Following 2 months of increased immunosuppression, she failed to show any significant improvement in pulmonary function, suggesting ongoing respiratory and diaphragmatic muscle weakness (Table 1). Consequently, NIPPV in the form of bilevel positive airway pressure was initiated. She tolerated nightly NIPPV of 10/5 cm H2O very well, with improvement in sleep quality, refreshed feeling on awakening, and resolution of orthopnea.

She has been adherent to NIPPV, and PFTs at 1 year showed improvement in her restrictive pulmonary impairment with a corresponding improvement in the sitting to supine drop in FVC and an improvement in the inspiratory muscle strength. The decline in her FVC from sitting to supine position has progressively improved, as shown in Table 1. Her pleuritic chest and shoulder pain, however, persisted despite imaging evidence of resolution of the bilateral small pleural effusions. We plan to continue NIPPV and have reduced her immunosuppression to a stable maintenance dose of prednisone 10 mg and mycophenolate 1,000 mg bid.

  • 1.

    SLS is a rare manifestation of SLE with presenting features of orthopnea, restriction on PFTs, and diaphragmatic dysfunction in the absence of parenchymal abnormalities on imaging.

  • 2.

    Patients suspected of having SLS should have a thorough evaluation of diaphragmatic function, including sitting-supine spirometry, inspiratory and expiratory pressures, and fluoroscopy and/or ultrasound to evaluate for diaphragm function impairment.

  • 3.

    Treatment of SLS based on few cases reported in literature includes augmenting immunosuppression with prednisone and steroid-sparing agents like azathioprine, mycophenolate, cyclophosphamide, and/or rituximab.

  • 4.

    Supporting diaphragmatic function with theophylline has been reported. We report the usefulness of NIPPV in supporting the paretic diaphragms as in other neuromuscular disorders in addition to immunosuppressive therapies to prevent nocturnal hypoventilation and support quality of sleep

Financial/nonfinancial disclosures: None declared.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.


Figures

Figure Jump LinkFigure 1 Chest radiograph, posteroanterior (A) and lateral (B) views, revealing a small left pleural effusion.Grahic Jump Location
Figure Jump LinkFigure 2 CT scan of the chest showing a small left pleural effusion (A) with low lung volumes (B).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Pulmonary Function Tests

Dlco = diffusing capacity of the lung for carbon monoxide; DL/VA = diffusing capacity per unit alveolar volume; MEP = maximal expiratory pressure; MIP = maximal inspiratory pressure; PFT = pulmonary function test.

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