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 Table of Contents  
Year : 2016  |  Volume : 4  |  Issue : 1  |  Page : 6-9

Pleura: In connective tissue diseases

Department of Pulmonary Medicine, Burdwan Medical College, Burdwan, West Bengal, India

Date of Web Publication23-Dec-2015

Correspondence Address:
Kaushik Saha
Rabindra Pally, 1st Lane, P.O. Nimta, Kolkata - 700 049, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2320-8775.172482

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Connective tissue diseases (CTDs) (or collagen vascular diseases) represent a heterogeneous group of immunologically mediated disorders that affects many organs of the body including pleura. Frequency, presentation, and prognosis of pleural involvement depend on the underlying CTD. Connective tissue disorders may be heritable such as Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta; and autoimmune such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis, mixed connective tissue disease (MCTD), Sjögren's syndrome (SS), dermatomyositis (DM), and polymyositis (PM). The subject of this review is to describe the variety of pleural disorders observed in the most frequent types of CTD: SLE, RA, scleroderma, SS, DM, PM, and MCTD.

Keywords: Dermatomyositis, mixed connective tissue disease, pleural effusion, rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis

How to cite this article:
Saha K. Pleura: In connective tissue diseases. J Assoc Chest Physicians 2016;4:6-9

How to cite this URL:
Saha K. Pleura: In connective tissue diseases. J Assoc Chest Physicians [serial online] 2016 [cited 2023 Mar 25];4:6-9. Available from: https://www.jacpjournal.org/text.asp?2016/4/1/6/172482

  Introduction Top

Pleura are an important organ of the body, and its involvement in the form of effusion of pneumothorax may be due to a primary pathology or any systemic illness. Among the systemic diseases, connective tissue disease (CTD) is one of the most important causes of pleural affection. Capillary permeability of the pleura is increased in CTD-associated effusions due to direct infiltration of the pleura or by an immune mechanism. There is the presence of circulating immune complexes in the blood or pleural fluid in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Activation immune system and complement system releases different proteolytic enzymes, from the neutrophils and cytokines from the macrophages, which would not only affect the capillary permeability but might also modulate the migration of the fibroblasts, playing a relevant role in the extension of the pleural lesion.[1]

The aim of this review is to describe the pathogenesis, clinical findings, and characteristics of the pleural disease associated with CTD.

  Systemic Lupus Erythematosus Top

SLE is a classical autoimmune inflammatory disease affecting mostly women (ratio 9:1) of child-bearing age group. Respiratory involvement is more common in male. The most common initial presentation of the disease is arthritis, photosensitive rash, autoimmune cytopenia, and glomerulonephritis. Pleural effusion can be the presenting symptom in 5% of SLE patients and during the course of the disease eventually 30–50% patients develop pleural affection.[1],[2] Pleural involvement may be asymptomatic although pleuritic chest pain occurs in 45–60% of patients without the radiological appearance of pleural effusion.[3] Lupus pleuritis typically presented with chest pain, fever, cough, and dyspnea. Pleural effusion tends to be bilateral but may be unilateral; usually small to moderate but may be massive. Effusion usually develops as a part of generalized serositis but may be due to other reasons such as renal failure, infection, heart failure, or pulmonary embolism.[4]

Lupus effusions are due to localized immune complex mediated inflammation of the pleura with activation of the complement system.[5] Pleural effusion is commonly exudative (high protein >3.5 g/dL but lactate dehydrogenase [LDH] <500 U/L) with leukocyte count ranges between 500 and 15,000/µL.[6],[7] Nucleated cells commonly neutrophils predominate in the exudates, but lymphocytes can be present in early effusions. Lupus effusions have pH higher than 7.30 and a low glucose level. Low complement and high antinuclear antibody (>1/160) titer are suggestive, but not diagnostic, of lupus exudates.[8],[9] The Presence of lupus erythematosus cells is highly specific but has low sensitivity.[10] Pleural biopsy can be done to exclude malignancy and tuberculosis; in lupus pleuritis, it will show infiltration of lymphocytes and plasmacytes with a specific immunofluorescence nuclear staining pattern either with anti-IgM, anti-IgG, or anti-C3.[5] Pleural effusion in SLE can be drug-induced and suspected by the presence of florid symptoms of SLE and disappearance of symptoms after withdrawal of the drug.[10]

Small effusions usually resolve spontaneously. In some cases, low dose of corticosteroids needed and provided rapid relief of symptoms.[11] Pleurodesis or pleurectomy may be needed rarely in refractory cases of lupus effusions.

  Rheumatoid Arthritis Top

RA is a chronic inflammatory disease due to an immune response results from a complex interaction between genetic susceptibility and environmental exposure.[12] It generally affects the small joints of hand but can affect any synovial joints. Pleural affection (pleuritis, pleural effusion, pneumothorax, bronchopleural fistula, and empyema) is the most common intrathoracic manifestation of RA, observed in 5% of RA patients.[13] Juric et al. found evidence of pleural disease (thickening and/or pleural effusion) in 24% of the radiographies of men and 16% of women with RA.[14] Majority of patients with RA-associated pleural effusion are middle-aged men (80%) with high titers of rheumatoid factor (RF), rheumatoid nodules (80%), and a higher prevalence of HLA-B8 and Dw3.[14],[15],[16],[17],[18]

Pleural effusion in RA usually small, asymptomatic, and unilateral (mostly on the left side) in 70% of cases but may be bilateral, produces chest pain (30–50% of cases) and migratory (from one side to another).[19],[20],[21] Rheumatoid pleural effusion (RPE) usually occurs years after the diagnosis of RA but can precede or occur simultaneously with the beginning of the joint disease in 25% of cases. RPE can be transitory, recurring, or chronic (may persist for years).[17],[22]

RPE may be serous, cloudy, greenish-yellow, milky, or occasionally hemorrhagic in appearance [Table 1].[1],[22] In most of the cases, RPE is exudative with high protein content and in early phases the cells in the fluid are neutrophils and later on lymphocytes predominate. The characteristic cytology of RPE is a triad of giant multinucleated macrophages, elongated macrophages, and a necrotic background material in the absence of mesothelial cells. Chronic RPE (80% of cases) is usually characterized by pH <7.20, low glucose level (in 80% of cases under 50 mg/dL), with a pleural liquid (PL)/serum
Table 1: Characteristics of pleural effusion in rheumatoid arthritis

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ratio <0.5, high levels of LDH (>1000 U/L), RF titer higher than 1/320 (generally higher in PL than in blood), total hemolytic complement, and low complement components, with an increase in immune complexes in the PL.[22] Contrarily, in acute RPE (15–20% of cases), the pH and glucose levels are usually normal. Glucose level in RPE usually low due to blockage of entry of glucose into the pleural fluid by thickened pleura or due to more consumption of glucose by the inflamed pleura. Empyema in RA may be sterile due to massive exudation of leukocytes and fibrinoid detritus to the pleural space or necrosis of the rheumatoid nodules that, by means of bronchopleural fistula, cause pyopneumothorax.[23] Pseudochylothorax associated with RA is due to pleural fibrous thickening causing blockage of drainage of the liquid through the parietal lymph nodes.[24] Chylothorax in RPE is due to lymphatic obstruction due to secondary amyloidosis that on occasion appears in RA.[25],[26]

For diagnosis of RPE, pleural biopsy usually not needed but can be done to exclude tuberculosis or malignancy or in cases of chylous effusion.[27] Thoracoscopy is useful in suspected cases of RPE; nonspecific inflammation is observed on the surface of visceral pleura while granular, slightly inflamed, and thickened appearance with numerous small granules that measure around 0.5 mm in diameter found on the surface of parietal pleura.[1]

In most of the cases, RPE is small, asymptomatic and does not require any intervention unless any alternative diagnosis is suspected. Resolution of effusion can take 3–4 weeks or even several months and in 50% of cases thickening of the pleura, trapped lung, and infection can occur.[11] In large symptomatic effusions, therapeutic thoracentesis, intrapleural corticosteroids or fibrinolytics, and oral corticosteroids can be used as a treatment option for resolution of effusion.[4],[15] In refractory effusions, pleurodesis may be needed and in cases of trapped lung, decortication can be performed to relieve the dyspnea.[28] RA-associated empyema is treated with large bore tube thoracotomy drainage with broad spectrum antibiotics due to the presence of underlying necrotic rheumatoid subpleural nodules.[4] Pneumothorax can be found in 6% cases of RA, which can be unilateral, bilateral, or recurrent. It usually takes about 2 weeks to get resolve despite chest drainage.[1],[29]

  Systemic Sclerosis Top

It is an autoimmune disease of the connective tissue of unknown etiology.[30] The incidence of pleural effusion in systemic sclerosis (SSc) ranges between 7% and 15%.[31] Pleural involvement is more common with diffuse cutaneous SSc subgroup and can often be associated with pericardial effusion. Mostly effusion in SSc is exudative but can be transudative due to chronic renal insufficiency or accompanying heart failure.[31],[32] Recurrent spontaneous pneumothorax can occur due to the frequent presence of subpleural cysts.[33]

  Mixed Connective Tissue Disease Top

Mixed connective tissue disease (MCTD) is characterized by combination of clinical features of SSc, SLE, and inflammatory myopathy, whose diagnosis currently requires three of the following criteria: Synovitis or myositis (one of the two), hand edema, Raynaud's phenomenon, acroscleroderma, and serologic evidence of positive anti-snRNP in at least one moderate titer.[34] Pleural effusion in MCTD is usually bilateral with an incidence of 50% and due to immunological lesions in the pleura.[35] It is mostly exudative with a predominance of lymphocytes, high levels of proteins (3.5 g/dL), and LDH (400 U/L) and with completely normal glucose values.[36]

  Sjögren's Syndrome Top

It is a chronic inflammatory autoimmune disease with lymphocytic infiltration of the exocrine glands and of multiple extraglandular areas such as lungs, thyroids, kidneys, or hepatobiliary tract.[37] Sjögren's syndrome (SS) can be primary, i.e., isolated, or secondary, i.e., associated with other CTD, more frequently with RA. Pleural involvement can occur in the form of effusion, (unilateral or bilateral), nodules, thickening (associated with recurring pneumonia and atelectasis), and pleural adherences.[38] Effusion usually more common with secondary SS and exudative with a high content of B-lymphocytes (fundamentally CD 3+ and CD 20+), normal levels of pH, and glucose and low levels of adenosine deaminase. Pleural biopsy is indicated in cases of SS associated effusion to exclude lymphoma.[39] Effusions usually resolve either spontaneously or with corticosteroids.[40]

  Polymyositis/dermatomyositis Top

It is a type of inflammatory myopathy characterized by proximal muscle weakness, high muscle enzymes in serum (especially creatine kinase), electromyographic data of myopathy and infiltrates of inflammatory cells in the muscle tissue. There are three subtypes of inflammatory myopathy such as polymyositis (PM), dermatomyositis (DM), and inclusion body myositis.[41] Pleural involvement is rare in PM or DM and usually associated with interstitial lung disease.[42],[43] Pleural aspiration is must in these cases as malignancy often associated with DM.[44] Pneumothorax and pneumomediastinum results from rupture of alveoli in the framework of an interstitial lung disease.[45]

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  References Top

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