Acute Pancreatitis Caused by Severe Legionella pneumophila Infection

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Case Reports

Acute Pancreatitis Caused by Severe Legionella pneumophila Infection B. Mégarbane, S. Montambault, I. Chary, M. Guibert, O. Axler, F.G. Brivet

Summary We report three cases of severe community-acquired Legionella pneumophila pneumonia with acute pancreatitis. Pancreas involvement is unusual. The clinical presentations consisted of painless pancreatitis with only elevation of serum pancreatic enzymes (case 1), tender abdomen with edematous pancreas on computed tomography scan (case 2) and necrosis (case 3). We discuss the possible mechanisms of L. pneumophila associated acute pancreatitis for which the pathophysiology is still undetermined: infection, toxin release or cytokine secretion.

Key Words Pancreatitis · Legionella pneumophila · Pneumonia · Pathogenesis · Respiratory failure Infection 2000; 28: 329–331

Introduction Legionnaires’ disease is responsible for severe community and hospital pneumonia with possible diffuse systemic infection [1]. In addition to pneumonia, clinical presentation usually includes multisystem involvement such as rhabdomyolysis, acute renal failure, encephalopathy, diarrhea or hepatitis. Legionella is a rare infectious cause of pancreatitis with unknown incidence [2]. To date, less than ten cases have been reported [3–10]. In this report, we present three cases of pancreatitis among 14 successive patients hospitalized in our intensive care unit (ICU) for community-acquired severe Legionnaires’ disease, identified by retrospective review over an 8 year period.

Case Reports Case 1 A 37-year-old man with a previous history of pulmonary tuberculosis, alcohol intake and smoking (15 packs/year) was admitted because of fever, chills, productive cough and confusion. He had a temperature of 38.5 °C, blood pressure of 170/92 mmHg and a Glasgow coma score of 15. He presented with diffuse mottling and focal pulmonary crepitations with no tenderness or organomegaly

Infection 28 · 2000 · No. 5 © URBAN & VOGEL

on abdominal palpation. Arterial gases on room air showed pH 7.44, partial pressure of oxygen (PaO2) 54 mmHg and partial pressure of carbon dioxide (PaCO2) 27 mmHg. Serum analysis revealed creatinine 346 µmol/l, aspartate aminotransferase (AST) 621 IU/l (N < 27), alanine aminotransferase (ALT) 140 IU/l (N < 45), creatine phosphokinase (CPK) 8,569 IU/l (N < 120), lactic dehydrogenase (LDH) 2,266 IU/l (N < 275), amylase 400 IU/l (N < 160) and lipase 727 IU/l (N < 170) (Table 1). Chest X-ray revealed medium lobe alveolar consolidation. Examination of CSF was normal and blood cultures were negative. Abdominal ultrasonography showed an homogeneous pancreas with normal size and regular outlines. The Simplified Acute Physiologic Score II (SAPS II) was 22 and the Ranson score was 3. Antibiotic therapy included amoxicillin 4 g/24 h iv and spiramycin 9 x 106 IU/24 h iv. Only spiramycin was continued when sputum culture grew Legionella pneumophila. Seroconversion was determined by an indirect immunofluorescence assay with a fourfold rise in serum titer to 1 : 256. Respiratory failure required noninvasive ventilation and renal failure required high doses of furosemide and hemodialysis. On day 5 serum amylase increased to a value of 918 IU/l and lipase to 1,508 IU/l. The patient left the ICU on day 15 and a complete recovery was made 1 month later with normalization of biological and radiographic analyses.

Case 2 A 46-year-old man with a previous history of chronic alcoholism and smoking (30 packs/year) was admitted because of fever, chills, dyspnea, fatigue, headaches and watery diarrhea for 3 days despite a 2 day treatment with amoxicillin/clavulanic acid. Physical examination revealed a temperature of 40 °C, a Glasgow coma score of 14, blood pressure of 98/50 mmHg and a respiratory rate of 28/min. He was icteric, his abdomen was very sensitive with hepatomegaly and pulmonary auscultation revealed diffuse crepitations. Laboratory analysis showed pH 7.43, PaO2 55 mmHg (fractional inspired oxygen [FIO2] 21%), PaCO2 25 mmHg, creatinine 236 µmol/l, AST 1,172 IU/l, ALT 413 IU/l, CPK 388 IU/l, LDH 2,808 IU/l, amylase 128 IU/l and lipase 245 IU/l (Table 1). Chest X-ray revealed alveolar consolidation of the right lower lobe with pleural effusion. CSF B. Mégarbane (corresponding author), S. Montambault, I. Chary, M. Guibert, O. Axler, F.G. Brivet Dept.of Medical Intensive Care, Antoine Béclère Hospital, 157 Rue de la Porte de Trivaux, F-92 140 Clamart, France; Phone: (+33/14) 5374957, Fax: -6312277; e-mail: [email protected] Received: February 11, 2000 • Revision accepted: July 24, 2000

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was normal and blood cultures negative. His condition rapidly worsened, requiring transfer to the ICU for mechanical ventilation. Initial antibiotic therapy consisted of ceftriaxone 2 g/24 h and erythromycin 3 g/24 h. The SAPS II score was 48 and the Ranson score was 5. Diagnosis of L. pneumophila infection was made by culture of tracheal aspirations and seroconversion by an indirect immunofluorescence assay with more than a fourfold increase of titer to 1 : 128, 15 days later. Rifampicin 1.5 g/24 h was added in view of hemodynamic failure requiring norepinephrine 0.3 mg/kg/min, generalized seizures with normal cerebral computed tomography (CT scan), acute respiratory distress syndrome with PaO2/FIO2 100 mmHg and oliguric acute renal failure (creatinine 733 µmol/l) requiring hemodialysis. Amylase values reached 965 IU/l, lipase 3,043 IU/l on day 5 and abdominal sonography and CT scan confirmed the presence of an edematous pancreatitis (Balthazar scoring B) and ascitic effusion without necrosis. Examination of ascitic fluid revealed protein 78 g/l and white cell count 0.86 109/l with 66% polymorphonuclear leukocytes.The patient was treated symptomatically with parenteral nutrition for 17 days. Anti-Legionella antimicrobial bitherapy was continued for 30 days. ICU management was complicated by bacteremic methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia. The patient was extubated on day 25 and discharged on day 40. Two months later, pancreatic tests and repeated abdominal CT were normal, serum creatinine 132 µmol/l and chest X-ray showed persistent moderate interstitial images considered as adult respiratory distress syndrome sequelae.

perature was 40 °C, pulse rate 130/min, respiratory rate 30/min and blood pressure 135/75 mmHg. Crackles were heard over the right axilla and palpation of the abdomen showed only tenderness. Laboratory findings revealed pH 7.41, PaO2 74 mmHg (FIO2 21%), PaCO2 48 mmHg, creatinine 216 µmol/l, ALT 312 IU/l, AST 700 IU/l, conjugated bilirubin 44 µmol/l, LDH 2,550 IU/l and CPK 30,473 IU/l. Serum amylase and lipase were 630 IU/l and 520 IU/l and rose to 755 IU/l and 1,569 IU/l within 4 days (Table 1). CSF analysis and cerebral CT scan were normal. The Ranson score was 6 and the SAPS II was 33. Chest X-ray and CT revealed left lower, right upper and medium lobe alveolar consolidations (Figure 1). Culture of sputum and alveolar lavage fluid was positive for L. pneumophila. The indirect immunofluorescence assay titer rose from 1 : 128 on admission to more than 1 : 512 on day 15. Abdominal X-ray was negative for pancreatic calcifications and abdominal CT showed normal gall bladder and biliary ducts, normal kidneys, but diffuse enlargement of the pancreas with intra and peripancreatic hypodensities, peripancreatic fat infiltration and necrosis along the renal fascia (Balthazar scoring E) (Figure 2). The patient was first treated with cefotaxime 3 g/24 h, which was discontinued upon diagnosis of Legionnaires’ disease. The treatment then comprised ciprofloxacin at doses adapted to the creatinine clearance for 21 days, enteral nutrition with jejunal tube, hemodialysis and blood transfusion. The subsequent course was uncomplicated with progressive improvement of thoracic X-ray, renal function and laboratory tests.All laboratory parameters and abdomen CT were normalized 6 weeks after admission and the patient was discharged.

Case 3 A 41-year-old West Indian man was hospitalized because of mental confusion, dyspnea, fever and mild abdominal pain. He had no medical history, no excessive alcohol consumption but was a smoker (15 packs/year). On examination, he was found to be mildly lethargic and disoriented without other neurological signs. His tem-

Discussion The pancreas is an unusual extrapulmonary site of L. pneumophila infection [1]. Pancreatitis appears to be generally concurrent with primary pneumonia [3–10].As in the case of our first patient, pancreatitis may be painless and revealed

Table 1 Clinical presentation, X-ray findings and treatments of pancreatitis associated with L. pneumophila acute pneumonia.

Case 1

Case 2

Case 3

Patient characteristics

M, 37 years Chronic alcoholic, smoker

M, 46 years Chronic alcoholic, smoker

M, 41 years West Indian, smoker

Abdominal signs

Normal palpation

Diarrhea, sensitive abdomen

Abdominal pain, tenderness

SAPS II score

22

48

33

Ranson score

3

5

6

Serum amylase on admission (IU/l)

400

128

630

918 (day 5)

965 (day 5)

755 (day 4)

727

245

520

Maximum value (IU/l) Serum lipase on admission (IU/l)

1,508 (day 5)

3,043 (day 5)

1,569 (day 4)

X-ray findings

Maximum value (IU/l)

Homogeneous pancreas

Edematous pancreatitis

Necrotizing pancreatitis

Sputum culture

L. pneumophila

L. pneumophila

L. pneumophila

Serum Legionella titer

4-fold rise

> 4-fold rise

4-fold rise

Antibiotics

Spiramycin

Erythromycin + rifampicin

Ciprofloxacin

Nutrition

Enteral

Parenteral

Enteral through a jejunal tube

Complications

Renal failure, hospital infection

Renal failure, shock, ARDS

Renal failure

Outcome

Alive without sequelae

Alive, chest X-ray images

Alive without sequelae

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Figure 1 Chest X-ray showing multilobar alveolar consolidations.

only by elevated serum amylase or lipase with possible CTscan enlargement of the pancreas [3–5, 8]. In contrast, as seen in case 3, it may represent a serious illness leading to necrotizing and hemorrhagic pancreatitis [7] or pancreatic cysts [6]. The three cases presented here are proven cases of L. pneumophila infection. In each case L. pneumophila was isolated in sputum culture during severe pneumonia with a corresponding significant rise in antibody titer, ruling out any cross-reaction in immunofluorescence tests [4, 9]. Pancreatitis was confirmed by X-ray findings and by increases in serum lipase, eliminating the usual difficulties in assessing serum amylase in acute renal failure patients [4, 10]. L. pneumophila infection was multisystemic in our three patients with hypoxemic pneumonia, acute renal failure, rhabdomyolysis and mental confusion. Acute renal failure occurred in each of our cases, however pancreatitis may occur in its absence [4, 6, 8].Anti-Legionella therapy in severe presentations consists of iv macrolides, quinolones or one of the two in association with rifampicin.These antibiotics, with excellent intracellular and tissue penetration properties, were appropriate in these cases of associated pancreatitis. Acute pancreatitis appears to be secondary to Legionella multivisceral infection, as suggested by the documented rise in lipase levels, peaking around days 4–5, without initial hemodynamical failure and correlating with the beginning of the patient’s disease and the favorable outcome with specific antibiotic therapy. However, it is difficult to determine definitively whether other factors, especially alcohol or possible pancreatic duct obstruction by sludge, may have played a part in the associated pancreatitis [4]. Extrapulmonary infection is mostly likely due to bacteremic seeding during the course of pneumonia and is associated with immunosuppression or death. Hematologic dissemination of Legionella to different organs may occur


Figure 2 Abdominal CT scan showing pancreatitis with edematous pancreas (dotted arrow), infiltration of renal fascia (curved arrow) and necrosis (straight arrow).

through phagocytic cells and impairment of cellular immunity or dysfunction of phagocytic cells may contribute to facilitate such diffusion. The pathogenesis of pancreas injury is unknown and may be secondary to pancreatic cell infection, Legionella toxin release or cytokines and effector cellinduced inflammation. However, our experience highlights the risk of acute pancreatitis in critically ill patients with legionellosis.

References 1. 2.

Stout JE, Yu VL: Legionellosis. N Engl J Med 1997; 337: 682–687. Parenti DM, Steinberg W, Kang P: Infectious causes of acute pancreatitis. Pancreas 1996; 13: 356–371. 3. Kesavan CR, Pitchumoni CS, Marino WD: Acute painless pancreatitis as a rare complication in Legionnaires’ disease. Am J Gastroenterol 1993; 88: 468–469. 4. Westblom TU, Hamory BH: Acute pancreatitis caused by Legionella pneumophila. South Med J 1988; 81: 1200–1201. 5. Case Records of the Massachusetts general hospital (case 371987). N Engl J Med 1987; 317: 694–702. 6. Eitrem R, Forsgren A, Nilsson C: Pneumonia and acute pancreatitis most probably caused by a Legionella longbeachae infection. Scand J Infect Dis 1987; 19: 381–382. 7. Bollaert PE, Maurizi M, Laprevote-Heully MC, Lambert H, Larcan A: Pancréatite aiguë nécrotico-hémorragique au cours d’une maladie des légionnaires. Presse Med 1986; 15: 1732. 8. Michel O, Naeije N, Csoma M, Sergysels R, de Coster A: Acute pancreatitis in Legionnaires’ disease. Eur J Respir Dis 1985; 66: 62–64. 9. Arneborn P, Kallings I: Acute pancreatitis possibly caused by Legionella micdadei. Scand J Infect Dis 1985; 17: 229–231. 10. Gordan V, Zmyslinski RW, Postic B: Legionnaires’ disease complicated by acute pancreatitis: case report. Milit Med 1980; 145: 345–347.

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