American Journal of Therapeutics 23, e933–e936 (2016)
Gastrointestinal Variant of Lemierre Syndrome: Fusobacterium nucleatum Bacteremia–Associated Hepatic Vein Thrombosis: a Case Report and Literature Review Lin Zheng, MD, PhD1* and Badri Giri, MD2
Fusobacterium nucleatum is a gram-negative bacillius commonly found in oropharynx and is traditionally associated with Lemierre syndrome, which is characterized by history of recent oropharyngeal infection, internal jugular vein thrombosis, and isolation of anaerobic pathogens, mainly Fuosobacterium necrophorum. However, recent evidence indicated that F. nucleatum is also a normal resident of human gut. Less than a dozen of case reports had linked F. nucleatum to gastrointestinal variant of Lemierre syndrome with portal vein thrombosis. However, F. nucleatum bacteremia– associated hepatic vein thrombosis is very rare. We report a case of a 73-year-old man who had hepatic vein thrombosis associated with F. nucleatum bacteremia, most likely from subclinical primary infection affecting the lower gastrointestinal tract. The underlying pathophysiology and treatment options are discussed here. With rapid increase in reporting of Lemierre syndrome, this case deserves particular attention from clinicians. Keywords: Fusobacterium nucleatum, Lemierre syndrome, hepatic vein thrombosis
INTRODUCTION Known as postanginal septicemia or necrobacillosis, Lemierre syndrome is characterized by acute primary infection of the oropharynx, usually by Fusobacterium necrophorum, causing secondary thrombophlebitis of the internal jugular vein. When jugular vein thrombosis occurs, there is inflammation and consequent septic thrombophlebitis, which gives rise to distant emboli that usually migrate to pulmonary capillaries.1 As the consequence, the most frequently involved sites of septic metastases are the lungs, followed by
1
Division of Hospital Medicine, Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ; and 2Pulmonary and Critical Medicine Fellowship Program, Department of Medicine, Texas A&M HSCCOM - Scott & White Healthcare, Temple, TX. *Address for correspondence: Division of Hospital Medicine, Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Dorrance 222, One Cooper Plaza, Camden, NJ 08103. E-mail: [email protected]
the joints (knee, hip, sternoclavicular joint, shoulder, and elbow).2 The septic metastasis and abscess formation in muscle, long bones, liver, heart,3–5 although extremely rare, had been reported. Fusobacterium spp has been linked to portal vein thrombosis in less than a dozen of cases. Here, we report a rare case of hepatic vein thrombosis associated with Fusobacterium spp. in a patient without the classical primary cephalic infective focus that characterizes Lemierre syndrome. To the best of our knowledge, this the third case reported in the literature linking Fusobacterium spp. to hepatic vein thrombosis.
CASE PRESENTATION A 73-year-old African American man with medical history significant for hypertension, diabetics, and coronary artery disease presented with 2-week history of fever. He had an emergency room (ER) visit 5 days ago. The workups, including complete blood count, basic metabolic panel, and lactate were within the reference range. Two sets of blood culture were collected.
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e934
He was discharged home with presumed diagnosis of viral syndrome. His fever persisted. He returned to ER with fever of 103°F and new-onset, dull, epigastric abdominal pain. The pain had been increasing in density and was discomforting to the patient. There was no radiation and nothing made it better or worse. The patient denied any recent history of sick contact or travel. There was no nasal congestion, sore throat, trouble swallowing, or cough. He also denied any shortness of breath. He denied any diarrhea or hematochezia. He is a nonsmoker and social drinker. On admission, the patient had fever of 103°F and blood pressure of 132/44 mm Hg. His heart rate was 110 per minute and oxygen saturation on room air was 97%. Physical examination revealed that the patient was tachycardiac but had a benign abdomen without any evidence of tenderness, guarding, or rebound. There was no jaundice, ascites, or stigmata of chronic liver disease. The rest of the patient’s cardiovascular, respiratory, and abdominal examination was normal. Initial investigations revealed white blood cell count of 11.6 3 103/mL, with 94% of neutrophils and elevated erythrocyte sedimentation rate (78 mm/h) and Creactive protein (11.8 mg/dL). Liver tests were essentially normal (total bilirubin, 0.7 mg/dL; direct bilirubin, 0.2 mg/dL; alkaline phosphatase, 82 U/L; aspartate aminotransferase 12 U/L; and alanine transferase, 16 U/L). His amylase/lipase was also within the reference range. Other tests, including basic metabolic panel, coagulation tests, urine analysis, and chest radiography were essentially negative. Rapid human immunodeficiency virus screening was also negative. The blood cultures collected 5 days before remained negative on admission. Two more sets of blood cultures and urine culture were collected. The patient was stated on empiric cefepime 1 gram, intravenously, twice a day and admitted to the general medicine floor. Because of persistent abdominal discomfort, the computed tomography (CT) of the abdomen and pelvis with intravenous contrast was ordered on the second hospital day. It demonstrated posterior right hepatic vein occlusion with thrombus and venous infarct in the posterior right lobe of the liver. The patient was started on enoxaparin 1 mg/kg subcutaneously twice a day for immediate anticoagulation. Coumadin therapy was also initiated. Hematology/ oncology was consulted for hepatic vein thrombosis. Hypercoagulopathy tests were ordered, which all came back negative later. The patient remained febrile for the first 2 hospital days, although he had been on empirical cefepime. On hospital day 3, the blood cultures from previous ER visit grew gram-negative rods, which eventually turned out to be Fusobacterium nucleatum after total 9 American Journal of Therapeutics (2016) 23(3)
Zheng and Giri
days’ incubation. All blood cultures collected on this admission also grew F. nucleatum after the prolonged incubation. The final isolation showed it is susceptible to penicillin, cefoxitin, and clindamycin. Because F. nucleatum is known to be associated with Lemierre syndrome, extensive workups had been ordered in the efforts to identify the infectious source in the local oropharyngeal space. CT of the neck with intravenous contrast failed to show any obvious source of infection or internal jugular vein thrombosis. A Panorex of the mandible also showed no evidence of focal abscess. CT of the head and chest did not show any evidence of infection or underlying malignancy. His tumor markers, including CEA and CA19-9, were all negative. The antibiotic had been changed to clindamycin per infectious disease consultant’s recommendation. The patient became afebrile and improved significantly. He was subsequently discharged on clindamycin and enoxaparin for anticoagulation bridging. Two months later, an outpatient colonoscopy did not identify any obvious abnormality except diverticulosis.
DISCUSSION Fusobacterium spp. are part of the normal flora of the oral cavity, gastrointestinal (GI) tract, upper respiratory tract, and female genital tract.6 Until recently, F. nucleatum was thought to primarily be a component of the oral microbiota of humans and only an occasional resident of the gut. However, this was built on culture-based examination of stool, which usually does not contain high numbers of live, epithelium-associated bacteria. Recently, using fluorescence in situ hybridization, Swidsinski et al7 demonstrated an association between invasive Fusobacterium spp. (including F. nucleatum) cells with inflamed appendix tissues, suggesting that the gut could be a hitherto unrecognized niche for this pathogen. Moreover, Strauss et al reported that there is a strong relationship between F. nucleatum and inflammatory bowel disease. In their study, Fusobacterium spp. were isolated from 63.6% of patients with GI disease compared with 26.5% of healthy controls (P 5 0.01). In total, 69% of all Fusobacterium spp. recovered from patients were identified as F. nucleatum.8 Further studies demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of patients with Crohn disease evoked significantly greater MUC2 (Mucin 2) and tumor necrosis factor alpha gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection.9 F. nucleatun infection has also found to be associated with www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e935
Lemierre Syndrome Variant
colorectal carcinoma10,11 in several studies. However, it is still unclear whether this association is involved in the pathogenesis of colorectal cancers or if F. nucleatum simply tends to explore the microenvironment created by colorectal cancers. In any case, F. nucleatum looks like a regular resident of GI tract and the underlying GI malignancy should be ruled out in case of GI variant of Lemierre syndrome. Septic thrombophlebitis of the portal vein, also known as pylephlebitis, is usually a complication of any intraabdominal or pelvic infection that occurs in the region drained by the portal venous system, especially appendicitis and diverticulitis. Because the hepatic portal circulation exclusively drains the GI tract, it is probable that the source of our patient’s infection was the lower GI tract. The thrombogenic ability of Fusobacterium spp. has been well known.12 Similar to F. necrophorum, F. nucleatum can bind human plasminogen, which may be activated into plasmin by host plasminogen activators. The locally generated proteolysis is involved in tissue damage and penetration through host barrier, therefore causing serious infections.13 Furthermore, in the less than a dozen of cases reported that linking Fusobacterium spp. to portal vein thrombosis, more than half of them were attributed to F. nucleatum4,14–19; strongly suggesting a GI variant of Lemierre syndrome is more likely caused by F. nucleatum residing in the gut. Fusobacterium spp. is gram-negative, non-spore forming, and strictly anaerobic species. The current consensus is that Fusobacterium should always be treated as a pathogen, although it is a common occurrence in the human body.20 Usually, Fusobacterium spp. is susceptible to penicillin, clindamycin, and metronidazole, but there is a various response to second- and thirdgeneration cephalosporins. There is arising penicillin resistant because of b-lactamase production,20 therefore b-lactamase resistant antibiotics with anaerobic coverage, such as metronidazole, are recommended.21 The role of anticoagulation in treating Lemierre syndrome or its GI variant is still unclear. The decision to initiate anticoagulation is based on personal experience or preference rather than randomized clinical trials.1 However, in patient with high risks, if there is no contraindication, anticoagulation should still be considered.22 Surgical intervention is reserved for cases with persistent showering of septic emboli or continued propagation of the thrombosis.1 In our case, imaging studies, tumor makers, and colonoscopy failed to identify any gross anatomic and functional abnormality of the GI tract. Nevertheless, given the history of abdominal pain before admission and the absence of other systemic illness, we consider that the hepatic vein thrombosis was most www.americantherapeutics.com
probably due to a subclinical primary infection affecting the lower GI tract. The hepatic vein thrombosis associated with Fusobacterium spp. is very rare, and so far, there are 2 cases reported in the literature.19,23 Compared with Lemierre syndrome, illness due to primary foci caudal to the head carries a higher mortality rate24; however, metastatic abscess formation does not generally occur.25 Short courses of antibiotic treatment25 may be effective in these patients as compared with Lemierre syndrome in which abscess formation necessitates longer courses of antibiotics, often for 6 weeks or more. It is important to exclude underlying malignancy in patients with non-head primary foci because up to 69% of patients with GI or urogenital primary infection with F. necrophorum have underlying malignancies of the affected system.26
REFERENCES 1. Bondy P, Grant T. Lemierre’s syndrome: what are the roles for anticoagulation and long-term antibiotic therapy? Ann Otol Rhinol Laryngol. 2008;117:679–683. 2. Chirinos JA, Lichtstein DM, Garcia J, et al. The evolution of Lemierre syndrome: report of 2 cases and review of the literature. Medicine (Baltimore). 2002; 81:458–465. 3. Bisharat N, Goldstein L, Raz R, et al. Gram-negative anaerobic endocarditis: two case reports and review of the literature. Eur J Clin Microbiol Infect Dis. 2001;20:651– 654. 4. Etienne M, Gueit I, Abboud P, et al. Fusobacterium nucleatum hepatic abscess with pylephlebitis associated with idiopathic CD4(+) T lymphocytopenia. Clin Infect Dis. 2001;32:326–328. 5. Lee MJ, Ha YE, Park HY, et al. Osteomyelitis of a long bone due to Fusobacterium nucleatum and Actinomyces meyeri in an immunocompetent adult: a case report and literature review. BMC Infect Dis. 2012; 12:161. 6. Brook I. Fusobacterial infections in children. J Infect. 1994; 28:155–165. 7. Swidsinski A, Dorffel Y, Loening-Baucke V, et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut. 2011;60:34–40. 8. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 2011;17:1971–1978. 9. Dharmani P, Strauss J, Ambrose C, et al. Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha. Infect Immun. 2011;79:2597–2607. 10. Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306. American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e936 11. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–298. 12. Henry S, DeMaria A Jr, McCabe WR. Bacteremia due to Fusobacterium species. Am J Med. 1983;75:225–231. 13. Darenfed H, Grenier D, Mayrand D. Acquisition of plasmin activity by Fusobacterium nucleatum subsp. nucleatum and potential contribution to tissue destruction during periodontitis. Infect Immun. 1999;67:6439–6444. 14. Bultink IE, Dorigo-Zetsma JW, Koopman MG, et al. Fusobacterium nucleatum septicemia and portal vein thrombosis. Clin Infect Dis. 1999;28:1325–1326. 15. Soo R, Gosbell I, Gallo J, et al. Septic portal vein thrombosis due to Fusobacterium necrophorum. Aust N Z J Med. 1999;29:569–570. 16. Verna EC, Larghi A, Faddoul SG, et al. Portal vein thrombosis associated with Fusobacterium nucleatum septicemia in a patient with ulcerative colitis. J Clin Gastroenterol. 2004;38:611–612. 17. El Braks R, Harnois F, Boutros N, et al. Mesenteric adenitis and portal vein thrombosis due to Fusobacterium nucleatum. Eur J Gastroenterol Hepatol. 2004;16:1063– 1066. 18. Schweigart JH, Klotsas A, Schelenz S, et al. Portal vein thrombosis despite anticoagulation in a person with diabetes. J R Soc Med. 2005;98:161–163. 19. Le Roux K, Seve P, Gomard E, et al. Lemierre syndrome variant: hepatic abscesses and hepatic venous thrombosis
American Journal of Therapeutics (2016) 23(3)
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21.
22.
23.
24.
25.
26.
due to Fusobacterium nucleatum septicemia. Rev Med Interne. 2006;27:482–486. Aliyu SH, Marriott RK, Curran MD, et al. Real-time PCR investigation into the importance of Fusobacterium necrophorum as a cause of acute pharyngitis in general practice. J Med Microbiol. 2004;53:1029–1035. Appelbaum PC, Philippon A, Jacobs MR, et al. Characterization of beta-lactamases from non-Bacteroides fragilis group Bacteroides spp. belonging to seven species and their role in beta-lactam resistance. Antimicrob Agents Chemother. 1990;34:2169–2176. Phan T, So TY. Use of anticoagulation therapy for jugular vein thrombus in pediatric patients with Lemierre’s syndrome. Int J Clin Pharm. 2012;34:818–821. Campoamor Serrano MT, Galiana Martin D, Noval Menendez J, et al. Hepatic abscesses and hepatic venous thrombosis due to Fusobacterium necrophorum septicemia: Lemierre syndrome variant. Med Clin (Barc). 2007; 129:197–198. Hagelskjaer LH, Prag J, Malczynski J, et al. Incidence and clinical epidemiology of necrobacillosis, including Lemierre’s syndrome, in Denmark 1990-1995. Eur J Clin Microbiol Infect Dis. 1998;17:561–565. Hagelskjaer Kristensen L, Prag J. Human necrobacillosis, with emphasis on Lemierre’s syndrome. Clin Infect Dis. 2000;31:524–532. Brook I, Frazier EH. Aerobic and anaerobic infection associated with malignancy. Support Care Cancer. 1998;6:125–131.
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Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Gastrointestinal Variant of Lemierre Syndrome: Fusobacterium nucleatum Bacteremia–Associated Hepatic Vein Thrombosis: a Case Report and Literature Review Lin Zheng, MD, PhD1* and Badri Giri, MD2
Fusobacterium nucleatum is a gram-negative bacillius commonly found in oropharynx and is traditionally associated with Lemierre syndrome, which is characterized by history of recent oropharyngeal infection, internal jugular vein thrombosis, and isolation of anaerobic pathogens, mainly Fuosobacterium necrophorum. However, recent evidence indicated that F. nucleatum is also a normal resident of human gut. Less than a dozen of case reports had linked F. nucleatum to gastrointestinal variant of Lemierre syndrome with portal vein thrombosis. However, F. nucleatum bacteremia– associated hepatic vein thrombosis is very rare. We report a case of a 73-year-old man who had hepatic vein thrombosis associated with F. nucleatum bacteremia, most likely from subclinical primary infection affecting the lower gastrointestinal tract. The underlying pathophysiology and treatment options are discussed here. With rapid increase in reporting of Lemierre syndrome, this case deserves particular attention from clinicians. Keywords: Fusobacterium nucleatum, Lemierre syndrome, hepatic vein thrombosis
INTRODUCTION Known as postanginal septicemia or necrobacillosis, Lemierre syndrome is characterized by acute primary infection of the oropharynx, usually by Fusobacterium necrophorum, causing secondary thrombophlebitis of the internal jugular vein. When jugular vein thrombosis occurs, there is inflammation and consequent septic thrombophlebitis, which gives rise to distant emboli that usually migrate to pulmonary capillaries.1 As the consequence, the most frequently involved sites of septic metastases are the lungs, followed by
1
Division of Hospital Medicine, Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ; and 2Pulmonary and Critical Medicine Fellowship Program, Department of Medicine, Texas A&M HSCCOM - Scott & White Healthcare, Temple, TX. *Address for correspondence: Division of Hospital Medicine, Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Dorrance 222, One Cooper Plaza, Camden, NJ 08103. E-mail: [email protected]
the joints (knee, hip, sternoclavicular joint, shoulder, and elbow).2 The septic metastasis and abscess formation in muscle, long bones, liver, heart,3–5 although extremely rare, had been reported. Fusobacterium spp has been linked to portal vein thrombosis in less than a dozen of cases. Here, we report a rare case of hepatic vein thrombosis associated with Fusobacterium spp. in a patient without the classical primary cephalic infective focus that characterizes Lemierre syndrome. To the best of our knowledge, this the third case reported in the literature linking Fusobacterium spp. to hepatic vein thrombosis.
CASE PRESENTATION A 73-year-old African American man with medical history significant for hypertension, diabetics, and coronary artery disease presented with 2-week history of fever. He had an emergency room (ER) visit 5 days ago. The workups, including complete blood count, basic metabolic panel, and lactate were within the reference range. Two sets of blood culture were collected.
1075–2765 Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e934
He was discharged home with presumed diagnosis of viral syndrome. His fever persisted. He returned to ER with fever of 103°F and new-onset, dull, epigastric abdominal pain. The pain had been increasing in density and was discomforting to the patient. There was no radiation and nothing made it better or worse. The patient denied any recent history of sick contact or travel. There was no nasal congestion, sore throat, trouble swallowing, or cough. He also denied any shortness of breath. He denied any diarrhea or hematochezia. He is a nonsmoker and social drinker. On admission, the patient had fever of 103°F and blood pressure of 132/44 mm Hg. His heart rate was 110 per minute and oxygen saturation on room air was 97%. Physical examination revealed that the patient was tachycardiac but had a benign abdomen without any evidence of tenderness, guarding, or rebound. There was no jaundice, ascites, or stigmata of chronic liver disease. The rest of the patient’s cardiovascular, respiratory, and abdominal examination was normal. Initial investigations revealed white blood cell count of 11.6 3 103/mL, with 94% of neutrophils and elevated erythrocyte sedimentation rate (78 mm/h) and Creactive protein (11.8 mg/dL). Liver tests were essentially normal (total bilirubin, 0.7 mg/dL; direct bilirubin, 0.2 mg/dL; alkaline phosphatase, 82 U/L; aspartate aminotransferase 12 U/L; and alanine transferase, 16 U/L). His amylase/lipase was also within the reference range. Other tests, including basic metabolic panel, coagulation tests, urine analysis, and chest radiography were essentially negative. Rapid human immunodeficiency virus screening was also negative. The blood cultures collected 5 days before remained negative on admission. Two more sets of blood cultures and urine culture were collected. The patient was stated on empiric cefepime 1 gram, intravenously, twice a day and admitted to the general medicine floor. Because of persistent abdominal discomfort, the computed tomography (CT) of the abdomen and pelvis with intravenous contrast was ordered on the second hospital day. It demonstrated posterior right hepatic vein occlusion with thrombus and venous infarct in the posterior right lobe of the liver. The patient was started on enoxaparin 1 mg/kg subcutaneously twice a day for immediate anticoagulation. Coumadin therapy was also initiated. Hematology/ oncology was consulted for hepatic vein thrombosis. Hypercoagulopathy tests were ordered, which all came back negative later. The patient remained febrile for the first 2 hospital days, although he had been on empirical cefepime. On hospital day 3, the blood cultures from previous ER visit grew gram-negative rods, which eventually turned out to be Fusobacterium nucleatum after total 9 American Journal of Therapeutics (2016) 23(3)
Zheng and Giri
days’ incubation. All blood cultures collected on this admission also grew F. nucleatum after the prolonged incubation. The final isolation showed it is susceptible to penicillin, cefoxitin, and clindamycin. Because F. nucleatum is known to be associated with Lemierre syndrome, extensive workups had been ordered in the efforts to identify the infectious source in the local oropharyngeal space. CT of the neck with intravenous contrast failed to show any obvious source of infection or internal jugular vein thrombosis. A Panorex of the mandible also showed no evidence of focal abscess. CT of the head and chest did not show any evidence of infection or underlying malignancy. His tumor markers, including CEA and CA19-9, were all negative. The antibiotic had been changed to clindamycin per infectious disease consultant’s recommendation. The patient became afebrile and improved significantly. He was subsequently discharged on clindamycin and enoxaparin for anticoagulation bridging. Two months later, an outpatient colonoscopy did not identify any obvious abnormality except diverticulosis.
DISCUSSION Fusobacterium spp. are part of the normal flora of the oral cavity, gastrointestinal (GI) tract, upper respiratory tract, and female genital tract.6 Until recently, F. nucleatum was thought to primarily be a component of the oral microbiota of humans and only an occasional resident of the gut. However, this was built on culture-based examination of stool, which usually does not contain high numbers of live, epithelium-associated bacteria. Recently, using fluorescence in situ hybridization, Swidsinski et al7 demonstrated an association between invasive Fusobacterium spp. (including F. nucleatum) cells with inflamed appendix tissues, suggesting that the gut could be a hitherto unrecognized niche for this pathogen. Moreover, Strauss et al reported that there is a strong relationship between F. nucleatum and inflammatory bowel disease. In their study, Fusobacterium spp. were isolated from 63.6% of patients with GI disease compared with 26.5% of healthy controls (P 5 0.01). In total, 69% of all Fusobacterium spp. recovered from patients were identified as F. nucleatum.8 Further studies demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of patients with Crohn disease evoked significantly greater MUC2 (Mucin 2) and tumor necrosis factor alpha gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection.9 F. nucleatun infection has also found to be associated with www.americantherapeutics.com
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e935
Lemierre Syndrome Variant
colorectal carcinoma10,11 in several studies. However, it is still unclear whether this association is involved in the pathogenesis of colorectal cancers or if F. nucleatum simply tends to explore the microenvironment created by colorectal cancers. In any case, F. nucleatum looks like a regular resident of GI tract and the underlying GI malignancy should be ruled out in case of GI variant of Lemierre syndrome. Septic thrombophlebitis of the portal vein, also known as pylephlebitis, is usually a complication of any intraabdominal or pelvic infection that occurs in the region drained by the portal venous system, especially appendicitis and diverticulitis. Because the hepatic portal circulation exclusively drains the GI tract, it is probable that the source of our patient’s infection was the lower GI tract. The thrombogenic ability of Fusobacterium spp. has been well known.12 Similar to F. necrophorum, F. nucleatum can bind human plasminogen, which may be activated into plasmin by host plasminogen activators. The locally generated proteolysis is involved in tissue damage and penetration through host barrier, therefore causing serious infections.13 Furthermore, in the less than a dozen of cases reported that linking Fusobacterium spp. to portal vein thrombosis, more than half of them were attributed to F. nucleatum4,14–19; strongly suggesting a GI variant of Lemierre syndrome is more likely caused by F. nucleatum residing in the gut. Fusobacterium spp. is gram-negative, non-spore forming, and strictly anaerobic species. The current consensus is that Fusobacterium should always be treated as a pathogen, although it is a common occurrence in the human body.20 Usually, Fusobacterium spp. is susceptible to penicillin, clindamycin, and metronidazole, but there is a various response to second- and thirdgeneration cephalosporins. There is arising penicillin resistant because of b-lactamase production,20 therefore b-lactamase resistant antibiotics with anaerobic coverage, such as metronidazole, are recommended.21 The role of anticoagulation in treating Lemierre syndrome or its GI variant is still unclear. The decision to initiate anticoagulation is based on personal experience or preference rather than randomized clinical trials.1 However, in patient with high risks, if there is no contraindication, anticoagulation should still be considered.22 Surgical intervention is reserved for cases with persistent showering of septic emboli or continued propagation of the thrombosis.1 In our case, imaging studies, tumor makers, and colonoscopy failed to identify any gross anatomic and functional abnormality of the GI tract. Nevertheless, given the history of abdominal pain before admission and the absence of other systemic illness, we consider that the hepatic vein thrombosis was most www.americantherapeutics.com
probably due to a subclinical primary infection affecting the lower GI tract. The hepatic vein thrombosis associated with Fusobacterium spp. is very rare, and so far, there are 2 cases reported in the literature.19,23 Compared with Lemierre syndrome, illness due to primary foci caudal to the head carries a higher mortality rate24; however, metastatic abscess formation does not generally occur.25 Short courses of antibiotic treatment25 may be effective in these patients as compared with Lemierre syndrome in which abscess formation necessitates longer courses of antibiotics, often for 6 weeks or more. It is important to exclude underlying malignancy in patients with non-head primary foci because up to 69% of patients with GI or urogenital primary infection with F. necrophorum have underlying malignancies of the affected system.26
REFERENCES 1. Bondy P, Grant T. Lemierre’s syndrome: what are the roles for anticoagulation and long-term antibiotic therapy? Ann Otol Rhinol Laryngol. 2008;117:679–683. 2. Chirinos JA, Lichtstein DM, Garcia J, et al. The evolution of Lemierre syndrome: report of 2 cases and review of the literature. Medicine (Baltimore). 2002; 81:458–465. 3. Bisharat N, Goldstein L, Raz R, et al. Gram-negative anaerobic endocarditis: two case reports and review of the literature. Eur J Clin Microbiol Infect Dis. 2001;20:651– 654. 4. Etienne M, Gueit I, Abboud P, et al. Fusobacterium nucleatum hepatic abscess with pylephlebitis associated with idiopathic CD4(+) T lymphocytopenia. Clin Infect Dis. 2001;32:326–328. 5. Lee MJ, Ha YE, Park HY, et al. Osteomyelitis of a long bone due to Fusobacterium nucleatum and Actinomyces meyeri in an immunocompetent adult: a case report and literature review. BMC Infect Dis. 2012; 12:161. 6. Brook I. Fusobacterial infections in children. J Infect. 1994; 28:155–165. 7. Swidsinski A, Dorffel Y, Loening-Baucke V, et al. Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum. Gut. 2011;60:34–40. 8. Strauss J, Kaplan GG, Beck PL, et al. Invasive potential of gut mucosa-derived Fusobacterium nucleatum positively correlates with IBD status of the host. Inflamm Bowel Dis. 2011;17:1971–1978. 9. Dharmani P, Strauss J, Ambrose C, et al. Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha. Infect Immun. 2011;79:2597–2607. 10. Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306. American Journal of Therapeutics (2016) 23(3)
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
e936 11. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–298. 12. Henry S, DeMaria A Jr, McCabe WR. Bacteremia due to Fusobacterium species. Am J Med. 1983;75:225–231. 13. Darenfed H, Grenier D, Mayrand D. Acquisition of plasmin activity by Fusobacterium nucleatum subsp. nucleatum and potential contribution to tissue destruction during periodontitis. Infect Immun. 1999;67:6439–6444. 14. Bultink IE, Dorigo-Zetsma JW, Koopman MG, et al. Fusobacterium nucleatum septicemia and portal vein thrombosis. Clin Infect Dis. 1999;28:1325–1326. 15. Soo R, Gosbell I, Gallo J, et al. Septic portal vein thrombosis due to Fusobacterium necrophorum. Aust N Z J Med. 1999;29:569–570. 16. Verna EC, Larghi A, Faddoul SG, et al. Portal vein thrombosis associated with Fusobacterium nucleatum septicemia in a patient with ulcerative colitis. J Clin Gastroenterol. 2004;38:611–612. 17. El Braks R, Harnois F, Boutros N, et al. Mesenteric adenitis and portal vein thrombosis due to Fusobacterium nucleatum. Eur J Gastroenterol Hepatol. 2004;16:1063– 1066. 18. Schweigart JH, Klotsas A, Schelenz S, et al. Portal vein thrombosis despite anticoagulation in a person with diabetes. J R Soc Med. 2005;98:161–163. 19. Le Roux K, Seve P, Gomard E, et al. Lemierre syndrome variant: hepatic abscesses and hepatic venous thrombosis
American Journal of Therapeutics (2016) 23(3)
Zheng and Giri
20.
21.
22.
23.
24.
25.
26.
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