Intra-thoracic rheumatoid arthritis: Imaging spectrum of typical findings and treatment related complications

Abstract

Non-cardiac thoracic manifestations of rheumatoid arthritis (RA) cause significant morbidity and mortality among RA patients. Essentially all anatomic compartments in the chest can be affected including the pleura, pulmonary parenchyma, airway, and vasculature. In addition, treatment-related complications and opportunistic infections are not uncommon. Accurate diagnosis of intra-thoracic disease in an RA patient can be difficult as the radiologic findings may be nonspecific and many of these conditions may coexist. This review article serves to highlight the multitude of RA-related intra-thoracic pathological processes, emphasize differential diagnosis, diagnostic conundrums and discuss how tailoring of CT imaging and image-guided biopsy plays a key role in the management of RA-related pulmonary disease.

Keywords: Drug toxicity; Interstitial lung disease; Pleural disease; Rheumatoid arthritis; Rheumatoid nodule.

Fig. 1

Empyema necessitans (extrapleural transthoracic extension of empyema). 62-year-old female with history of rheumatoid arthritis complicated by empyema, recalcitrant to multiple chest tube drainages. Contrast-enhanced CT shows multi-loculated pleural collection with enhancing pleural abnormality (arrow) extending into the chest wall (arrowheads). Teaching point: Nombination of pleuritis, underlying parenchymal changes and treatment-related immunosuppression predispose patients to severe empyema.

Fig. 2

Nodular pleural thickening simulating malignancy. 70-year-old female with history of rheumatoid arthritis (RA) and left breast cancer status post radiation therapy. (a) CT. Nodular left pleural thickening (arrows) in this patient is an indeterminate finding that may represent rheumatoid inflammation, malignancy or infection. (b) Pleural biopsy showed necrotizing granulomatous inflammation without evidence of malignancy. Gram, fungal, and acid-fast stains were negative for organisms. Teaching point: Nodular pleural thickening in RA patients frequently mimics malignancy such as metastatic disease and mesothelioma.

Fig. 3

Pleural thickening and rheumatoid arthritis associated interstitial lung disease (RA-ILD). 66-year-old female with history of rheumatoid arthritis. (a) CT. Reticular abnormality, traction bronchiectasis and peripheral groundglass opacities in both lower lobes (arrowheads), consistent with RA-ILD. (a and b) CT. A pleural-based ovoid soft tissue mass in the left lower hemithorax (arrows). (c) CT-guided core-needle biopsy was consistent with eosinophillic pleuritis and pleural fibrosis. Teaching point: Mass-like pleural thickening in rheumatoid arthritis patients may mimic malignancy including primary pleural malignancy and often requires percutaneous core needle biopsy for accurate diagnosis.

Fig. 4

Ruptured necrobiotic nodules complicated by hydropneumothorax and empyema. 35-year-old female with rheumatoid arthritis. (a) CT. A ruptured subpleural necrobiotic nodule in the right lower lobe (white arrowhead) with associated small hydropneumothorax (black arrowhead). (b) CT few weeks later. Formation of bronchopleural fistula adjacent to the necrobiotic nodule (black arrow). (c) CT few weeks later following chest tube drainage, open thoracotomy and talc pleurodesis (white arrow). Enlarging hydro-pneumothorax (black arrowheads) secondary to underlying bronchopleural fistula and marked pleural thickening due to empyema resistant to treatments. Teaching point: Subpleural location of cavitary necrobiotic rheumatoid nodules predisposes the patient to recurrent pneumothoraces and infection within the pleural space.

Fig. 5

Treatment of recurrent hydropneumothorax and pleural effusion with surgical thoracostomy and creation of Clagett window. 57-year-old female with advanced rheumatoid arthritis on methotrexate with recurrent right hydropneumothorax and left rheumatoid pleural effusion, resistant to conventional management. (a) CT. Latissimus dorsi muscle flap in the left chest wall (black arrow). Necrobiotic nodules in both lungs (arrowheads). (b) CT. Packing material in the right thoracic window (white arrow). Teaching point: Recurrent hydropneumothoraces and empyemas recalcitrant to conservative management may require extensive surgery such as surgical thoracostomy and thoracomyoplasty.

Fig. 6

Usual interstitial pneumonia (UIP). 63-year-old female with long-standing history of rheumatoid arthritis. (a, b) CT. Bilateral lower lobe predominant subpleural reticular opacity and honeycombing. Biopsy confirmed the diagnosis of UIP. Teaching point: Multilicity of CT patterns may be seen; however, UIP is the most common pattern of interstitial lung disease in rheumatoid arthritis patients.

Fig. 7

Nonspecific interstitial pneumonia (NSIP). 76-year-old male with longstanding history of rheumatoid arthritis with subcutaneous rheumatoid nodules. (a and b) CT. Moderate peripheral reticular opacities and groundglass opacities with minimal honeycombing predominantly in the lower lobes. Biopsy showed changes most consistent with fibrotic NSIP. Teaching point: NSIP and UIP are common patterns of rheumatoid-associated inter-stitial lung disease. NSIP and UIP can have overlapping imaging features. In such cases, biopsy is required to make the diagnosis.

Fig. 8

Organizing pneumonia. 49-year-old female with RA on etanercept presenting with chest heaviness and nonproductive cough. (a) Initial CT. Bilateral peribronchial and subpleural consolidation with associated architectural distortion and traction bronchiectasis, which did not improve with antibiotics. Bronchoscopy was negative for infection. Wedge biopsy was consistent with organizing pneumonia. (b) CT chest few months later. Significant worsening of disease correlating with patient's declining pulmonary function and respiratory failure. Teaching point: Organizing pneumonia mimics pneumonia; hence, if the diagnosis is suspected clinically, prompt bronchoscopy should be performed to rule out infection before initiating steroids.

Fig. 9

Large airway disease and progressive bronchiectasis. 58-year-old female with RA and severe bronchiectasis with superimposed MAI infection. (a) CT. Cylindrical bronchiectasis (arrowheads) with mosaic attenuation pattern. (b) CT obtained 6 years later. Progression of bronchiectasis, now varicose and cystic (arrows). Persistent areas of mosaic attenuation in both lungs suggest air trapping due to small airway involvement. Teaching point: Rheumatoid arthritis is an important cause of non-cystic fibrosis bronchiectasis, which can predispose to subsequent infection.

Fig. 10

Small airway disease, follicular bronchiolitis. 40-year-old female with rheumatoid arthritis whose pulmonary function test showed marked obstructive pattern. (a) CT. Mild bronchial wall thickening and mosaic attenuation in both lungs suggesting air trapping. (b and c), Transbronchial biopsy. Dense peribronchial lymphoid infiltrate with follicular hyperplasia, causing bronchiolar luminal narrowing and obliteration. Teaching point: Imaging findings in symptomatic patients with small airways disease can be very subtle. Tailoring of CT protocols and use of paired inspiratory and expiratory imaging is helpful to accentuate air trapping.

Fig. 11

Mixed small airway and small vessel disease. 44-year-old male with rheumatoid arthritis on prednisone and methotrexate with acute on chronic dyspnea, found to have pulmonary hypertension. (a and b) CT. Predominantly peripheral consolidation and groundglass opacities (arrows). Infection screen was negative. Open lung wedge biopsy demonstrated bronchiolitis with acute and chronic inflammation, significant pulmonary arteriolar disease with medial hypertrophy and intimal proliferation out of proportion to the airway disease. Pulmonary hypertension was thought to be secondary to vascular involvement by RA. Teaching point: Small vessel disease may manifest as mosaic perfusion and pulmonary arterial hypertension or mixed consolidative and groundglass abnormality due to hemorrhage secondary to capillaritis.

Fig. 12

Methotrexate-induced acute hypersensitivity pneumonitis. 56-year-old woman who was started on methotrexate few weeks prior to presenting with worsening dyspnea. CT. Bilateral poorly defined ground-glass attenuation (arrows). Differential diagnosis includes RA-related interstitial lung disease, opportunistic infection, and adverse drug reaction. Radiologic abnormality and symptoms resolved following withdrawal of methotrexate. Teaching point: Drug toxicity may mimic infection. Temporal association with treatment history helps in making a diagnosis.

Fig. 13

Etanercept causing mediastinal adenopathy. 56-year-old male with severe rheumatoid arthritis (RA) on etarnercept. (a and b) CT. Multiple moderately enlarged mediastinal lymph nodes (arrowheads). Lymph node biopsy was performed to exclude lymphoproliferative disease. (c and d) Low power (20×) & high power (200×) images of mediastinal nodes showed non-caseating granulomatous inflammation. Teaching point: Mediastinal nodal enlargement may be seen in RA patients due to underlying connective tissue disorder and RA-related interstitial lung disease; however, progressive nodal enlargement raises suspicion for malignancy or sarcoidosis. Knowledge of treatment history with drugs such as TNF-α antagonists may avoid invasive procedures in select patients.

Fig. 14

Aspergillosis. 57-year-old female with history of rheumatoid arthritis (RA). CT. Focal right upper lobe consolidation (arrow) represents invasive aspergillosis. Aspergillus was isolated from bronchoalveolar lavage. Peripheral subpleural reticulation and honeycombing (arrowheads) is consistent with RA-related interstitial lung disease (RA-ILD). Diffuse groundglass opacity in both lungs was thought to be due to pulmonary edema. Teaching point: A variety of processes can be seen in RA patients, including severe RA-ILD, superimposed infection related to immunosuppression, all contributing to respiratory failure.

Fig. 15

Angioinvasive aspergillosis. 52-year-old female with history of rheumatoid arthritis (RA) with fever, shortness of breath and seizure. (a) CT. Consolidation with cavitation in the right upper lobe represents invasive aspergillosis (arrows). Aspergillus was isolated from bronchoalveolar lavage. (b) Contrast-enhanced T1-weighted MR image of the brain. Multiple enhancing cerebral foci (arrowheads) were presumed to represent angioinvasive aspergillosis. Teaching point: Opportunistic infection secondary to immunosuppression is not uncommon among RA patients.

Fig. 16

Mycobacterium avium-intracellulare (MAI) infection. CT. Thick-walled cavitary lesion in the left lower lobe (arrow) in an asymptomatic patient. Biopsy showed abscess with necrotizing granulomata and associated acid-fast bacilli. Note also mosaic attenuation suggesting air trapping, consistent with the patient's severe obstructive ventilatory deficit (FEV1 <35% predicted). Teaching point: New large cavitary lesion in a rheumatoid arthritis patient is suspicious for infection such as tuberculosis and atypical mycobacterial infection. Multiple small cavitary nodules may be due to rheumatoid nodules, drug-related nodulosis or septic emboli.