Case Report: Spontaneous Bacterial Pleural Empyema in Liver Cirrhosis

Digestive Diseases and Sciences, Vol. 43, No. 5 (May 1998), pp. 1129 ± 1132

CASE REPORT

Spontaneous Bacterial Pleural Empyema in Liver Cirrhosis RUDOLF KIRCHMAIR, MD, FRANZ ALLERBERGER, MD, ISOLDE BANGERL, MD, CLAUDIA E GGER, MD, KARIN NACHBAUR, MD, JOSEF R. PATSCH, MD, and WO LFGANG V O GE L, MD KEY WORDS: liver cirrhosis; pleural e mpye ma; spontaneous bacterial pe ritonitis; live r transplantation.

Patie nts with live r cirrhosis are known to suffe r from a varie ty of immune de fe cts, ie, comple ment de® cie ncy, neutrophil dysfunction, and re ticuloe ndothe lial cell dysfunction (1). These de fe cts pre dispose live r cirrhosis patie nts to opportunistic infections. The most promine nt of the se is spontane ous bacterial pe ritonitis, which has attracte d conside rable scienti® c inte rest ove r the last decade (for re vie w se e 1). Pathogene sis of spontane ous bacterial pe ritonitis involve s se veral steps: ® rst, translocation of bacte ria from the gut into lymphatics and the n into the blood; second, prolonge d bacteriemia, and third, infe ction of ascites. A second bacte rial infection, spontane ous bacterial pleural empyema has bee n reporte d only once in the literature (2). We he re report on two patie nts with e nd-stage live r cirrhosis awaiting transplantation, who de velope d spontane ous bacterial pleural e mpye ma without classical signs of in¯ ammation. Both patie nts had concomitant ascite s without e vide nce of bacterial infe ction of this ¯ uid. CASE REPORTS Case 1. Patie nt L.G., a 55-ye ar-old man with end-stage primary biliary cirrhosis presented for a routine check-up while on the waiting list for liver transplantation. At presentation the patie nt complaine d of poor appe tite, dyspnea, progressive weight loss, and was mildly e ncephalopathic. He was on spironolactone , furosemide, ranitidine, cholestyramine, and we ekly infusions of human albumin. O n clinical e xamination the patie nt showed all the stigmata of chronic

Manuscript rece ived February 25, 1997; accepted Octobe r 15, 1997. From the De partme nt of Internal Medicine, the Institute for Hygiene, and the Departmen t of Radiology II, Unive rsity of Innsbruck, Innsbruck, Austria. Address for reprint re que sts: Dr. W. Vogel, Department of Internal Medicine, University of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria.

liver disease: gross ascites, small liver, and splenomegaly. He was afe brile and normotensive. On laboratory e xamination erythrocyte sedimentation rate was 100 mm/hr, bilirubin was 4.2 mg/dl (0.0 ± 1.0), ASAT was 26 units/liter (2± 18), g -glutamyltransfe rase 78 units/liter (5± 28), alkaline phosphatase 930 units/liter (60 ± 170), and prothrombin time was 66% (normal . 70). He was hypoalbuminemic with albumin of 2693 mg/dl (3500 ± 5500) and hypergammaglobulinemic with IgG of 2395 mg/dl (770 ± 1510) , IgM of 681 mg/dl (70 ± 150) , and IgA of 663 mg/dl (108 ± 325) . Blood ® lm showed hype rchromic, macrocytous ane mia of hemoglobin 83 g/liter (133± 177) , me an corpuscular hemoglobin 34.6 pg (27± 32), mean corpuscular volume 101 ¯ (77± 96) and thrombocytopenia of 60 g/liter (140 ± 400) but normal leukocyte count of 5.4 g/lite r, with slightly increased neutrophils of 77.5% (55± 75) and lymphopenia of 12.5% (15± 40) in leukocyte subsets. a 1 Fetoprotein was in the normal range , IgG antibodies we re positive for cytomegalovirus (CMV ) and Epstein-Barr virus (EBV), and no serological signs for human immunode® ciency virus (HIV ) we re detectable. At 13.4 ng/ml (normal range . 60 ng/ml) liver me tabolic function was badly impaired, as shown by a monoethyl glycine xylidide (MEGX) test. Chest x-ray showed pleural e ffusion of the right side and a CT scan of the abdomen showed liver cirrhosis with open portal vein and ascites but no tumor. Because of fe ver up to 38.5 °C in this immunocompromised patie nt awaiting liver transplantation, an empirical intrave nous antibiotic the rapy, ® rst with cefamandole , than combined with cipro¯ oxacin, was starte d. Feve r decreased only te mporarily, howeve r, and pleural e ffusion further increase d, as shown by chest x-ray. Pleurocente sis was performed and reve aled pleural e mpyema. Laboratory ® ndings, microscopic, and microbiological e xamination of pleural ¯ uid are summarize d in Table 1. Afte r the rapy of pleural e mpye ma by thoracostomy and further antibiotic the rapy, pleural decortication was performed to preve nt the reappearance of effusion. The patient was subsequently successfully transplanted with e xcellent long-te rm results (follow up: 20 months). Case 2. Patie nt M.S., a 46-ye ar-old woman with end-stage liver disease (Child stage C) presente d for routine follow-up on the waiting list for liver transplantation. a 1 Antitrypsin de® ciency of the Pi MZ phenotype was pre-

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1998 Plenum Publishing Corporation

KIRCHMAIR ET AL T ABLE 1. LABORATORY , MICROSCOPIC,

AND

M ICROBIOLOGICAL FINDINGS

IN

Patient 1 (L.G .) Laboratory tests of Pleural ¯ uid Cells Prote in LDH Microbiologic culture

Laboratory tests of ascitic ¯ uid Cells Prote in LDH Microbiologic culture Feve r Le ukocytosis

P LEURAL E FFUSION Patient 2 (M.S.)

515,000/ m l ( . 95% ne utrophils) 5060 mg/dl 30720 units/liter Staphylococcus aureus

162,200/ m l ( . 95% neutrophils) 1960 mg/dl 12651 units/liter Streptococcus interm edius Prevotella sp. Capnocytophaga sp.

nd*

nd

600/ m l (mesothe lial ce lls, leucocytes) 1780 mg/dl 63 units/liter sterile

2

1 1

1 1

2

*nd: not dete rmine d.

sumed to be the cause of her disease. She reported that ascites had spontaneously broken through a large umbilical hernia. She was the refore admitte d to the hospital for observation and further investigation. All clinical and laboratory ® ndings showed impaired liver function with malnutrition, erythrocyte sedimentation rate of 110 mm/hr, hype rgammaglobulinemia, a prothrombin time of 47% , and a MEGX te st of 14.9 ng/ml. He r kidney function was slightly impaired with a serum creatinine of 1.6 mg/dl (0.7± 1.4) . Afte r admission ascites slowly reaccumulated, but the patient remaine d clinically stable. Routine surveillance laboratory testing repeate dly showed normal C-reactive protein, white blood cell count, normal blood pressure, and stable liver function te sts. The patient was on spironolactone, furosemide, propanolol, calcium and vitamin D, misoprostol, ranitidine, and a low-sodium diet. Within 10 days of her hospital stay she required two sessions of paracente sis of 4 ± 5 liters without evidence of portal ve in thrombosis. The further course was uneventful, until on day 12 the patie nt complained about sudden dyspnea. Ultrasound investigation showed ascites to have reaccumulated and, for the ® rst time, evidence of massive pleural e ffusion. The ultrasound picture of the ¯ uid contents of the two cavitie s we re diffe rent, howeve r, showing clear ª ¯ uidº in the abdomen but e chogenic ª ¯ uidº in the thorax. Diagnostic and the rapeutic pleurocentesis showed more than 2 liters of pus. In the same session diagnostic and the rapeutic parace ntesis was performed, showing clear, amber-colored ascites with no neutrophils on cytologic examination. Bacteriological examination proved ascites to be sterile, while Capnocytoph aga sp., Prevotella sp., and Streptococcus intermedius we re cultured in the pleural ¯ uid. Further chemical details are summarized in Table 1. The patie nt was tre ate d with surgical drainage (Figure 1) and imipenem 500 mg three time s a day intravenously. After one we ek of treatme nt effusion had complete ly resolved and three we eks afte r onset the patie nt was successfully transplanted without infectious complications and with e xce llent long-term results (follow up: 16 months).

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DISCUSSION Pleural e mpye ma is a serious complication of infe ctions adjace nt to the pleural space (for re view se e 3). Empye ma usually re sults from pne umonia but may also be cause d by contiguous infe ctions of the e sophagus, mediastinum, pharynx, or subdiaphragm atic tissue s that e xtend to the pleura (4). Both traum atic and iatroge nic injury to adjace nt structure s can le ad to secondary ple ural e mpyema. Microbial pathoge ns causing pleural empyema in various patie nt groups re ¯ ect the freque ncy of the microbe s these patie nts are e xpose d to. In overtly healthy adults pleural e mpyema is most commonly caused by aerobic bacte rias such as Staphylococcus au reus, viridians streptococci, and Streptococcus pneu m oniae. Gingivitis or pyorrhe a and a predisposition to aspiration by alte red consciousne ss, as in alcoholic patie nts, predispose to anae robic ple ural empye ma, most ofte n caused by Prevotella sp., Fu sobacteriu m sp., and Peptostreptococcus sp., Staphylococcus au reus is the most common microbial pathoge n in ple ural e mpyema following chest traum a or surge ry. Patie nts immunocom promise d by malignancy, collage n vascular disease, or immunode ® cie ncy disorde rs are prone to ple ural involve ment with fungal, tube rculous, or ae robic gram-ne gative bacillary infe ction (3). Cirrhosis of the live r cause s se vere and comple x alte rations of the immune syste m, such as ne utrophil dysfunction, comple ment de® cie ncy, and reticuloe ndothe lial dysfunction, pre disposing to infe ctions such as spontane ous bacterial pe ritonitis (SBP) (1). Spontane ous pleural e mpye ma has be e n reporte d only once (2) as a complication of live r cirrhosis, although hydrothorax, e spe cially on the right side , is Digestive Diseases and Sciences, Vol. 43, No. 5 (May 1998)

PLEURAL EMPYEMA IN LIVER CIRRHOSIS

Fig 1. Chest x-ray of patient M.S. afte r pleuroce ntesis and insertion of a drainage, still showing signi® cant pleural e ffusion at the right side.

quite common in the se patie nts (5). O ur patie nts, both suffering from e nd-stage live r cirrhosis, deve lope d pleural e mpye ma without a history of pre vious pleural puncture or dise ase s pre disposing to ple ural e mpyema, e g, absce ss, pne umonia, or bronchie ctasis. Continuous infection of ple ural e ffusion from infe cted ascite s in SBP was e xclude d by simultane ous parace ntesis in one patie nt, re vealing sterile , ne utroDigestive Diseases and Sciences, Vol. 43, No. 5 (May 1998)

phil ne gative ascites. Ple ural e mpye ma was thus considere d spontane ous. O ne of the most common and be st characte rize d spontane ous infections in patie nts with cirrhosis and ascite s is spontane ous bacte rial pe ritonitis (for re vie w se e 1). SBP is characte rize d by incre ase d neutrophil 3 counts ( . 250/mm ) in ascites and by a positive ascitic ¯ uid culture (usually monom icrobial) and deve lops

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KIRCHMAIR ET AL

without an obvious source of infe ction (1, 6, 7). According to the current view se veral ste ps are involve d in the pathoge nesis of SBP (1). First, gut bacte ria (e specially Escherichia coli and Klebsiella sp.; se ldom anae robes or e nte rococci) translocate into mese nte ric lymphatics. Se cond, bacte ria reach the blood and afte r prolonge d bacteriemia ® nally infe ct the ascitic ¯ uid. Growth of bacte ria is facilitate d in ascitic ¯ uid of low prote in concentration, corre lating with low opsonic activity (8). Pathoge ne tically similar to SBP, he matoge nic infe ction of hydrothorax, promote d by prolonge d bacte rie mia and comple x immunologic de fe cts, might play an important role in the de ve lopment of spontane ous bacte rial ple ural e mpyema. In summary, our case s de monstrate that spontane ous ple ural e mpye ma can occur as a se rious complication of live r cirrhosis. This dise ase can be pre sent without the classical signs of se vere bacterial infe ction and the refore its incide nce can be unde re stimated. The ® ndings in our patie nts argue against a continuous infe ction through infe cted ascite s. Infection of pre existing ple ural effusions during prolonge d bacte riemia in a patie nt with diffuse immune de fects, as in live r cirrhosis, is the most like ly pathoge ne tic mechanism. Spontane ous ple ural empye ma should be considere d in a patie nt with live r cirrhosis and ple ural e ffusion, whose physical condition de te riorate s and who has no or only minor in¯ ammatory signs. SUMMARY Spontane ous bacterial peritonitis is a well-known complication of patie nts with live r cirrhosis and ascites. Anothe r bacterial infe ction, spontane ous ple ural e mpyema, has so far bee n reporte d only once in association with live r cirrhosis. We he re re port on two patie nts with Child C live r cirrhosis and ascite s await-

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ing live r transplantation, who de velope d se vere ple ural e mpye ma without pre ceding pleuroce nte sis. In the male patie nt with primary biliary cirrhosis, microbiological culture of pleural e mpye ma showed Staph ylococcus aureu s to be the infectious age nt; in the se cond, a female patie nt with a 1-antitrypsin de® ciencyassociat e d live r cirrhosis, Capn o cyto ph aga sp., Prevotella sp., and Streptococcu s interm ediu s were cultured. In both patie nts, although empye ma was exte nsive and caused seve re dyspne a, clinical and laboratory signs of in¯ ammation we re mode rate . Both patie nts had ascite s without signs of bacterial peritonitis. Spontane ous bacterial ple ural empyema should be conside red in patie nts with e nd-stage live r cirrhosis and might be prese nt with or without eve n minor in¯ ammatory signs. REFERENCES 1. Runyon BA: Pathogene sis and diagnosis of spontaneous bacte rial peritonitis in cirrhosis. In The rapy in Live r Diseases. J Rode s, V Arroyo (e ds). Barcelona, Ediciones Doyma, 1992, pp 388 ± 396 2. Flaum AM: Spontaneous bacte rial empyema in cirrhosis. Gastroenterology 70:416 ± 417, 1976 3. Bryant RE, Salmon CJ: Ple ural e mpye ma. Clin Infect Dis 22:747± 764, 1996 4. Simth JA, Mullerworth MR, We stlake GW, Tatoulis J: Empye ma thoracis: A 14-year e xperie nce in a teaching ce nter. Ann Thorac Surg 84:387± 402, 1991 5. Liebermann FL, Pete rs RL: Cirrhotic hydrothorax. Arch Intern Med 125:114 ± 117, 1970 6. Hoefs JC, Runyon BA: Spontaneous bacterial pe ritonitis. Dise ase-A-Month 31:1± 48, 1985 7. Corre ia JP, Conn HO : Spontaneous bacte rial peritonitis in cirrhosis: Endemic or epidemic. Med Clin North Am 59:963± 981, 1975 8. Runyon BA: Patients with de ® cie nt ascitic ¯ uid opsonic activity are predisposed to spontaneous bacterial pe ritonitis. Hepatology 8:632± 635, 1988

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