Respiratory Complications of

Rheumatic Diseases

Peter LuceConsultant in General and Chest Medicine

University Hospital Lewisham

Relevant Issues

Clinical• Imaging• Lung Function• BAL• Biopsy• Treatment

Diseases• Rheumatoid Arthritis• Scleroderma• SLE• Sjögren’s syndrome• MCTD• Dermatomyositis

Causes of diffuse parenchymal lung disease (DPLD) >400

Acute• Infection, Allergy, Toxins, Vasculitis, ARDS

Episodic• Eosinophilic pneumonia, Churg-Strauss,• Vasculitis, Extrinsic allergic alveolitis, • Cryptogenic organising pneumonia

Chronic secondary to environment• Dust, Fungi • Drugs - Antibiotics

- Anti-rheumatics: gold, penicillamine- Chemotherapy: bleomycin, methotrexate

Causes of diffuse parenchymal lung disease (DPLD) >400

Chronic with systemic disease• Connective tissue diseases

RA, AS, SLE, Scleroderma, Sjögren’s syndrome,MCTD, Polymyositis, Behçet’s

• Neoplastic• Vasculitis• Sarcoid• Inherited

Clinical Evaluation - I

Clinical Assessment• Detailed timescale• Get all old chest X-rays• Environmental, occupation, pets, travel• Smoking and drug history • Cardiac disease• HIV risk• Family history

Clinical Evaluation - II

Respiratory symptoms and signs• Dyspnoea• Cough, especially in lymphangitis, sarcoid,

CFA and COP• Pleurisy (50% in SLE, 25% in RA)• Chest pain - pneumothorax• Haemoptysis

Clinical Evaluation - III

Clinical Findings• Fine end respiratory crackles (up to 90%)• Clubbing

(50% in CFA, 75% in RA-associated lung disease)

• Pulmonary hypertension• Cor pulmonale

Laboratory Investigations

• full blood count and eosinophils• urea and electrolytes• liver function tests• rheumatoid factor• anti-nuclear antibodies• (ANCA, ABMA, ACE)

Imaging I

Diagnosis• Chest X-ray

– may be normal at presentation– very non-specific

• HRCT– 94% sensitive, 85% sensitive– radiation dose 7 times chest X-ray dose

Imaging II

Disease Activity and Diagnosis• HRCT very specific for CFA and FA in relation

to pre-existing rheumatic disease• Can delineate fibrosis• Traction bronchiectasis• Ground glass appearance of alveolitis• Peripheral fibrosis is better survival predictor

than central fibrosis

Imaging III

Benefits of HRCT• Increased likelihood of diagnosis from an

extensive disease and potential biopsy site• Clinical and HRCT should give 80% of correct

diagnoses in DPLD• Biopsy may not be needed• Valuable in determining activity and prognosis

Imaging IV

Other imaging• Gallium scanning• DTPA• PET• (MRI)

Lung function testingDiagnosis• Restrictive pattern commonest - often

combined with airflow obstruction• Spirometry and gas transfer best measure• Exercise testing not helpful• Cannot distinguish inflammation and fibrosis

Monitoring• Vital capacity and TLCO most appropriate

measures• Inadequate data as serial predictors

Bronchoalveolar lavage

• Increased granulocytes in fibrosing alveolitis with/without rheumatic disease

• Increased lymphocytes in granulomatous or drug-induced toxicity

• Helpful in diagnosis of infection or malignancy

• Role in monitoring unclear

Lung biopsy

• Needle biopsy useful for focal lesions only

• Transbronchial biopsy good for sarcoid, malignancy or COP

• Not useful for staging fibrosing alveolitis• Open lung biopsy or VATS

Rheumatoid Arthritis -Diffuse parenchymal lung disease

• Risk high in men, smokers, nodular RA, family history, high RF or ANA

• Severity of joint disease not predictor of DPLD• Differential diagnosis - infections, gold, MTXTreatment• Steroids alone (1 study) improved exercise

tolerance; COP markedly improved• Immunosuppressants, especially azathioprine,

improved exercise tolerance• Treat as CFA

Rheumatoid Arthritis -Other pulmonary manifestations

Pleural disease• pleural effusion 5%, pleuritic pain 20%• commoner in males• exudate with low glucose• rheumatoid factor usually in high titres

(careful with empyema)

Rheumatoid Arthritis -Other pulmonary manifestations

Pulmonary nodules• 1-2cms; may cavitate, cause haemoptysis,

cause pneumothorax or become colonised with aspergillus

Obliterative bronchiolitis• Progressive airflow obstruction• Primary or secondary to gold, sulphasalazine,

penicillamine or NSAID

Rheumatoid Arthritis -Other pulmonary manifestations

• Cricoarytenoid arthritisEspecially females in association with temporomandibular disease

• Vocal cord nodules• Pulmonary and pleural infections

Worse with steroids• Pulmonary arteritis • Lung cancer• Bullae and Pneumothorax

SLE - IPleural disease• Pleuritis in up to 50%, may be recurrent• Pleural effusion in 20%, usually exudate• Also associated with pericarditis• NSAIDs, rarely steroids and immunosuppressives

DPLD• Infection most common cause• Acute lupus pneumonitis 0.9% + alveolar

haemorrhage (17%) worse post partum• Chronic pneumonitis 13%• Treat as for CFS, results unclear

SLE - II

Other respiratory complications• Pulmonary hypertension• Pulmonary thromboembolism• Respiratory muscle involvement and

shrinking lung syndrome

Scleroderma -Interstitial fibrosis

• Interstitial fibrosis in 80%

• CXR abnormal in 13-78% but 44% with normal CXR at presentation have abnormal HRCT

• DLCO sensitive, associated with anti Scl-70; anti-centromere Ab often with normal DLCO

• DLCO<40% normal ⇒ 9% 5 year survival DLCO>40% normal ⇒75% 5 year survival

• Treatment - some evidence for steroids and cyclophosphamide

Scleroderma -Pulmonary Hypertension

• Pulmonary hypertension in 50% • Pulmonary artery pressure > 20mmHg at rest • Primary pulmonary hypertension or secondary to

cardiac or interstitial lung disease• 9% limited scleroderma have clinical pulmonary

hypertension• 65% limited scleroderma have pulmonary

hypertension on biopsy or PM• Isolated pulmonary hypertension, 40% 2yr survival

Scleroderma -Pulmonary hypertension

• Vasodilators• Calcium antagonists• Anticoagulants• Prostacyclin• Transplantation

Other rheumatic conditions

• Sjögren’s syndrome• Dermatopolymyositis• Ankylosing Spondylitis• Vascular disease

– Wegener’s granulomatosis– Churg-Strauss syndrome

Drugs and Interstitial Lung Disease

Pneumonitis• Methotrexate• Gold• Penicillamine• Cyclophosphamide• Chlorambucil• Azathioprine• Sulphasalazine• NSAID

Fibrosis• Methotrexate• Gold• Cyclophosphamide• Chlorambucil• Azathioprine• Sulphasalazine

Drugs and Interstitial Lung Disease

Bronchospasm

• Methotrexate• Salicylates• NSAID

BronchiolitisObliterans• Methotrexate• Cyclophosphamide• Salicylates• NSAID• Colchicine

The Future

• Increased understanding of relationship between – intracellular matrix– signalling proteins– fibroblast proliferation

• Possible roles for interferons and perfenidone