efusi

Weekly Clinicopathological Exercises

F O U N D E D B Y R I C H A R D C . C A B O T

N

ANCY

L

EE

H

ARRIS

, M.D.,

Editor

W

ILLIAM

F. M

C

N

EELY

, M.D.,

Associate Editor

J

O

-A

NNE

O. S

HEPARD

,

M.D.,

Associate Editor

S

ALLY

H. E

BELING

,

Assistant Editor

S

TACEY

M. E

LLENDER

,

Assistant Editor

C

HRISTINE

C. P

ETERS

,

Assistant Editor

N Engl J Med, Vol. 346, No. 11

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Case Records of the Massachusetts General Hospital

CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL

Case 8-2002

PRESENTATION OF CASE

A 56-year-old woman was admitted to the hospitalbecause of a persistent left-sided pleural effusion.

The patient had a history of rheumatoid arthritis,which had become disabling about two years beforethe current admission. She had otherwise been welluntil six months before admission, when she enteredanother hospital because of pleuritic left-sided chestpain. Analysis of a specimen of arterial blood obtainedwhile the patient was breathing ambient air revealedthat the partial pressure of oxygen was 66 mm Hg, thepartial pressure of carbon dioxide 24 mm Hg, and thepH 7.46. The urine was normal, and cultures of urineand blood were sterile. The hematocrit was 35.1 per-cent; the white-cell count was 9900 per cubic mil-limeter, with 65 percent neutrophils, 17 percentlymphocytes, 15 percent monocytes, 2 percent eo-sinophils, and 1 percent basophils; the platelet countwas 261,000 per cubic millimeter; and the mean cor-puscular volume was 100.1 µm

3

. The prothrombintime, partial-thromboplastin time, and

D

-dimer valuewere normal. The glucose level was 115 mg per deci-liter (6.4 mmol per liter), and the albumin level was3.3 g per deciliter. The levels of electrolytes, aspartateaminotransferase, and alanine aminotransferase werenormal. The level of thyrotropin was slightly low, at0.28 mU per milliliter, but the free thyroxine and tri-iodothyronine levels were normal, as were the levels ofurea nitrogen, creatinine, conjugated and total biliru-bin, and alkaline phosphatase.

Chest radiographs obtained at this time showed aleft-sided pleural effusion and a patchy opacity in theleft lower lobe; the size of the heart was normal (Fig.1). A ventilation–perfusion scan revealed a low prob-

ability of pulmonary embolism. Thoracentesis yield-ed cloudy fluid that contained 120,000 red cells and97,400 white cells per cubic millimeter; of the whitecells, 78 percent were neutrophils, 7 percent lympho-cytes, 9 percent monocytes, and 6 percent eosinophils.The specific gravity of the specimen was 1.030; theglucose level was 47 mg per deciliter (2.6 mmol perliter), the cholesterol level was 143 mg per deciliter(3.7 mmol per liter), the albumin level was 2.3 g perdeciliter, the total protein level was 4.6 g per deciliter,the amylase level was 31 U per liter, and the lactate de-hydrogenase level was 1565 U per liter. Microscopicalexamination of the fluid showed no acid-fast bacilli,fungi, or other microorganisms; anaerobic, fungal, andmycobacterial cultures were sterile. A chest radiographobtained after the thoracentesis disclosed a substantialdecrease in the size of the left-sided pleural effusion;an area of increased density at the base of the left lung;and a nodule, 8 mm in diameter, in the left upper lobethat had not been clearly identified on the previousexamination.

Antibiotic therapy was begun. A computed tomo-graphic (CT) scan of the thorax (Fig. 2), obtained

Figure 1.

Posteroanterior Chest Radiograph Showing a Left-SidedPleural Effusion and a Patchy Opacity in the Left Lower Lobe.

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The New England Journal of Medicine

without the administration of contrast material,showed the left-sided pleural effusion as well as air-space disease in the lingula and left lower lobe, sus-pected to be atelectasis; centrilobular emphysema andbullous disease were also present and were worse inthe upper lobes than in the lower lobes. No definiteendobronchial lesion or lymphadenopathy was iden-tified, and the heart appeared normal. On the eighthhospital day, repeated chest radiographs revealed in-creased aeration at the base of the left lung and againshowed the opacity in the left lower lobe; the pleuraleffusion had decreased further in size. The next day,the patient was discharged.

Sixteen weeks before the current admission, the pa-tient returned to the same hospital because of chestpain. Repeated radiographs of the chest disclosed in-creased density at the left lung base; the effusion hadincreased in size, and there was underlying atelecta-sis, pneumonia, or both. The right lung and heart re-mained normal. Antibiotics were administered.

Four weeks later, the patient returned to the samehospital because of fever and cough. The findings onchest radiographs were unchanged. Twelve days later,CT scanning showed the small, left-sided pleural effu-sion and subsegmental atelectasis or scarring in the lin-gula but no other abnormalities. Eighteen days later,chest radiographs again showed the effusion, as wellas decreased parenchymal density at the left lung base,and again showed scarring or subsegmental atelectasisin the lingula. Two weeks later, findings on additionalradiographs of the chest were unchanged.

Sixteen days before the current admission, the pa-tient consulted a pulmonologist because of the persist-ent left-sided pleural effusion. Physical examination re-vealed decreased breath sounds and a few rhonchi atthe left lung base but no other abnormalities. Thefindings on a thoracic CT scan were unchanged, ex-

cept for the appearance of bilateral axillary lymphnodes; a few of the nodes on the right side were min-imally enlarged, but they contained fat and were notconsidered abnormal. An abdominal and pelvic CTscan obtained on the same day was unremarkable. Thepatient was referred to this hospital.

She had a 30-pack-year history of cigarette smok-ing but had stopped smoking three months earlier. Shehad no known exposure to asbestos or other indus-trial dusts and no recent history of chills, sweats, spu-tum production, hemoptysis, headache, bone pain, orweight loss. Her only current medication was predni-sone (10 or 20 mg daily). She had taken methotrexatebut had discontinued it six months before admissionbecause she believed that it worsened her breathing.She had also reportedly taken etanercept, an inhibitorof tumor necrosis factor, but the timing and dosagewere uncertain.

The temperature was 36.9°C, the pulse was 108,and the respirations were 18. The blood pressure was135/75 mm Hg.

On physical examination, the patient appeared com-fortable at rest. There were prominent rheumatoid de-formities that involved the hands, ankles, and knees,and the gait was very slow. No rash or cervical lym-phadenopathy was found. Soft, bilateral axillary lymphnodes were palpated; the nodes on the right side wereslightly enlarged. The lungs were clear except for ev-idence of the left-sided pleural effusion. The heartand abdomen were normal. There was peripheral ede-ma (++) bilaterally, without signs of deep venousthrombosis.

The hematocrit was 40.4 percent; the white-cellcount was 11,000 per cubic millimeter, with 71 per-cent neutrophils, 22 percent lymphocytes, 5 percentmonocytes, 1 percent eosinophils, and 1 percent ba-sophils; the platelet count was 348,000 per cubic mil-limeter. The prothrombin time was normal, and thepartial-thromboplastin time was in the low-to-normalrange, at 22.7 seconds. The glucose level was 122 mgper deciliter (6.8 mmol per liter). The levels of ureanitrogen, creatinine, and electrolytes were normal. Anelectrocardiogram revealed sinus tachycardia at a rateof 105 beats per minute, with left atrial enlargementand minor, nonspecific ST-segment and T-wave abnor-malities.

A diagnostic procedure was performed.

DIFFERENTIAL DIAGNOSIS

D

R

. D

EBORAH

A. Q

UINN

*: May we review theradiographs?

D

R

. T

HERESA

C. M

C

L

OUD

(Cardiothoracic Radi-ology): A series of radiographs was obtained over

Figure 2.

CT Scan of the Thorax Showing a Left-Sided PleuralEffusion (Arrows).

*Assistant physician, Pulmonary and Critical Care Unit, MassachusettsGeneral Hospital; instructor in medicine, Harvard Medical School.




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about a six-month period. On the initial radiograph(Fig. 1), there is evidence of a left-sided pleural effu-sion, and there is a patchy opacity in the left lower lobethat suggests the presence of atelectasis underlying theeffusion. The chest radiograph obtained after thora-centesis shows a decrease in the size of the effusion,but there is a persistent opacity, probably atelectasis, inthe left lower lobe; there is also a small nodule, 8 mmin diameter, in the left upper lobe. On a subsequentCT scan (Fig. 2), no nodule is seen, but the scan con-firms the presence of the left-sided pleural effusion.In addition, other scans reveal patchy air-space diseaseinvolving the anterior portion of the left lower lobeand the lingula, as well as some atelectasis in the leftlower lobe. In summary, over a period of about sixmonths a left-sided pleural effusion and a few nonspe-cific opacities at the base of the left lung were notedon multiple imaging studies.

D

R

. Q

UINN

: The first step in developing a differen-tial diagnosis of a pleural effusion is to establish wheth-er the effusion is a transudate or an exudate by analysisof fluid obtained at thoracentesis. Transudative effu-sions are caused by imbalances in the plasma osmoticor hydrostatic pressures and occur in congestive heartfailure, cirrhosis of the liver, and the nephrotic syn-drome. Exudative effusions are caused by impairmentof the lymphatic drainage of the pleural space or bypleural inflammation and are found in a wide rangeof illnesses.

1

The features of exudative effusions may be used ascriteria to distinguish them from transudative effusions(Table 1). In this case, the lactate dehydrogenase levelof 1565 U per liter and the cholesterol level of 143 mg

per deciliter meet the criteria for an exudative effusion.On the basis of the patient’s history, the possible caus-es of an exudative effusion in this case include hy-pothyroidism, pulmonary embolism, asbestosis, drugs,cancer, infections (including fungal infections, nocar-dial infections, actinomycosis, and tuberculosis), andrheumatoid pleuritis. Findings in the pleural fluid canhelp one differentiate among these possible diagnoses.This patient’s pleural fluid was cloudy, with highcounts of red and white cells, a predominance of neu-trophils, and a low glucose level. The pH of the pleuralfluid was not recorded, but this information wouldhave been helpful.

The physicians caring for this patient considered thepossibility of hypothyroidism. Hypothyroidism has ob-vious symptoms, and it sometimes causes a pleural ef-fusion.

2

However, in that circumstance the pleural-fluid glucose level is not low, as it was in this case.Furthermore, this patient’s free thyroxine and triiodo-thyronine levels were normal, making hypothyroidisman unlikely cause of the effusion.

Pulmonary embolism is also a consideration. Pleu-ral effusions in cases of pulmonary embolism are usu-ally small and unilateral

3

and are often bloody, withmore than 10,000 red cells per cubic millimeter. Thenumber of white cells is variable, with a predominanceof either neutrophils or lymphocytes.

3

In this case, aventilation–perfusion lung scan showed a low proba-bility of pulmonary embolism; in addition, the resultof a

D

-dimer test was normal, although the techniquefor measuring the

D

-dimer is not reported. This pa-tient had no known risk factors for pulmonary embo-lism, so other diagnoses seem more likely.

*PF denotes pleural fluid, and LDH lactate dehydrogenase. To convert the value for cholesterol tomillimoles per liter, multiply by 0.02586.

†The modified Light criteria had higher sensitivity and specificity for identifying an exudate in thesame study population.

3

T

ABLE

1.

I

NDICATORS

OF

E

XUDATIVE

P

LEURAL

E

FFUSIONS

.*

I

NDICATOR

S

ENSITIVITY

FOR

E

XUDATE

S

PECIFICITY

FOR

E

XUDATE

R

EFERENCE

percent

Light criteriaPF protein:serum protein >0.5PF LDH >200 U/literPF LDH:serum LDH >0.6

98 72–82 Gottehrer et al.,

2

Bynum and Wilson,

3

Epler et al.

4

Modified Light criteriaPF protein:serum protein >0.5PF LDH >45% upper limit of normalPF LDH:serum LDH >0.6

Increased† Increased† Bynum and Wilson

3

Cholesterol and LDHPF cholesterol >45 mg/dlPF LDH >200 U/liter

99 98 Epler et al.

4

AlbuminSerum albumin ¡ PF albumin <1.2 g/dl

95 100 Hillerdal

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A benign pleural effusion is the most commonmanifestation of asbestosis in the first 20 years afterexposure to asbestos.

4

The effusion may be serosan-guineous or just bloody, usually with a red-cell countof less than 6000 per cubic millimeter and occasional-ly with a predominance of eosinophils. The glucoselevel in the pleural fluid in persons with this type ofeffusion equals the serum glucose level,

1

and the ef-fusion can persist for several months.

5

Consideringthis patient’s low glucose level, her high cell counts,the absence of eosinophilia, and the absence of knownexposure to asbestos, a diagnosis of benign asbestos-related pleural effusion seems unlikely.

Several medications have been shown to cause drug-induced pleural effusions, including procainamide (as-sociated with a lupus-like reaction), nitrofurantoin,dantrolene, methysergide, procarbazine, methotrexate,bromocriptine, practolol, amiodarone, mitomycin, ble-omycin, and minoxidil.

1

This patient had been treatedwith methotrexate for her rheumatoid arthritis, butshe had discontinued it six months before the currentadmission because of shortness of breath. In a seriesof 45 patients treated for rheumatoid arthritis withmethotrexate for three years, there were no reports ofpleural effusions.

6

Most reported cases of pleural effu-sion during methotrexate therapy involve patients be-ing treated for a malignant tumor.

7,8

The effusion inthis case persisted, even though the patient had notbeen treated with methotrexate for six months, andtherefore methotrexate appears to be an unlikely cause.This patient had also been treated with etanercept, aninhibitor of tumor necrosis factor that has not been as-sociated with the development of pleural effusions.

9

Because this patient had a 30-pack-year history ofsmoking, it is possible that the effusion was due tocancer. A pleural effusion may be the first sign of can-cer, in which case the most common sites of the pri-mary tumor are the lung and the breast. The effusionstend to range from moderate to massive, with 90 per-cent larger than 500 ml and 59 percent larger than1000 ml. They can be unilateral or bilateral.

10

Thecharacteristics of the pleural fluid in these cases arenonspecific, although a low pH and a low glucose lev-el have been associated with shorter survival.

10,11

Thispatient had had a small, persistent effusion for sixmonths, and at the time of admission she had nosymptoms such as hemoptysis, chest pain, dyspnea,cough, bone pain, or weight loss that would suggestthe presence of a malignant tumor.

The patient had been taking prednisone daily foran unknown length of time and had previously takenmethotrexate. Infections due to immunosuppressionand pleural effusion, such as actinomycosis, nocardialinfection, aspergillosis, cryptococcosis, and histoplas-mosis, are therefore diagnostic possibilities.

6,12-15

Par-asitic infections, bacterial infections with parapneu-

monic effusions, and atypical forms of pneumonia(including those caused by viruses, mycoplasma, Q fe-ver, and legionella) have been associated with pleuraleffusions

1

but are unlikely diagnoses in this case be-cause of the indolent course and the absence of acutesymptoms at the time of admission.

At presentation, actinomycosis and nocardial infec-tion have similar radiologic features, including homo-geneous, dense air-space disease. Abscess formation,pleural thickening, and chest-wall involvement arecommon. Chronic pneumonia with cough and feveris often present.

12,16,17

In fungal diseases such as as-pergillosis and histoplasmosis, the pleural-fluid glucoselevels equal the serum glucose levels.

1

Aspergillosis of-ten causes nodular pleural thickening and is associatedwith tuberculosis or postoperative lung infection.

18

Inthe current case, the absence of pleural changes, thenegative cultures for fungus, the indolent course, thelow glucose level in the pleural fluid, and the absenceof a history of travel to areas where histoplasmosis isendemic make fungal disease an unlikely diagnosis.

Tuberculous effusions are estimated to occur in4 percent of newly diagnosed cases of tuberculosis.

1

The effusions are usually small to moderate in size, butthey can be massive. They occur more often on theright side than on the left but may be bilateral.

19

Thewhite-cell count has been reported to range from2000 to 8000 cells per cubic millimeter,

19,20

with ap-proximately 44 percent of these effusions containingmore than 50 percent lymphocytes.

19

A predominanceof neutrophils has also been reported

19-21

and has beenfound to occur early in the disease.

1

Mycobacteriumtuberculosis

is cultured from the pleural fluid in 35to 64 percent of cases of tuberculous effusions; stain-ing for acid-fast bacilli is positive in less than 10 per-cent.

1,19-21

If more than 5 percent of the cells in thepleural fluid are mesothelial, the presence of a tuber-culous effusion can be ruled out,

22

but mesothelialcells either were not present in this patient’s speci-men or were not measured. Any inflammatory proc-ess can cause a paucity of mesothelial cells.

CT scanning can be helpful in distinguishing tuber-culous effusions from other types of pleural effusions,and it can reveal small areas of cavitation not seen onchest films.

23

In a series of 24 patients with tubercu-lous pleurisy,

23

only 2 patients had no evidence of en-larged hilar or mediastinal nodes, cavitary lung disease,or fibronodular parenchymal changes. Both of thesepatients had rib enlargement, and one had a subcap-sular tissue mass. In a series of 66 patients with tu-berculous pleurisy,

24

all but 1 had pleural thickeningof more than 1 cm. The patient under discussion hadno pleural thickening. She did have an 8-mm nodulein the left upper lobe, a finding that may be consis-tent with an old tuberculous infection. However, be-cause of the absence of other findings consistent with




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tuberculosis on CT scanning, tuberculous pleurisy isnot likely in this case.

This patient had rheumatoid arthritis, which had be-come disabling two years before admission. On phys-ical examination, she had prominent rheumatoid de-formities involving the hands, ankles, and knees.Several extraarticular features of rheumatoid arthritismay involve the lung; they include pulmonary fibrosis,upper-lobe fibrobullous disease, necrobiotic nodules,pulmonary hypertension, Caplan’s syndrome, bronchi-olitis obliterans, follicular bronchiolitis, and pleural ef-fusion.

12

Pulmonary manifestations may precede orfollow the diagnosis of rheumatoid arthritis.

25

Pleuraleffusion, which may recur more than 10 years afterthe diagnosis,

25

has been found to be one of the mostfrequent manifestations of rheumatoid arthritis in thelung; the incidence varies from 2 to 52 percent.

25

Pleural effusion in cases of rheumatoid arthritis hasa striking male predominance, in contrast to pleuraleffusion in articular rheumatoid arthritis, which has afemale predominance.

25

Seventy-one to 95 percent ofrheumatoid effusions occur in men.

25-27

The averageage of patients with rheumatoid effusions is 51 to 57years,

25,26,28,29

and more than 50 percent of patientsare over the age of 50.

26

This type of effusion is usu-ally unilateral

26,27

but has been reported to occur bi-laterally,

27

and the pleural fluid is usually yellow-greenbut may be turbid, opaque, clear, straw-colored, orbloody.

26,27,30

Rheumatoid effusions can resolve inthree to four weeks, but characteristically they persistfor several months or years.

25,27

Several laboratory findings are characteristic of pleu-ral fluid in patients with rheumatoid effusions. Pleural-fluid glucose levels are less than 30 mg per deciliter(1.7 mmol per liter) in 66 percent of rheumatoid ef-fusions and less than 50 mg per deciliter (2.8 mmolper liter) in 80 percent.

26

When the effusion is per-sistent, the glucose level decreases over time.

31

ThepH of the pleural fluid is generally 7.00 to 7.13.

28,31

A low pleural-fluid glucose level and a low pleural-fluid pH are not specific to rheumatoid arthritis; theyare also found in cases of empyema, tuberculosis, andmalignant tumors.

10,28,32

The low glucose levels appearto be caused by blockage of the transfer of glucosefrom the blood to the pleura,

1,27

and the low pH re-sults from the metabolism of glucose and the accumu-lation of lactate and carbon dioxide.

32

The white-cellcounts in rheumatoid effusions are variable: during theacute phase there is a predominance of neutrophils,but in the chronic phase there is a predominance oflymphocytes.

31

The rheumatoid factor in the pleuralfluid is characteristically greater than 1:320,

29 but highlevels of rheumatoid factor in the pleural fluid are alsofound in cases of bacterial pneumonia, tuberculosis,and carcinoma.1 The combination of a low pH, a lowglucose level, and a low C4 level in the pleural fluid

is a good indicator of the presence of rheumatoid ef-fusion.28 Rheumatoid factor and complement levelswere not measured in this case.

For a variety of reasons — the persistence of thepleural effusion; the low pleural-fluid glucose level; thehigh levels of lactate dehydrogenase and cholesterol;the absence of evidence of pleural thickening, hilar ormediastinal lymphadenopathy, or other important pa-renchymal changes on the CT scans; and the absenceof fever, cough, chest pain, weight loss, bone pain, anddyspnea at the time of diagnosis — I believe that theprobable cause of the pleural effusion is rheumatoidarthritis.

CLINICAL DIAGNOSIS

Pleural effusion with a parapneumonic, malignant,or rheumatoid cause.

DR. DEBORAH A. QUINN’S DIAGNOSIS

Pleural effusion caused by rheumatoid arthritis.

PATHOLOGICAL DISCUSSION

DR. EUGENE J. MARK: The diagnostic procedurewas video-assisted thoracoscopy and drainage of the

Figure 3. Lymphocytic Infiltrate (Arrows) in the Adipose Tissueof the Chest Wall beneath the Parietal Pleura (P), Consisting ofEdematous Connective Tissue with Proliferating Capillaries (He-matoxylin and Eosin, ¬150).

P


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pleural effusion. The surgeon removed 150 ml ofthick, yellow, cloudy fluid and saw a white, fibrinous,exudative membrane on top of a thickened and in-flamed pleura. He débrided the membrane and tooka biopsy specimen of the parietal pleura and the un-derlying chest wall.

Histopathological examination of the pleural spec-imen showed a progression of changes rarely foundin a single specimen, including fibrin layered on thesurface, neutrophilic debris in areas without fibrin,and a lymphocytic infiltrate in the adipose tissue be-neath the parietal pleura (Fig. 3). These changes arecommonly observed in patients who have benign pleu-ral effusions from various causes. In this case, however,more specific changes were found. There were pali-sading histiocytes and fibroblasts, which were ori-ented perpendicularly to the serosal surface (Fig. 4),as well as hyperplastic mesothelial cells and multinu-cleated cells with vacuolated cytoplasm (Fig. 5). Suchmultinucleated cells are infrequently found in casesof rheumatoid pleuritis; when seen in cases of pleu-

Figure 4. Palisading, Elongated Histiocytes and Fibroblasts (be-tween Arrows) That Are Perpendicular to the Serosal Surfaceof the Parietal Pleura (Hematoxylin and Eosin, ¬250).

Figure 5. Hyperplastic Mesothelial Cells and MultinucleatedCells (M), Some with Vacuolated Cytoplasm (Arrow), along theSurface of the Serosa (Hematoxylin and Eosin, ¬500).

M

M

Figure 6. Rheumatoid Nodule with Central Necrosis (N), Bound-ed in Part by Palisading Histiocytes (Arrow), in the Parietal Pleura(Hematoxylin and Eosin, ¬150).The serosal surface is covered by fibrin.

N



N Engl J Med, Vol. 346, No. 11 · March 14, 2002 · www.nejm.org · 849

ral effusion, they strongly suggest the presence of arheumatoid effusion.33 Finally, a microscopical rheu-matoid nodule with central necrosis was present in thethickened pleura and was bounded in part by pali-sading histiocytes (Fig. 6).

The histopathological changes in rheumatoid pleu-ritis34-37 are listed in sequence in Table 2. Althoughpleural effusions and fibrinous pleuritis are relativelycommon in patients with systemic rheumatoid disease,rheumatoid nodules in the pleura are less common

than rheumatoid disease in the lung parenchyma.38,39

At autopsy, active or chronic rheumatoid disease isfound in the lung or pleura in up to 50 percent ofpatients with systemic rheumatoid disease40; a small-er proportion of such patients have clinical or radi-ographic manifestations of rheumatoid disease in thepleura or lung during life.

DR. JOSEPH F. ARENA (Neurosurgery): What isthe ultimate prognosis for patients with rheumatoidpleuritis?

DR. QUINN: Patients generally do well. If the ef-fusions persist, patients may eventually have pleuralthickening.

DR. MARK: This patient has been well since thethoracoscopy, with no additional signs or symptomsof disease in the chest. The progression of rheumatoiddisease is better assessed by arthritis than by pleuritis.

ANATOMICAL DIAGNOSIS

Rheumatoid pleuritis.

REFERENCES

1. Sahn SA. The pleura. Am Rev Respir Dis 1988;138:184-234.2. Gottehrer A, Roa J, Stanford GG, Chernow B, Sahn SA. Hypothyroid-ism and pleural effusions. Chest 1990;98:1130-2.3. Bynum LJ, Wilson JE III. Characteristics of pleural effusions associated with pulmonary embolism. Arch Intern Med 1976;136:159-62.

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TABLE 2. SEQUENCE OF HISTOPATHOLOGICAL

CHANGES IN RHEUMATOID PLEURITIS.

Fibrin

Neutrophilic exudate

Lymphocytic inflammation

Mesothelial hyperplasia

Multinucleated mesothelial cells

Palisading histiocytes

Rheumatoid nodule

Fibrosis


850 · N Engl J Med, Vol. 346, No. 11 · March 14, 2002 · www.nejm.org


toid arthritis in pleural effusion: a case report. Acta Cytol 1981;25:33-9.34. Baggenstoss AH, Rosenberg EF. Visceral lesions associated with chronic infectious (rheumatoid) arthritis. Arch Pathol 1943;35:503-16.35. Lee SS, Trimble RB. Rheumatoid arthritis with bloody and cholester-ol pleural effusion. Arch Pathol Lab Med 1985;109:769-71.36. Case Records of the Massachusetts General Hospital (Case 27-1982). N Engl J Med 1982;307:104-12.37. Case Records of the Massachusetts General Hospital (Case 37-1992). N Engl J Med 1992;327:873-80.

38. Portner MM, Gracie WA Jr. Rheumatoid lung disease with cavitary nodules, pneumothorax and eosinophilia. N Engl J Med 1966;275:697-700.39. Tserkezoglou A, Metakidis S, Papastamatiou-Tsimara H, Zoitopoulos M. Solitary rheumatoid nodule of the pleura and rheumatoid pleural effu-sion. Thorax 1978;33:769-72.40. Hunninghake GW, Fauci AS. Pulmonary involvement in the collagen vascular diseases. Am Rev Respir Dis 1979;119:471-503.

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