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for dyspnea. Two adults who showedsevere arthritis in their hands had beenpreviously diagnosed of rheumatoidarthritis. No visceral involvement wasfound other than lung disease.Biological results showed normal mus-cle enzyme values. Chest x-ray and CTscan revealed small lungs withoutparenchymal or pleural involvement.Pulmonary function tests indicated thepresence of restrictive disease with nor-mal carbon monoxide transfer. Thealveolar-arterial gradient was withinnormal limits. Maximal inspiratory pres-sure was slightly low and maximal expi-ratory pressure was within normallimits. Sleep studies ruled out nocturnalhypoventilation and mild sleep-apneasyndrome was observed in 2 previousheavy snorers. During the follow-upperiod (10 to 46 months) none of thepatients deteriorated.

Conclusions: Shrinking lung syndromeaffects a small proportion of patientswith lupus and may also occur in chil-dren. It should be suspected in patients

Shrinking Lung Syndrome: APulmonary Manifestation ofSystemic Lupus ErythematosusDiurnal Findings and Nocturnal Events

Elsa Naval, MD*

Christian Domingo, MD, FCCP*

Jordi Gratacós, MD†

Montserrat Bosque, MD‡

Manel Luján, MD*

Albert Marín, MD*

*S. Pneumologia, †S. de Reumatologia, ‡S. de Pediatria, Corporació Parc Taulí, Institut UniversitariParc Tauli-FPT Universitat Autonoma de Bellaterra, Barcelona, Spain

KEY WORDS: shrinking lung syn-drome, systemic lupus erythematosus,nocturnal events

ABSTRACTObjectives: To describe the diurnal andnocturnal findings of 4 adults (3 women)and one child with systemic lupus ery-thematosus and shrinking lung syn-drome.

Design: A prospective observationalstudy.

Setting: A 750 teaching-bed-hospitalwith a reference population of 350,000people.

Interventions: Clinical history, bloodanalysis, imaging test, pulmonary func-tion tests, maximal inspiratory and expi-ratory pressures, arterial blood gases,and sleep studies.

Measurements and Results: Patientswere referred to the pneumology service

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with lupus who present exertional dysp-nea without apparent cause. The condi-tion does not seem to affect sleepphysiology, the clinical features tendtowards stabilization regardless of thetreatment prescribed. The origin of thesyndrome seems to be a self-limitedmyositis of the diaphragm.

INTRODUCTIONSystemic lupus erythematosus (SLE) isan inflammatory disease of unknownorigin. It occurs most frequently inwomen at fertile ages, though it has alsobeen reported in males, children, and theelderly. Any organ or system may beaffected: the skin, musculoskeletal sys-tem, kidney, nervous system, digestivetract, cardiocirculatory system or lungs.1

Fifty percent of SLE patients pres-ent pleuropulmonary manifestations.Pleuritis is the most frequent disorder,occurring in approximately 45% ofcases. Other forms of pulmonary impair-ment are lupus pneumonitis (acute orchronic), pulmonary hemorrhage, oblit-erating bronchiolitis with organizedpneumonia, pulmonary vascular diseasein the form of pulmonary thromboem-bolism and plexogenic pulmonaryhypertension, interstitial pulmonaryimpairment (more frequent in otherconnective tissue disorders such asrheumatoid arthritis or systemic sclero-sis), and finally impairment of the respi-ratory muscles, especially of thediaphragm, which may lead to a respira-tory disorder without visceral lunginvolvement. This condition is known asshrinking lung syndrome (SLS).1 Todate, the experience on the evolution ofthese patients is controversial and thereis no information about nocturnal respi-ratory behavior.

The aim of this study is to describethe diurnal and nocturnal behavior of 4adults and one child with SLS and SLE.

MATERIAL AND METHODSPopulation Four adult patients (3 women and 1man), aged between 51 and 76, referredto the Pneumology Service for exertion-al dyspnea and one pediatric patientreferred to the Pediatric Service at ourhospital for fever and pleural effusion.

MethodologyThe following examinations were per-formed in all patients during their firstvisit to the Pneumology Service: clinicalhistory, with special attention to lengthof evolution of the SLE and its form ofpresentation; physical examination;blood analysis including erythrocyte sed-imentation rate, hemogram, generalblood biochemistry (antinuclear anti-bodies, muscle enzymes, C-reactive pro-tein, Rheumatoid factor); imaging tests(x-rays of chest, hands and feet andchest computed tomography scan [CTscan]) and pulmonary function tests(PFTs). Pulmonary function tests werecarried out in our pulmonary functionlaboratory, which is equipped with auto-mated PFT equipment (MedGraphicssystem 1070 Series 2E/1085) for pul-monary volume, diffusion, spirometrytesting and an automated pletysmo-graphic cabin for pulmonary volume andairway resistance testing. Maximal inspi-ratory pressure (MIP) and maximalexpiratory pressure (MEP) were alsodetermined using a manometer(Sibelmed manometer 163, Sibel S.A.,Barcelona, Spain) Arterial blood gaseswere measured with a radial punctureusing local anesthesia, while the patientwas breathing room air (RadiometerABL 500).

In the adults, respiratorypolysomnographies were performedwith a Nocturnal Simplified Polygraph(Sibel home 300, Sibel S.A., Barcelona,Spain), which records nasal/oral airflow(nasal cannula and thermistor), chestwall impedance, oxygen saturation, car-

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diac frequency, snoring, and body posi-tion.2 For the adults, the studies wereperformed in the sleep laboratory of ourhospital. In the pediatric patient, a noc-turnal domiciliary pulse-oximetry(Pulsox 3-Minolta) was performed.Mediterranean population reference val-ues were used.3 For the pediatric patient,the reference values of the SpanishSociety of Lung Disease (SEPAR)4 andPolgar values were used.5 For MIP andMEP, Wilson’s predicted values wereused.6 During follow-up all the comple-mentary examinations were repeated.Patients were controlled on an outpa-tient basis at our hospital’s pneumologyand rheumatology services.

RESULTSIn the past fourteen years, 126 cases ofSLE have been diagnosed at our hospi-tal. Only 5 cases of SLS have beendetected: 4 adults and one child (agerange, 10 to 76).

Clinical HistoryAll patients met the AmericanRheumatism Association (ARA) criteriafor SLE. Two cases presented strikingarticular impairment with high degree ofdeformation and little erosion (Figure1); they were classified as an overlapsyndrome with SLE and rheumatoidarthritis (also called “Rupus”). In 4

patients, SLS presented as dyspnea oneffort, 10, 12, and 20 years after SLEdiagnosis. In one of the cases, a patientwith a prior diagnosis of seronegativeRA, SLE, presented as SLS.

Dyspnea was the predominant respi-ratory symptom and the reason for con-sultation. The dyspnea did not progressduring follow-up (in one patient the dys-pnea was difficult to evaluate due to theextent of her articular limitations).

BiologyIn addition to the alterations typical ofSLE, all patients had normal antinuclearantibody titers, rheumatoid factor wasnegative, and normal levels of muscleenzymes (CK and aldolases) at the timeof diagnosis were obtained. During fol-low-up no increase in CK or aldolasevalues was observed. Renal functionremained unimpaired in all cases.

Pulmonary FunctionPatients presented a restrictive ventila-tory alteration without alteration in car-bon monoxide transfer (normal KCO),stable MEP, but low MIP. Arterial bloodgases showed a normal or slightlyincreased alveolar-arterial oxygen gradi-ent.

Individual values are shown in Table1. The mean values of the PFTs in theadults showed a restrictive ventilatoryalteration: FEV1/FVC: 74 ± 2%; FEV1:1482 mL ± 262 mL (64 ± 8%); FVC:2010 mL ± 434 mL (63 ± 4%); TLC:3665 mL ± 1143 mL (68 ± 6%); RV:1417 ± 516 mL ( 71 ± 9%). CO transferstudy showed: DLCO: 60 ± 10 %;DLCO mL/min/mmHg: 13.3 ± 1.6 ; KCO(DLCO/AV): 91 ± 13 %; KCO(DLCO/AV)mL/min/mmHg: 4.7 ± 0.8;MEP %: 95.5 ± 21.7; MIP %: 82.25 ±10%. The values of the pediatric patientare the following: FEV1/FVC: 97%;FEV1: 1340 mL (56%); FVC: 1380 mL(71%); MIP 74 cmH2O; MEP: 81cmH2O.

Figure 1. Chest x-ray of patient 1. Observe thedecreased number of intercostal spaces aswell as the absence of pleural and parenchy-mal lung disease.

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Respiratory PolysomnographyTwo adults, who had a history of snoringbefore the beginning of the diseaseshowed a mild sleep apnea syndrome(SAS) but none referred diurnal hyper-somnia. In the other 2 cases, respiratorypolysomnography was completely nor-mal. In the pediatric patient, the noctur-nal pulse-oximetry was normal (MeanSp02: 96.8%; Time spent Sp02<90%:0,0%; 4% average dips/hour: 0.5). Thesleep studies also ruled out episodes ofhypoventilation (see Table 2). The poly-graphic studies were repeated after ayear and no significant changes wereobserved.

Imaging Results Chest x-ray in this condition shows acharacteristic elevation of thediaphragm, with reduction of the num-ber of intercostal spaces (between 5 and7) and, as a result, a reduction in lungsize. Chest x-ray did not reveal intersti-

tial infiltrates but in 2 patients there wasbibasilar atelectasis associated with theelevated diaphragm. CT scan confirmedthe absence of any interstitial disease.

Treatment At the time of diagnosis the patientswere receiving treatment with oral corti-coids (dose 4 to 20 mg/day). One patientwas also administered delayed theo-phylline at 10 mg/Kg/weight at the onsetof symptoms without any clinicalimprovement.

Follow-upLength of follow-up varied between 18and 46 months. None of the subjects pre-sented progression of dyspnea, analyticalchanges in the immunological study,radiological images, or in the nocturnalstudies. The only change observed in therespiratory function study was a reduc-tion of the MIP in one case, at 3 monthsand 2 years after diagnosis of the SLS.

Table 1. Pulmonary Function Test*

Patient 1 Patient 2 Patient 3 Patient 4

FEV1/FVC (%) 77 74 71 74

FEV1 (%) 76 64 60 57

(mL) 1290 1520 1840 1280

FVC (%) 68 66 61 58

(mL) 1670 2050 2610 1710

TLC (%) 65 72 75 62

(mL) 2920 3400 5350 2990

VC (%) 61 75 70 61

(mL) 1580 2400 3180 1890

RV (%) 71 62 85 69

(mL) 1340 1060 2170 1100

DLCO (%) 73 64 51 52

DLCO (mL/min/mmHg) 14.10 14.67 13.38 11.10

KCO (%) 108 82 78 98

KCO (mL/min/mmHg) 5.56 4.64 3.68 5.28

MIP (%) 97 * 75 77 80

MEP (%) 128 82 86 86

*Data given in a percentage form (%) are percent of predicted normal values. FEV1 indicates forced expiratory vol-ume in the first second; FVC, forced vital capacity; TLC, total lung capacity; VC, vital capacity; RV, residual volume;DLCO, diffusion lung capacity; KCO, DLCO/VA (alveolar volume), MIP, maximal inspiratory pressure; and MEP,maximal expiratory pressure. *During the following of MIP value decreased 48%.

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DISCUSSIONThe connective tissue diseases causemultisystemic alterations, and theirimpact on the lung is particularly impor-tant. The type of pulmonary impairmentin SLE varies widely. Possibly the leastcommon manifestation is the SLS, whichin fact is exclusive to SLE.1 The clinicalpresentation of SLS tends to be suba-cute dyspnea, without any other accom-panying respiratory manifestations.Chest x-ray reveals reduced lung vol-umes (with at most 7 intercostal spaces)without evidence of occupation of thepulmonary fields or pleural impairment.Spirometry indicates a restrictive venti-latory defect that is confirmed byreduced lung volumes. Diffusing capaci-ty is not impaired. The absence of inter-stitial pulmonary impairment isconfirmed by the observation of normalpulmonary parenchyma on chest CTscan. The biological anomalies typical ofSLE are seen; interestingly, muscleenzymes are normal.

All patients met the ARA criteriafor SLE. Case 4, a woman in whomseronegative RA had been diagnosedseveral years before, was referred to ourservice for dyspnea. Clinically, she hadarticular deformation in both wrists,though hand x-rays ruled out the pres-ence of the erosive changes characteris-tic of RA. The dyspnea was attributed toSLS and the previous diagnosis of RAwas rectified.

Four of our cases were referred fordyspnea, the most frequent symptom of

SLS.1 In common with other reports, theresults of radiological, biological, andfunctional studies in our series showedreductions in FVC and MIP in theabsence of pulmonary parenchymalpathology. These findings indicate animpairment of the respiratory muscles.Though it is true that the MIP and MEPmeasurements reflect alterations of therespiratory muscles as a whole and donot distinguish between muscle groups,the diaphragm is the primary respiratorymuscle. The elevation of both hemidi-aphragms and the compression of thelungs (which on occasion producesbibasilar laminar atelectasis, as in 2 ofour cases) also confirms the involvementof the diaphragm and might be responsi-ble for the slightly increased alveolar-arterial oxygen gradient and slightlydecreased KCO occasionally found dueV/Q mismatch.

Unlike previous reports of SLS, westudied the respiratory behavior of ourpatients during sleep. In 2 cases, a mildSAS was detected although the absenceof diurnal hypersomnia when the respi-ratory polysomnography was performedand the fact that patients had a historyof snoring before the diagnosis of SLSmade us think that their sleep physiolog-ic status did not change before and afterthe SL. So we considered unlikely thepossibility that the SLS was the triggerof a SAS. In the remaining 2 cases, wedid not observe any phenomena sugges-tive or compatible with SAS. In thepediatric patient, the absence of sugges-

Table 2. Polysomnograhic Studies*

Patient 1 Patient 2 Patient 3 Patient 4

BMI (Kg/m2) 29 25 26 27

AHÍ 2 1 14 24

Initial SpO2 (%) 96 97 97 98

Mean SpO2(%) 94 96 96 97

Sp02< 90 (%) 0 0 0 0

*BMI indicates body mass index; AHI, apnea/hypopnea index; and Sp02, oxygen saturation measured by the pulse-oximeter.

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tive clinical data of SAS and the absenceof typical oxygen desaturations7 duringsleep also ruled out the diagnosis ofSAS. This point is important, as it rulesout any alteration of the pharyngealmuscles, which might have favored air-way obstruction during sleep. We con-clude that the clinical effect of themuscle impairment seems to be restrict-ed to the diaphragm and is not particu-larly severe at night given that it doesnot cause hypoventilation.

The clinical evolution of SLS showsa clear tendency towards stabilization.No central changes were observed dur-ing follow-up. The existing treatment ofthe patients was maintained (oral corti-costeroids in most cases) and in one casetheophylline was added without appear-ing to modify the course of the illness.The experiences reported by differentauthors vary, but our follow-up period isamong the longest in the literature andwe believe that most of these patientsstabilize once diagnosis is made.

SLS has been reported almost exclu-sively in adults, possibly because theincidence of SLE is far higher in adultsthan in children. Our 10-year old patientdeveloped a respiratory alteration com-patible with SLS 3 months after improv-

ing his clinical situation and disappear-ance of the pleural effusion. The patientwas treated with corticosteroids at aninitial dose of 0.5 mg/Kg weight/day; thedose was progressively reduced over a 6-month period, at the end of which thepatient was asymptomatic. After eight-een months the patient continued topresent a functional respiratory alter-ation compatible with a pulmonaryrestriction (Forced Spìrometry: FVC:2.20 L- 56%; FEV1. 2.0L- 62%;FEV1/FVC: 91%). It is well known thatfunctional evaluation in children pres-ents the added problem that pulmonarydevelopment and its assessment via afunctional study depends on a range ofaspects, among them the predictionequations used. We first used theSEPAR equations4 and then corroborat-ed the results with the Polgar equations5;we did not find notable changes in theclinical interpretation of the spirometryresults. The patient’s absolute values forFVC and FEV1 improved slightly (820mL and 660 mL respectively), but thiswas due mainly to the lung growth thataccompanies development. The subject’sheight increased from 143 cm to 156during the follow-up period. The spirom-etry, MIP, and MEP values, obtained atthe end of follow-up (after 18 monthsand obviously after the end of corticoidtreatment), were still compatible withSLS. We conclude therefore that thepatient presented SLS (the history of apleural effusion with total resolution as

Figure 2. The CT scan, of patient number 3,rules out the presence of interstitial disease.

Figure 3. The x-ray of the righthand of patient3 shows animportant defor-mation of hermetacarpopha-langic joints withlack of boneerosion, which istypical inrheumatoidarthritis.

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shown on the chest CT scan does notaccount for the presence of a pulmonaryrestriction) associated with SLE.

Interestingly, SLS presents inpatients with SLE with little or no vis-ceral impairment. SLS is then often thecondition that leads patients to seekmedical attention. Furthermore, SLS hasonly been reported in SLE patients, andhas not been observed in other connec-tive tissue diseases; so SLS seems tooccur in particularly benign forms ofSLE, in which there is little visceralinvolvement. In addition, a clinical pic-ture suggestive of SLS should alert theclinician to the possibility of SLEbecause the condition has only beendescribed in the context of lupus.

The etiopathogenesis of the processis controversial. Gibson et al8 andMartens et al9 reported a reduction intransdiaphragmatic pressure (measuredby esophageal and gastric balloon), sug-gesting diaphragm weakness. Theseauthors attributed the muscle weaknessto the SLE. At one point, it was suggest-ed that corticosteroids treatment mightbe the cause of the myopathy, but thispossibility was ruled out because somepatients presented SLS before thebeginning of treatment. However,Laroche et al10 reported normal transdi-aphragmatic pressure (measured by the“sniff” maneuver) in some of theirpatients and conclude that the weaknessof the respiratory muscles is not thecause of the syndrome. Moreover, theseauthors suggested the possibility ofphrenic nerve impairment as the causeof the syndrome although the majorityof studies of nerve conduction havefound no phrenic nerve lesions.8,9

Although we did not attempt to studyphrenic nerve involvement, weobserved, in our series, elevateddiaphragms in both hemithorax and arespiratory function compatible withmuscular involvement. The possibilitythat both phrenic nerves were affected

at the same time seemed unlikely.Moreover a phrenic nerve palsy wouldimpair respiratory function much morethan observed. A polygraphic nocturnalstudy that ruled out the involvement (atleast to a clinically relevant degree) ofthe pharyngeal muscles, as the cause ofthe nocturnal obstructive phenomenatypical of SAS, was also performed. Theimpairment, therefore, appears to berestricted to the respiratory muscles,basically the diaphragm muscle. It isinteresting that all our cases presentednormal muscle enzyme values, but webelieve that this is due to the fact thatthe patients presented clinical respirato-ry disorders after the outbreak of myosi-tis, during which increases in CK andaldolase values would have been detect-ed.

To conclude, we believe that SLSaffects a small proportion of SLEpatients but may be under diagnosed indaily clinical practice. It should be sus-pected in lupus patients who presentexertional dyspnea without an apparentcause, with x-ray findings of pulmonaryrestriction and normal pulmonaryparenchyma. The condition does notseem to affect sleep physiology and inour experience tends to stabilize, howev-er, is not influenced by treatment.Therefore, it seems advisable to avoidmeasures that may cause iatrogenia,such as adding oral corticoids or increas-ing the dose. Although not definitelydemonstrated, the hypothesis that thissyndrome might be due to a myositisprobably limited to the diaphragm mus-cle is attractive. Finally, physicians mustkeep in mind that the condition mayalso occur in children.

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Pulmonary manifestations of Systemic LupusErythematosus. Clinics Chest Med.1998;19:641-665.

2. Ballester E, Solans M, Vila X, et al.Evaluation of a portable respiratory record-

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3. Roca J, Sanchis J, Agustí-Vidal A, et al.Spirometric reference values for aMediterranean population. Bull EurPhysiopathol Respir. 1986;22:217-224.

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