Modica, Angela MD*; Nicolini, Enrico MD*; Nicolini, Alessandra MD*; D'Orazio, Alida MD*; Nunnari, Giuseppe MD, PhD†; Pavone, Piero MD, PhD*‡
*U.O. of Pediatrics Azienda Ospedaliera Civile-OMPA, Ragusa, Italy; †Division of Infectious Diseases, Thomas Jefferson University, Philadelphia, PA and ‡Department of Pediatrics, University of Catania, Italy.
Address correspondence and reprint requests to Piero Pavone, MD, PhD, Department of Pediatrics, University of Catania, Via S. Sofia 78 - 95125 Catania, Italy. E-mail: firstname.lastname@example.org
Yersinia enterocolitica is a well-known cause of acute enteritis. In its classical form, the disease is self limiting and is characterized by abdominal pain which, in some cases, may resemble acute appendicitis, thus leading to emergency appendectomy. In adults and children older than 7 years, a chronic form is also described, with recurrent abdominal pain, constipation, mesenteric lymphadenopathy, reactive arthritis, Reiter syndrome, and other autoimmune-like disorders often linked with HLA B27 antigen positivity. We report on a case of intestinal obstruction 1 year after emergency appendectomy as the first clinical manifestation of Yersinia enterocolitica infection. To our knowledge, this is the first report in Italy of this clinical association.
Yersinia enterocolitica is a gram-negative motile aerobic bacterium belonging to the Enterobacteriaceae family.1 Y. enterocolitica is distributed worldwide with a higher frequency of isolation in cooler climates and is typically seen during the winter. It can be characterized by biochemical testing, phage typing, plasmid analysis, or serotyping. Serotyping of Y. enterocolitica is based on specific somatic O antigens. The most common serotypes responsible for outbreaks in Europe are O:3 and O:9.1-3 Geographic differences are apparent in the frequency and distribution of Y enterocolitica: while serogroup O:8 Y. enterocolitica infections are diminishing in the United States, animal carriage and infection with this serogroup is apparently on the rise in other parts of the world including Italy.1 Diagnosis of Y. enterocolitica infection is made by culture (56% sensitive) and by serology (84% sensitive) within 1 week of symptoms. Selective medium, such as CIN agar, has been reported to appear to be more sensitive. Combined culture and serology testing is 88% sensitive for disease. In chronic infection, sensitivity of cultural methods decreases dramatically to 20-25%, thus diagnosis is preferably made by serological tests.1-4
B.A., a 9-year-old boy born at term by iterative caesarian section from healthy nonconsanguineous parents, was admitted to the Division of Pediatrics of the Hospital Civile of Ragusa (Ragusa, Italy) for continuous vomiting, abdominal pain, and low-grade fever (37.5°C max). Since he was 1 year old, he had suffered from recurrent mild abdominal pain. At the age of 8, there was a significant increase of the abdominal pain that led to emergency appendectomy with signs of mild inflammation at histological examination; at that time no specific investigations were carried out. From the operation the child presented with heavy colic abdominal pain associated with constipation and low-grade fever at least once a month. At admission, physical examination showed impaired general conditions, acetonemic breath, coated tongue, and diffuse abdominal pain at palpation. The rest of the clinical examination was otherwise normal. His weight was 32 kg (73th PC), height was 142 cm (90th PC), body temperature was 36.5°C, heart rate was 100 beats per minute. Routine laboratory findings, including total serum protein and albumin, gamma-GT, CPK, coagulation studies (prothrombin time, activated partial thromboplastin time, fibrinogen concentration), immunoglobulins, total immunoglobulin E levels, and anti-streptolysin O titer, were all within the normal values as were the full autoimmune profile. Stool culture and fecal occult blood as well as Adenovirus and Rotavirus tests were negative. Electrocardiogram was normal. The abdominal x-ray showed multiples ileal air-fluid levels. At discharge, after 4 days, his clinical condition was good and the patient was asymptomatic. Two days later, the patient was readmitted in our ward for the recurrence of severe abdominal pain and biliary vomiting. Upon physical examination, the child was severely ill-looking with pale, dry skin; his tongue was coated but humidified. There was diffuse pain at slight-touch palpation of the abdomen; 2-hand palpation showed mild tenderness of the upper quadrants. Weight and height were identical to those of his previous admission. Routine laboratory tests revealed total WBC count of 11,300/mm3 with 81.4% neutrophils, slight elevation of erythrocyte sedimentation rate (22 mm at the end of 1 hour) and of C-reactive protein (21.9 mg/L). Stool culture, fecal occult blood, Adenovirus, and Rotavirus tests were still negative. Abdominal x-ray was normal. Abdominal ultrasound (US) scan showed multiple enlarged mesenteric lymph nodes causing restriction of intestinal lumen with increased upstream peristalsis. Pancolonoscopy with visualization of the last part of the ileal tract showed cobbled-surface mucosa with lymphatic hyperplasia. Broader range serological tests were still negative except for IgG against Y. enterocolitica serotype O3 1/320. In view of these laboratory findings, the boy was given cotrimoxazole therapy for 2 weeks with a complete recovery of the described clinical signs and symptoms. After 3 weeks, antibody titer against Yersinia was 1/160, and control abdominal US scan showed markedly reduced mesenteric lymph nodes. Upon re-evaluation after 4 months, the child was symptom-free and in good general health.
Our work shows an atypical presentation of chronic Yersiniosis, a sporadic infection in southeastern Sicily: Y. enterocolitica in the Italian territory is more common in the northern (cooler) areas and is rare in the southern regions and in the islands.5 One year after appendectomy, the subject came to our attention due to the presence of recurrent abdominal pain and intestinal obstruction. Thus, this is the first report in Italy, to our knowledge, of this clinical association. Moreover, the finding of negative stool cultures and the absence of specific signs explains the delay in diagnosis. The wide range of diagnostic tests, together with x-ray, US scan, endoscopic and histological studies, gives us more detailed information of the disease.1-3 Tuohy et al2 described a 3 and 1/2-year-old girl who presented with persistent abdominal pain, fever, vomiting, and diarrhea accompanied by rash, oral ulceration, anemia, and an elevated sedimentation rate. Colonoscopy revealed focal ulceration from the rectum to the cecum with histology of severe active colitis with mild chronic changes. Diagnosis of Crohn disease was made and glucocorticoid therapy was begun. By the ninth hospital day, admission cultures grew Y. enterocolitica, and trimethoprim/sulfamethoxazole was begun followed by prompt clinical improvement.
The presentation and clinical studies supported a differential diagnosis, namely, appendicitis, lymphoma, chronic IBD, functional constipation, as well as infectious mesenteric adenitis caused by Y. enterocolitica, Y. pseudotuberculosis, and Mycobacterium tuberculosis. Colonoscopy and biopsy histology revealed the presence of mucosal inflammation and lymphatic hyperplasia. Finally, the abdominal US scan showing hyperplastic, enlarged mesenteric lymph nodes and the finding of high IgG titers against Y. enterocolitica clarified the diagnosis. Later questioning of the family showed a history of frequent pork chitterlings consumption.4-8 In any case, an early diagnosis is very difficult and it can be only raised by merging all the aforementioned investigations.
This case highlights the importance of considering infectious causes in the differential diagnosis of chronic abdominal pain associated with constipation and of waiting for serological tests before excluding Yersiniosis even in the presence of repeated negative stool cultures. In fact, in chronic intestinal Yersiniosis, stool cultures are typically sterile, but serological tests remain positive for about 6 to 12 months. Antibody titers usually go down after appropriate antibiotic therapy.7-10 Physicians, especially pediatricians, must be aware of this known, but uncommon, conditions to prevent the complication and to start the correct therapy as soon as possible.
Patients and their families must be queried for risk factors leading to Yersinia infection. Specifically, they should be questioned about any exposure to pork products, especially chitterlings, often prepared and/or consumed during the holiday season. Finally, our case demonstrates that Yersinia enterocolitis may present with the constellation of terminal ileitis, mesenteric adenitis, features of appendicitis, protracted abdominal symptoms, or intestinal obstruction associated with fever.
The authors thank Prof Lorenzo Pavone (University of Catania) for evaluation and criticism of the manuscript. Dr Bridgewood (University of Catania) is gratefully acknowledged for editing the manuscript.
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