Desferal

* Patients who are homozygous for thalassemia major are at risk for Yersinia enterocolitica infections. We present a case of a 4-year-old child with intussusception of the terminal ileum whose past medical history was significant for beta-thalassemia. His monthly blood transfusions for this condition may have put him at risk for Y enterocolitica enterocolitis. The pathogenesis of this disease relates to the role of iron as an essential growth factor for Yersinia, and this patient's transfusions left him in an iron-overloaded state, despite treatment with Desferal. Our patient's unusual presentation of intussusception was secondary to the mass effect caused by lymphoid hyperplasia, specifically hypertrophied Peyer's patches in the ileum caused by Y enterocolitica infection. To our knowledge, this is the first such case of intussusception caused by Yersinia to be reported.

(Arch Pathol Lab Med. 2001;125:1486-1488)

We describe a case of intussusception of the terminal ileum, accompanied by necrotizing lymphadenitis with extensive infarction in a 4-year-old child with thalassemia major. Yersinia enterocolitica infection typically causes gastroenteritis and mesenteric adenitis. Reported complications include appendicitis, small bowel gangrene, intestinal perforation, hepatic and splenic abscesses, and septicemia.

REPORT OF A CASE

A 4-year-old Vietnamese boy was hospitalized with a 3-day history of crampy abdominal pain, diarrhea, bloody stools with mucus, intermittent emesis, and fevers to 40 deg C. His past medical history was significant for thalassemia major, and he had received blood transfusions once every 3 to 4 weeks for the previous 3 years. His last transfusion, of 225 mL packed red blood cells, had occurred 4 days prior to admission. He had also received weekly Desferal treatment over the previous 1.5 years.

On admission, the child appeared ill and was dehydrated and tachypneic. His abdomen was distended, with diffuse tenderness, guarding, and peritoneal signs in the right lower quadrant but with positive bowel sounds. Computed tomographic scan of the abdomen revealed an inflammatory process in the right lower quadrant, with a small amount of free air, and fluid collection consistent with an abscess. Blood chemistry results were as follows: sodium, 122 mmol/L; potassium, 2.6 mmol/L; bicarbonate, 19 mmol/L; glucose, 7.6 mmol/L; albumin, 21 g/L; aspartate aminotransferase, 88 U/L; alanine aminotransferase, 25 U/L; lipase, 152 U/L. Hemoglobin was 10.7 g/dL, and hematocrit 0.32. Blood cultures grew Y enterocolitica. The patient underwent exploratory laparotomy, ileocecectomy, and ileostomy. Findings at surgery included an inflammatory mass in the right lower quadrant. The terminal ileum was intussuscepted into the cecum, and the appendix was erythematous and bulging but not perforated. This segment was resected because of its inflammatory and necrotic nature. Postoperatively, the patient had a distal intestinal obstruction requiring reduction of a volvulus. Subsequent blood cultures grew Bacterioides ovatus but were negative for Yersinia. Antibiotic therapy was revised, and the patient was discharged 2 weeks after admission.

PATHOLOGIC FINDINGS

Surgical specimens included a section of terminal ileum measuring 10 x 4 x 4 cm that telescoped into the ileocecal region (Figure 1). There was a section of cecum measuring 9 x 5 x 4 cm with ascending colon and with an appendix attached that measured 5 x 1 x 1 cm. All of the serosal surfaces were erythematous. Two tan-yellow papillary mucosal nodules measuring 5 X 3 cm and 4 X 3 cm were noted in the ileum. Numerous yellow patchy plaques, measuring 2 x 2 cm, were present on the colonic mucosal surface (Figure 2). Microscopically, extensive, severe, transmural, acute and chronic inflammation, ulceration, abscess formation, lymphoid hypertrophy, focal necrosis, and focal peritonitis were present in the terminal ileum, cecum, right colon, and appendix. Lymph nodes showed necrotizing lymphadenitis with extensive infarction (Figures 3 and 4).

COMMENT

Yersinia enterocolitica is a gram-negative coccobacillus with worldwide distribution that commonly causes gastroenteritis and mesenteric adenitis in children and adolescents. Reported complications have included severe enterocolitis involving the ileocecal region, appendicitis, small bowel gangrene, intestinal perforation, peritonitis, hepatic and splenic abscesses, chronic abscess formation in the inguinal region, and fatal septicemia.1 To our knowledge, intussusception has not been previously reported.

Intussusception is more common in infants aged 4 to 10 months, with a peak at 7 months. It is proposed that hypertrophied Peyer's patches, possibly resulting from viral infection, act as a mechanical lead point for intussusception. The intussusceptum in our case was in the terminal ileum, secondary to the mass effect caused by the lymphoid hyperplasia. In one prospective study of 261 patients (228 children and 33 adults) with intussusception, 88% of the cases were idiopathic, without any definite leading point. In these cases, the ileocecal area was the site most commonly involved (82%), hypertrophic Peyer's patches of the terminal ileum being responsible for 39% of the idiopathic intussusceptions of the ileocecal area.2 Other studies have had similar findings.3-5 The blood supply to the invaginated section is seriously impaired, and in our case this caused edema and necrosis. The intussuscipiens, the ileocecal region, also showed necrosis.

Patients who are homozygous for thalassemia major are at risk for serious Y enterocolitica infections. The cause of this increased susceptibility is related to systemic iron overload and the use of iron chelators.6 Over a period of 10 years, invasive Yersinia infection was diagnosed in patients with beta-thalassemia at a frequency 5000 times greater than in the general population.7 In a prospective study, during a 12-month period, 10% of the 144 thalassemic patients developed one episode of symptomatic infection with pathogenic phenotypes of Y enterocolitica. Nine had focal infection (64%), 8 of whom were diagnosed with acute enterocolitis and 1 with acute tonsillitis. Five (36%) had systemic infection.8 The 2 most common presentations of Y enterocolitica infections are enterocolitis and pseudoappendicular syndrome, characterized by high temperature, abdominal pain, and tenderness to palpation in the right lower quadrant.9

Pathogenesis of Y enterocolitica infection relates to the role of iron as an essential growth factor. Bacteria acquire iron by producing and releasing high-affinity chelators called siderophores. These bind and solubilize ferric iron by competing with transferrin. The iron-siderophore complexes enter the bacterial cells following binding to specific receptors. Deferoxamine is a bacterial siderophore obtained from Streptomyces piloce that is used as a chelating agent in the treatment of acute iron toxicity and in chronic iron overload. Yersinia enterocolitica is unusual among bacteria in that it requires iron for growth and has receptors for siderophores but cannot produce siderophores endogenously. It has been demonstrated that deferoxamine greatly enhances the susceptibility of iron-overloaded mice to Y enterocolitica, reducing the median lethal dose more than 1000 000-fold.10 In addition, deferoxamine is a known growth factor for Yersinia in vitro.

This is the first case, to our knowledge, of intussusception as a complication of Y enterocolitica enterocolitis. Recommendations from this and previous articles indicate that in a patient with iron overload, the clinician should be alerted to the possibility of Yersinia infection when abdominal symptoms and fever occur. The index of suspicion should be raised for patients with beta-thalassemia, especially if the symptoms occur shortly after a blood transfusion.

References

1. Abcarian P, Demas B. Systemic Yersinia enterocolitica Infection associated with iron overload and deferoxamine therapy. Am J RadioL 1991;157:773-775.

2. Monno R, Valenza M, Quarto M, et al. Yersinia enterocolitica infection in a boy with beta thalassemia major. Pediatr Infect Dis J. 1994;13:233-234.

3. Schenken J, Kruger R, Schultz L. Papillary lymphoid hyperplasia of the terminal ileum: an unusual cause of intussusception and gastrointestinal bleeding in childhood. Pediatr Surg. 1975;20:259-265.

4. Hasegawa T, Ueda S, Tazuke Y, et al. Colonoscopic diagnosis of lymphoid

hyperplasia causing recurrent intussusception: report of a case. Surg Today. 1998; 28:301-304.

5. Meyerson S, Desai T, Polidori G, Raval M, Ehrinpreis M. A case of intussusception and lymphoid hyperplasia in a patient with AIDS. Am] Gastroenterol. 1993;88:303-306.

6. Mavrommati P, Ladis V, Lagona E, Giannaki M, Raftopoulou A, Hatzis T. ARDS in a patient with homozygous beta-thalassemia due to yersinosis. Intensive Care Med. 1999;25:226-229.

7. Adamkiewicz T, Berkovitch M, Krishnan C, Polsinelli C, Kermack D, Olivieri N. Infection due to Yersinia enterocolitica in a series of patients with B-thalassemia: incidence and predisposing factors. Clin Infect Dis. 1998;27:1362-1366.

8. Cherchi G, Cossellu S, Pacifico L, et al. Incidence and outcome of Yersinia enterocolitica infection in thalassemic patients. Contrib Microbiol Immunol. 1995;13:16-18.

9. Perniola R, Petracca M, DeRinaldis C, Perrone A, Pizzolante M. A severe case of Yersinia enterocolitica infection in a thalassemic patient. Ital] Gastroenterol Hepatol. 1997;29:82-83.

10. Pang L. Intussusception revisited: clinicopathologic analysis of 261 cases, with emphasis on pathogenesis. South Med]. 1989;82:215-228.

Marilyn G. Hansen, MD; Gary Pearl, MD, PhD; Marc Levy, MD

Accepted for publication May 9, 2001.

From the Department of Pathology, Orlando Regional Medical Center (Drs Hansen and Pearl) and Nemours Children's Clinic (Dr Levy), Orlando, Fla.

Reprints: Marilyn G. Hansen, MD, Department of Pathology, Orlando Regional Medical Center, 1414 South Orange Ave, Orlando, FL 32806 (e-mail: mghansen1@msn.com).

Copyright College of American Pathologists Nov 2001
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