Pulmonary Manifestations Of Rheumatoid Arthritis

Pulmonary Manifestations Of Rheumatoid Arthritis Dr. Gina Rohekar Overview  Major catagories of pulmonary disease associated with RA:       Pleural effusion Nodular lung disease Diffuse interstitial fibrosis BOOP (bronchiolitis obliterans organizing pneumonia) Pulmonary vasculitis Alveolar hemmorhage   Obstructive disease Infections History  Pulmonary  Diffuse manifestations of RA first described in 1948 by Ellman and Ball RA pulmonary fibrosis in 3 patients with Rheumatoid Arthritis And The Lung  Broad differential for pleuropulmonary disease in those with rheumatologic disorders:  Secondary to, or associated with the underlying rheumatic disease Secondary to immunosuppression (infection) Secondary to drug therapy Coexistant medical problems Overlap syndromes     Epidemiology  Difficult to characterize the epidemiology of pulmonary manifestations  Heterogenous  Early patient populations versus late disease versus hospital studies versus autopsy findings closely monitored and quickly treated  Community  Living  Patients Pleural Effusion  Most of RA common pulmonary manifestation incidental finding on CXR  Often  Post-mortem  Can studies  almost 50% of patients with RA have pleural effusions be uni- or bilateral, resolve, recur or persist for months Pleural Effusion  Patients  often asymptomatic ?Reduced physical activity prevents symptoms  Most common symptoms: pleuritic pain, dyspnea, cough effusions can precede or occur simultaneously with joint symptoms in 25% common in men with high RF titer and active arthritis  Pleural  More Pleural Effusion  Pleural effusion findings:  Exudative fluid  Low compliment level  Low glucose  High LDH  Low pH (<7.2)  High protein  RF level higher than serum RF level  High PMNs with RA cells and mononuclear cells  RA cells  polymorphonuclear leukocytes containing dense black granules  Release rheumatoid factor when disintegrated Unique pleural fluid findings in RA. Triad of comet cells, giant cells and background of granular material. Seen in as many as 80% of pleural specimens and are considered unique to RA. These findings are the result of the exfoliation of pleural components from regions of granulomatous pleuritis. The RA cell (or ragocyte) is a leukocyte with small cytoplasmic lipid inclusions containing RF. These may also be seen in TB. Source: Johns Hopkins Arthritis Pleural Effusion  Treatment:  None needed if asymptomatic thoracentesis or pleurodesis steroids steroids  Repeated  NSAIDs,  Intrapleural  Probably RA best to control the underlying Other Pleural Abnormalities  Empyema  Necrosis and cavitation of rheumatoid nodule leading to effusion fistula  Bronchopleural  Pyopneumothorax  Chronic pleural thickening  chyliform effusion or lung entrapment Nodular Lung Disease  Pulmonary nodules in RA first described by Caplan in 1953  Discovered multiple bilateral nodules on CXR of coal miners with RA  Caplan’s syndrome: Pneumoconiosis in RA patient leading to multiple basilar pulmonary nodules and mild airflow obstruction  Only  Can pulmonary manifestation specific for RA occur before, with or after the joint manifestations of RA  Usually asymptomatic, but can cause coughing and rarely hemoptysis Nodular Lung Disease Nodular Lung Disease  Usually  Range multiple, bilateral nodules from few millimeters to several centimeters in size occur just below the pleura or associated with interlobular septa lead to bronchopleural fistula, pneumothorax, abcess or cavition remain static, resolve, increase in size or undergo malignant transformation common in men, ?association with smoking  Typically  Can  Can  More Nodular Lung Disease Nodular Lung Disease Nodular Lung Disease  Histologically  Central similar to RA nodules found elsewhere necrosis, palisading epithelioid cells, mononuclear cell infiltrate and associated vasculitis syndrome  nodules often contain coal dust  Caplan’s Nodular Lung Disease Nodular Lung Disease  Management suffices  usually observation  Transbronchial biopsy or transthoracic needle aspiration to rule out malignancy or other pathologic process Diffuse Interstitial Fibrosis  Described in ~40% of RA patients similar to IPF  Frequently  Chronic inflammatory changes in the alveolar wall with the presence of large mononuclear cells in the alveolar spaces  As disease progresses  fibrosis with obliteration of alveoli and dilatation of bronchioles  Early disease tends to affect the lung bases; late disease affects the apices Diffuse Interstitial Fibrosis  More  Most common in those with severe RA modifiable risk factor: smoking  >25 pack-year smoking history significantly more likely to have radiographic evidence of ILD  More common age 50-60, in men and in seropositive and erosive joint disease occurs about five years after joint symptoms present, but can predate them  Usually Diffuse Interstitial Fibrosis  Occurs mostly in those with subcutaneous nodules and high RF  Symptoms:  Also:  CXR progressive SOBOE and productive cough most common increased RR, clubbing, crepitations at lung bases, pulmonary hypertension  Reticulated pattern with progression to fine nodularity and honeycombing Diffuse Interstitial Fibrosis  Histology:  Usual interstitial pneumonitis (UIP), the pathologic correlate of IPF, which is most common Nonspecific interstitial pneumonitis (NSIP) Lymphocytic interstitial pneumonitis (LIP) Desquaminative interstitial pneumonitis (DIP) Bronchiolitis obliterans with organizing pneumonia (BOOP) Mixed morphology      Diffuse Interstitial Fibrosis  Prognosis for IPF is poor, but appears better than  Treatment usually includes corticosteroids, azathioprine or other immunomodulating medications (e.g., cyclophosphamide) lung tranplantation Usually better results in those with RA associated interstitial fibrosis than those with IPF  Usually too many comorbidities for transplantation surgery (e.g., osteoporosis, decreased mobility)   ?Single  ?Newer therapies (e.g., TNF blockers) Diffuse Interstitial Fibrosis BOOP  Number  Study of studies have noted an association between RA and BOOP of open lung biopsies from 40 patients with parenchymal lung disease and RA  BOOP second most common finding following rheumatoid nodules present with cough, SOB, malaise, weight loss and fever noted on physical exam  Patents  Crackles BOOP  Diagnostic  ESR:  CXR:  PFTs: tests: usually elevated bilateral parenchymal opacities, often with preserved lung volume restrictive physiology with decreased DLCO and hypoxemia  HRCT:  uni- or bilateral consolidation Often patchy and peripheral BOOP  Biopsy shows patchy intraluminal polypoid plugs of immature fibroblast tissue within bronchioles  Terminal bronchioles and peribronchiolar alveolar spaces may also be involved BOOP  Prognosis  Most  If good for those patients who receive treatment respond to oral corticosteroid therapy not tolerated, cyclophosphamide used  Antibiotics not helpful Pulmonary Vasculitis  Vascular  inflammation can affect any organ site in those with RA Most commonly the skin  Seen  titers in patients with severe RA, high RF Usually other signs of systemic vasculitis in Caucasians, uncommon in those of African ancestry  Can lead to pulmonary hypertension  Usually Pulmonary Vasculitis  RA associated pulmonary vasculitis has been treated with corticosteroisds and cytotoxic medications (e.g., cylcophosphamide) and gold salts tried with varying results  Penacillamine Alveolar Hemorrhage  Diffuse  Causes   bleeding from the pulmonary vasculature leading to blood-filled alveoli a “classic” triad Hemoptysis Diffuse infiltrates  Anemia  Erythrocytes  and fibrin fill the airspaces Often also see hemosiderin-filled macrophages  88% of those with alveolar hemorrhage and RA have capillaritis limited to the alveolar wall Alveolar Hemorrhage  Diagnosis DLCO aided by measurement of  DCLO will be increased due to carbon monoxide binding to the erythrocytes in the alveoli Obstructive Pulmonary Disease  Found  Can in 38-68% of patients with RA be upper or lower obstruction  Upper obstruction more common in women and those with longstanding disease    Ankylosis of the cricoarytenoid joint Rheumatoid nodule on vocal cord Vasculitis of recurrent laryngeal or vagus nerves Obstructive Pulmonary Disease  Lower airway obstruction to estimate prevalence  Difficult  Some studies suggest as high as 60%, but prevalence in non-smokers 0-24% ? Association with underlying Sjögren’s syndrome   Primary abnormality on autopsy is fibrous narrowing or obliteration of airways 1-6 mm in diameter with SOB, crackles and high-pitched wheezes shows hyperinflated lung  Present  CXR Infections  Persistent  Many problem in those with RA confounding factors, especially corticosteroid or immunosuppressive medication  May mask the signs of infection  Lymphocyte  Patients abnormalities in RA? with RA have greater occurrence of bronchitis, bronchiectasis and pneumonia than controls with degenerative joint disease Drug Related Pulmonary Disease Drug Related Pulmonary Disease  Methotrexate:  Presents  Usually with dyspnea, cough and fever subacute  50% of cases diagnosed within 32 weeks of initiating MTX with MTX causes high rate of recurrence of lung injury of patients who develop lung disease due to MTX will die of this complication  Re-challenge  17% Summary  Patient with RA presenting with respiratory symptoms needs to be completely evaluated  Rheumatoid associated lung disease Pleural effusion Nodular lung disease Diffuse interstitial fibrosis BOOP (bronchiolitis obliterans organizing pneumonia) Pulmonary vasculitis Alveolar hemmorhage Obstructive disease Infections Summary  Also remember:  Pulmonary  Coexistent disease secondary to medications used to treat RA medical conditions (asthma, CHF) clinical syndromes  Overlapping Any Questions? 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