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Clinical manifestations and diagnosis of Yersinia infections

Clinical manifestations and diagnosis of Yersinia infections
Author:
Robert V Tauxe, MD, MPH
Section Editors:
Stephen B Calderwood, MD
Sheldon L Kaplan, MD
Deputy Editor:
Elinor L Baron, MD, DTMH
Literature review current through: Dec 2022. | This topic last updated: Jan 21, 2022.

INTRODUCTION — In the genus Yersinia, three species are important human pathogens: Yersinia pestis, Yersinia enterocolitica, and Yersinia pseudotuberculosis [1,2]. The yersinioses are zoonotic infections of domestic and wild animals; humans are considered incidental hosts that do not contribute to the natural disease cycle.

Y. enterocolitica and Y. pseudotuberculosis cause yersiniosis, a diarrheal illness; human infection with Y. enterocolitica is much more common than human infection with Y. pseudotuberculosis. The clinical manifestations and diagnosis of these infections will be reviewed here. The epidemiology, microbiology, pathogenesis, and treatment of these infections are discussed separately. (See "Treatment and prevention of Yersinia enterocolitica and Yersinia pseudotuberculosis infection" and "Epidemiology, microbiology, and pathogenesis of Yersinia infections".)

Y. pestis causes plague and is discussed separately. (See "Epidemiology, microbiology and pathogenesis of plague (Yersinia pestis infection)" and "Clinical manifestations, diagnosis, and treatment of plague (Yersinia pestis infection)".)

CLINICAL MANIFESTATIONS — Major clinical manifestations include acute yersiniosis (eg, acute febrile gastroenteritis) and pseudoappendicitis syndrome. A variety of complications (both gastrointestinal and extraintestinal) and post-infectious sequelae have also been described, as outlined in the following sections [3].

Acute yersiniosis — The incubation period for yersiniosis is typically 4 to 6 days (range 1 to 14 days) [4-6].

Clinical manifestations of acute yersiniosis include diarrhea, abdominal pain, and fever; nausea and vomiting may also occur [7]. The onset of Yersinia gastroenteritis can be more subacute than other diarrheal pathogens [8,9]. In a Norwegian study including 67 cases of sporadic yersiniosis, an average of more than a week elapsed before patients sought medical care and almost two weeks elapsed before a stool culture was obtained [8]. The median duration of diarrhea for yersiniosis can also be longer than for other causes of acute gastroenteritis. In five case series, the duration ranged from 12 to 22 days (table 1) [8-12]. Prolonged illnesses were observed in each case series, and some patients reported persistent diarrhea or abdominal pain up to a year following acute illness. Nevertheless, yersiniosis cannot be readily distinguished clinically from other causes of acute diarrhea. In some circumstances, localization of abdominal pain to the right lower quadrant may be a diagnostic clue for yersiniosis. (See "Approach to the adult with acute diarrhea in resource-rich settings" and 'Pseudoappendicitis' below.)

Pharyngitis may be an accompanying presenting symptom. Sore throat was reported by up to 20 percent of patients in some case series (table 1) [8,9,13,14]. In one outbreak, Y. enterocolitica was isolated from throat cultures in 14 patients, illustrating the propensity for involvement of lymphoid tissue, such as the tonsils [14]. This symptom can be a helpful diagnostic clue since no other cause of acute bacterial diarrhea routinely causes pharyngitis.

Yersinia septicemia can occur during acute infection, particularly among infants and individuals with impaired immunity or iron-overload states (table 2) [15,16]. Rapid onset septic shock has been described in a report of 55 cases associated with blood transfusion, with an overall fatality of 50 percent [17]. In addition, transient bacteremia may be more common than previously recognized, even among otherwise healthy persons [18]. In Eastern Siberia and Japan, a scarlet-fever like syndrome associated with Y. pseudotuberculosis has been described; this is characterized by fever, systemic illness, arthralgias, and a morbilliform or confluently erythematous rash that ultimately desquamates [19].

Following Yersinia gastroenteritis, stool shedding of organisms may persist beyond the duration of diarrhea. Among 67 cases of yersiniosis in Norway, shedding was observed among 47 percent of patients following resolution of symptoms and lasted a median of 40 days (range 17 to 116 days) after onset of illness [8]. Shedding may be reduced by antimicrobial treatment.

Children — The most prominent clinical manifestations in young children are fever and diarrhea [20]. Bloody diarrhea tends to be observed more frequently among children than adults. In case series of mainly pediatric patients, 20 to 60 percent reported bloody diarrhea (table 1) [5,6,13]. In contrast, in a series of 29 adults with yersiniosis, bloody diarrhea was noted in only 7 percent of cases [12].

High fever and vomiting are relatively common in children; abdominal pain is observed relatively infrequently. These manifestations may be clinical clues for distinguishing from infection with Shiga toxin producing Escherichia coli (STEC), such as E. coli O157:H7, which may present with bloody stools, pronounced abdominal pain, and minimal fever. (See "Shiga toxin-producing Escherichia coli: Clinical manifestations, diagnosis, and treatment".)

Pseudoappendicitis — Acute yersiniosis presenting with right lower abdominal pain, fever, vomiting, leukocytosis, and mild diarrhea may be confused with acute appendicitis. At surgery, findings include visible inflammation around the appendix and terminal ileum and inflammation of the mesenteric lymph nodes; the appendix itself is generally normal. Yersinia can be cultured from the appendix and involved lymph nodes [21].

One outbreak of yersiniosis among children was identified because of an unusually high number of cases of suspected appendicitis; approximately 42 percent of identified cases underwent surgery [22]. In other outbreaks, the rates of surgical intervention have ranged from 0 to 14 percent (table 1) [5,6,13].

In regions where the incidence of yersiniosis is high, an appreciable fraction of appendectomies occur in the setting of yersiniosis [23-25]. In a Belgian study of 2861 patients who underwent appendectomy for clinically suspected appendicitis, pathogenic Y. enterocolitica was cultured from the appendix of 3.6 percent [23]. In 56 of 73 patients (75 percent) with an appendix culture that grew Y. enterocolitica, mesenteric adenitis and/or terminal ileitis were observed on gross examination instead of frank appendicitis [24].

Complications

Gastrointestinal — Gastrointestinal complications of acute yersiniosis are in general rare, and include [4,26-32]:

Diffuse ulcerating ileitis and colitis

Intestinal perforation

Peritonitis

Intussusception

Paralytic ileus

Toxic megacolon

Necrotic small bowel

Cholangitis

Mesenteric vein thrombosis

Extraintestinal — Extraintestinal complications of acute yersiniosis are also rare, and include [4,26-32]:

Septicemia

Hepatic abscess

Splenic abscess

Renal abscess

Pharyngeal abscess

Endocarditis

Mycotic aneurysm

Infection of indwelling catheters and prostheses

Meningitis

Osteomyelitis

Septic arthritis

Lung abscess

Empyema

Ophthalmitis

Suppurative lymphadenitis

Skin manifestations (carbuncle, granuloma, vesiculobullous lesions, pustules, wound infection)

Myocarditis, glomerulonephritis, and liver failure have all been reported following yersiniosis, but are extremely rare.

Post-infectious sequelae — The most common post-infectious sequelae are erythema nodosum and reactive arthritis; these are particularly common in Northern Europe and, for the latter, among those with the HLA-B27 tissue type [33].

Erythema nodosum has been observed to occur following acute infection in up to 30 percent of patients in Finland, particularly among young women; it is less frequently recognized elsewhere [34]. It typically occurs in the month after acute infection and is self-limited.

Reactive arthropathy has been described in up to 30 percent of adult patients affected in an outbreak of Y. pseudotuberculosis infections in Finland; most patients had HLA-B27 tissue type [35]. Reactive arthritis typically affects the large weight-bearing joints and begins several weeks after the onset of acute infection. Symptoms can be self-limited, lasting three to five months, or can persist and follow a relapsing pattern [3]. In a ten-year follow-up study of Finnish patients with reactive arthritis, 52 percent reported mild peripheral joint symptoms, 36 percent reported chronic low back pain, and 36 percent had radiographic evidence of sacroiliitis [36]. (See "Reactive arthritis".)

The time course of these complications mirrors the humoral immune response to bacterial infections. The pathogenesis of reactive arthropathy reflects “molecular mimicry” (eg, the antigenic similarity of Yersinia antigens to antigens in the joints of susceptible individuals). The immune response to Yersinia antigens can cross-react against host antigens. Some studies have identified Yersinia-like antigens in synovial fluid, although it is unlikely that these reflect microbial growth in joints [37,38].

Yersinia also shares an antigen with thyroid tissue that resembles the thyrotropin (TSH) binding site. Therefore, individuals with Graves disease may have antibodies that cross react with Yersinia [39]. However, there is no evidence that yersiniosis actually triggers thyroiditis [40].

Prognosis — Overall mortality from yersiniosis is relatively low. In one study including 458 Norwegian patients, only two fatalities occurred during the acute phase of illness [41]. Similarly, among 1373 cases of yersiniosis in the United States between 1996 and 2007, 18 deaths (1.2 percent) were reported [42]. Of the cases identified, 30 percent were hospitalized and 3 percent had documented bacteremia.

DIAGNOSIS — There are no distinct clinical, radiologic, hematologic, or chemical findings that confirm the diagnosis of yersiniosis. The diagnosis is established by culture isolation from stool, mesenteric lymph nodes, pharyngeal exudates, peritoneal fluid, or blood [40]. Stool culture is the preferred clinical specimen for patients with intestinal symptoms, and stool shedding of organisms may continue for weeks after acute infection. In the setting of clinical pharyngitis, throat culture should also be obtained. Blood cultures may be diagnostic as well. Specimens of appendix or mesenteric lymph nodes obtained at surgery should be cultured. For clinical circumstances in which abscess material, pleural fluid, or other focal suppurative samples are obtained, these should be cultured as well. Culture techniques are described separately. (See "Epidemiology, microbiology, and pathogenesis of Yersinia infections", section on 'Laboratory isolation'.)

Syndrome-based panels of rapid culture-independent diagnostic tests (CIDTs) have become common in clinical settings. In the United States in 2019, 57 percent of Yersinia infections reported to the Centers for Disease Control and Prevention's FoodNet program were diagnosed by CIDT, often followed by reflex culture [43]. The growing use of CIDT platforms has likely contributed to the rapid increase in reported yersiniosis. The incidence reported to FoodNet in 2019 increased by 153 percent compared with 2016 to 2018 [43]. When such platforms are used, routine culture of the specimens yielding the positive signal and submission of the isolate to a reference laboratory should still be performed; this is important to secure the diagnosis, determine antimicrobial susceptibility and the presence of virulence determinants and strengthen public health surveillance [44]. Sequence-based surveillance for Y. enterocolitica will also depend on having an isolate [45]. Commercial CIDT panels are not likely to include a test for Y. pseudotuberculosis.

Evaluation of the performance of rapid CIDTs for Y. enterocolitica is challenging given the rarity of these infections. Two multiplex platforms showed sensitivity of 48 to 100 percent and specificity of 99.6 to 100 percent [46]. Automated diagnostic systems can also lead to confusing results, such as misidentification of Y. pestis as Y. pseudotuberculosis [47].

Serologic tests are not used routinely in the United States but have been used for diagnosis of yersiniosis in Europe and Japan [40]. Simple agglutination assays have been developed for diagnosis of yersiniosis. In addition, enzyme linked immunosorbent assays (ELISA) and immunoblotting can be used to detect IgG, IgA, and IgM class antibodies. A positive IgM assay supports the diagnosis of acute yersiniosis, as does a fourfold rise in antibody titers between acute and convalescent titers drawn several weeks apart. However, serologic findings must be interpreted with care in areas where the background seroprevalence to Yersinia antigens is high [48]. In addition, the assays can be positive in some inflammatory states, and individuals with post-infectious sequelae can have oscillating antibody titers depending upon the activity of their illness [40].

Immunofluorescence assays have been developed but are not widely available [49].

SUMMARY

Yersinia enterocolitica and Yersinia pseudotuberculosis cause yersiniosis, a diarrheal illness. Clinical manifestations of acute yersiniosis include diarrhea, abdominal pain, and fever; nausea and vomiting may also occur. Yersiniosis cannot be readily distinguished clinically from other causes of acute diarrhea that also present with these symptoms. Pharyngitis may be an accompanying presenting symptom; this can be a helpful diagnostic clue since no other cause of acute bacterial diarrhea routinely causes pharyngitis. (See 'Acute yersiniosis' above.)

Acute yersiniosis presenting with right lower abdominal pain, fever, vomiting, leukocytosis, and understated diarrhea may be confused with acute appendicitis. At surgery, findings include visible inflammation around the appendix and terminal ileum and inflammation of the mesenteric lymph nodes; the appendix itself is generally normal. Yersinia can be cultured from the appendix and involved lymph nodes. (See 'Pseudoappendicitis' above.)

A number of gastrointestinal and extraintestinal complications and post-infectious sequelae can occur. The most common post-infectious sequelae are erythema nodosum and reactive arthritis; these are particularly common in Northern Europe and, for the latter, among those with the HLA-B27 tissue type. (See 'Complications' above and 'Post-infectious sequelae' above.)

The diagnosis of yersiniosis is established by culture isolation from stool, mesenteric lymph nodes, pharyngeal exudates, peritoneal, fluid or blood. Stool culture is the preferred clinical specimen for patients with intestinal symptoms, and stool shedding of organisms may continue for weeks after acute infection. In the setting of clinical pharyngitis, throat culture should also be obtained. Specimens of appendix or mesenteric lymph nodes obtained at surgery should be cultured. If diagnostic panels using rapid culture-independent tests were used for the diagnosis, positive tests should be followed up with culture. (See 'Diagnosis' above and "Epidemiology, microbiology, and pathogenesis of Yersinia infections", section on 'Laboratory isolation'.)

Serologic tests are not used routinely in the United States but have been used for diagnosis of yersiniosis in Europe and Japan. A positive IgM assay supports the diagnosis of acute yersiniosis, as does a fourfold rise in antibody titers between acute and convalescent titers drawn several weeks apart. Serologic findings must be interpreted with care in areas where the background seroprevalence to Yersinia antigens is high, and cross-reactivity can occur in the setting of some inflammatory states. (See 'Diagnosis' above.)

  1. Butler T. Plague and other Yersinia infections, Plenum Medical Books Co., New York 1983.
  2. McNally A, Thomson NR, Reuter S, Wren BW. 'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution. Nat Rev Microbiol 2016; 14:177.
  3. van der Heijden IM, Res PC, Wilbrink B, et al. Yersinia enterocolitica: a cause of chronic polyarthritis. Clin Infect Dis 1997; 25:831.
  4. Cover TL, Aber RC. Yersinia enterocolitica. N Engl J Med 1989; 321:16.
  5. Tacket CO, Ballard J, Harris N, et al. An outbreak of Yersinia enterocolitica infections caused by contaminated tofu (soybean curd). Am J Epidemiol 1985; 121:705.
  6. Lee LA, Gerber AR, Lonsway DR, et al. Yersinia enterocolitica O:3 infections in infants and children, associated with the household preparation of chitterlings. N Engl J Med 1990; 322:984.
  7. El Qouqa IA, El Jarou MA, Samaha AS, et al. Yersinia enterocolitica infection among children aged less than 12 years: a case-control study. Int J Infect Dis 2011; 15:e48.
  8. Ostroff SM, Kapperud G, Lassen J, et al. Clinical features of sporadic Yersinia enterocolitica infections in Norway. J Infect Dis 1992; 166:812.
  9. Tauxe RV, Vandepitte J, Wauters G, et al. Yersinia enterocolitica infections and pork: the missing link. Lancet 1987; 1:1129.
  10. Marks MI, Pai CH, Lafleur L, et al. Yersinia enterocolitica gastroenteritis: a prospective study of clinical, bacteriologic, and epidemiologic features. J Pediatr 1980; 96:26.
  11. Naqvi SH, Swierkosz EM, Gerard J, Mills JR. Presentation of Yersinia enterocolitica enteritis in children. Pediatr Infect Dis J 1993; 12:386.
  12. Feeney GF, Kerlin P, Sampson JA. Clinical aspects of infection with Yersinia enterocolitica in adults. Aust N Z J Med 1987; 17:216.
  13. Tacket CO, Narain JP, Sattin R, et al. A multistate outbreak of infections caused by Yersinia enterocolitica transmitted by pasteurized milk. JAMA 1984; 251:483.
  14. Tacket CO, Davis BR, Carter GP, et al. Yersinia enterocolitica pharyngitis. Ann Intern Med 1983; 99:40.
  15. Gayraud M, Scavizzi MR, Mollaret HH, et al. Antibiotic treatment of Yersinia enterocolitica septicemia: a retrospective review of 43 cases. Clin Infect Dis 1993; 17:405.
  16. alMohsen I, Luedtke G, English BK. Invasive infections caused by Yersinia enterocolitica in infants. Pediatr Infect Dis J 1997; 16:253.
  17. Guinet F, Carniel E, Leclercq A. Transfusion-transmitted Yersinia enterocolitica sepsis. Clin Infect Dis 2011; 53:583.
  18. Centers for Disease Control and Prevention (CDC). Red blood cell transfusions contaminated with Yersinia enterocolitica--United States, 1991-1996, and initiation of a national study to detect bacteria-associated transfusion reactions. MMWR Morb Mortal Wkly Rep 1997; 46:553.
  19. Amphlett A. Far East scarlet-like fever: A review of the epidemiology, symptomatology, and role of superantigenic toxin: Yersinia pseudotuberculosis-derived mitogen A. Open Forum Infect Dis 2016; 3:1.
  20. American Academy of Pediatrics. Yersinia enterocolitica and Yersinia pseudotuberculosis infections (Enteritis and other illnesses). In: Red Book: 2018 Report of the Committee on Infectious Diseases, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village 2018. p.891.
  21. Shorter NA, Thompson MD, Mooney DP, Modlin JF. Surgical aspects of an outbreak of Yersinia enterocolitis. Pediatr Surg Int 1998; 13:2.
  22. Black RE, Jackson RJ, Tsai T, et al. Epidemic Yersinia enterocolitica infection due to contaminated chocolate milk. N Engl J Med 1978; 298:76.
  23. Niléhn B, Sjöström B. Studies on Yersinia enterocolitica. Occurrence in various groups of acute abdominal disease. Acta Pathol Microbiol Scand 1967; 71:612.
  24. Van Noyen R, Selderslaghs R, Bekaert J, et al. Causative role of Yersinia and other enteric pathogens in the appendicular syndrome. Eur J Clin Microbiol Infect Dis 1991; 10:735.
  25. Puylaert JB, Bodewes HW, Vermeijden RJ, et al. [Bacterial ileocecitis, a "new" disease]. Ned Tijdschr Geneeskd 1991; 135:2176.
  26. Black RE, Slome S. Yersinia enterocolitica. Infect Dis Clin North Am 1988; 2:625.
  27. Reed RP, Robins-Browne RM, Williams ML. Yersinia enterocolitica peritonitis. Clin Infect Dis 1997; 25:1468.
  28. Blinkhorn RJ Jr, Marino JA. Lateral pharyngeal abscess due to Yersinia enterocolitica. Am J Med 1988; 85:851.
  29. Krogstad P, Mendelman PM, Miller VL, et al. Clinical and microbiologic characteristics of cutaneous infection with Yersinia enterocolitica. J Infect Dis 1992; 165:740.
  30. Crowe M, Ashford K, Ispahani P. Clinical features and antibiotic treatment of septic arthritis and osteomyelitis due to Yersinia enterocolitica. J Med Microbiol 1996; 45:302.
  31. Kellogg CM, Tarakji EA, Smith M, Brown PD. Bacteremia and suppurative lymphadenitis due to Yersinia enterocolitica in a neutropenic patient who prepared chitterlings. Clin Infect Dis 1995; 21:236.
  32. Jaspers CA, Begashaw K. Case report: an unusual presentation of Yersinia enterocolitica infection. Neth J Med 2001; 59:98.
  33. Leirisalo-Repo M. Yersinia arthritis. Acute clinical picture and long-term prognosis. Contrib Microbiol Immunol 1987; 9:145.
  34. Ahvonen P. Human yersiniosis in Finland. II. Clinical features. Ann Clin Res 1972; 4:39.
  35. Vasala M, Hallanvuo S, Ruuska P, et al. High frequency of reactive arthritis in adults after Yersinia pseudotuberculosis O:1 outbreak caused by contaminated grated carrots. Ann Rheum Dis 2014; 73:1793.
  36. Leirisalo-Repo M, Suoranta H. Ten-year follow-up study of patients with Yersinia arthritis. Arthritis Rheum 1988; 31:533.
  37. Granfors K, Jalkanen S, von Essen R, et al. Yersinia antigens in synovial-fluid cells from patients with reactive arthritis. N Engl J Med 1989; 320:216.
  38. Granfors K, Merilahti-Palo R, Luukkainen R, et al. Persistence of Yersinia antigens in peripheral blood cells from patients with Yersinia enterocolitica O:3 infection with or without reactive arthritis. Arthritis Rheum 1998; 41:855.
  39. Shenkman L, Bottone EJ. Antibodies to Yersinia enterocolitica in thyroid disease. Ann Intern Med 1976; 85:735.
  40. Bottone EJ. Yersinia enterocolitica: the charisma continues. Clin Microbiol Rev 1997; 10:257.
  41. Saebø A, Lassen J. Survival and causes of death among patients with Yersinia enterocolitica infection. A Norwegian 10-year follow-up study on 458 hospitalized patients. Scand J Infect Dis 1992; 24:613.
  42. Long C, Jones TF, Vugia DJ, et al. Yersinia pseudotuberculosis and Y. enterocolitica infections, FoodNet, 1996-2007. Emerg Infect Dis 2010; 16:566.
  43. Tack DM, Ray L, Griffin PM, et al. Preliminary Incidence and Trends of Infections with Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2016-2019. MMWR Morb Mortal Wkly Rep 2020; 69:509.
  44. Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis 2017; 65:1963.
  45. Hunter E, Greig DR, Schaefer U, et al. Identification and typing of Yersinia enterocolitica and Yersinia pseudotuberculosis isolated from human clinical specimens in England between 2004 and 2018. J Med Microbiol 2019; 68:538.
  46. Khare R, Espy MJ, Cebelinski E, et al. Comparative evaluation of two commercial multiplex panels for detection of gastrointestinal pathogens by use of clinical stool specimens. J Clin Microbiol 2014; 52:3667.
  47. Tourdjman M, Ibraheem M, Brett M, et al. Misidentification of Yersinia pestis by automated systems, resulting in delayed diagnoses of human plague infections--Oregon and New Mexico, 2010-2011. Clin Infect Dis 2012; 55:e58.
  48. Mäki-Ikola O, Heesemann J, Toivanen A, Granfors K. High frequency of Yersinia antibodies in healthy populations in Finland and Germany. Rheumatol Int 1997; 16:227.
  49. Hoogkamp-Korstanje JA, de Koning J, Samsom JP. Incidence of human infection with Yersinia enterocolitica serotypes O3, O8, and O9 and the use of indirect immunofluorescence in diagnosis. J Infect Dis 1986; 153:138.
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