Infectious Disease Pathology
Case 3 -
Gastrointestinal Yersinia Enterocolitica Infection
Laura W. Lamps, Univ of AR/Medical Sciences, Little Rock, AR
Click on slide thumbnail images for an enlarged view.
If you have any difficulties viewing these slides, email the webmaster.
The patient is a 12 year old boy with a several month history of vomiting and abdominal pain. He did not complain of diarrhea. Upper GI series showed an ileal stricture. Upper endoscopy was normal. Colonoscopy showed a normal colon; the ileum could not be intubated due to the stricture. The patient underwent a segmental resection of the ileum and right colon.
This case illustrates the characteristic features of gastrointestinal Yersinia infection, and this
infection may closely mimic Crohn's disease.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Sections of the right colon, ileum, and appendix showed large areas of ulceration grossly, with
thickening of the wall of the bowel and an ileal stricture just proximal to the ileocecal valve.
Microscopic sections showed broad areas of ulceration as well, along with prominent lymphoid tissue,
transmural lymphoid aggregates in a linear pattern, and epithelioid granulomas. The granulomas were
associated with prominent lymphoid tissue, and extended transmurally into the subserosal fat. Special
stains for AFB and GMS were negative. A research PCR test for Yersinia enterocolitica was positive.
The major differential diagnoses for Yersinia infection include other infectious processes,
particularly Mycobacteria. The negative AFB stain and the lack of caseous necrosis is evidence against
mycobacterial infection, and PCR for mycobacteria can also be useful. Other causes of granulomatous
inflammation in the GI tract, such as sarcoidosis, should also be considered (see Case Discussion below).
Crohn's disease is the major entity in the differential diagnosis in this case. Yersinia infection is
usually a self limited process with no further sequelae for the patient, although it can sometimes cause
chronic gastrointestinal disease. Both Crohn's and yersiniosis may show very similar histologic
features, including transmural lymphoid aggregates, skip lesions, and fissuring ulcers. Features that
may favor Crohn's include cobblestoning of mucosa and creeping fat grossly, and microcsopic changes of
chronicity including marked crypt distortion, thickening of the muscularis mucosa, pyloric metaplasia,
and prominent neural hyperplasia. Some cases are indistinguishable on histologic grounds alone. This
particular case showed focal neural hyperplasia, but no pyloric-type metaplasia or marked crypt
distortion. Interestingly, upon clinical follow-up, this adolescent patient was initially treated on and
off based on the clinical presumption of Crohn's disease, and did fairly well although he was still
Interestingly, he did best during the times that he was empirically treated with antibiotics for
presumed overgrowth of bacteria in the small bowel. He was eventually lost to follow up.
Gastrointestinal Yersinia enterocolitica infection
Yersinia is one of the most common causes of bacterial enteritis in Western and Northern Europe. It
has a worldwide distribution; the incidence of infection is rising within both Europe and the United
States, although this may be due to better methods of detection and wider recognition of Yersinia as
important enteric pathogens. Y. enterocolitica (YE) and Y. pseudotuberculosis (YP) are the two species
pertinent to human gastrointestinal disease.
Yersinia infection can be transmitted by both food and water, and the bacteria are associated with
meat, dairy products, chocolate, poultry, and produce. Pork-related infection has been particularly well
documented. Infection also can be acquired from animals, albeit rarely. Yersinia has a preference for
cold temperatures, thus there is a natural affinity for refrigerated food, and there is speculation that
infection is more common in cooler months. Familial, hospital-acquired, transplacental, and
transfusion-associated infections also have been well-documented.
These Gram-negative coccobacilli cause appendicitis (primarily granulomatous), ileitis, colitis, and
mesenteric lymphadenitis. Infection with either species may cause symptoms and signs of an acute
abdomen, chronic abdominal pain, and diarrhea. Although yersiniosis is usually a self-limited process,
chronic infections (including chronic colitis) and persistent abdominal pain have been well documented.
Risk factors for serious infection include immunocompromise or debilitation, diabetes mellitus, and
cirrhosis. Iron overload and desferoxamine therapy are also a risk factor for yersiniosis; iron is an
essential growth factor, but these bacteria lack siderophores to capture iron, thus they are dependent
upon siderophores synthesized by other bacteria or administered therapeutically (desferoxamine) or an
iron-rich environment. Complications of gastrointestinal Yersinia infection include sepsis, abscess
formation, perforation, and obstruction from inflammatory masses.
Infants, children, and young adults are most commonly infected. Patients commonly present with
diarrhea (variably bloody), abdominal pain (which may be diffuse, periumbilical, or right lower
quadrant), nausea, vomiting, and weight loss. Fever, pharyngitis, and leukocytosis may be present as
well. Symptoms often have been present for weeks to months, leading to a misdiagnosis of chronic
idiopathic inflammatory bowel disease. Reactive polyarthritis and erythema nodosum are also associated
with Yersinia infection.
Yersinia is harbored in meats, poultry, milk, eggs, and water, and colonizes many domestic pets and
farm animals. Pathogenic Yersinia strains are thought to invade the mucosa of the intestine and multiply
within Peyer's patches and the regional nodes to which they drain. Further spread is hematogenous. It
is postulated that in some patients organisms can survive for extended periods of time within Peyer's
patches, leading to chronic yersiniosis.
Yersinia preferentially involves the ileum, right colon, and appendix, although any area of the bowel
can be affected. Involvement may be segmental or patchy. Grossly, involved bowel has a thickened,
edematous wall with nodular inflammatory masses centered on Peyer's patches. Aphthoid and linear ulcers
may be seen, along with mucosal friability, edema, and loss of vascular pattern. Exudates are variably
present. The macroscopic findings may mimic chronic idiopathic inflammatory bowel disease, particularly
Crohn's disease. Involved appendices are enlarged and hyperemic, similar to nonspecific acute
suppurative appendicitis, and perforation is common. Involved lymph nodes may show gross foci of
The inflammatory pattern in yersiniosis is variable. Both suppurative and granulomatous patterns of
inflammation may be seen, and a mixture of the two is common. YE typically features epithelioid
granulomas, along with hyperplastic Peyer's patches and overlying ulceration. Caseous necrosis is rare,
but some cases (particularly YP infection) show granuloams with central microabscesses, often accompanied
by mesenteric adenopathy. There is significant overlap between the histological features of YE and YP
infection, however, and either species may show epithelioid granulomas with prominent lymphoid cuffing,
lymphoid hyperplasia, transmural lymphoid aggregates, mucosal ulceration, and lymph node involvement.
The transmural inflammation, fissuring and/or aphthoid ulcers, focal architectural distortion, presence
of skip lesions, and granulomas may closely mimic Crohn's disease. Some patients show only an "acute
self-limited/infectious colitis" type pattern.
Involved mesenteric lymph nodes often show follicular hyperplasia with scattered microabscesses and
epithelioid granulomas. Nonspecific reactive lymphoid hyperplasia without microabscesses or granulomas
is also a frequent finding in infected patients.
Culture is the mainstay of diagnosis, although Yersinia may be very difficult to culture in patients
who are not bacteremic. If yersiniosis is suspected, pharyngeal culture may also be helpful, since the
organism can cause pharyngitis and persist in the lymphoid tissue of this area for some time. As above,
successful culture also requires cold enrichment. Serologic studies may also be helpful if there is a
marked elevation in titer. However, there is significant cross-reactivity with other organisms, as well
as problems with false negativity in immunocompromised patients, the elderly, and young children.
Molecular detection by PCR works very well, and can be performed out of paraffin blocks, but is not
widely available. Gram stains are usually not helpful for the diagnosis of Yersinia, since the organisms
are small, hard to detect, and almost impossible to distinguish from other enteric flora.
The differential diagnosis primarily includes other infectious processes and Crohn's disease. Acid
fast stains, mycobacterial PCR, and the presence of a positive PPD help distinguish Yersinia infection
from mycobacterial infection. Granulomas are unusual in Salmonella infection, and stool cultures are
invaluable in yielding a diagnosis of salmonellosis. Sarcoidosis, foreign body reaction to fecal
material, and granulomatous inflammation secondary to delayed (interval) appendectomy with antibiotic
therapy are also in the differential diagnosis of Yersinia-associated granulomatous appendicitis.
Lymphogranuloma venereum and cat scratch disease may affect the mesenteric lymph nodes and produce
similar histologic features, but these organisms (especially cat scratch disease) only rarely involve the
Crohn's disease and yersiniosis may be extremely difficult to distinguish from one another. In
addition to the gross and microscopic similarities, Yersinia DNA has been detected in many cases of
longstanding Crohn's disease; however, the significance of this remains unclear. Features favoring
Crohn's disease include fistula formation, cobblestoning of mucosa, presence of creeping fat, and
histologic changes of chronicity including marked crypt distortion, thickening of the muscularis mucosa,
pyloric metaplasia, and prominent neural hyperplasia. However, some cases are simply indistinguishable
on histologic grounds alone.
Isolated granulomatous appendicitis, in the past, was frequently interpreted as representing primary
Crohn's disease of the appendix. However, patients with granulomatous inflammation confined to the
appendix rarely (less than ten percent) develop generalized inflammatory bowel disease.
Review of the Literature/Treatment Options :
Most gastrointestinal Yersinia infections in immunocompetent patients are either self-limited, or
resolve with a course of oral antibiotics. Debilitated patients, patients with iron overload, or those
in whom the infection has disseminated may require intensive supportive care and IV antibiotics.
Occasionally surgery is indicated for bowel obstruction or GI bleeding. Cases of Yersinia-associated
granulomatous appendicitis usually present similarly to nonspecific acute appendicitis, and thus proceed
to appendectomy. Usually no further treatment is indicated for these patients.
Yersinia infection of the GI tract should be considered when the histologic features described above
are present, especially in the context of a patient who 1) has an atypical presentation for Crohn's
disease, especially if symptoms are of acute onset (although it is important to remember that intestinal
yersiniosis can also be a chronic process); 2) has ingested food associated with Yersinia infection
preceding the illness 3) has granulomatous appendicitis; and/or 4) has features suggestive Crohn's
disease, but something is odd, such as numerous granulomas, lack of features of chronicity, or lymph
nodes with numerous granulomas. The distinction between Crohn's disease and yersiniosis is very
important, since the treatment, natural histories and chronic sequelae of the two diseases are so
Since the distinction may be impossible to make on histologic grounds alone, ancillary tests such as
stool culture, PCR, and serologic studies should be used to help clarify the diagnosis.
- Attwood SEA, Cafferkey MT, Keane FBV. Yersinia infections in surgical practice. Br J Surg 76:499-504, 1989.
- Attwood SEA, Cafferkey MT, West AB, et al. Yersinia infection and acute abdominal pain. Lancet 1(8532): 529-33, 1987.
- Bronner MP. Granulomatous appendicitis and the appendix in idiopathic inflammatory bowel disease. Sem Diag Pathol 21: 98-107, 2004.
- Boqvist S, Pettersson H, Svensson A, Andersson Y. Sources of sporadic Yersinia enterocolitica infection in children in Sweden, 2004: a case control study. Epidemiol Infect 137:897-905, 2009.
- Bulbuloglu E, Ciralik H, Kantarceken B, et al. Yersinia pseudotuberculosis colitis presented with severe gastrointestinal bleeding. Turk J Gastroenterol 21:179-82, 2010.
- Cover TL and Aber RC. Yersinia enterocolitica. New Eng J Med: 321:16- 24, 1989.
- Dudley TH, Dean PJ. Idiopathic granulomatous appendicitis, or Crohn's disease of the appendix revisited. Hum Pathol 24:595-601, 1993.
- El-Maraghi NRH, Mair N. The histopathology of enteric infection with Yersinia pseudotuberculosis. Am J Clin Pathol 71:631-639, 1979.
- Fredriksson-Ahomaa M, Stolle A, Korkeala H. Molecular epidemiology of Yersinia enterocolitica infections. FEMS Immunol Med Microbiol 47:315-29, 2006.
- Gleason TH, Patterson SD. The pathology of Yersinia enterocolitica ileocolitis. Am J Surg Pathol 6:347-355, 1982.
- Hovinen E, Sihvonen LM, Virtanen MJ, et al. Symptoms and sources of Yersinia enterocolitica infection: a case-control study. BMC Infect Dis 20:122, 2010.
- Huang JC, Appelman HD. Another look at chronic appendicitis resembling Crohn's disease. Mod Pathol :9(10):975-981,1996.
- Lamps LW, Madhusudhan KT, Greenson JK, et al. The role of Y. enterocolitica and Y. pseudotuberculosis in granulomatous appendicitis: a histologic and molecular study. Am J Surg Path 25:508-15, 2001.
- Lamps LW, Madhusudhan KT, Havens JM, et al. Pathogenic Yersinia enterocolitica and Yersinia pseudotuberculosis DNA is detected in bowel and mesenteric nodes from Crohn's disease patients. American Journal of Surgical Pathology 27 (2): 220-7, 2003.
- Lamps LW. Beyond acute inflammation: a review of appendicitis and infections of the appendix. Diag Histopathol 14:68-77, 2008.
- Mazzoleni G, deSa D, Gately J, Riddell RH. Yersinia enterocolitica infection with ileal perforation associated with iron overload and deferoxamine therapy. Dig Dis Sci 36:1154-60, 1991.
- Natkin J, Beavis KG. Yersinia enterocolitica and Yersinia pseudotuberculosis. Clin Lab Med 19:523-36, 1999.
- Paff JR, Triplett DA, Saari TN. Clinical and laboratory aspects of Yersinia pseudotuberculosis infections, with a report of two cases. Am J Clin Pathol 66:101-10, 1976.
- Saebo A, Lassen J. Acute and chronic gastrointestinal manifestations associated with Yersinia enterocolitica infection: a Norwegian 10-year follow- up study on 458 hospitalized patients. Ann Surg 215:250-5, 1992.
- Simmonds SD, Noble MA, Freeman HJ. Gastrointestinal features of culture-positive Yersinia enterocolitica infection. Gastroenterol 92:112-7, 1987.
- 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 Inf Dis 10:735-41, 1991.
- Vantrappen G, Agg HO, Ponette E, et al. Yersinia enteritis and enterocolitis: gastroenterological aspects. Gastroenterol 72:220-7, 1977.
- Winblad S, Nilehn B, Sternby NH. Yersinia enterocolitica (Pasteurella X) in human enteric infections. Brit Med J 2:1363-6, 1966.
- Yotsu R, Mii S, Hayashi R, et al. Erythema nodosum associated with Yersinia enterocolitica infection. J Dermatol 37:819-22, 2010.