Thorax 1985;40:371-375

Thoracoscopic, histological, and clinical findings innine case of rheumatoid pleural effusionP FAURSCHOU, D FRANCIS, P FAARUP

From Medical Department P and the Department ofPathology, Bispebjerg Hospital, Copenhagen, and theUniversity Institute ofPathology, Copenhagen, Denmark

ABSTRACr A characteristic thoracoscopic picture of a granular parietal pleural surface was foundin nine patients with rheumatoid pleurisy. Characteristic changes could be identified histo-pathologically in material obtained by biopsy. The rheumatoid pleural effusion resolved within an

average of 14 months and no serious complications developed after the pleurisy. It is concludedthat in rheumatoid pleural effusion a positive diagnosis can be made by thoracoscopy, preferablysupported by the identification of microscopic structural changes in the parietal pleura.

Rheumatoid pleurisy is at present a diagnosisreached only by exclusion.'-3 Certain biochemicalchanges in the rheumatoid pleural effusion, such aslow glucose and high lactate dehydrogenase con-centrations, are of diagnostic help but are notspecific,24 nor is the finding of the so calledrheumatoid arthritis cells (RA cells).45

In rheumatoid pleurisy "blind pleural biopsies"most often show non-specific inflammatory changes,and in most cases the purpose of the biopsy is toexclude other diseases.' 3 6-8 Specific rheumatoidlesions in the pleura corresponding to those found insubcutaneous rheumatoid nodules are seldomseen.3 " The subsequent clinical course of the dis-ease seems to vary greatly'-3The aim of the present study was to describe the

thoracoscopic appearance and the histopathologicalfeatures of the pleural surface together with the clin-ical course in nine cases of rheumatoid pleurisy.

Material and methods

Twelve hundred thoracoscopies were performedduring 10 years. In nine of the patients the pleuralsurface showed a unique granular appearance.Three parietal pleural biopsy specimens on averagewere taken from each patient and one visceralbiopsy specimen was taken in four of the patients;pleural fluid was examined in all. Seven of the nine

Address for reprint requests: Dr P Faurschou, Medical DepartmentP, Bispebjerg Hospital, Copenhagen NV, DK-2400, Denmark.

Accepted 3 December 1984

patients had classical rheumatoid arthritis (accord-ing to the American Rheumatism Associationcriteria'2) with rheumatoid pleural effusion, and twohad monosymptomatic pleurisy as the first manifes-tation of the rheumatoid disease, which presented asdefinite rheumatoid arthritis one and three monthslater respectively (table). There were seven men andtwo women, mean age 54 years. The clinical coursewas in each case ascertained from the case records,personal interview, and examination and in somepatients from the death certificates and necropsyreports. The definition used for remission of arthritiswas that a patient should have had no treatment andbeen free from complaints related to the joints.

Thoracocentesis with air insufflation andthoracoscopy were performed under local anes-thesia. The thoracoscope used was a rigid fibreopticscope (Storz), and the biopsy specimens were takenwith a spoon forceps.

Thoracoscopic biopsy specimens were formalinfixed and stained with haematoxylin eosin and vanGiesen Hansen. The pleural fluid was examined forglucose, protein, lactate dehydrogenase, RA cells,crystals, tumour cells, and bacteria.

Results

THORACOSCOPIC FINDINGSIn all cases the visceral pleural surface showed avarying degree of non-specific inflammation. In con-trast, the parietal pleural surface had in each case a"gritty" or frozen appearance. The surface lookedslightly inflamed and thickened with numerous smallvesicles or granules of about 0.5 mm in diameter

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Selected laboratory and clinical data on patients with rheumatoid arthritis and rheumatoid pleural effiusionsPatient Pleural effusion Characteristics of Clinical follow up afterNo and arthritis thoracoscopysex

Protein Glucose LDH RA Cholesterol Thoracocenteses/months Interval (y) from arthritis Stage*(gil) (mg/l OO ml) (U/i) cells crystals to thoracoscopy (pleurisy)

Volume offluid (ml)aspirated

I M 62 0 2000 + + 5/24 11 years(L) C Alive after lOywith3000 continuous activity of arthritis

2 M 49 25 5840 + - 9/36 2 years (R) C Alive after 10 y with3950 5 years (L) continuous activity of arthritis

10 2400 + - 5/12800

3 M 62 10 4500 + - 4/24 11 years (R) C Died after 8 y of perforated0 7500 + - 1300 appendicitis (N) with

continuous activity of arthritis attime of death

4 F 44 25 5720 + + 2/3 10 years (R) C Died after I y of pulmonary1500 embolus (N) with continuous

activity of arthritis at time of death5 M 44 30 7000 + + 2/12 10 years (L) C Died after 6 y of acute myocardial

600 infarction (N) with remission ofarthritis

6 M 99 0 7200 + - 3/9 3 years (L) C Alive after 10 y with remission ofarthritis

7 F - - - + + 6/14 30 years (L) C Alive after 10 y with continuous72 25 6200 2000 33 years (R) activity of arthritis

4/121100

8 M 88 0 3200 + - 2/2 -1/4 year (L) D Alive after 31/2 y without activity800 of arthritis the last 11/2 y

9 M 50 83 1731 + - 1/1 - 1/12 year (L) D Alive after 1 y with continuous500 activity of arthritis

Mean value 63 19 4844 4/141500

*C-classical: D-definite.LDH-lactate dehydrogenase; RA-rheumatoid arthritis: N-Necropsy.Conversion: traditional to SI units-Glucose: 1 mg/100 ml = 0.0555 mmol/l.

Fig 1 Thoracoscopic view of the costal parietal pleura inrheumatoid pleurisy, with a gritty, granular surface. Smallgranules are scattered all over the surface (patient 8).

(fig 1). These granules were identified all over theparietal pleura in eight of our cases: in one case theywere more unevenly distributed, being localisedmostly in the upper lateral part of the costal pleura.

Thoracoscopy was performed without any seriouscomplications. One patient required four days ofpleural drainage to expand the lung.

HISTOPATHOLOGICAL CHANGES IN THE PLEURAThe most constant finding was lack of a normalmesothelial cell covering. Instead a pseudostratifiedlayer of epithelioid cells was seen, which focallyformed multinucleated giant cells of a type differentfrom those of Langerhans, as well as foreign bodygiant cells (figs 2 and 3). In several instances theepithelioid cell layer was found as membranesparted from the stroma. The stroma was fibrous andshowed features of chronic focal inflammation,although it was only slightly infiltrated. There wereno granulomas or necrosis. The luminal outline ofthis stroma appeared slightly wavy because of regu-lar small papillae containing branching capillaries(figs 2 and 4). The size of these papillae and thedistance between them (0.1-0.5 mm) were similar to

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Thoracoscopic, histological, and clinical findings in nine cases of rheumatoid pleurc

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those of the small granules identified thoracoscopi-cally. The most characteristic histological appear-ance was found in the parietal pleural biopsy speci-mens from four of the patients. Scme of these fea-tures were found in the remaining parietal pleuralbiopsy specimens. In the four visceral pleural biopsyspecimens only non-specific inflammatory changeswere found.

THE PLEURAL FLUIDMacroscopically the fluid was cloudy, greenish yel-low, opalescent, and non-odorous. In all cases anexudate was present (table) (mean value of proteincontent 63 g/l). The glucose concentration was lowin eight patients (mean value 13 mg/100 ml (0.72mmol/l)) but in one case was as high as the bloodglucose (83 mg/100 ml (4.6 mmol/l)). The lactatedehydrogenase content was constantly high (meanvalue 4844 U/l). In all cases RA cells were present.Cytological examination showed the presence ofeosinophilic, amorphous material, cholesterol cryst-als, epithelioid cells, and scattered multinucleatedgiant cells. There were no tumour cells and all cut-tures were negative for bacteria.

CLINICAL COURSE OF RHEUMATO'D ARTHRITISAND RHEUMATOID PLEURISYThe average period between the onset of arthritisand the pleurisy was 13 years for seven of thepatients (table). Two patients had pleurisy as thefirst manifestation of the rheumatoid disease, fol-

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Faurschou, Francis, Faarup

T - g',x* Fig 4 Biopsy specimenfrom the parietal pleurafrom the same patient as infigure 1, showing theundulated surface coveredwith epithelioid cells. Thepapillary structure is easilyseen, as indicated byarrows. (van GiesenHansen, x330.),:.,.4 7~~~~~~~~~~~~~~~~~

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lowed by arthritis after one and three monthsrespectively. The pleural effusion lasted an averageof 14 months (range 1-36 months). The averagenumber of thoracocenteses was four per patient(range 1-9). The mean value for the total amount offluid removed was 1500 ml per patient (range 500-3950 ml). In seven cases the pleurisy was unilateral.The remaining two patients each developedrheumatoid pleurisy on the contralateral side afteran interval of three years.Four patients with persistent rheumatoid arthritis

were alive 10 years after thoracoscopy, showing noclinical or radiographic signs of pleural activity.Three patients with persistent rheumatoid arthritisdied from intercurrent diseases one, six, and eightyears after thoracoscopy. Patient 8 was alive afterthree years, having had remission of the arthritisover the last one and a half years. Patient 9 was aliveafter one year and suffered continuous activity ofthe rheumatoid arthritis.

Discussion

Thoracoscopy showed an identical and characteristicmacroscopic appearance of the parietal pleura in allour nine patients. This appeararnce was not seen inany other category of pleural disease,'3 14 and to ourknowledge it has not been previously described inthe literature except for one preliminary report in1974.)9 The lack of specific thoracoscopic findings intwo patients with rheumatoid pleural effusionreported by Jacobeaeus in 1925's could possibly be

ascribed to the relatively primitive thoracoscopicequipment used as well as to diagnostic problems.Champion et al'6 described the microscopic

changes in rheumatoid pleurisy as an opened outrheumatoid nodule with palisading epithelioid cellscovering the surface. We found a similar appearancein all of our cases that was most characteristic in thebiopsy specimens from the parietal pleural surface.Aru et al'7 claimed that the histological changes arecharacteristic and specific for rheumatoid pleurisy.There are several reasons for the absence of thisobservation among the reports on histologicalchanges in rheumatoid pleurisy. The pleurisy is sel-dom acute and is most often treated with simplethoracocenteses. Thoracoscopy is still a relativelyrarely used diagnostic tool, but may be useful whenblind thick needle biopsies fail to provide a diag-nosis. In our patients the absence of characteristichistological changes in material obtained by conven-tional biopsy could be explained by our observationthat the epithelioid cell layer is so easily detached,leaving the denuded raw surface of the slightlyinflamed stroma. Furthermore, the area of the lumi-nal stromal surface in thick needle biopsy specimenswill be too small for recognition of any regularity inthe papillary formations.The biochemical changes in the pleural fluid from

our patients did not differ from those described inprevious reports. In 80% the glucose concentrationin the pleural fluid is found to be low26918 '9 andeither high or in equilibrium with blood glucose con-centration in the remaining cases.' 10 19 This is also a

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Thoracoscopic, histological, and clinical findings in nine cases of rheumatoid pleural effusionfinding, however, in tuberculous pleurisy and malig-nant diseases of the pleura.2 4 The lactate dehydro-genase concentration was high but this finding isalso not specific.24 RA cells from the pleural fluidwere found in all our patients, in accordance withother reports,379202' but the RA cell is not specificfor rheumatoid pleural effusion as this cell is alsofound in other diseases of the pleura.45 A uniquecytological picture in rheumatoid pleural effusionhas been reported.22 24 Moreover, these findingsseem to be specific, as claimed by Engel et al.25 Bythe technique applied for the identification of theRA cells no abnormal cell types were observed inthe cytological specimens in our series.

In our patients rheumatoid pleural effusiondeveloped an average of 13 years after onset of thearthritis and the effusion resolved after an averageof 14 months, but there was a great variation in thisperiod (1-36 months), which is in accordance withthe report of Walker et al. ' No treatment other thanaspiration when clinically indicated was used andthis accords with accepted practice.' 3 In no cases didthe rheumatoid pleural effusion show simultaneousbilateral occurrence, although Walker et al' found afew patients with simultaneous bilateral rheumatoidpleurisy. In none of our patients were there seriouscomplications after the rheumatoid pleurisy, butsevere pleural changes necessitating decorticationhave been reported.'"

In conclusion, rheumatoid pleurisy is at present adiagnosis reached only by exclusion, but thethoracoscopic granular appearance of the parietalpleura and the histopathological changes seem to behighly diagnostic and offer an important supplementto other laboratory data.

References

1 Walker WC, Wright V. Rheumatoid pleuritis. AnnRheum Dis 1967;26:467-73.

2 Anonymous. Pleural effusion in rheumatoid arthritis.Lancet 1972;i:480-1.

3 Emerson P. Rheumatoid disease. In: Emerson P, ed.Thoracic medicine. London: Butterworth, 1981:610-2.

4 Faurschou P. Decreased glucose in RA cell positivepleural effusion. Eur J Respir Dis 1984;65:272-7.

5 Faurschou P, Faarup P. Granulocytes containing cyto-plasmic inclusions in human tuberculous pleuritis.Scand J Respir Dis 1973;54:341-6.

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