EOSINOPHILIC PLEURAL EFFUSION IN ADULTS AT SRINAGARIND HOSPITAL

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1 EOSINOPHILIC PLEURAL EFFUSION IN ADULTS AT SRINAGARIND HOSPITAL Wip Reechipichitkul nd Kittisk Chueskoolvnich Deprtment of Medicine, Sringrind Hospitl, Fculty of Medicine, Khon Ken University, Khon Ken, Thilnd Abstrct. The presence of pleurl eosinophili remins controversy in etiology nd prognosis. We conducted this study to evlute the etiology of eosinophilic pleurl effusion nd to define the fctors tht determine mlignncy in eosinophilic pleurl effusion. Between 1 August 1994 nd 1 July 2, 5 ptients were dignosed with eosinophilic pleurl effusion; 35 men nd 15 women verging 56.4 yers of ge. Most (96%) hd exudtive pleurl effusion. Mlignncy ws the most common (46%) estblished cuse followed by tuberculosis (1%), prpneumonic effusion (8%), nd empyem thorcis (2%). We encountered only one cse of pneumothorx nd prsitic pleurl effusion (from Strongyloides stercorlis). Unknown cuses constituted 22% of cses. The etiology of those who hd previously undergone thorcocentesis did not differ from those hving their first thorcocentesis. Ptients with mlignnt pleurl effusion hd significnt longer durtion of clinicl symptoms (>1 month) nd weight loss thn benign pleurl effusion. The medin durtion of symptoms in benign pleurl effusion ws 14 dys. Fever ws more chrcteristic in ptients with benign thn in those with mlignnt pleurl effusion. The percentge of eosinophils in pleurl fluid nd blood did not differ between the two groups. Pleurl fluid eosinophils in mlignnt vs benign pleurl effusion were 26.6% (rnge 1% to 63%), nd 3.6% (rnge 1% to 93%), respectively. We concluded tht, pleurl eosinophili did not indicte benign conditions which would spontneously resolve. Mlignnt pleurl effusion should be considered especilly in res mlignncy is prevlent. INTRODUCTION Eosinophilic pleurl effusion is confirmed by the presence of 1 or more percent eosinophils mong the leukocytes in the pleurl fluid (Light, 1995). This occurs in 5% to 8% of exudtive pleurl effusion (Shn, 1988), but its dignostic significnce is controversil. Light et l (1973) rgued tht the presence of pleurl fluid eosinophili milittes gretly ginst tuberculosis nd mlignnt neoplsm, nd emphsized tht it frequently occurs in ssocition with pneumothorx. Similrly, Veress et l (1979) reported 3 eosinophilic pleurl effusions with self-limiting diseses nd fvorble outcome. So it would seem tht the presence of pleurl fluid eosinophili considerbly reduces the probbility of Correspondence: Wip Reechipichitkul, Deprtment of Medicine, Sringrind Hospitl, Fculty of Medicine, Khon Ken University, Khon Ken 42, Thilnd. mlignncy or tuberculosis nd increses the likelihood of n underlying benign disorder such s pneumothorx, previous thorcocentesis, benign sbestosis effusions, prsitic diseses, nd idiopthic effusions (Adelmn et l, 1984). Notwithstnding, Rubins nd Rubins (1996) conducted prospective cohort study to determine the dignostic nd prognostic significnce of eosinophilic pleurl effusion nd found tht mlignncy ws s prevlent mong eosinophilic s noneosinophilic pleurl effusions. However, ptients with eosinophilic pleurl effusion hd better survivl. A high percentge of mlignncy in eosinophilic pleurl effusion ws lso reported by Rintwn et l (1998). Consequently, mlignncies my be common in eosinophilic pleurl effusion where mlignncy is prevlent (Kuhn et l, 1989). The objective of our study ws to define : 1) the etiology of eosinophilic pleurl effusion, nd 2) the fctors tht determine mlignncy in eosinophilic pleurl effusion. 374 Vol 34 No. 2 June 23

2 EOSINOPHILIC PLEURAL EFFUSION MATERIALS AND METHODS A cross sectionl study ws conducted between August 1, 1994 nd July 31, 2 t Sringrind Hospitl, Khon Ken University, Thilnd. Ptients 15 yers or older with pleurl fluid eosinophils 1% were included. Ptient s chrts nd lbortory finding were reviewed. Dt collection included: demogrphic dt, initil clinicl symptoms nd signs, history of previous thorcocentesis, pleurl fluid nlyses, pleurl biopsy, bnorml chest rdiogrphs, blood eosinophili, nd finl dignosis. Dignostic criteri Trnsudtive or exudtive pleurl effusion ws defined by Light s criteri (1995). A mlignncy ws dignosed when neoplstic pleurl tissue nd/or fluid cytology were confirmed. A dignosis of tuberculous pleurl effusion ws defined by positivity of ny one of the following : 1) Mycobcterium tuberculosis identified in culture of the pleurl fluid nd/or sputum; 2) Cseting grnuloms in the bsence of ny clinicl evidence of srcoidosis, tulremi, or fungl infection in the pleurl tissue; 3) A response to ntituberculous drugs revelved by n improvement of clinicl symptoms nd clering of chest rdiogrphs. The dignostic criteri for other diseses were: 1) Pneumothorx - ir in pleurl spce, 2) Prpneumonic effusion - ny pleurl effusion ssocited with bcteril pneumoni, lung bscess, or bronchiectsis, 3) Empyem thorcis - pus in pleurl spce or Grm stin nd/or bcteril pthogen cultured from the pleurl fluid, 4) Chylous pleurl effusion - milky ppernce of the pleurl fluid due to high level of cholesterol, 5) Meigs syndrome - presence of scitis nd pleurl effusion in ptients with benign ovrin or uterine tumor resolved fter removl of the ovrin or uterine tumor, 6) Unknown etiology - investigtion reveled no definite dignosis or finl investigtion could not be done becuse of the ptient lost to follow-up. Ethics The Ethics Committee of the Fculty of Medicine, Khon Ken University, Thilnd, pproved this reserch. Sttisticl nlysis Men nd stndrd devition were clculted for continuous dt, nd number nd percentge for the ctegoricl dt. Group comprisons were mde using the unpired Student s t-test for continuous vribles, nd χ 2 or Fisher s test for ctegoricl one. P-vlues <.5 were considered significnt. RESULTS During the study period, 5 ptients (35 men nd 15 women) verging 56.4 yers (rnge, 16 to 87 yers) were dignosed with eosinophilic pleurl effusion. Nerly hlf of them (46%) hd n underlying disese such s dibetes mellitus (14%), mlignncy (8%), or old pulmonry tuberculosis (6%). Over hlf (54%) smoked cigrettes (Tble 1). The men durtion of symptoms ws 4.8 dys (rnge, 1 to 21 dys). The most common clinicl symptoms were cough (76%), dyspne (68%), fever (48%), weight loss (46%), nd pleuritic chest pin (34%) (Tble 2). Exudtive pleurl effusion ws found in 48 ptients (96%). Only two presented with trnsudtive pleurl effusion cused by nephrotic syndrome secondry to systemic lupus erythremtosus nd volume overlod from cute post streptococcl glomerulonephritis. Hlf (48%) of the ptients developed right-sided pleurl effusion, 42% left-sided, nd 1% bilterl. Mlignncy ws the most common estblished cuse of eosinophilic pleurl effusion (46%) (Tble 3). Among our 5 subjects with eosinophilic pleurl effusions, 24 (48%) hd history of previous thorcocentesis, wheres for 26 (52%) it ws their first time of thorcocentesis. Notwithstnding, there ws not ny significnt difference in the etiology of the two groups. The four common cuses of eosinophilic pleurl effusion were: mlignncy, unknown, tuberculous pleurl effusion, nd prpneumonic effusion. The 23 mlignncies included: 11 denocrcinom of unknown origin, 6 bronchogenic crcinom (4 denocrcinom nd 2 squmous cell crcinom cell type), 1 cervicl crcinom, 1 osteosrcom, 1 cholngiocrcinom, 1 medullry thyroid crcinom, nd 2 of n unknown cell type. Prsitic pleurl effusion ccounted for 1 cse which ws Vol 34 No. 2 June

3 Tble 1 Ptient s chrcteristics. Ptient s chrcteristics n = 5 Age, yers (men, SD) 56.4 (16.4) Mle : femle rtio 35:15 Underlying diseses (%) None 54 Present 46 Dibetes mellitus 14 Mlignncy : 8 Heptom 2 CA cervix 2 Osteosrcom 2 Medullry thyroid crcinom 2 Old pulmonry TB 6 Coronry hert disese 6 Chronic obstructive pulmonry disese 4 Vlvulr hert disese 4 Chronic renl filure 4 Others 14 Smoking (%) Present 54 Absent 18 Undetermine 28 Some ptients hd more thn 1 underlying diseses. Tble 2 Clinicl symptoms of 5 ptients. Clinicl symptoms % Cough 76 Dyspne 68 Fever 48 Weight loss 46 Pleuritic chest pin 34 Anorexi 32 Chest discomfort 3 Ftique 18 Hemoptysis 14 Edem 4 Abdominl distention 4 Shoulder pin 2 Neck mss 2 Sore throt 2 Low bck pin 2 Altertion of conscious 2 LUQ bdominl pin 2 DVT right lower extremity 2 Horseness nd dysphgi 2 Every ptients hd more thn 1 clinicl symptoms. cused by Strongyloides stercorlis. One cse in the unknown group presented with chylous pleurl effusion - the finl investigtion of which could not be done becuse the ptient did not return for follow-up. A comprison of ptients with mlignnt vs benign pleurl effusion ws presented in Tble 4. There ws no sttisticlly significnt difference between the groups in ge, sex, or smoking. Ptients with mlignnt pleurl effusion hd significntly longer durtion of clinicl symptoms ( 1 month). Weight loss ws the only clinicl symptom found more often in sufferers of mlignnt pleurl effusion thn benign pleurl effusion. Ptients with fever preferred benign more thn mlignnt pleurl effusion, eventhough it ws not sttisticlly significnt. There ws no difference in the history of previous thorcocentesis found between groups. The percentge of eosinophils in the pleurl fluid of those with mlignnt pleurl effusion ws 26.6% (rnge, 1% to 63%), not sttisticlly different from those with benign pleurl effusion (3.6%, rnge 1% to 93%). The pleurl fluid profile, bnorml chest rdiogrphs, nd blood eosinophili could not be used to differentite these two conditions. DISCUSSION Almost ll cses (96%) of eosinophilic pleurl effusion were exudtive. In this study, we found mlignncy ws the most frequent cuse of eosinophilic pleurl effusion. This high figure my be explined by the high prevlence of mlignncy in our study popultion, s observed in other reports (Kuhn et l, 1989; Rubins nd Rubins, 1996; Rintwn et l, 1998; Mrtinez- Grci et l, 2). Eventhough previous thorcocentesis or previously introduced of ir or blood into the pleurl spce, cn be the primry cuse or concomitnt finding, there ws no difference in the etiology of our who hd previous thorcocentesis nd those who hd thorcocentesis for the first time. Tuberculosis ws the most common cuse of benign eosinophilic pleurl effusion (Kmel et l, 1989; Bssiri et l, 1997). Our finding indicted mlignncy nd tuberculosis were the two most common cuses of eosinophilic pleurl effusions (combined 56%). This strongly contrsts with the conception tht pleu- 376 Vol 34 No. 2 June 23

4 EOSINOPHILIC PLEURAL EFFUSION Tble 3 Etiology of eosinophilic pleurl effusion. Etiology Previous thorcocentesis First thorcocentesis Totl n (%) n (%) n (%) 1. Mlignncy 11 (22) 12 (24) 23 (46) 2. Unknown 6 (12) 5 (1) 11 (22) 3. Tuberculous pleurl effusion 2 (4) 3 (6) 5 (1) 4. Prpneumonic effusion 3 (6) 4 (8) 5. Empyem 6. Pneumothorx 7. Meigs syndrome 8. Nephrotic syndrome secondry to SLE 9. APSGN 1. Subphrenic collection 11. Strongyloides stercorlis Totl 24 (48) 26 (52) 5 (1) SLE = Systemic lupus erythremtosus; APSGN = Acute post streptococcl glomerulonephritis. Tble 4 Clinicl nd lbortory finding of ptients with mlignnt nd benign pleurl effusions. Mlignncy Benign p-vlue (n=23) (n = 16) Age, yrs (men, SD) Mle : femle Smoking (%) Durtion of symptoms Medin (dys) > 1 month (%) Symptoms nd signs (%) Fever Weight loss Pleuritic chest pin Hemoptysis Lymphdenopthy Heptomegly Previous thorcocentesis (%) Pleurl fluid profiles Color (%) Bloody Serosnguinous Cells WBC, cells/mm 3 (men, SD) RBC > 1, cells/ mm 3 (%) % Eosinophils (men, SD) % Eosinophils in first thorcocentesis (men, SD) Protein, g/dl (men, SD) Abnorml chest rdiogrphs other thn pleurl effusion (%) Blood eosinophils > 7 cells/ mm (1) 15: ,759 (1,843) (16.2) 24.5 (1) 4.9 (1.2) (16.2) 12: ,76 (2,132) (24.6) 3.3 (22.5) 4.6 (1.6) p-vlue <.5 (Student s t-test for continuous vribles, chi-squre or Fisher s test for ctegoricl vribles). Vol 34 No. 2 June

5 rl eosinophili reduces the probbility of mlignncy nd tuberculosis (Veress et l, 1979; Adelmn et l, 1984). Prpneumonic effusion nd empyem thorcis were the second most common cuses of benign eosinophilic pleurl effusion. These benign conditions were lso found in other studies (Wysenbeek et l, 1985; Kuhn et l, 1989; Rubins nd Rubins, 1996). Pneumothorx ws found in only one cse, in contrst to comments tht pleurl eosinophili ws norml rection of the pleur to the introduction of ir (Spriggs, 1979). Despite our being in n re endemic for prsitic infesttions, prsitic pleurl effusion ws encountered only once from Strongyloides stercorlis, which is rre cuse of eosinophilic pleurl effusion (Goyl, 1998; Emd, 1999). Other prsites tht cuse eosinophilic pleurl effusion but not found in our study include prgonimisis (Rintwn et l, 1998; Ashitni et l, 2), sprgnosis (Ishii et l, 21), hydtid disese, mebisis, or scrisis (Light, 1995). Unknown etiologies in our study ccounted for 22%, similr to other studies (Adelmn et l, 1984; Rubins nd Rubins, 1996). A longer durtion ( 1 month) of clinicl symptoms nd weight loss were significntly found in ptients with mlignnt pleurl effusion. On the other hnd, ptients with benign pleurl effusion hd medin durtion of clinicl symptoms 14 dys. Fever ws experienced more commonly mong sufferers of benign diseses. The mount of eosinophils in pleurl fluid nd blood could not be used to differentite mlignnt nd benign diseses. Chrcteristics of the pleurl fluid nd pleurl fluid profile lso did not exhibit significnt differences. A long durtion of clinicl symptoms in mlignnt eosinophilic pleurl effusion my fvor better prognosis in mlignnt eosinophilic thn noneosinophilic pleurl effusion. Rubins nd Rubins (1996) reported the medin survivl in noneosinophilic effusion 7.7 months compred to 16.8 months for those with eosinophilic pleurl effusion. ACKNOWLEDGEMENTS The uthors thnk Mr Bryn Roderick Hmmn for his ssistnce with the English-lnguge presenttion of the mnuscript. REFERENCES Adelmn M, Albeld SM, Gottlieb J, Hponik EF. Dignostic utility of pleurl fluid eosinophili. Am J Med 1984; 77: Ashitni J, Kummoto K, Mtsukur S. Prgonimus westermni with multifocl lesions in lungs nd skin. Intern Med 2; 39: Bssiri AG, Morris W, Kirsch CM. Eosinophilic tuberculous pleurl effusion. West J Med 1997; 166: Emd A. Exudtive eosinophilis pleurl effusion due to Strongyloides stercorlis in dibetic mn. South Med J 1999; 92: Goyl SB. Intestinl strongyloidisis mnifesting s eosinophilic pleurl effusion. South Med J 1998; 91: Ishii H, Muke H, Inoue Y, et l. A rre cse of eosinophilic pleuritis due to sprgnosis. Intern Med 21; 4: Kmel A, Chbbou A, el Ghrbi B. Eosinophilic pleurl effusion. Rev Pneumol Clin 1989; 45: Kuhn M, Fitting JW, Leuenberger P. Probbility of mlignncy in pleurl fluid eosinophili. Chest 1989; 96: Light RW. Clinicl mnifesttions nd useful tests. In: Light RW, ed. Pleurl diseses. 3 rd ed. Bltimore: Willims & Wilkins, 1995: Ligh RW, Erozn YS, Bll WC. Cells in pleurl fluid: Their vlue in differentil dignosis. Arch Intern Med 1973; 132: Mrtinez-Grci MA, Cses-Viedm E, Cordero- Rodriguez PS, et l. Dignostic utility of eosinophils in the pleurl fluid. Eur Respir J 2; 15: Rintwn P, Bngpttnsiri K, Chowlit P, Sngsyn P. Etiology nd clinicl implictions of eosinophilic pleurl effusion. Southest Asin J Trop Med Public Helth 1998; 29: Rubins JB, Rubins HB. Etiology nd prognostic significnce of eosinophilic pleurl effusion. Chest 1996; 11: Shn SA. The pleur : stte of the rt. Am Rev Respir Dis 1988; 138: Spriggs AI. Pleurl eosinophili due to pneumothorx. Act Cytol 1979; 23: 425. Veress JF, Koss LG, Schreiber K. Eosinophilic pleurl effusion. Act Cytol 1979; 23: Wysenbeek AJ, Lhv M, Aelion JA, Kufmnn L. Eosinophilic pleurl effusion : review of 36 cses. Respirtion 1985; 48: Vol 34 No. 2 June 23

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