PICTORIAL REVIEW Thoracic Involvement in Connective
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JBR–BTR, 2015, 98: 3-19. PICTORIAL REVIEW THORACIC INVOLVEMENT IN CONNECTIVE TISSUE DISEASES: RADIO- LOGICAL PATTERNS AND FOLLOW-UP G. Serra1, A.-L. Brun1, P. Ialongo2, M.-L. Chabi1, P.A. Grenier1 Connective tissue diseases (CTDs) are a heterogeneous group of idiopathic inflammatory diseases involving various organs. A thoracic involvement is frequent, and chest-CT represents the imaging technique of reference in its assess- ment. Pulmonary abnormalities related to CTDs are various; although several disease-specific aspects have been described, the two most clinically relevant complications are represented by interstitial lung disease and pulmonary arterial hypertension. The early identification of a thoracic involvement, with the adoption of specific therapies, can significantly change patient’s prognosis. The aim of this article is to review the most common typical and atypical CT features of thoracic involvement occurring in CT, especially focusing on interstitial lung disease. Key-word: Connective tissue, diseases – Lung, interstitial disease – Hypertension, pulmonary. Connective tissue diseases (CTDs) at the time of diagnosis of CTD, or chronic inflammation in the alveolar are a heterogeneous group of in- more commonly manifest later in the walls. The patients usually response flammatory diseases derived from course of the disease (5, 6). well to corticosteroid therapy and an immunologic deregulation affect- The most common histopatholog- have a good prognosis. However pa- ing various organs. A thoracic in- ic patterns of ILD seen in the setting tients with OP associated with CTD volvement (pulmonary, pleural or of CTDs are non specific interstitial seem to have a greater tendency to mediastinal) can be frequently pneumonia (NSIP), usual interstitial develop fibrosis and a higher mortal- found; its frequency and expression pneumonia (UIP), organizing pneu- ity than patients with cryptogenic depends on the type of disease, and monia (OP), diffuse alveolar damage OP (5, 6). The CTD, typically associ- may induce an extremely wide range (DAD), and lymphocytic interstitial ated with LIP, is SJOS; however LIP of abnormalities (1-3). pneumonia (LIP). may also occasionally be seen in SLE All CTDs can present a pulmonary NSIP is the most common histo- and RA (Table I). involvement: rheumatoid arthritis pathologic and high resolution CT Patients with CTD and chronic ILD (RA), progressive systemic sclerosis pattern of ILD seen in patients with similar to those with idiopathic ILD, (PSS), systemic lupus erythemato- CTDs, particularly PSS, PM/DM and may develop acute exacerbation. sus (SLE), polymyositis and derma- MCTD. It is characterized histologi- Such acute exacerbation is most tomyositis (PM/DM), mixed connec- cally by relatively homogeneous ex- common in chronic ILD associated tive tissue disease (MCTD), Sjögren pansion of the alveolar walls by in- with RA but may be seen in PSS, PM/ syndrome (SJOS), and relapsing flammation, fibrosis or both. UIP is DM and SJOS. Despite intensive an- polychondritis (RP). The identifica- the second most commonly pattern ti-inflammatory immunosuppressive tion of a pulmonary involvement at of chronic ILD and seen most fre- therapy, the prognosis of acute exac- its initial stage is crucial, as an early quently in patients with PSS and RA. erbation of CTD associated with ILD treatment can often improve pa- The pathologic findings of UIP con- is poor, with high mortality rate (5). tients’ prognosis. Interstitial lung sist of patchy heterogeneous pattern Occasionally, patients with CTD disease and pulmonary arterial hy- with foci of normal lung, interstitial without evidence of prior ILD may pertension, both significantly affect- inflammation, fibrosis and honey- present with acute respiratory dis- ing morbidity and mortality in these combing. Fibroblastic foci are pres- tress syndrome due to DAD (8). This patients, represent the two most ent but less extensive in CTD than in pattern may be the initial manifesta- clinically relevant thoracic manifes- idiopathic pulmonary fibrosis, and tion of lung involvement in these pa- tations (1, 4). this feature probably accounts for tients with rapid progression to re- the better prognosis in these pa- spiratory failure. This presentation Interstitial lung disease (ILD) tients (5, 7). has been described most commonly The most common CTD associat- in patients with SLE and PM/DM. The most common CTDs associ- ed with OP is PM/DM. OP also occurs CT is commonly used in the initial ated with ILD are RA, PSS, SLE, PM/ in increased frequency in RA and has evaluation and follow-up of patients DM, MCTD and SJOS. ILD may been described in SLE and SJOS. with CTD and clinically suspected precede the clinical and laboratory The histologic pattern of OP is made or proven ILD. The CT findings of manifestations of CTDs for several of intraluminal plugs of granulation chronic ILD seen in patients with months or years, and be present to- tissue within alveolar ducts and sur- CTD are similar to those seen in idio- gether with systemic manifestations rounding alveoli associated with pathic interstitial pneumonia (9). In the context of ILD occurring in a pa- tient having a CTD, CT is particularly helpful at it often shows more than From: 1. Service de Radiologie Polyvalente et Oncologique – Groupe Hospitalier Pitié-Salpêtrière, Charles Foix, APHP Université Pierre et Marie Curie, Paris, France et one pulmonary disease. Diagnostic 2. Service de Radiologie, Hôpital San Camillo-Forlanini, Rome, Italy. precision in CTD-ILD is challenging Address for correspondence: Pr Ph. A. Grenier, Service de Radiologie Polyvalente et because of a wide range of potential Oncologique - Groupe Hospitalier Pitié-Salpêtrière, Charles Foix, APHP, 83, Bld de simultaneous pathologies and the l’Hôpital, 75651 Paris, France. E-mail: [email protected] possibility of concurrent CTD (i.e. serra-.indd 3 19/02/15 15:50 4 JBR–BTR, 2015, 98 (1) Table I. — Thoracic manifestations of connective tissue diseases. RA PSS SLE PM/DM MCTD SJOS RP UIP +++ + ++ + ++ + NSIP ++ +++ ++ ++ +++ ++ OP + + + +++ + DAD + + ++ ++ + Follicular bronchiolitis/LIP + + + +++ Alveolar hemorrhage + + +++ + Aspiration pneumonia ++ ++ + Tracheobronchial WT/Stenosis +++ Bronchiectasis ++ + ++ + Obliterative bronchiolitis ++ + ++ Nodules ++ PAH + +++ + + ++ Pleural effusion ++ + ++ Diaphragm dysfunction + ++ + UIP Usual Interstitial Pneumonia RA Rhumatoid Arthritis NSIP Non Specific Interstitial Pneumonia PSS Progressive Systemic Sclerosis OP Organizing pneumonia SLE Systemic Lupus Erythomatosus DAD Diffuse Alveolar Damage PM/DM Polymyositis/Dermatomyositis LIP Lymphocytic Interstitial Pneumonia MCTD Mixed Connective Tissue Disease WT Wall thickening SJOS Sjögren’s syndrome PAH Pulmonary Arterial Hypertension RP Relapsing Polychondritis rheumatoid arthritis and Sjögren Pulmonary arterial hypertension sia of bronchus-associated lymphoid syndrome). In addition further pos- (PAH) tissue (BALT) with the follicles dis- sible confounders include the pres- tributed along the bronchioles. Fol- ence of smoking or drug-related ab- PAH is defined as mean resting licular bronchiolitis is part of the normalities and immunosuppression pulmonary artery pressure higher or spectrum of lymphoproliferative dis- related infection (1). Actually ILD, equal to 25 mmHg and a pulmonary ease and may be sometimes overlap particularly NSIP, OP and DAD may capillary wedge pressure lower than with LIP. Most cases of follicular also be a reaction pattern to many 15 mmHg. Patients with CTD present bronchiolitis or lymphocytic bronchi- drugs. Because most patients with a higher risk to develop PAH, with or olitis are associated with CTD, espe- CTD are treated with anti-inflam- without the association with pulmo- cially RA, SJOS and PSS. matory or immunosuppressive med- nary interstitial involvement (1, 4). Bronchial inflammation (follicular ication, drug-induced lung disease Clinical presentation, symptoms and bronchitis) may result in bronchiec- should always be considered in the therapeutic approach are the same tasis unrelated to interstitial lung fi- differential diagnosis, or a potential of those of a primary pulmonary hy- brosis. Bronchiectasis and/or associ- cause of the lung abnormalities (10). pertension. PSS and MCTD are the ated obliterative bronchiolitis occur Patients with drug-induced pulmo- two entities more frequently associ- relatively frequently in patients with nary toxicity usually present sub- ated with PAH (12); it is less frequent RA, SJOS and SLE. acute clinical symptoms (fever, dys- in case of SLE and unusual in pa- Airway wall thickening and lumi- pnea, cough) progressing over many tients with RA and PM/DM (Table I). nal narrowing due to inflammatory weeks. The identification of a drug- The physiopathologic process ex- and fibrotic changes in cartilage are induced pulmonary involvement is plaining the development of pulmo- characteristic of RP. based on an exclusion diagnosis: nary hypertension in patients with Alveolar hemorrhage due to capil- pulmonary infection or acute exacer- CTDs has not been completely clari- laritis is a well-known complication bation of interstitial pneumonia fied yet (13). The histopathologic of SLE, and may also occur in pa- should always be taken into first con- features resemble those of a primary tients with RA, PSS, PM/DM or sideration (5). pulmonary hypertension. A throm- MCTD. Because patients with CTD are boembolic origin could be suggest- Other extrapulmonary thoracic treated with steroids or other