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Radiología. 2013;55(2):107---117

www.elsevier.es/rx

UPDATE IN RADIOLOGY

Lung disease associated with connective tissue disease�

R. Ysamat Marfáa,∗, A. Benito Ysamata, S. Espejo Péreza, M. Blanco Negredoa,R. Roldán Molinab

a Servicio de Radiología, Hospital Universitario Reina Sofía, Córdoba, Spainb Servicio de Reumatología, Hospital Universitario Reina Sofía, Córdoba, Spain

Received 20 December 2011; accepted 21 March 2012

KEYWORDSConnective tissuedisease;Interstitialpneumonia;Interstitial lungdisease;Computedtomography

Abstract Connective tissue diseases are often associated with lung diseases that lead to highmorbidity and mortality, including interstitial disease, airway disease, pleural lesions, andvascular disease. High resolution CT offers high sensitivity for detecting parenchymal diseaseand potentially reversible lesions, thus helping to guide treatment. This article emphasizesinterstitial pneumonia in association with connective tissue disease and the characteristics thatdifferentiate this entity from idiopathic types. Likewise, we review the most common pulmonarymanifestations of each connective tissue disease with the aim of providing the radiologist with apractical approach to the diagnosis and management of these diseases in daily clinical practice.© 2011 SERAM. Published by Elsevier España, S.L. All rights reserved.

PALABRAS CLAVEEnfermedades deltejido conectivo;Neumoníasintersticiales;Enfermedadintersticial pulmonar;Tomografíacomputarizada

La patología pulmonar asociada a las enfermedades del tejido conectivo

Resumen Las enfermedades del tejido conectivo se asocian con frecuencia a un amplionúmero de patologías como las enfermedades intersticiales y de la vía aérea, las lesionespleurales y la patología vascular, que presentan una alta morbilidad y mortalidad en estospacientes. La tomografía computarizada de alta resolución tiene una alta sensibilidad enla detección de la enfermedad parenquimatosa y de la vía aérea, lo que permite diagnosticar lafibrosis establecida, o bien lesiones potencialmente reversibles, y facilita la correcta indicacióndel tratamiento en estos pacientes. En este artículo se hace una especial incidencia en las neu-

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monías intersticiales asociadas a las enfermedades del tejido conectivo y en sus características

diferenciales con respecto a las formas idiopáticas. También, se revisan las manifestaciones pul- monares más frecuentes en cadaun enfoque práctico en el diagn© 2011 SERAM. Publicado por El

� Please cite this article as: Ysamat Marfá R, et al. La patología pulmo2013;55:107-17.

∗ Corresponding author.E-mail address: roserysamat@gmail.com (R. Ysamat Marfá).

2173-5107/$ – see front matter © 2011 SERAM. Published by Elsevier Esp

conectivopatía, con la intención de proporcionar al radiólogoóstico y manejo de estas afecciones en la clínica diaria.sevier España, S.L. Todos los derechos reservados.

nar asociada a las enfermedades del tejido conectivo. Radiología.

aña, S.L. All rights reserved.

1 R. Ysamat Marfá et al.

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Table 1 Current classification of Idiopathic InterstitialPneumonias. Correlation between histologic pattern andclinical diagnosis.

Abbreviation Histologic pattern Clinical diagnosis

UIP/FPI Usual interstitialpneumonia

Usual interstitialpneumonia

NSIP Nonspecificinterstitialpneumonia

Nonspecificinterstitialpneumonia

COP Organizingpneumonia

Cryptogenicorganizingpneumonia

DAD/AIP Diffuse alveolardamage

Acute interstitialpneumonia

RB-PID Respiratorybronchiolitis

Respiratorybronchiolitis-associatedinterstitial lungdisease

DIP Desquamativeinterstitialpneumonia

Desquamativeinterstitialpneumonia

LIP Lymphoidinterstitialpneumonia

Lymphoidinterstitialpneumonia

is

pwbhdistinguish it from NSIP. Lesions are predominantly basaland subpleural, and in most cases there is honeycomb-ing at diagnosis; therefore, absence of honeycombingmakes UIP unlikely and should lead to an alternative

Table 2 Frequency of parenchymal involvement in the dif-ferent connective tissue diseases.

RA SLE SCL DM/PM SjS MCTD

UIP ++ + + ++ + +NSIP + + +++ +++ ++ +++COP + + ++ +LIP ++ +DAD + ++ + ++

Bronchiolitis +++ ++

RA: rheumatoid arthritis; DAD: diffuse alveolar damage; DM/PM:dermato/polymyositis; MCTD: mixed connective tissue disease;SCL: scleroderma: SLE: systemic lupus erythematosus; LIP:

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08

ntroduction

onnective tissue diseases (CTD) are often associated with wide range of lung conditions that result in significantorbidity and mortality. These associations are varied, ran-

ing from parenchymal, pleural and airway lung disease, toascular, heart and musculoskeletal involvement; althoughach CTD is usually associated with a specific entity.1 Forhis reason, the presence of lesions related to the under-ying CTD such as joint erosions, esophageal dilation, ornlargement of the pulmonary artery may assist the radi-logist in the diagnosis of lung lesions. However, in somef the patients, the lung disease may precede the clini-al symptoms of the collagen disease.1 In addition, sincehese patients are immunocompromised, infections are onef the most common causes of respiratory disease, and theyhould be considered in the evaluation of lung abnormalitiesn chest imaging in patients with ETC.2 Lastly, drug-relateddverse reactions should also be included in the differentialiagnosis.

Therefore, the diagnosis and clinical management ofhese patients is complex and should be based on theombination of different diagnostic approaches: clinicalymptoms, laboratory and imaging findings.2

The aim of this paper is to review the pulmonary man-festations associated with the CTDs, with an emphasis onnterstitial and airway disease, and on the high-resolutionomputed tomography (HRCT) findings, which facilitatearly diagnosis of these conditions.

nterstitial lung disease associatedith connective tissue diseases

iffuse interstitial lung diseases are a common manifesta-ion of CTDs, with histologic and radiologic patterns similaro those found in the idiopathic forms. Therefore, dif-use interstitial lung diseases can be classified using theonsensus Classification of the Idiopathic Interstitial Pneu-onias (IIP) of the ATS/ERS 20023 (Table 1). The pneumoniasost commonly associated with CTDs are the nonspecific

nterstitial pneumonia (NSIP) and the usual interstitial pneu-onia (UIP), common in scleroderma (SCL) and rheumatoid

rthritis (RA), respectively.4,5 Organizing pneumonia is alsoommonly found in CTDs, usually in association with otheristologic patterns of interstitial pneumonia.6 Lymphoidnterstitial pneumonia (LIP) is found in Sjögren’s syndromeSjS).7 The pattern of diffuse alveolar damage (DAD)3,8

s seen in acute exacerbations of pulmonary fibrosis andupus-related pneumonia. Desquamative interstitial pneu-onia (DIP) does not have a clear correlation with CTDs,ut a few cases of DIP associated with RA have beeneported.1

Each entity is defined by a characteristic histologicattern; however, except for pulmonary fibrosis withIP pattern on HRCT, the histologic pattern is not cor-elated with a sufficiently defined radiologic pattern that

ould allow the radiologist to make a confident diagnosis.3,9

ecause of the overlap of HRCT features between the differ-nt entities, surgical biopsy is needed to make a confidentiganosis.3

Source: Adapted from the American Thoracic Society/EuropeanRespiratory Society.3

The frequency of appearance of IIPs in the different CTDss summarized in Table 2. The most common radiologic pre-entation of each IIP is shown in Table 3.

Histologic features of UIP include a heterogeneous,atchy pattern where areas of normal parenchyma alternateith areas at different stages with inflammation, fibro-lastic foci, fibrosis and honeycombing.3 This ‘‘temporaleterogeneity’’ is characteristic of the UIP and it helps

3

lymphoid interstitial pneumonia; NSIP: nonspecific interstitialpneumonia; UIP: usual interstitial pneumonia; COP: cryptogenicorganizing pneumonia; SSJ: Sjögren’s syndrome.+: less common; ++: common; +++: more common.

Lung disease associated with connective tissue disease 109

Table 3 Radiological presentation of interstitial pneumonias associated with connective tissue diseases.

Distribution HRCT findings

UIP/IPF PeripheralSubpleuralBasal predominance

Reticulation, honeycombing, architecturaldistortion, tractionbronchiectasis/bronchiolectasis, ground-glass

NSIP Peripheral/subpleural or peribronchovascularBasalSymmetrical

Ground-glass, reticulation, consolidations(subpleural sparing)

Organizingpneumonia

Peripheral/subpleural or peribronchial ConsolidationNodules

Diffuse alveolardamage/AIP

Diffuse Ground-glass, condensationTraction bronchiectasis in late stages

LIP Diffuse Ground-glass, septal lines, centrilobular nodules,perivascular cystic airspace formation

IPF: idiopathic pulmonary fibrosis; AIP: acute interstitial pneumonia; LIP: lymphoid interstitial pneumonia; NSIP: nonspecific interstitialpneumonia; UIP: usual interstitial pneumonia.

diagnosis.10 The typical radiologic features, which correlatewith the histologic appearance, include bilateral and sym-metrical reticulation, with subpleural and posterior basalpredominance.11 Honeycombing is a common finding thatsupports the diagnosis of UIP,12,13 while ground-glass atten-uation is rare or nonexistent (Fig. 1). UIP is the histologicpattern most commonly seen in patients with rheumatoidarthritis.2,5,14

Figure 1 Interstitial lung disease with radiologic pattern ofUIP in a male patient with long-standing rheumatoid arthritis.Axial HRCT image shows bilateral and symmetrical reticulation,with subpleural and basal predominance, associated with trac-tion bronchiectasis (arrowheads) and honeycombing (arrows).

Unlike UIP, the typical histologic feature of NSIP istemporal and spatial homogeneity. Changes range from pre-dominant inflammation, with uniform thickening of thealveolar septa and infiltrate of lymphocytes and plasmacells (cellular NSIP), to uniform interstitial thickeningwith preservation of the alveolar architecture (fibroticNSIP).8,13,15 The radiologic pattern may overlap with that ofUIP, but ground-glass attenuation is usually more common inNSIP and is the salient feature of cellular NSIP,11,13 and hon-eycombing is rare at diagnosis.7,12 Lower lobe predominancewith peribronchovascular distribution and subpleural sparingis very suggestive of NSIP7,13 (Fig. 2). This is the most com-mon interstitial pneumonia associated with CTDs,6 and it isbeen suggested that NSIP is a lung manifestation of undif-ferentiated connective tissue disease.16 While this may bethe case in some patients, to date, no clear evidence hasvalidated this hypothesis, and the subject remains open todebate, pending further research.15,17

The term ‘‘lung-dominant CTS’’ or ‘‘autoimmune-featured interstitial lung disease’’ has been recently

Figure 2 Radiologic pattern of NSIP in a patient withpolymyositis. Axial HRCT image shows fine reticular pattern andground-glass opacity, basal and peribronchial (thick arrows),associated with traction bronchiectasis (arrowheads). Subpleu-ral sparing is suggestive of NSIP (long arrows).

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roposed, encompassing those patients with interstitial dis-ase, positive antibodies and histologic features of CTD, buto not meet the diagnostic criteria for a specific CTD.18

hese patients usually show a histologic and radiologic pat-ern of UIP, and have a prognosis similar to those withdiopathic pulmonary fibrosis and worse than thoseith interstitial pneumonia associated with a CTD.19

One characteristic of the interstitial pneumonias inatients with CTD is the presence of coexisting histologicatterns on the same biopsy specimen,6 a finding that is,ccording to some authors, very suggestive of CTD.6,20

The prognosis of the interstitial pneumonias associatedith CTD is usually better than that of the idiopathic forms.his would explain, in part, why UIP is the most com-on histologic pattern in IIPs, while the most commonattern in CTD-associated pneumonias is NSIP,4,6,21 whichas a more favorable prognosis. In addition, the progno-is of the UIP pattern associated with a CTD is better thanIP with idiopathic pulmonary fibrosis.4,21,22 The histologicattern differs between the two groups, with less exten-ive honeycombing and fibroblastic foci, and a higher ratef germinal and inflammatory centers in patients with aTD than with idiopathic pulmonary fibrosis.22,23 However,o significant differences have been found between therognosis of patients with NSIP associated with a CTD andhose with idiopathic NSIP.21 Clinical findings and prognosisf organizing pneumonia associated with a CTD are simi-ar to those of idiopathic organizing pneumonia; however,he former tends to recur and HDCT usually shows tractionronchiectasis.24

Acute exacerbation of interstitial pneumonia, similar tohat of idiopathic pulmonary fibrosis, also occurs in inter-titial pneumonias associated with a CTD and has beeneported in patients with dermatomyositis (DM), RA, SCLnd systemic lupus erythematosus (SLE). Acute exacerba-ion is more common and has poorer prognosis in RA withistologic pattern of UIP and in DM.25,26 The histologicattern is that of DAD, associated or not with organiz-ng pneumonia.8 HRCT shows ground-glass attenuation ande novo peripheral, multifocal or diffuse consolidation.8

iven its high mortality rates, this condition should be con-idered by the radiologist in the presence of suggestiveadiologic changes in patients with CTD and interstitial lungisease.25

Sensitivity of chest radiography for the detection of inter-titial lung disease is very low. In addition, the clinicalymptoms are not useful in the evaluation of interstitialisease since dyspnea may be caused by a number of fac-ors and lung function tests are not representative in thearly stages of the disease.2 Conversely, HRCT providesood sensitivity and specificity and is able to provide aonfident diagnosis of interstitial lung disease and fibrosis.2

n addition, this technique allows multiplanar reformattedmages and has the advantage of being an affordable andon-invasive technique. The main limitation is the lack ofeliable criteria for establishing a correlation between thextent of the lesions and the presence of subclinical orlinically significant disease.2,27 HRCT also plays in impor-

ant role in the detection of signs suggestive of potentiallyeversible disease. As in IIPs, the presence of ground-glasspacities without signs of fibrosis (traction bronchiectasisnd honeycombing) is suggestive of reversibility and good

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R. Ysamat Marfá et al.

esponse to treatment.28,29 On the other hand, the absencef ground-glass opacity and presence of signs of fibrosis onRCT should avoid unsuccessful treatments with potentiallyoxic drugs.2

A multidisciplinary approach to lung disease associatedith CTD is paramount for an accurate diagnosis and man-gement of these patients. The high diagnostic accuracyf HRCT, in conjunction with an adequate evaluation ofhe clinical and functional features, bronchoalveolar lavageBAL) and laboratory studies make that lung biopsy could berimarily reserved for cases with atypical clinical or radio-ogic presentation.30

ther lung conditions associatedith connective tissue diseases

nfections

t should be highlighted that lung infections are commonn patients with CTD due to their impaired immu-ity. For this reason, infections should be ruled outhen lung consolidation or nodules are detected. Theost common infections are bacterial, and are a major

ause of death in patients with SLE.31 Immunosuppres-ive drugs and the new generation of biologic agentssed to treat rheumatic diseases have resulted in anncreased incidence of infections caused by opportunis-ic pathogens, especially Mycobacterium tuberculosis andtypical mycobacteria,32 fungi and Pneumocistis jiroveci.1,2

creening chest radiographs and BAL are indicated andungal or mycobacterial infection should be suspectedn the presence of parenchymal abnormalities in theseatients.1

dverse drug reactions

any of the drugs used to treat CTDs result in pul-onary side effects, rendering it more difficult to evaluate

adiologic findings in these patients. This occurs morerequently in RA. Pulmonary toxicity caused by methotrex-te manifests within months of starting therapy in---10% of patients, with NSIP being the most commonattern.33

The new biologic agents (monoclonal antibodies), espe-ially anti-TNF, have been related to diffuse interstitial lungisease (mainly UIP and NSIP), sarcoid-like lesions, acutexacerbation of interstitial disease, pulmonary vasculitis,ypersensitivity pneumonitis and pneumonias with negativeultures, among others.34,35

ung neoplasms

atients with CTDs have an increased risk of lung cancer,avored by pulmonary fibrosis, common in RA and SCL, or byhe paraneoplastic etiology of DM/PM.2,36 A higher incidence

f lymphoma has also been identified in patients with RA andSj.37 Therefore, histologic diagnosis is required to rule outalignancy when new lung nodules are identified in theseatients.37

Lung disease associated with connective tissue disease 111

Figure 3 Male patient with rheumatoid arthritis and a biopsy-confirmed diagnosis of constrictive bronchiolitis. Axial HRCTimage shows diffuse cylindrical bronchiectasis (white arrows)

Figure 4 Male patient with rheumatoid arthritis who presentswith dyspnea. Inspiratory and expiratory axial HRCT. (A) Inspi-ratory HRCT image shows no abnormalities. (B) Expiratory HRCTshows mosaic pattern with bilateral radiolucent areas cor-r(

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and centrilobular nodules with a patchy distribution (blackarrows).

Radiologic findings in lung disease associatedwith different connective tissue diseases

Rheumatoid arthritis

RA is often related to lung abnormalities on HRCT, althoughrespiratory symptoms occur later in the course of the dis-ease.

The earliest pulmonary manifestation is airway disease,being constrictive bronchiolitis and follicular bronchioli-tis the most common histologic patterns.6,38 Cylindricalbronchiectasis is also a common finding in patients withRA, associated or not with bronchiolitis.5,37 Constrictivebronchiolitis is characterized by concentric peribronchio-lar fibrosis with luminal narrowing and obliteration.39 InRA, constrictive bronchiolitis may appear associated or notwith use of penicillamine therapy.40 Follicular bronchiolitisis a type of cellular bronchiolitis characterized by the pres-ence of lymphoid follicles with bronchial and peribronchialdistribution41 and it is seen in patients with CTDs, partic-

ularly AR6 and SSj.40 HRCT shows mosaic perfusion and airtrapping,1,42 associated with cylindrical bronchiectasis andbronchiolectasis (Fig. 3). Centrilobular nodules are also seenin follicular bronchiolitis, an evidence of bronchiolar and

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esponding to air trapping and consistent with bronchiolitisarrows).

eribronchiolar lesion.40,42 Expiratory HRCT is always recom-ended in these patients to rule out air trapping, indicative

f bronchiolitis, which may be subclinical in many patients1

Fig. 4).Interstitial lung disease is more common in men1 and

sually appears once the clinical symptoms of RA arestablished, but in some of the patients, the lung diseaserecedes RA.14 It is usually associated with restriction ofespiratory function parameters.14 Several studies haveonfirmed that the radiologic pattern of UIP is more commonhan NSIP in patients with AR,43 unlike the rest of CTDs. Theost common HRCT finding is the presence of peripheral

eticulation associated with varying degrees of honey-ombing, depending on the series2 (Fig. 1). In a series of3 patients with pulmonary disease associated with RA,anaka et al.5 reported reticulation on HRCT in 98% of casesnd ground-glass opacity in 90%. The radiologic patternf UIP was the most common (26 patients), followed bySIP (19 patients), bronchiolitis (11 patients) and orga-

izing pneumonia (5 patients). In 13 of the 17 patientsith available histologic analysis, the histologic patternorrelated with the radiologic findings. In another seriesith 18 RA patients who underwent surgical biopsy for

112 R. Ysamat Marfá et al.

Figure 5 Male patient with long-standing rheumatoid arthri-tis. Coronal chest CT shows cavitated rheumatoid nodules withb

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Figure 6 Limited scleroderma. Radiologic pattern of NSIP.Axial HRCT image shows ground-glass pattern associated withfiw

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ilateral distribution (arrows).

uspected interstitial lung disease,14 UIP was the mostommon histologic pattern, with a higher incidence inen and smokers, while NSIP was seen more frequently inomen and non-smokers. RA patients with UIP pattern haveorse prognosis than those with NSIP.43,44

Rheumatoid nodules have been reported in 4% of theatients with AR37 and, as in interstitial lung disease, andhey are seen more frequently in men. Nodules are usu-lly associated with the presence of subcutaneous nodulesnd positive rheumatoid factor, but they can precede theR manifestations.37 Rheumatoid nodules are usually sub-leural, multiple and well-defined, and may often undergoavitation (Fig. 5). Complications such as pneumothorax andiopneumothorax secondary to rupture of rheumatoid nod-les have been reported. Its course varies from spontaneousegression to stabilization.37,45,46

Consolidation is often seen in patients with RA, mainlyn the lower zones with a peripheral distribution.5 Presencef consolidation is suggestive of organizing pneumonia,5,24

hich in turn may be secondary to drugs or infection. How-ver, this radiologic pattern is unspecific and, when present,

differential diagnosis between organizing pneumonia,

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igure 7 Systemic scleroderma. Axial (A) and coronal (B) HRCTronchiectasis (white arrow) and honeycombing (arrowhead) in RLresence of esophageal dilation (*) suggests a diagnosis of scleroder

ne reticulation (*) and traction bronchiectasis (white arrows),ith basal predominance. Absence of honeycombing.

nfection or acute exacerbation of interstitial pneumoniahould be considered.

Pleural abnormalities are a common finding in patientsith RA, and pleural thickening is seen more often thanleural effusion on CT.37

cleroderma

nterstitial lung disease is the most common lung condi-ion in patients with SCL, and the most common cause ofeath in these patients.2 In SCL, unlike what happens in RA,SIP is more frequent than UIP,4 which correlates with theypical HRCT findings (ground-glass opacity associated withne reticulation typically subpleural, basal and posterior)Fig. 6). The radiologic pattern in SCL is often similar tohat of fibrotic NSIP, with traction bronchiectasis and bron-

hiolectasis (Fig. 7).47,48 Honeycombing is absent or mild,lthough it has been reported in up to 37% of patients withCL associated with symptomatic interstitial lung disease.47

images show a bilateral reticular pattern (arrows), tractionL. The lesions have a subpleural and basal distribution. Thema.

113

Figure 8 Systemic lupus erythematosus. (A) Pulmonary hem-orrhage in a patient with lupus erythematosus. Axial HRCTimage shows bilateral, patchy ground-glass opacities (whitearrows). (B) Interstitial lung disease in a patient with lupuserythematosus and restrictive spirometry pattern. Axial HRCTiu

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Lung disease associated with connective tissue disease

The presence of honeycombing at diagnosis is corre-lated with restrictive functional impairment and a worseprognosis.4,47 Tashkin et al.49 reported significant lung func-tion impairment in patients with honeycombing on thebaseline HRCT treated with placebo during one year, but thiswas not observed in patients treated with cyclophosphamideduring the same period. However, the positive effect seenin the second group did not persist one year after discon-tinuing therapy. Pulmonary fibrosis associated with SCL hasbetter prognosis than idiopathic pulmonary fibrosis.50

Pulmonary hypertension (PHT) is particularly common inpatients with limited SCL.27,51 Enlargement of the main andproximal pulmonary arteries is seen on CT; however, normal-sized pulmonary arteries do not exclude the diagnosis.Pericardial thickening or effusion also correlates with thepresence of echocardiographic pulmonary hypertension.52

Launay et al. compared 47 patients with SCL, PHT and inter-stitial lung disease with 50 patients with SCL and HTP, butfound no interstitial disease. The first group had more fre-quently diffuse SCL and worse prognosis than the secondgroup. The presence of pericardial effusion was predictiveof a poor outcome.53

SCL is associated with a higher risk of lung cancer, regard-less of the presence of other risk factors.36

Esophageal abnormalities are common and the presenceof esophageal dilation in a patient with interstitial lung dis-ease is suggestive of SCL (Fig. 7). Esophageal dysmotilitymay cause aspiration pneumonia in these patients.

Systemic lupus erythematosus

The most common pleuropulmonary manifestation of LES ispleuritis (found in 77.8% of necropsies), associated or notwith effusion.31 Infection is the most frequent pulmonarycomplication, and sepsis is a major cause of death in LESpatients.31,54 Pulmonary hemorrhage is also an importantcomplication of this condition55 characterized by patchyor diffuse ground-glass opacity or consolidation on CT(Fig. 8A). DAD accounts for 22% of all pulmonary abnor-malities in LES and is usually associated with pulmonaryhemorrhage, edema or pleural effusion.55 Lupus pneumoniacorresponds histologically to varying degrees of hemorrhageand DAD, which manifests as ground-glass opacity and exten-sive consolidation on CT.54

Interstitial lung disease is less common than in the restof CTDs, but mild HRCT changes are found in one-third ofasymptomatic patients, usually ground-glass opacity associ-ated with intralobular reticulation, interlobular septal linesand parenchymal bands56 (Fig. 8B).

Other abnormalities associated with LES include pul-monary hypertension (less common than in SCL), diaphrag-matic weakness, and thrombosis secondary to antiphospho-lipid syndrome, frequently associated with LES.1,54

Polymyositis/dermatomyositis

NSIP is the most common pulmonary disease in patients

with PM/DM, followed by organizing pneumonia.6,57 Radio-logic findings are correlated with histologic findings,being ground-glass opacity, intralobular reticulation, trac-tion bronchiectasis and consolidation the most frequent

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mage show ground-glass opacities (arrows), intralobular retic-lation and septal lines (circle).

adiologic findings, with a lower lobe predominance58

Fig. 2). Consolidation is more commonly seen in PM/DM thann the rest of CTDs, and the histologic pattern corresponds torganizing pneumonia (Fig. 9),6,57,59 with acute pulmonaryecompensation with underlying histopathology of DADoften leading to patient demise)59 and aspiration pneumo-ia secondary to the muscle disease.1,2 Lung abnormalitiesay precede muscle and skin lesions in 33% of patients, and

here is no relation between the severity of skin/muscleesions and the appearance of interstitial lung disease.60

In a series of 28 patients with DM (12 patients) and PM16 patients), Fujisawa et al.26 concluded that patients withM had worse response to corticosteroid therapy and worserognosis than those with PM. DAD was seen in three patientsith DM but in none of the PM patients. No differences inSIP frequency were observed between DM and PM.

It is worth noting that DM/PM and antisynthetasentibody-positive patients frequently have interstitial lungisease (50---70%),1,60 which may precede myositis in 53% ofases.61 The antisynthetase syndrome consists of the pres-nce of antisynthetase antibodies associated with myositis,nterstitial disease, Raynaud’s phenomenon, joint pain,

xanthema on the hands, and fever.62 Anti-Jo-1 is the mostommonly identified antisynthetase antibody, but anti-PL-, -PL-12, -EJ, -OJ, -KS, -Zo, and -YRS are also relatedo the syndrome.60,61 Conversely, interstitial disease is less

114 R. Ysamat Marfá et al.

Figure 9 Female patient with polymyositis and anti-Jo-1-positive antibodies. Radiologic pattern of organizingpneumonia. Axial HRCT images show nodular and lineal ground-glass opacity in both lung bases, with peribronchial andpu

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Figure 10 Sjögren’s syndrome. (A) Patient with primary Sjö-gren’s syndrome and advanced interstitial lung disease. AxialHRCT image of the middle lung field shows micronodules (cir-cles), ground-glass opacity associated with fine reticulation(white arrow) and traction bronchiectasis (black arrow). (B andCs

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erilobular distribution (arrows); mild subpleural basal retic-lation (white circle).

ommonly found (10%) in DM/PM and anti-Jo-1-negativeatients.1,57,62

jögren’s syndrome

jS is relatively common, and it may develop in isolation (pri-ary SjS) or associated with other CTDs, more frequently RA

secondary SjS). The histologic patterns associated with thisyndrome include NSIP, bronchiolitis, organizing pneumo-ia, UIP, LIP, primary pulmonary lymphoma and amyloidosis.4

n two series of 18 and 33 patients with primary SjSnd lung biopsy,20,63 NSIP was the most common histologicnding, with good correlation between the histologic andadiologic pattern of NSIP on HRCT (positive predictivealue of HRCT 94%).20 Other HRCT findings include bron-hiolitis pattern (air trapping, bronchial wall thickening,ronchiectasis/bronchiolectasis and tree-in-bud), peribron-hovascular air cysts, nodules, septal lines, and ground-glasspacity (Fig. 10).

Air cysts, consolidations, ground-glass opacity, sep-

al lines and nodules have been described in LIP andymphoma.63,64 Septal lines, nodules and cysts have alsoeen found in amyloidosis.63 Therefore, these findings areot correlated with a specific histologic pattern in SjS, and

phau

) Patient with primary Sjögren’s syndrome. Axial HRCT imageshow perivascular air cysts (arrows).

iopsy is required to typify the disease.20,63 In a series of0 patients with primary SjS, Franquet et al.65 reported CTbnormalities in 17 patients, being bronchiolar changes andarenchymal lines, followed by ground-glass opacity, theost common findings. The presence of micronodules, tree-

n-bud, and honeycombing was also observed. The radiologicndings of SjS generally correspond to a combination of

nterstitial lung disease and airway disease.

ixed connective tissue disease

ixed connective tissue disease (MCTD) is characterized by aombination of LES, SCL and PM/DM findings, and the pres-nce of anti-RNP antibodies. Pulmonary abnormalities areommon and similar to those seen in previously describedTDs. In a series of 44 patients with MCTD, Bodolay et al.66

eported active interstitial lung disease in 66% of patients.round-glass opacity alone (78%) or in association with mildbrosis and parenchymal lines (21%) was the most commonRCT finding. The peripheral distribution of lesions with

ower lobe predominance is compatible with the radiologic66,67

attern of NSIP. Honeycombing is very rare. Pulmonary

ypertension is present in 4% of patients with MCTD and is major cause of patient demise, ahead of respiratory fail-re and heart failure.67 CT may demonstrate an enlarged

R

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Lung disease associated with connective tissue disease

pulmonary artery. Other associated findings include pleuralthickening and effusion27 and esophageal abnormalities.67

Conclusion

CTDs are associated with a wide spectrum of lung condi-tions, which result in significant morbidity and mortality.The radiologist should be familiar with these entities andsystematically evaluate the radiologic images in order todiagnose interstitial, airway, pleural or vascular disease, andcorrelate these findings with the underlying CTD. It shouldbe taken into account that lung changes may precede CTDsymptoms and that, in some cases, the radiologic patternof NSIP, the detection of lung cysts or coexistence of aninterstitial and bronchiolar pattern should raise the suspi-cion of underlying CTD. HRCT plays an important role in theearly detection of pulmonary disease in patients with CTDand in the detection of subclinical pulmonary disease in cer-tain situations such as SCL and antisynthetase syndrome,facilitating an early treatment. In addition, the high rateof infections, drug-related adverse reactions and a higherincidence of lung cancer and lymphoma should always beconsidered in patients with pulmonary disease associatedwith a CTD.

A multidisciplinary approach involving clinical,radiologic and histologic findings provides a more accuratediagnosis and treatment of these diseases.

Ethical responsibilities

Human and animal protection. The authors declare that noexperiments involving animals or humans have been carriedout for this study.

Data confidentiality. The authors declare that no data frompatients are shown in this article.

Right to privacy and informed consent. The authorsdeclare that no data from patients are shown in this article.

Authorship

1. Responsible for the integrity of the study: RYM.2. Conception of the study: RYM.3. Design of the study: RYM, ABY, SEP, MBN and RRM.4. Data acquisition: RYM, ABY, SEP and MBN.5. Analysis and interpretation of data: RYM, ABY, SEP, MBN

and RRM.6. Statistical analysis: N/A.7. Bibliographic search: RYM, ABY and RRM.8. Writing of the article: RYM, ABY and RRM.9. Critical review with intellectually relevant contrib-

utions: RYM, ABY, SEP, MBN and RRM.10. Approval of the final version: RYM, ABY, SEP, MBN and

RRM.

Conflicts of interest

The authors declare not having any conflict of interests.

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