Continuing Education Activity

Yersinia pseudotuberculosis causes a food-borne infection characterized by self-limited mesenteric lymphadenitis that mimics appendicitis. This activity reviews the evaluation and management of Yersinia pseudotuberculosis and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Review the pathophysiology of Yersinia pseudotuberculosis.
• Outline the typical presentation of a patient with Yersinia pseudotuberculosis.
• Explain the recommended management of Yersinia pseudotuberculosis.
• Summarize interprofessional team strategies for improving care coordination and communication regarding the management of patients with Yersinia pseudotuberculosis.

Introduction

The genus Yersinia comprises a group of gram-negative rod-shaped bacteria that are broadly distributed in the environment. This genus encompasses 17 different species of which 3 organisms are virulent to humans. These include Yersinia pestis, Yersinia enterocolitica, and Yersinia pseudotuberculosis. Both Y. enterocolitica and Y. pseudotuberculosis are known to cause an enteric illness; however, Y. pseudotuberculosis is rare in humans compared to Y. enterocolitica, which is more commonly seen.[1][2][3]

Etiology

Yersinia pseudotuberculosis infection is usually acquired through the consumption of contaminated foods and water. Yersinia pseudotuberculosis is present in the soil and can be seen in fresh farm-produced plants and root vegetables. It has numerous animal reservoirs and is abundant in wildlife, including birds, rodents, rabbits, deer, dogs, cats, and cattle.[2][4][5]

The incubation period varies from 5 to 10 days. A latent period of 2 to 20 days has been reported, with peak incidence rates at 4 days after ingestion.

Epidemiology

United States

• No specific pattern of Yersinia pseudotuberculosis infection has been reported. Most Yersinia outbreaks have been associated with Yersinia enterocolitica rather than Yersinia pseudotuberculosis.

International

• The distribution of Yersinia pseudotuberculosis infection is worldwide. Most cases occur in winter due to enhanced growth characteristics in cold temperatures.
• Epidemics due to Y. pseudotuberculosis have occurred in the Russian Far East, and Japan during the 2nd half of the 20th century causing the 'Far East Scarlet-like Fever'(FESLF).
• Y. pseudotuberculosis has a sporadic distribution in Europe.[5]

Mortality/Morbidity

• Yersinia pseudotuberculosis has a low case-fatality rate. However, the rare sepsis-associated illnesses caused by Y. pseudotuberculosis infection in patients with chronic liver disease has a mortality rate that exceeds 75%.

Race

• Yersinia pseudotuberculosis infection has no specific racial or ethnic predilection.

Sex

• Yersinia pseudotuberculosis infection is more common in men than in women. The postinfectious complications of arthritis and erythema nodosum are more common in women than in men.

Age

• Seventy-five percent or more of patients with Yersinia pseudotuberculosis infection are ages five to 15 years.

Pathophysiology

The enteropathogen, Yersinia pseudotuberculosis, requires a large inoculum to produce the disease. The primary virulence factor is a plasmid-encoded protein that causes increased invasiveness. Yersinia pseudotuberculosis survives intracellularly.

Yersinia pseudotuberculosis inhabits and grows in the gastrointestinal tract, initially in the Peyer's patches, and then spreading to the liver and the spleen through the mesenteric lymph nodes or directly.[2]

Yersinia pseudotuberculosis has a siderophore-mediated iron scavenging system that contributes to its virulence.[6] Patients with iron overload disorders like venous congestion, hemochromatosis, cirrhosis, and hemolytic anemias are, therefore, at a slightly higher risk for systemic infections.[7]

Histopathology

In general, the appendix will appear normal, but the nearby mesenteric lymph nodes and Peyer's patches may show epithelioid granulomatous lesions, coagulative necrosis, and lymphoid hyperplasia, and can resemble tuberculosis. The small bowel may develop microabscesses, cryptic hyperplasia, and shortening of villi. Granulomatous abscesses form in organs like the liver, spleen, lungs, kidneys, and intestines when the organism spreads during sepsis.[8]

History and Physical

Y. pseudotuberculosis causes self-limiting acute gastroenteritis and mesenteric lymphadenitis that mimics acute appendicitis. Enteritis is usually seen in children as opposed to the mesenteric adenitis seen in adults.[5] Symptoms include abdominal pain, fever, vomiting, and diarrhea. The abdominal pain is often located in the right lower quadrant and may mimic appendicitis. 

Other problems associated with Yersinia pseudotuberculosis infection include terminal ileitis and intussusception, more commonly in children. In most cases, enterocolitis lasts one to three weeks. Erythema nodosum, arthralgias, reactive arthritis, ankylosing spondylitis, and lumbar facet joint disease can occur. A sporotrichoid pattern of disease has been associated with Yersinia pseudotuberculosis infection. Cutaneous manifestations include erythema of the face and neck, conjunctival hyperemia, strawberry tongue, punctate skin rash, and desquamation. Ophthalmic findings such as uveitis and conjunctivitis have also been reported. 

Physical findings caused by Yersinia pseudotuberculosis infection may be grouped into three main categories: systemic, enteric, and rheumatologic.

• Systemic findings include jaundice, hypotension, and lymphadenopathy
• Enteric findings include abdominal tenderness with or without rebound over McBurney point
• Rheumatologic involvement includes joint effusion, tenderness, or decreased range of movement and may be asymmetric in distribution.

Patients with immunosuppression and iron-overload states such as hemochromatosis, venous congestion, hemolytic anemia, and cirrhosis are at risk for sepsis.[9][10][11]

Evaluation

The laboratory diagnosis of Yersinia pseudotuberculosis requires confirming the presence of the organism to support the clinical diagnosis. The acquisition by culture-positive sources such as blood, cerebrospinal fluid, peritoneal fluid, synovial fluid, or other organ-based biopsy is confirmatory.[12][13]Microbiology

• Yersinia pseudotuberculosis is a gram-negative, coccobacillus that is differentiated by its fermentation of sorbitol and ornithine decarboxylase activity, among other features. The optimum growth occurs on MacConkey medium at 20 to 35 degrees C. Yersinia pseudotuberculosis is aerobic and facultatively anaerobic. It grows slowly on blood and chocolate agar plates. It forms small gray and translucent colonies at 24 to 72 hours. It has a good growth pattern on MacConkey or eosin-methylene blue agar plates but is enhanced noticeably at a temperature lower than 28 degrees C when it becomes motile at 25 degrees C. Yersinia pseudotuberculosis is oxidase-negative, catalase-producing, and urea-splitting, and does not ferment lactose.

Stool

• Isolation from stool is difficult given the slow growth pattern. Stool culture yield may be increased with cold enrichment, special culture media, or alkali treatment.

Blood, Peritoneal and Synovial Fluids, and Pharyngeal Exudate

• Might yield Yersinia pseudotuberculosis

Serology

• Enzyme-linked immunosorbent assay and agglutination tests may be obtained; the antibodies (against the O antigen) may appear soon after the onset of illness and wane over two to six months. Hemagglutination reaction tests that detect the pili of either Yersinia pseudotuberculosis or Yersinia pestis have been developed. Hemagglutination titers of 1:160 or higher suggest a true infection.
• Cross-reaction between antibodies with other organisms may obscure the diagnostic picture. These other organisms include other Yersinia, Brucella, Vibrio, Rickettsia, and Salmonella.
• Sodium dodecyl sulfate-polyacrylamide gel electrophoresis is a reliable serologic procedure for the diagnosis of Yersinia pseudotuberculosis or Yersinia enterocolitica infection.

In patients with mesenteric lymphadenitis, computed tomography (CT) scans or ultrasound may reveal enlarged mesenteric lymph nodes and peritoneal findings including inflammation of the appendix and terminal ileitis.

In pneumonic or septic presentations, a chest x-ray may reveal infiltrates suggestive of acute pneumonia.

In the rare Kawasaki disease–like variant, Izumi fever, electrocardiogram (ECG) abnormalities may suggest ischemia if aneurysms compromise coronary artery circulation. These abnormalities are more likely to develop in children.

Treatment / Management

Yersinia pseudotuberculosis infection is usually self-limited. More toxic presentations, including septic syndromes or severe dehydration, may require hospitalization. General supportive care is needed.[14][15]

Though antibiotics are not required for a mild illness, serious manifestations like sepsis occurring in a patient with immunosuppression or chronic liver disease warrant the usage of antibiotics.[2]

The fluoroquinolone group of drugs was found to be the most effective in the treatment of Y. pseudotuberculosis as per in-vitro and in-vivo murine studies. Antibiotics belonging to other classes were unable to inhibit the bacterial growth to a significant extent as compared to fluoroquinolones.[16][17][18] Nevertheless, antibiotics like ampicillin, ceftriaxone, doxycycline, and gentamycin have been successful in the treatment of Y. pseudotuberculosis and its complications following previously documented case reports.[19][20][21]

Exploratory laparotomy may be warranted in patients with complications such as severe GI bleeding, and intestinal obstruction. However, this intervention is not common.[22][23]

Differential Diagnosis

• Appendicitis
• Pancreatitis
• Inflammatory bowel disease
• Gastroenteritis
• Scarlet fever
• Toxic shock syndrome
• Leptospirosis

Prognosis

The majority of cases of Yersinia pseudotuberculosis are mild and self-limited. In immunocompromised patients and those with chronic liver disease, the disease can be fatal. [Level 3][24][25] These patients may develop a severe disease that can lead to sepsis and generalized involvement of the intestine.

Complications

• Reactive arthritis[26]
• Septic arthritis[27]
• Uveitis[28]
• Acute tubulointerstitial nephritis[29][30]
• Terminal ileitis
• Severe GI bleeding
• Intussusception
• Intestinal abscess[22]
• Intestinal obstruction[23]
• Sepsis
• Death

Postoperative and Rehabilitation Care

The diarrhea, fever, and anorexia may last a few days or weeks and thus the patient should be kept NPO (nil per os). IV hydration is recommended during this time period.

Consultations

Consult gastroenterology, or surgery if invasive diagnostic or therapeutic interventions are warranted. For unusual presentations, rheumatologic, dermatologic, or ocular complications, additional consultation with an infectious disease specialist should be considered.

Deterrence and Patient Education

The patient should be educated on food hygiene and the fact that the organism is cold tolerant. There is no vaccine available.

Pearls and Other Issues

• Yersinia pseudotuberculosis is caused by a cold-tolerant bacterium and is a rare cause of foodborne disease.
• It can present with self-limited enterocolitis or pseudoappendicitis.
• Even though the mortality rate is low in healthy people, it can be fatal in immunocompromised patients and those with iron overload.
• Treatment for severe disease is with fluoroquinolones, beta-lactams, and aminoglycosides, usually used as a combination therapy.

Enhancing Healthcare Team Outcomes

Patients with Yersinia pseudotuberculosis infection should be managed by an interprofessional team approach. Because the infection can mimic many other disorders, consultation with an infectious disease specialist, a gastroenterologist, and a surgeon should be sought. [Level 3][14][27] Healthcare workers at all levels should be educating the public on food hygiene and the proper cooking of food. Nurses are often the last to see the patients in the emergency department and at discharge and are in a prime position to educate the patient and the family about proper food practices. The nurse should also educate the patient on the signs and symptoms of the infection so that the patient seeks immediate care.