History

Fact Explanation
History rheumatoid arthritis [4] Rheumatoid arthritis is a chronic systemic autoimmune disease characterized by joint inflammation and extra-articular manifestations. Interstitial lung disease (ILD) is a recognized complication of rheumatoid arthritis (RA) causing significant increased morbidity and mortality. [1] Main lung pathology is usual interstitial pneumonitis (UIP). Other manifestations includes bronchiectasis, bronchiolitis, and pulmonary nodules. [1] Lung disease is related to two factors. One is disease itself causing lung problems and the other thing is drugs such as disease modifying antirheumatoid medications causing lung disease. All areas of the lung such as pleura, airways, parenchyma, and vasculature are vulnerable for interstitial and pleural disease. The severity and long duration of joint disease is associated with the increased risk for the lung disease. [3]
Use of disease modifying antirheumatoid medications(DMARDS) [4] Drugs like methotrexate, gold, penicillamine and etanercept etc have a potential for causing drug-induced interstitial pneumonitis. Leflunomide is unlikely to cause lung problems compared to methotrexate. Chronic prednisone use has shown to increase the risk pneumonia in RA patients. Doses greater than 10 mg/day may double this risk. [1,2]
Shortness of breath [5] Interstital lung disease is a recognized complication of the rheumatoid arthritis. Patients sometimes may not complain dyspnea due to an overall decrease in physical activity with advanced arthritic symptoms. [1]
Cough [1] Usually presents with non-productive dry cough [1,5] Productive sputum may be associated with bronchiectasis.
Fever [2] Fever may be an indication for an infectious etiology. [2]
Weight loss [2] Bronchiectasis is a common finding in these people. Rheumatoid arthritis also increases the risk of lung malignancy. [2]
Smoking Smoking can trigger alveolar epithelial cell apoptosis and enhance the disease progression. [7] Citrullination of proteins in the lung, frequently thought to be incited by smoking, which will lead to the production of anticitrullinated protein antibodies (ACPAs)that may important in the pathogenesis of lung disease.
Other extra-articular manifestations [1,4] Rheumatoid arthritis is a systemic disease affecting the heart, vascular system, skin, kidney, nerves, and eyes. Kidney involvement may cause proteinuria and kidney failure. [1]
Recurrent infections [6] Pancytopenia can be seen in these patients, [5] Reduced white cell count may predispose to recurrent infections. Rheumatoid arthritis itself is a factor for reduced immunity and immunosuppressive treatment will also be a contributory factor. Recurrent infections
References
  1. HAMBLIN MARK J., HORTON MAUREEN R.. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma. Pulmonary Medicine [online] 2011 December, 2011:1-12 [viewed 17 August 2014] Available from: doi:10.1155/2011/872120
  2. SCOTT DAVID L. Interstitial lung disease and disease modifying anti-rheumatic drugs. The Lancet [online] 2004 April, 363(9416):1239-1240 [viewed 17 August 2014] Available from: doi:10.1016/S0140-6736(04)15969-2
  3. KIM EUNICE J.. Rheumatoid Arthritis-Associated Interstitial Lung Disease. Chest [online] 2009 November [viewed 17 August 2014] Available from: doi:10.1378/chest.09-0444
  4. BROWN EM, GARNEAU KL, TSAO H, SOLOMON DH. DMARD non-use in low-income, elderly rheumatoid arthritis patients: results of 86 structured interviews Arthritis Res Ther [online] 2014, 16(1):R30 [viewed 10 September 2014] Available from: doi:10.1186/ar4459
  5. SIDHU HS, BHATNAGAR G, BHOGAL P, RIORDAN R. Imaging Features of the Pleuropulmonary Manifestations of Rheumatoid Arthritis: Pearls and Pitfalls J Clin Imaging Sci [online] :32 [viewed 10 September 2014] Available from: doi:10.4103/2156-7514.82244
  6. BROWN KK. Rheumatoid Lung Disease Proc Am Thorac Soc [online] 2007 Aug 15, 4(5):443-448 [viewed 10 September 2014] Available from: doi:10.1513/pats.200703-045MS
  7. BEHR J. The Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis Dtsch Arztebl Int [online] 2013 Dec, 110(51-52):875-881 [viewed 15 September 2014] Available from: doi:10.3238/arztebl.2013.0875

Examination

Fact Explanation
Clubbing Rheumatoid lung disease is associated with bronchiectasis. [1,5]
Dyspnea [5] Lung fibrosis may damage the alveolar capillary membrane causing reduced gas exchange. It may be rapidly progressive dyspnea. [5]
Hoarseness [5] Due to the sclerosis of the cricoarytenoid joint. [1]
Features of lung fibrosis [5] -Tracheal deviation to affected side -reduced lung expansion -Fine end inspiratory crackles Due to lung fibrosis [3]
Inspiratory crackles [2] May be bilateral fine crepitations in the lung fibrosis where as bronchiectasis may produce coarse crepitations. [2]
Joint involvement and joint deformities [4] Rheumatoid arthritis causes symmetrical peripheral poluarthritis [4] with the involvement of the small joints of hand and feet, mainly metarcarpophalangeal, proximal interohalangeal joints, wrist, and metatarsophalangeal joints. Joints will be swollen and tender. Other joints such as elbow, knee, shoulders, spine are occasionally involved. Chronic inflammation of the joints can lead to various joint deformities including boutonnieres, swan neck and ulnar deviation of the wrist.
Subcutaneous nodules [4] Skin may contained nodules[4] which may sometimes get ulcerated.
Tachycardia and arrhythmias [6] Involvement of the cardiac tissue may affect the electrical function of the heart. [6]
Focal neurological signs Atlanto-axial joint involvement affects the spinal cord. Haemorrhagic stroke is also common in these patients. [7]
Splenomegaly [8] Neutropenia together with splenomegaly in these patients is called, felty’s syndrome.[8]
References
  1. HAMBLIN MARK J., HORTON MAUREEN R.. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma. Pulmonary Medicine [online] 2011 December, 2011:1-12 [viewed 17 August 2014] Available from: doi:10.1155/2011/872120
  2. KIM EUNICE J.. Rheumatoid Arthritis-Associated Interstitial Lung Disease. Chest [online] 2009 November [viewed 17 August 2014] Available from: doi:10.1378/chest.09-0444
  3. WALKER WC, WRIGHT V. Diffuse interstitial pulmonary fibrosis and rheumatoid arthritis. Ann Rheum Dis [online] 1969 May, 28(3):252-259 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1031173
  4. SURESH E. Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know J R Soc Med [online] 2004 Sep, 97(9):421-424 [viewed 10 September 2014] Available from: doi:10.1258/jrsm.97.9.421
  5. SIDHU HS, BHATNAGAR G, BHOGAL P, RIORDAN R. Imaging Features of the Pleuropulmonary Manifestations of Rheumatoid Arthritis: Pearls and Pitfalls J Clin Imaging Sci [online] :32 [viewed 10 September 2014] Available from: doi:10.4103/2156-7514.82244
  6. KAPLAN MJ. Cardiovascular complications of Rheumatoid Arthritis - Assessment, prevention and treatment Rheum Dis Clin North Am [online] 2010 May, 36(2):405-426 [viewed 10 September 2014] Available from: doi:10.1016/j.rdc.2010.02.002
  7. TURESSON C, MCCLELLAND RL, CHRISTIANSON TJ, MATTESON EL. Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis Ann Rheum Dis [online] 2007 Jan, 66(1):70-75 [viewed 10 September 2014] Available from: doi:10.1136/ard.2006.052506
  8. SANDUSKY WR, RUDOLF LE, LEAVELL BS. Splenectomy for control of neutropenia in Felty's syndrome. Ann Surg [online] 1968 May, 167(5):744-751 [viewed 10 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387126

Differential Diagnoses

Fact Explanation
Bronchiectasis [4] In bronchiectasis, there is an abnormal and permanent dilatation of conducting airways. [4] Bronchiectasis patients often have a long-term history of cough and daily mucopurulent sputum production. In an acute exacerbation, they usually develops hemoptysis from airway damage, thick foul smelling sputum and increased sputum production over the baseline. In pneumonia, the sputum production is acute in onset and it may be rusty sputum. They are prone to get recurrent respiratory tract infections. [4] On examination they have wasting, pallor and clubbing. These patients are also vulnerable to get infections of the lung.
Idiopathic Pulmonary fibrosis [3] There is progressive fibrosis due to the proliferation of the fibroblasts in the lung parenchyma. They also can present the respiratory features like cough, shortness of breath and wheezing along with signs of consolidation. There will be diffuse pulmonary infiltrates on chest x-ray with associated fibrosis. [1] Exact diagnosis requires radiological (HRCT) or histological evidence. [3]
Hypersensitivity Pneumonitis [2] This occurs due to the exposure to various allergens, and they present with respiratory symptoms such as cough , shortness of breath and wheezing. Sometimes they also can develop systemic features like fever and weight loss. [3] Blood allergen specific antibody level may be elevated. It may present as acute, subacute or chronic form. This occur due to the exposure to various allergens, and they present with respiratory symptoms such as cough , shortness of breath and wheezing. Sometimes they also can develop systemic features like fever and weight loss. [2] Blood allergen specific antibody level may be elevated. It may present as acute, subacute or chronic form.
References
  1. GROSS THOMAS J., HUNNINGHAKE GARY W.. Idiopathic Pulmonary Fibrosis. N Engl J Med [online] 2001 August, 345(7):517-525 [viewed 27 June 2014] Available from: doi:10.1056/NEJMra003200
  2. LACASSE YVES, GIRARD MéLISSA, CORMIER YVON. Recent Advances in Hypersensitivity Pneumonitis. Chest [online] 2012 July [viewed 27 June 2014] Available from: doi:10.1378/chest.11-2479
  3. BEHR J. The Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis Dtsch Arztebl Int [online] 2013 Dec, 110(51-52):875-881 [viewed 10 September 2014] Available from: doi:10.3238/arztebl.2013.0875
  4. HABESOGLU MA, UGURLU AO, EYUBOGLU FO. Clinical, radiologic, and functional evaluation of 304 patients with bronchiectasis Ann Thorac Med [online] 2011, 6(3):131-136 [viewed 10 September 2014] Available from: doi:10.4103/1817-1737.82443

Investigations - for Diagnosis

Fact Explanation
Rheumatoid factor [4] This is not a specific investigation for rheumatoid arthritis. [6] But is present in nearly 80% of the patients. It is also an antibody mainly belongs to IgG , where there is an excessive production or reduced clearance than normal people.
Anticitrullinated protein antibodies (ACPAs) [4] These are antibodies to citrullinated peptides and they are quite specific for rheumatoid arthritis. ACPAs[4] is involved in the synovial inflammation through the deposition of immune complexes and targeting of synovial antigens. Presence of this indicates a poor prognosis.
X-ray of the joints [4] Inflammation of the synovial joints may affect the joint cavity and the surrounding bone and cartilage leading to periarticular osteopenia [4] and bone resorption.
Chest X-ray [2] This is the initial investigation of choice. [5] Lung fibrosis,Pleural effusion and thickening of pleura can be seen in the chest x-ray.Also pulmonary hypertension secondary to lung fibrosis may be a feature.Caplan's syndrome is a condition with peripheral, well-defined nodules in the lung parenchyma.[5] Even normal chest x-ray may have airflow obstruction. [5]
High-resolution chest CT (HRCT) [2] Demonstrates increased reticular markings, ground-glass opacities and/or consolidation bilaterally with or without honeycombing consistent with an interstitial lung . [1,2] Other findings include pleural involvement, rheumatoid nodules, bronchiectasis, emphysema, or even bronchiolitis. Subpleural consolidation with patchy ground glass infiltrates areseen in bronchiolitis obliterans-organizing pneumonia.
Open lung biopsy [2] This is the is the only definitive procedure which has the ability to accurately diagnose an interstitial lung disease. This is rarely done. [1]
Bronchoscopy [1] Bronchoalveolar lavage cell count may be useful to evaluate the infectious aetiology in the presence of fever. [1]
References
  1. HAMBLIN MARK J., HORTON MAUREEN R.. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma. Pulmonary Medicine [online] 2011 December, 2011:1-12 [viewed 17 August 2014] Available from: doi:10.1155/2011/872120
  2. KIM EUNICE J.. Rheumatoid Arthritis-Associated Interstitial Lung Disease. Chest [online] 2009 November [viewed 17 August 2014] Available from: doi:10.1378/chest.09-0444
  3. WALKER WC, WRIGHT V. Diffuse interstitial pulmonary fibrosis and rheumatoid arthritis. Ann Rheum Dis [online] 1969 May, 28(3):252-259 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1031173
  4. SURESH E. Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know J R Soc Med [online] 2004 Sep, 97(9):421-424 [viewed 10 September 2014] Available from: doi:10.1258/jrsm.97.9.421
  5. SIDHU HS, BHATNAGAR G, BHOGAL P, RIORDAN R. Imaging Features of the Pleuropulmonary Manifestations of Rheumatoid Arthritis: Pearls and Pitfalls J Clin Imaging Sci [online] :32 [viewed 10 September 2014] Available from: doi:10.4103/2156-7514.82244
  6. ZURAW BL, O'HAIR CH, VAUGHAN JH, MATHISON DA, CURD JG, KATZ DH. Immunoglobulin E-rheumatoid factor in the serum of patients with rheumatoid arthritis, asthma, and other diseases. J Clin Invest [online] 1981 Dec, 68(6):1610-1613 [viewed 15 September 2014] Available from: doi:10.1172/JCI110418

Investigations - Fitness for Management

Fact Explanation
Pulmonary function tests (PFTs) [1] Total lung capacity and forced vital capacity at and diffusing capacity (DLCO) will be either normal or reduced. [1] Clinical worsening is defined when the forced vital capacity (FVC)is reduced by 10%. [1]
Erythocyte sedimentation rate [2] Is usually elevated due to the chronic inflammation. [2]
Full blood count There will be low haemoglobin due to anaemia of chronic disease. These patients will have reduction of all the cell counts leading to pancytopenia. Neutropenia together with splenomegaly in these patients is called, felty’s syndrome. MTX drug toxicity may cause reduction of the serum absolute lymphocyte count below 500 cells/mm3. [1]
References
  1. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma. Pulmonary Medicine [online] 2011 December, 2011:1-12 [viewed 17 August 2014] Available from: doi:10.1155/2011/872120
  2. SURESH E. Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know J R Soc Med [online] 2004 Sep, 97(9):421-424 [viewed 10 September 2014] Available from: doi:10.1258/jrsm.97.9.421

Investigations - Followup

Fact Explanation
Erythocyte sedimentation rate [2] Will be reduced with the treatment, this is used as marker of clinical improvement. [1]
Rheumatoid factor Is also used as a marker of disease monitoring. [2]
X-ray of the synovial joints Previously affected joints with radiographic erosions need imaging to see the clinical improvement with the DMARD therapy. [2]
References
  1. KIM EUNICE J.. Rheumatoid Arthritis-Associated Interstitial Lung Disease. Chest [online] 2009 November [viewed 17 August 2014] Available from: doi:10.1378/chest.09-0444
  2. SURESH E. Diagnosis of early rheumatoid arthritis: what the non-specialist needs to know J R Soc Med [online] 2004 Sep, 97(9):421-424 [viewed 10 September 2014] Available from: doi:10.1258/jrsm.97.9.421

Investigations - Screening/Staging

Fact Explanation
Serum electrolytes, blood urea and serum creatinine Kidney involvement may cause proteinuria and kidney failure. This may be due to amyloidosis or Disease modifying anti rheumatoid medications(DMARDS). [1]
Electrocardiogram and echocardiogram All the three layers of the heart can get affected with rheumatoid disease. Myocardial ischaemia, arrhythmias, heart failure may be occurred. Diffuse lung capacity DLCO, is one of the most sensitive test available to screen for the presence interstitial lung disease in rheumatoid arthritis. [1]
Pulmonary imaging studies eg:- high-resolution CT [HRCT] scan, chest radiograph [2] These are recommend as follow-up imaging when the DLCO is reduced to less than 70% of predicted, this is because there s a possibility of having normal pulmonary function tests despite having pulmonary damage. [1]
Chest X-ray [2] A chest radiograph should be taken at the time RA is diagnosed, then repeated at intervals If there is any evidence of lung disease such as loss of lung volumes or interstitial markings further evaluation should be done. [2]
References
  1. HAMBLIN MARK J., HORTON MAUREEN R.. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma. Pulmonary Medicine [online] 2011 December, 2011:1-12 [viewed 17 August 2014] Available from: doi:10.1155/2011/872120
  2. KIM EUNICE J.. Rheumatoid Arthritis-Associated Interstitial Lung Disease. Chest [online] 2009 November [viewed 17 August 2014] Available from: doi:10.1378/chest.09-0444

Management - General Measures

Fact Explanation
Supportive management [2] Supplementary oxygen, and mechanical ventilatory support may be needed in advanced disease. [2]
Nutrition This is particularly important due to several factors. Anaemia is there due to the chronic disease, bronchiectasis [2] may cause protein loss via the sputum.
Monitoring [1] Half of patients that develop methotrixate drug toxicity will be symptomatic within the first 6–8 months of treatment. Therefore monitoring is important with lung functions, and chest imaging for the early detection of the disease. [1] This should be done atleast anually in patients with rheumatoid arthritis. [2]
References
  1. SCOTT DAVID L. Interstitial lung disease and disease modifying anti-rheumatic drugs. The Lancet [online] 2004 April, 363(9416):1239-1240 [viewed 17 August 2014] Available from: doi:10.1016/S0140-6736(04)15969-2
  2. KIM EJ, COLLARD HR, KING TE JR. Rheumatoid Arthritis-Associated Interstitial Lung Disease: The Relevance of Histopathologic and Radiographic Pattern Chest [online] 2009 Nov, 136(5):1397-1405 [viewed 10 September 2014] Available from: doi:10.1378/chest.09-0444

Management - Specific Treatments

Fact Explanation
Glucocorticoids [1] When there is ground glass infiltrates on HRCT, glucocorticoids may be helpful. 0.75 mg/kg/day prednisone during the initial four weeks of treatment, then 0.5 mg/kg/day for the next four weeks, then 20 mg/day for four weeks tapering to 10 mg/day for the next 6 weeks, and then 5 mg/day for 6 weeks is the usualtreatment schedule. [1]
Cyclophosphamide [4] 2 mg/kg/day orally) is started with the lower-dose prednisone (0.25 mg/kg/day) for steroid nonresponders. [1] Cyclosporine is used to treat both acute pneumonitis and progressive pulmonary fibrosis. [4] N-Acetylcysteine (NAC) is an antioxidant that has shown to be effective at retarding the progression in lung function in idiopathic pulmonary fibrosis (IPF .
Rituximab [3] This anti-CD20 antibody is used to treat the refractory to anti-TNF-α therapy. [4]
Monitoring the response to therapy [2] Response to treatment is considered when 10% improvement in the FVC or 15% improvement in the DLCO occurs at 12 weeks. [1] If the FVC and DLCO remain stable over a two-year period, medical regimen can be withheld.
References
  1. HAMBLIN MARK J., HORTON MAUREEN R.. Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma. Pulmonary Medicine [online] 2011 December, 2011:1-12 [viewed 17 August 2014] Available from: doi:10.1155/2011/872120
  2. KIM EJ, COLLARD HR, KING TE JR. Rheumatoid Arthritis-Associated Interstitial Lung Disease: The Relevance of Histopathologic and Radiographic Pattern Chest [online] 2009 Nov, 136(5):1397-1405 [viewed 10 September 2014] Available from: doi:10.1378/chest.09-0444
  3. KAPLAN MJ. Cardiovascular complications of Rheumatoid Arthritis - Assessment, prevention and treatment Rheum Dis Clin North Am [online] 2010 May, 36(2):405-426 [viewed 10 September 2014] Available from: doi:10.1016/j.rdc.2010.02.002
  4. BROWN KK. Rheumatoid Lung Disease Proc Am Thorac Soc [online] 2007 Aug 15, 4(5):443-448 [viewed 10 September 2014] Available from: doi:10.1513/pats.200703-045MS