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Pulmonary Manifestations of Connective Tissue Diseases

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Pulmonary Manifestations of Connective Tissue Diseases 內科學誌 2015：26：177-185 Pulmonary Manifestations of Connective Tissue Diseases Te-Wei Hseun, and Ren-Guang Wu Department of Internal medicine, Chung-Kang Branch, Cheng-Ching General Hospital Abstract Pulmonary involvement in connective tissue diseases (CTDs) often causes significant morbidities and mortalities. During disease course, most patients with connective tissue diseases show signs of involvement of the lung, vasculature, the pleura, and the diaphragm. Pleurisy, coughing, and dyspnea are often the first clues to make the diagnosis. Interstitial lung disease is the most frequent pulmonary manifestation. Differen- tial diagnosis includes respiratory infection and medication-associated lung toxicity. In some asymptomatic patients, abnormal pulmonary function tests (PFTs), including the diffusing capacity for carbon monoxide (DLCO) or abnormal chest high resolution CT (HRCT), may be presented. Descriptions of radiologic patterns and pathologic findings used in the idiopathic interstitial pneumonias are now being applied to patients with CTDs. Corticosteroid or immunosuppressant may be administered based on the disease severity. (J Intern Med Taiwan 2015; 26: 177-185) Key Words: Connective tissue diseases (CTDs), Interstitial lung disease (ILD), Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), Sjögren syndrome (SjS), Systemic sclerosis (SSc), Dermatomyositis (DM) / polymyositis (PM) Connective tissue diseases (CTDs) contain have a compelling reason to order serologic autoan- a heterogeneous group of autoimmune disorders tibody tests to diagnose CTD (Table 1). characterized by the presence of autoantibodies and Many CTDs involve the lungs either directly or autoimmune-mediated organ damage. They include as a complication of treatment of the CTDs. Several systemic lupus erythematosus (SLE), rheumatoid different components of the respiratory system may arthritis (RA), Sjögren syndrome (SjS), systemic be involved, including the airways, vessels, paren- sclerosis (SSc), dermatomyositis (DM) / polymyositis chyma, pleura, and respiratory muscles1. A com- (PM), mixed connective-tissue disease (MCTD), etc. prehensive evaluation is indicated for CTD patients Serological testing is primarily applied to with respiratory symptoms to explore a wide range confirm a specific diagnosis and, in some cases, to differential diagnosis that includes respiratory evaluate disease activity relative to CTDs. Based on infection, medication-associated lung toxicity, auto- a high index of clinical suspicion, physicians should immune mediated lung injury, and cardiovascular Reprint requests and correspondence：Dr. Te-Wei Hseun Address：Department of Medicine,Department of Internal medicine, Chung-Kang Branch, Cheng-Ching General Hospital, Taichung, Taiwan Correspondence to: RG Wu. No.118, Sec. 3, Taichung Port Rd., Xitun Dist., Taichung City 407, Taiwan 177-185_01_1269宣德威E.indd 177 2015/9/4 上午 09:37:00 178 T. W. Hseun, and R. G. Wu complications. Different CTDs had varied incidence CTD-related ILD have a better prognosis than and prevalence of each component of the respiratory idiopathic ILD. Usually, they are more indolent in tract. (Table 2). Interstitial lung diseases (ILD) are progression than IPF. An exception is RA-related common pulmonary complications of the CTDs. ILD with UIP findings. However, mortality is high Some evidence suggests that the incidence of in patients with CTDs who develop ILD and pul- ILD is increasing in CTDs patients. Recent studies monary hypertension. In patients with RA and SLE have shown radiographic prevalence rates of sub- who develop ILD, mortality is 3-4 times higher clinical ILD ranging from 33% to 57%5-7. This than that in the general population. The median sur- increment may be related to an increased use of vival of all patients with RA-related ILD has been diagnostic bronchoscopy, high-resolution computed reported to be approximately 5 years9. tomography (HRCT), pulmonary function tests PM/DM and systemic sclerosis are associated (PFTs), and video-assisted thoracoscopic surgery. with higher mortalities than other CTDs. Acute pro- ILD associated with CTDs may consist of gressive subtype usually lead to high mortality than several histological subtypes. Each had differ- chronic subtype. Kang et al found that in Korean ent clinical manifestation and radiologic finding8 patients with PM/DM, ILD was observed in 40.3% (Table 3). and was associated with poor survival10. The 3-year Table 1. Autoantibodies in Connective tissue diseases1,2 Autoantibody RA SLE SSc SjS PM/DM MCTD RF + + + + Rare + ANA + + + + Rare + ds-DNA - + - - - - Anticentromere - - + Rare Rare - Scl-70 - - + - Rare - Anti-Jo - - - Rare + (ILD) - Smith antibody - + - - - - Anti-Ro/SSA and anti-La/SSB - + - + - - Anti-U1-RNP - - - - - + Anti-CCP + - - - - - ANA = antinuclear antibody; DM = dermatomyositis; ds-DNA = double-stranded DNA antibody; ILD = interstitial lung disease; MCTD = mixed connective-tissue disease; PM = polymyositis; RA = rheumatoid arthritis; RF = rheumatoid factor; RNP = ribonucleoprotein; SSc = systemic sclerosis; SLE = systemic lupus erythematosus; SjS = Sjögren syndrome; CCP = cyclic citrullinated peptide. Table 2. CTDs and pulmonary manifestations3,4 ILD Airways Pleural Vascular DAH Systemic sclerosis +++ - - +++ - Dermatomyositis/ +++ - - + - Polymyositis Rheumatoid arthritis ++ ++ ++ + - Sjögren’s syndrome ++ +++ + + - Systemic lupus erythematosus + + +++ ++ ++ MCTD ++ + + ++ - The number of + signs indicates relative prevalence of each manifestation. DAH = diffuse alveolar hemorrhage. 177-185_01_1269宣德威E.indd 178 2015/9/4 上午 09:37:00 Pulmonary Manifestations of Connective Tissue Diseases 179 survival rate for patients with systemic sclerosis and patients during the course of disease14. The chest pulmonary hypertension is 56%. pain is aggravated by deep breathing, motion or by change of position, and elicited by palpation of Specific CTDs the painful areas. Pleural effusions are likely to be Each CTD have its common component of pul- bilateral, small to moderate in size, and exudative. monary involvement. The pleural effusion in SLE is more likely have a normal glucose and pH and lower lactate dehydro- Systemic Lupus Erythematosus genase levels. A diagnostic thoracentesis is often SLE is characterized by autoantibody positiv- indicated for new effusion because other cause must ity and immune-mediated damage to different organ be excluded including infection, pulmonary embo- systems. It affects more often in women than in men. lism, and congestive heart failure. Pleural disease Pleuritis and pleural effusions are the most in SLE often responds to therapy with nonsteroidal common pulmonary manifestations of SLE11. Pleu- anti-inflammatory drugs (NSAIDs). If there is no ritis is also one of the American College of Rheu- response within a few days, moderate- to high-dose matology classification criteria for SLE12. Less glucocorticoids will be used. More severe disease commonly, lupus pneumonitis, pulmonary hem- may be required immunosuppressive agents. orrhage, chronic interstitial fibrosis, and venous thromboembolic may present. Infections are also DAH common and frequently lethal pulmonary complica- Diffuse alveolar hemorrhage is one of the life- tions of SLE. threatening pulmonary manifestations of SLE. DAH Patients with SLE and lung involvement must is and infrequent, occurring in less than 4% of hos- always be evaluated for infection, particularly that pital admission for SLE15. The most common symp- due to bacteria or viruses. Besides, tuberculosis, fun- toms included dyspnea, hemoptysis, and cough. gal infections, and opportunistic infections should The absence of hemoptysis should not exclude the also be considered in immunocompromised hosts13. diagnosis, approximately half of patients do not present with it. The bleeding may lead to anemia. Pleural Disease Patients with DAH often have active concurrent Pleuritic chest pain occurs in 30% to 60% of extrapulmonary disease with the most common being lupus nephritis. Chest radiography usually Table 3. Classification of Idiopathic Interstitial Pneumo- revealed bilateral alveolar infiltrates, compatible 5,8 nias with pulmonary edema or infection16. The diagnosis Major idiopathic interstitial pneumonias idiopathic pulmonary fibrosis (IPF) / Usual interstitial can be confirmed with sequential bronchoalveolar pneumonia (UIP)* lavage samples revealing persistently bloody fluid idiopathic nonspecific interstitial pneumonia (NSIP) with hemosiderin-laden macrophages, and adequate Desquamative interstitial pneumonia (DIP) Cryptogenic organizing pneumonia (COP) culture result may exclude infection. The most Acute interstitial pneumonia (AIP) common underlying histologic pattern on surgical Rare idiopathic interstitial pneumonias lung biopsy is capillaritis. Treatment with high-dose Idiopathic lymphoid interstitial pneumonia (LIP) idiopathic pleuroparenchymal fibroelastosis glucocorticoids in combination with cyclophospha- mide, and aggressive supportive measures has sig- Unclassifiable idiopathic interstitial pneumonias nificantly decreased mortality in some studies. In * The histopathological pattern of idiopathic pulmonary fibrosis is usual interstitial pneumonia (UIP). addition, the administration of plasmapheresis to 177-185_01_1269宣德威E.indd 179 2015/9/4 上午 09:37:00 180 T. W. Hseun, and R. G. Wu refractory cases may result in survival reported case Pleural Disease series17. Pleural disease is common in patients with RA, but it is usually subclinical. Asymptomatic Thromboembolic
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