PULMONARY DISEASE IN RHEUMATOID ARTHRITIS
Magdie Kohn, M.D. May 28, 2002
CASE
ID RFR PMHx 83 F w/ RA transferred from North Bay Can MTX be D/Ced given new resp sx? (1) Rheumatoid Arthritis - Diagnosed ~35 yrs ago - Involves hands, UE joints, hips & knees - Flares typically q2-3mo, stable - Previous nodule in early 1980s
CASE
PMHx - Previously txed w/ Gold, Penicillamine, Chloroquine - Never on steroids - On MTX x 5-10 yrs (2) CAD (3) Paroxysmal AFib (4) Hypothyroidism (5) Osteoporosis - Compression #s, hip # (THR) , rib #s (6) HH Ø HTN/DM
CASE
Meds MTX 12.5 mg q1wk ECASA 650 mg bid Actonel 5 mg OD Digoxin 0.125 mg OD Norvasc 5 mg OD Sotalol 80 mg OD Isordil 5 mg tid L-thyroxine 0.088 mg OD Folate, Vit D, Tylenol
CASE
HPI RA has been stable for years Admitted for 8 month hx of progressive SOBOE and decreased exercise tolerance Denies PND/orthopnea/worsening angina ?Fever but +chills, + drenching night sweats Decreased appetite, ~15 lb wt loss Mild hoarseness and dysphagia
CASE
HPI… cont’d Ø eye problems/rashes/other GI ssx Denies sicca ssx No recent travel No known hx TB or exposure to high risk individuals
CASE
Social Hx Lifelong non-smoker Minimal EtOH Widowed and lives alone in North Bay
CASE
O/E Thin but comfortable, no resp distress VS – Afebrile, SaO2 96% RA H&N – Eyes OK, Ø LN, Ø nasal/oral lesions Resp – Decreased BS L base, scant crackles R base, Ø wheezing, Ø clubbing CVS - JVP not elevated, HS N, +S4, Ømur/rubs Abdo – Unremarkable Skin – Ø rashes/skin lesions
CASE
O/E MSK L hip – reduced IR and ER L knee – Ø redness/swelling/warmth Mildly tender at tibial plateau Ø stress pain Multiple nodules primarily in UE joints & distal Ulnar deviation and MCP subluxation
CASE
Labs CBC N except lymphopenia (4.2/0.83) Lytes, Renal Fxn, Liver Enzymes, Ca Profile N ESR elevated at 81 Protein Electrophoresis shows broad band in γ region but no spike Sputum C&S negative, TB pending
CASE
Imaging
CXR Spiral CT
OVERVIEW
Lung Diseases Associated w/ RA: Interstitial Lung Disease (ILD) Pleural disease Rheumatoid Nodules Bronchiolitis Obliterans w/ Organizing Pneumonia Airway disease Vasculitis Pulmonary Hypertension Medication-Induced
INTERSTITIAL LUNG DISEASE
EPIDEMIOLOGY
The most common manifestation of lung disease in RA patients (Clin Chest Med 98, Am J Resp Crit Care Med 97) Some reports have estimated the prevalence to be 34-58% of patients Possible Risk Factors: severe RA, history of smoking, middle age, men, RF+
INTERSTITIAL LUNG DISEASE
CLINICAL PRESENTATION
Often asymptomatic until disease is advanced TNFα may play a significant role in pathogenesis SOBOE Non-productive cough Fever and chest pain less common Most patients have bibasilar crackles and clubbing on physical examination
INTERSTITIAL LUNG DISEASE
DIAGNOSIS
PFTs (restrictive pattern) Imaging (CXR, HRCT-often bilateral & peripheral) BAL (lymphocytosis, TNFα, fibronectin, superoxide anion, collagenase activity) Pathology (variable – reticular, reticulonodular, honeycombing)
INTERSTITIAL LUNG DISEASE
TREATMENT
Data includes mainly uncontrolled studies and case reports Steroids have yielded some positive results Typical dose of 1-1.5 mg/kg/d Cyclophosphamide, MTX, Imuran and Chloroquine have also been used w/ varying success
PLEURAL DISEASE
Common in RA, many patients are asymptomatic Autopsy series showed disease in 38-73% of patients (Ball Clin Rheum 1993) More common in middle aged males w/ active disease and subcutaneous nodules Presentation typically as pleuritis with or without pleural effusion Complications may include:pneumothorax, bronchopleural fistula and empyema May co-exist w/ nodules or ILD
PLEURAL DISEASE
Clinical Features: chest pain, SOB and fever are most common Pleural fluid analysis: WBC>5-10,000, low glucose, low pH, elevated protein and LDH, WBC w/ inclusion bodies/”RA cells” Need to differentiate effusions from infectious and malignant ones Tx: Usually resolve spontaneously, treat symptoms, NSAIDs, steroids
RHEUMATOID NODULES
Thought to be the only pulmonary manifestation that is specific for RA Occur ~20% RF+ patients Typically found subpleural or within the interlobular septae, peripheral in RUL, LUL and RML Pathology: same as other rheumatoid nodules, central necrosis w/ palisading epitheloid cells, mononuclear infiltrate, associate vasculitis Usually asymptomatic unless complications develop, follow w/ serial CXRs
RHEUMATOID NODULES
AIRWAYS DISEASE
UPPER AIRWAY DISEASE
Cricoarytenoid involvement is common and occurs ~75% of patients (J Rheum 1986) Most patients are asymptomatic SSx: throat pain/fullness, hoarseness, dysphagia, odynophagia, SOB, pain on coughing/speaking Dx: laryngoscopy, spirometry, CT scan Tx: anti-inflammatory therapy for acute attacks, more definitive therapy if chronic obstruction
AIRWAYS DISEASE
LOWER SMALL AIRWAYS DISEASE
Common in RA patients, association not well understood due to confounding factors Bronchiectasis may also be present Possible mechanisms: increased bronchial reactivity, recurrent infections, etc Symptoms similar to those without RA Tx: inhaled bronchodilators, steroids
BOOP
A proliferative bronchiolitis that typically occurs in response to a various of triggers, ie; infectious, etc It has been associated w/ RA itself as well as some of its therapies More common in women and RF+ disease SSx: fever, wt loss, malaise, cough, SOB, hypoxia ESR often elevated PFTs: restrictive picture, decreased DLCO HRCT: patchy consolidation often peripheral
BOOP
BOOP
Definitive diagnosis is sometimes difficult and lung biopsy may be required Treatment studies have been limited, small patient numbers Most patients respond to steroids, 1-1.5 mg/kg/d Cyclophosphamide often used if steroid failure
METHOTREXATE
EPIDEMIOLOGY
1ST used for RA in 1951 FDA approval in US in 1988 for RA Pulmonary toxicity first reported in the treatment of childhood leukemia in 1968 It is estimated that 1-5% patients treated w/ MTX for RA develop pulmonary toxicity (Clin Chest Med 1998)
METHOTREXATE
PATHOGENESIS
Not completely understood Unlikely related to folate deficiency Typically a hypersensitivity reaction Both an immune-mediated injury as well as direct cytotoxicity have been suggested Idiosyncratic, reintroduction of the drug is not always followed by recurrent injury
METHOTREXATE
PATHOLOGY
Non-specific evidence of hypersensitivity Alveolitis w/ epithelial cell hyperplasia The cytology is often dysplastic Small poorly formed granulomas and eosinophilic infiltration may be present
METHOTREXATE
RISK FACTORS
(Ann Intern Med 1998) Older age (OR 5.1) Pleuropulmonary involvement (OR 7.1) Previous DMARDs (OR 5.6) Hypoalbuminemia (OR 19.5) Diabetes Mellitus (OR 35.6)
METHOTREXATE
CLINICAL PRESENTATIONS
Acute/subacute interstitial pneumonitis Infections (PCP, crypto, aspergillosis, histo, parainfluenza, CMV) Other: BOOP, pulmonary fibrosis, lymphoma
METHOTREXATE
CLINICAL FEATURES
SOB Non-productive cough Fever and chills Malaise Crackles and cyanosis on physical examination
METHOTREXATE
DIAGNOSIS
History and physical examination CXR: diffuse bilateral interstitial infiltrates HRCT: ground glass, fibrosis Gallium: often abnormal BAL: lymphocytosis, low CD4/CD8 ratio, eosinophilia
METHOTREXATE
METHOTREXATE
Revised Searles & McKendry Criteria (J Rheum 1987):
Major Criteria: (1) Histopathology (2) Radiology (3) Biochemistry Minor Criteria: (1) SOB < 8 wks (2) Non-productive cough (3) SaO2 ≤ 9% (4) DLCO ≤ 70% (5) WBC ≤15
“Definite” if: Major 1/Major 2&3 plus 3/5 Minor criteria “Probable” if: Major 2&3 and 2/5 Minor criteria
METHOTREXATE
TREATMENT
Supportive therapy Withdrawal of MTX typically initial step Steroids may be helpful in hastening recovery Prognosis is generally quite good but one series reported a 17% mortality (Arthritis and Rheumatism 1997)
GOLD
As with MTX, also typically characterized by an acute pneumonitis, rarely obliterative bronchiolitis A relative rare complication Toxicity after 2-4 months of therapy or cumulative dose of 500 mg SSx: fever, cough, SOB, skin rash, eosinophilia Tx: D/C Gold tx, steroids may be necessary
PENICILLAMINE
Presentations include: ILD, obliterative bronchiolitis and pulmonary-renal syndrome w/ hemorrhage into alveoli Often difficult to distinguish from RA-lung disease Prognosis of OB is poor, steroids not very helpful
BACK TO CASE
Review:
83 F w/ RA > 30 years, non-smoker Previous rheumatoid nodules and pleural mass 8+ months of fever, chills, SOB, productive cough, weight loss RA appears quiescent
BACK TO CASE
Possibilities: - Progressive ILD - MTX lung injury - BOOP - Non RA related (infection, CA, etc.) Plan: - Hold MTX and watch for improvement - Transthoracic biopsy of pleural based mass