teries may develop, and vessels in which emboli are thought to arise unusual sites such as the splenic vein, from platelet thrombi at sites of irmesenteric vessels, digital vessels and regularity and narrowing, it seems the axillary artery are frequently logical to attempt treatment of priinvolved."' It has been widely ac- mary thrombocythemia with drugs cepted that thrombosis is the conse- that suppress platelet function. In the case just described, the quence of the greatly increased platelet mass together with a qualitative ischemic lesions of the extremities abnormality of the platelets.7 Spon- resolved completely and did not retaneous aggregation of platelets has cur during therapy with antiplatelet been demonstrated in vitro,5 and agents even though the platelet count platelet hyperaggregability has been remained elevated; this suggests a shown to correlate with the occur- protective effect of these drugs. It must be emphasized, however, that rence of thrombotic complications.8 Therapy for primary thrombocy- smaller doses of acetylsalicylic acid themia is directed at reducing the than were given to this patient can platelet mass. The use of radioactive affect platelet function for long pephosphorus or alkylating agents has riods; one might therefore expect the been shown to be effective in con- same results with a lower dose. Thertrolling the proliferative process as apeutic trials comparing the effectivewell as its complications.4'9"0 A pri- ness of two different doses may anmary role of platelets in the occlusive swer this question. process may account for the presence of thrombotic lesions without demonstrable arterial disease. Therapy References with antiplatelet agents has not been 1. GUNZ FW: Hemorrhagic thrombocythoroughly evaluated for this disease, themia: a critical review. Blood 15: 706, 1960 although some encouraging preliminary results have been reported with 2. SHECHTER FR, RASANSKY HN, LORZ such therapy for thrombotic comH: Hemorrhagic thrombocythemia. Am J Gastroenterol 38: 659, 1962 plications in the extremities."8"' As in transient ischemic attacks, in 3. FRICK PG: Primary thrombocythemia.
Helv Med Acta 35: 20, 1969 4. SINGH AK, WEThERLEY-MEIN G: Mi-
crovascular occlusive lesions in primary thrombocythaemia. Br J Haernatol 36: 553, 1977 5. VREEKEN J, VAN AKEN WG:
Spon-
taneous aggregation of blood platelets as a cause of idiopathic thrombosis and recurrent painful toes and fingers. Lancet 2: 1394, 1971 6. PRESTON FE,
EMMANUEL
IG, WIN-
FIELD DA, et al: Essential thrombocythaemia and peripheral gangrene. Br Med J 3: 548, 1974 7. ZUCKER S, MIELKE CH: Classification of thrombocytosis based on platelet function tests: correlation with hemorrhagic and thrombotic complications. J Lab Gun Med 80: 385, 1972 8. Wu KK: Platelet hyperaggregability and thrombosis in patients with thrombocythemia. Ann intern Med 88: 7, 1978 9. FOUNTAIN JR, LOSOWSKY MS: Hemor-
rhagic thrombocythaemia and its treatment with radioactive phosphorus. Q J Med 31: 207, 1962 10. BENSINGER TA, LOGUE GL, RUNDLES
RW: Hemorrhagic thrombocythemia; control of postsplenectomy thrombocytosis with melphalan. Blood 36: 61, 1970 11. BIERM.
R,
BONEU
B,
GUIRAUD
B,
et al: Aspirin and recurrent painful toes and fingers in thrombocythaemia (C). Lancet 1: 432, 1972
Yersinia enterocolitica septicemia with pneumonia D. PORTNOY,* MD; L.A. MARTINEZ,t MD, FRCP
plete resolution followed a 10-day The clinical manifestations of Yersinia enterocolitica infection are protean, but most are limited to the gastrointestinal tract. The first case of Y. enterocolitica septicemia with pneumonia to be reported in Canada is described below. This case, in a renal transplant recipient with chronic active hepatitis and portal hypertension, is worth noting since these underlying problems may have played a role in the dissemination of his disease. Serologic studies failed to show a rise in the agglutinating titre of antibodies to Y. enterocolitica. CoinFrom the department of microbiology and immunology, McGill University, Montreal *Senior resident tAssistant professor Reprint requests to: Dr. L.A. Martinez, Department of microbiology and immunology, McGill University, 3775 University St., Montreal, PQ H3A 2B4
The man had received a kidney transplant 5 years before, at which time he was known to have chronic active hepatitis with portal hypertenCase report sion. Medication taken prior to adA 57-year-old man was admitted mission consisted of prednisone, 15 to hospital complaining of fever, mg/d, and digoxin, 0.25 mg/d. anorexia, cough and shortness of At the time of admission the man's breath. He had had upper abdominal temperature was 38 0C, blood prescramping pain, watery diarrhea with sure 130/80 mm Hg, pulse rate 100 5 to 10 bowel movements per day beats/mm (and the rhythm irreguand fever for 1½ weeks prior to larly irregular) and respiratory rate admission. Several days after the 1 6/mm. Examination of the chest diarrhea's onset he took Lomotil® revealed decreased air entry over the (diphenoxylate hydrochloride and right lung field. No other adventiatropine) and the frequency of bowel tious sounds were noted. There was movements decreased to one to three hepatosplenomegaly. Results of phyper day. Five days prior to admission sical examination were otherwise unhe noticed the onset of a productive remarkable. A chest roentgenogram cough with yellowish expectoration, showed right upper and lower lobe increasing shortness of breath and infiltrates. The leukocyte count was 12.0 x spiking fever to 390C. The persistence of these symptoms led him to 1 09/L and the hemoglobin concentration was 15.3 g/dL. Y. enterocoseek medical attention. course of gentamicin therapy.
CMA JOURNAL/JANUARY 6, 1979/VOL. 120 61
utica was cultured from one blood sample, taken before antibiotic therapy was instituted, as well as from sputum, a throat swab and feces. The organism was further identified by Dr. L. Lafleur (h6pital Sainte-Justine, Montreal) as serotype 3, biotype 4. Serologic tests for antibodies to Y. enterocolitica were done by the national reference service for Yersinia, Ontario Ministry of Health, Toronto. Four serum specimens, including a sample obtained 6 months prior to the illness, were reactive, with an agglutinating titre for serotype 3 of 1:100. By the Kirby-Bauer disc sensitivity method the organism was found to be sensitive to kanamycin, gentamicm, sulfonamides, tetracycline and trimethoprim-sulfamethoxazole, and resistant to carbenicillin, amoxicillin and cephalosporins. The patient was treated with gentamicin, 180 mg/d intravenously. The minimum inhibitory concentration (MIC) and the minimum bacteriostatic concentration (MBC) were 0.4 .g/mL. Serum gentamicin concentrations 1 hour before and 1 hour after administration of the drug were 1.4 and 2.3 p.g/mL respectively. Several days after the onset of therapy the patient's condition improved remarkably. His temperature returned to normal and, his other symptoms disappeared. A chest roentgenogram taken on completion of a 10-day course of gentamicin showed resolution of the pneumonia, and no pathogenic organisms could be cultured from blood, sputum or stool. The patient had four dogs and two cats. No pathogenic organisms could be cultured from stool samples from the animals. Discussion Y. enterocolitica is a gram-negative pleomorphic coccobacillus that, over the years, was known under a variety of names.'4 In 1964 Frederiksen proposed the name Yersinia enterocolitica.5 The organism was first reported as a cause of human infection in 1939.6 By 1966 there had been only 23 reported cases.7 Since then the number of documented cases has increased, and there are now approximately 6000 known isolates of this organism.8'9 Although the earliest
cases appeared in the United States, most of the pertinent literature of the 1 960s originated in Europe. The organism was again reported in the American literature in 1969,10 and was first reported in Canada in 1971." The clinical manifestations of Y. enterocolitica infection are protean, and are mostly limited to the gastrointestinal tract. Enterocolitis is the most frequent presentation in young children, whereas acute mesenteric lymphadenitis and terminal ileitis are more likely to occur in older children and adults. Less common manifestations include septicemia,"'8 erythema nodosum,'7 arthritis,15 Reiter's syndrome,'8 myocarditis,'7 cellulitis,'4 meningitis'0 and pneumonia.'3 When septicemia does occur the mortality can be as high as 50%. Persons most likely to have septicemia are the elderly and individuals whose defence mechanisms have been compromised by immunosuppressive therapy or underlying disease.8 Rabson, Hallett and Koornhof"' noted that septicemia was more common in patients with iron overload, "Bantu siderosis" and cirrhosis, suggesting that in patients with cirrhosis the bacteria bypass the reticuloendothelial system of the liver and are disseminated via the peripheral blood. Our patient had chronic liver disease with portal hypertension, and was taking steroids. These factors may therefore have contributed to the dissemination of his infection. Serologic testing for antibodies has been stressed by many authors as an important means of confirming the diagnosis of Y. enterocolitica infection.8"4"' However, the agglutinating titre of antibodies to Y. enterocolitica in our patient's serum did not rise during the illness, and was the same as it had been 6 months prior to the onset of the illness. It is possible that the patient had been harbouring the organism for some time, and that the stable titre simply reflected the maximum antibody response in this immunosuppressed host. References 1. SCHLEIFSTEIN JI, COLEMAN MB: Bac-
teriurn enterocoliticum, annual report, division of laboratory research, New York State Department of Health, Albany, 1943, p 56 2. DIcKINsoN AB, MocQuoT G: Studies on the bacterial flora of the alimentary tract of pigs. I. Enterobacter-
62 CMA JOURNAL/JANUARY 6, 1979/VOL. 120
iaceae and other gram-negative bacteria. J Appi Bacteriol 24: 252, 1961 3. CARLSSON MG, RYD H, STERNEY NH: A case of human infection with Pas-
teurella pseudotuberculosis X. Acta Pathol Microbiol Scand [B] 62: 128, 1964 4. MOLLARET HH, DESTOMBES P: Les germes "X" en pathologie humaine.
Nouv Presse Med 72: 2913, 1964 5. FREDERIKSEN W: A study of some Yersinia pseudotuberculosis-like bacteria ("Bacterium enterocoliticum and Pasteurella "X"), in Proceedings of
the 14th Scandinavian Congress on Pathology and Microbiology, Oslo, Universiteitsforlaget Trykningssentral, Oslo, 1964, p 103 6. SCHLEIFSTEIN JI, COLEMAN MB: An unidentified microorganism resembling B. lignieri and Pasteurella pseudotuberculosis, and pathogenic for man. NY State J Med 39: 1749, 1939 7. TOMA 5, LAFLEUR L: Survey of the
incidence of Yersinia enterocolitica infection in Canada. AppI Environ Microbiol 28: 469, 1974 8. BOTTONE E: Yersinia enterocolitica: a panoramic view of a charismatic mi-
croorganism. CRC Crit Rev Microbiol 5: 211, 1977 9. TOMA 5, DEIDRIcK VR: Isolation of
Yersinia enterocolitica from swine. J C/in Microbiol 2: 478, 1975 10. SONNENWIRTH AC: Yersinia enterocolitica as an etiologic agent in meningitis. Bacteriol Proc 128: 87, 1969 11. ALBERT G, LAFLEUR L: Yersinia enterocolitica in children. Presentation of 24 cases observed at h6pital SteJustine, Montreal (abstr). Can J Public Health 62: 70, 1971 12. MOLLARET HH, OMLAND T, HENRIKSEN SD, et at: Les septic.mies humaines a "Yersinia enterocolitica". A propos de dix-sept cas r.cents. Nouv Presse Med 79: 345, 1971 13. SEBES JI, MARBY EH, RABINowITz JG: Lung abscess and osteomyelitis of rib due to Yersinia-enterocolitica.
Chest 69: 546, 1976 14. ABRAMOVITCH H, BUTAS CA: Septicemia due to Yersinia enterocolitica.
Can Med Assoc J 109: 1112, 1973 15. SPIRA TJ, KABINS SA: Yersinia enterocolitica septicemia with septic arthritis.
Arch intern Med 136: 1305, 1976 16. ERIKSSON M, OLcffi P: Case report: septicemia due to Yersinia enterocoutica in a non-compromised host.
Scand J infect Dis 7: 78, 1975 17. LEINo R, KALLIOMAKI JI: Yersiniosis as an internal disease. Ann intern Med
81: 458, 1974 18. SOLEM JH, LASSEN J: Reiter's disease following Yersinia enterocolitica infection. Scand J infect Dis 3: 83, 1971 19. RABSON AR, HALLETT AF, KooRNHOFF HJ: Generalized Yersinia en-
terocolitica infection. J infect Dis 131: 447, 1975
Helv Med Acta 35: 20, 1969 4. SINGH AK, WEThERLEY-MEIN G: Mi-
crovascular occlusive lesions in primary thrombocythaemia. Br J Haernatol 36: 553, 1977 5. VREEKEN J, VAN AKEN WG:
Spon-
taneous aggregation of blood platelets as a cause of idiopathic thrombosis and recurrent painful toes and fingers. Lancet 2: 1394, 1971 6. PRESTON FE,
EMMANUEL
IG, WIN-
FIELD DA, et al: Essential thrombocythaemia and peripheral gangrene. Br Med J 3: 548, 1974 7. ZUCKER S, MIELKE CH: Classification of thrombocytosis based on platelet function tests: correlation with hemorrhagic and thrombotic complications. J Lab Gun Med 80: 385, 1972 8. Wu KK: Platelet hyperaggregability and thrombosis in patients with thrombocythemia. Ann intern Med 88: 7, 1978 9. FOUNTAIN JR, LOSOWSKY MS: Hemor-
rhagic thrombocythaemia and its treatment with radioactive phosphorus. Q J Med 31: 207, 1962 10. BENSINGER TA, LOGUE GL, RUNDLES
RW: Hemorrhagic thrombocythemia; control of postsplenectomy thrombocytosis with melphalan. Blood 36: 61, 1970 11. BIERM.
R,
BONEU
B,
GUIRAUD
B,
et al: Aspirin and recurrent painful toes and fingers in thrombocythaemia (C). Lancet 1: 432, 1972
Yersinia enterocolitica septicemia with pneumonia D. PORTNOY,* MD; L.A. MARTINEZ,t MD, FRCP
plete resolution followed a 10-day The clinical manifestations of Yersinia enterocolitica infection are protean, but most are limited to the gastrointestinal tract. The first case of Y. enterocolitica septicemia with pneumonia to be reported in Canada is described below. This case, in a renal transplant recipient with chronic active hepatitis and portal hypertension, is worth noting since these underlying problems may have played a role in the dissemination of his disease. Serologic studies failed to show a rise in the agglutinating titre of antibodies to Y. enterocolitica. CoinFrom the department of microbiology and immunology, McGill University, Montreal *Senior resident tAssistant professor Reprint requests to: Dr. L.A. Martinez, Department of microbiology and immunology, McGill University, 3775 University St., Montreal, PQ H3A 2B4
The man had received a kidney transplant 5 years before, at which time he was known to have chronic active hepatitis with portal hypertenCase report sion. Medication taken prior to adA 57-year-old man was admitted mission consisted of prednisone, 15 to hospital complaining of fever, mg/d, and digoxin, 0.25 mg/d. anorexia, cough and shortness of At the time of admission the man's breath. He had had upper abdominal temperature was 38 0C, blood prescramping pain, watery diarrhea with sure 130/80 mm Hg, pulse rate 100 5 to 10 bowel movements per day beats/mm (and the rhythm irreguand fever for 1½ weeks prior to larly irregular) and respiratory rate admission. Several days after the 1 6/mm. Examination of the chest diarrhea's onset he took Lomotil® revealed decreased air entry over the (diphenoxylate hydrochloride and right lung field. No other adventiatropine) and the frequency of bowel tious sounds were noted. There was movements decreased to one to three hepatosplenomegaly. Results of phyper day. Five days prior to admission sical examination were otherwise unhe noticed the onset of a productive remarkable. A chest roentgenogram cough with yellowish expectoration, showed right upper and lower lobe increasing shortness of breath and infiltrates. The leukocyte count was 12.0 x spiking fever to 390C. The persistence of these symptoms led him to 1 09/L and the hemoglobin concentration was 15.3 g/dL. Y. enterocoseek medical attention. course of gentamicin therapy.
CMA JOURNAL/JANUARY 6, 1979/VOL. 120 61
utica was cultured from one blood sample, taken before antibiotic therapy was instituted, as well as from sputum, a throat swab and feces. The organism was further identified by Dr. L. Lafleur (h6pital Sainte-Justine, Montreal) as serotype 3, biotype 4. Serologic tests for antibodies to Y. enterocolitica were done by the national reference service for Yersinia, Ontario Ministry of Health, Toronto. Four serum specimens, including a sample obtained 6 months prior to the illness, were reactive, with an agglutinating titre for serotype 3 of 1:100. By the Kirby-Bauer disc sensitivity method the organism was found to be sensitive to kanamycin, gentamicm, sulfonamides, tetracycline and trimethoprim-sulfamethoxazole, and resistant to carbenicillin, amoxicillin and cephalosporins. The patient was treated with gentamicin, 180 mg/d intravenously. The minimum inhibitory concentration (MIC) and the minimum bacteriostatic concentration (MBC) were 0.4 .g/mL. Serum gentamicin concentrations 1 hour before and 1 hour after administration of the drug were 1.4 and 2.3 p.g/mL respectively. Several days after the onset of therapy the patient's condition improved remarkably. His temperature returned to normal and, his other symptoms disappeared. A chest roentgenogram taken on completion of a 10-day course of gentamicin showed resolution of the pneumonia, and no pathogenic organisms could be cultured from blood, sputum or stool. The patient had four dogs and two cats. No pathogenic organisms could be cultured from stool samples from the animals. Discussion Y. enterocolitica is a gram-negative pleomorphic coccobacillus that, over the years, was known under a variety of names.'4 In 1964 Frederiksen proposed the name Yersinia enterocolitica.5 The organism was first reported as a cause of human infection in 1939.6 By 1966 there had been only 23 reported cases.7 Since then the number of documented cases has increased, and there are now approximately 6000 known isolates of this organism.8'9 Although the earliest
cases appeared in the United States, most of the pertinent literature of the 1 960s originated in Europe. The organism was again reported in the American literature in 1969,10 and was first reported in Canada in 1971." The clinical manifestations of Y. enterocolitica infection are protean, and are mostly limited to the gastrointestinal tract. Enterocolitis is the most frequent presentation in young children, whereas acute mesenteric lymphadenitis and terminal ileitis are more likely to occur in older children and adults. Less common manifestations include septicemia,"'8 erythema nodosum,'7 arthritis,15 Reiter's syndrome,'8 myocarditis,'7 cellulitis,'4 meningitis'0 and pneumonia.'3 When septicemia does occur the mortality can be as high as 50%. Persons most likely to have septicemia are the elderly and individuals whose defence mechanisms have been compromised by immunosuppressive therapy or underlying disease.8 Rabson, Hallett and Koornhof"' noted that septicemia was more common in patients with iron overload, "Bantu siderosis" and cirrhosis, suggesting that in patients with cirrhosis the bacteria bypass the reticuloendothelial system of the liver and are disseminated via the peripheral blood. Our patient had chronic liver disease with portal hypertension, and was taking steroids. These factors may therefore have contributed to the dissemination of his infection. Serologic testing for antibodies has been stressed by many authors as an important means of confirming the diagnosis of Y. enterocolitica infection.8"4"' However, the agglutinating titre of antibodies to Y. enterocolitica in our patient's serum did not rise during the illness, and was the same as it had been 6 months prior to the onset of the illness. It is possible that the patient had been harbouring the organism for some time, and that the stable titre simply reflected the maximum antibody response in this immunosuppressed host. References 1. SCHLEIFSTEIN JI, COLEMAN MB: Bac-
teriurn enterocoliticum, annual report, division of laboratory research, New York State Department of Health, Albany, 1943, p 56 2. DIcKINsoN AB, MocQuoT G: Studies on the bacterial flora of the alimentary tract of pigs. I. Enterobacter-
62 CMA JOURNAL/JANUARY 6, 1979/VOL. 120
iaceae and other gram-negative bacteria. J Appi Bacteriol 24: 252, 1961 3. CARLSSON MG, RYD H, STERNEY NH: A case of human infection with Pas-
teurella pseudotuberculosis X. Acta Pathol Microbiol Scand [B] 62: 128, 1964 4. MOLLARET HH, DESTOMBES P: Les germes "X" en pathologie humaine.
Nouv Presse Med 72: 2913, 1964 5. FREDERIKSEN W: A study of some Yersinia pseudotuberculosis-like bacteria ("Bacterium enterocoliticum and Pasteurella "X"), in Proceedings of
the 14th Scandinavian Congress on Pathology and Microbiology, Oslo, Universiteitsforlaget Trykningssentral, Oslo, 1964, p 103 6. SCHLEIFSTEIN JI, COLEMAN MB: An unidentified microorganism resembling B. lignieri and Pasteurella pseudotuberculosis, and pathogenic for man. NY State J Med 39: 1749, 1939 7. TOMA 5, LAFLEUR L: Survey of the
incidence of Yersinia enterocolitica infection in Canada. AppI Environ Microbiol 28: 469, 1974 8. BOTTONE E: Yersinia enterocolitica: a panoramic view of a charismatic mi-
croorganism. CRC Crit Rev Microbiol 5: 211, 1977 9. TOMA 5, DEIDRIcK VR: Isolation of
Yersinia enterocolitica from swine. J C/in Microbiol 2: 478, 1975 10. SONNENWIRTH AC: Yersinia enterocolitica as an etiologic agent in meningitis. Bacteriol Proc 128: 87, 1969 11. ALBERT G, LAFLEUR L: Yersinia enterocolitica in children. Presentation of 24 cases observed at h6pital SteJustine, Montreal (abstr). Can J Public Health 62: 70, 1971 12. MOLLARET HH, OMLAND T, HENRIKSEN SD, et at: Les septic.mies humaines a "Yersinia enterocolitica". A propos de dix-sept cas r.cents. Nouv Presse Med 79: 345, 1971 13. SEBES JI, MARBY EH, RABINowITz JG: Lung abscess and osteomyelitis of rib due to Yersinia-enterocolitica.
Chest 69: 546, 1976 14. ABRAMOVITCH H, BUTAS CA: Septicemia due to Yersinia enterocolitica.
Can Med Assoc J 109: 1112, 1973 15. SPIRA TJ, KABINS SA: Yersinia enterocolitica septicemia with septic arthritis.
Arch intern Med 136: 1305, 1976 16. ERIKSSON M, OLcffi P: Case report: septicemia due to Yersinia enterocoutica in a non-compromised host.
Scand J infect Dis 7: 78, 1975 17. LEINo R, KALLIOMAKI JI: Yersiniosis as an internal disease. Ann intern Med
81: 458, 1974 18. SOLEM JH, LASSEN J: Reiter's disease following Yersinia enterocolitica infection. Scand J infect Dis 3: 83, 1971 19. RABSON AR, HALLETT AF, KooRNHOFF HJ: Generalized Yersinia en-
terocolitica infection. J infect Dis 131: 447, 1975
