Retrocecal appendicitis is uncommon and potentially difficult to diagnose. A ruptured retrocecal appendix may wall itself off, become asymptomatic, and then develop into a symptomatic retrocecal abscess with fever, diarrhea, and nausea. The development of a portal-mesenteric venous thrombosis-thrombus with pylephlebitis, however, is a much rarer complication of appendicitis (1-7). During an acute Epstein-Barr virus (EBV) infection, a 15.5-year-old boy with transient fever, vomiting, and diarrhea had portal vein and mesenteric vein thrombi caused by a perforated appendicitis.
A 15.5-year-old previously well boy experienced periumbilical pain 2.5 weeks before admission. One day later, he had sudden onset of right-side, cramping abdominal pain that lasted for a few hours without fever, nausea, or vomiting. A few days later a poor appetite, fatigue, fevers to 101°F, nonbilious vomiting, and non-bloody, watery diarrhea developed. The white blood cell (WBC) count was 5.4 × 103/µl; hemoglobin (Hb), 15.3 g/dl; platelets, 110 × 10.3/µl; segmental neutrophils, 77%; bands, 0%; lymphocytes, 9%; monocytes, 12%; total bilirubin, 3 mg/dl; direct bilirubin, 1.9 mg/dl; alkaline phosphatase, 212 U/l; alanine aminotransferase, 113 U/l; aspartate aminotransferase, 86 U/l; γ-glutamyl transpeptidase, 304 U/l; albumin, 4.5 g/dl; Epstein-Barr viral titers: viral capsid antigen IgM, 1:20; IgG, 1:640; Epstein-Barr virus-associated nuclear antigen, 1:80; and early antigen, 1:80. Assays for hepatitis A, B, and C were negative. He initially improved but had recurrent high fevers of 104°F to 105°F, rigors, persistent diarrhea, bilious emesis, and a 15-lb weight loss. He was reevaluated and had the following laboratory values: complete blood count: white blood cells 7.2 Thou/µl; segmental neutrophils, 81%; bands, 2%; leukocytes, 16%; monocytes, 1%; Hb, 13.8 mg/dl; platelets, 340 × 103/µl; liver function studies: total bilirubin, 1.0 mg/dl; alkaline phosphatase, 121 U/l; alanine aminotransferase, 38 U/l; aspartate aminotransferase, 24 U/l; γ-glutamyl transpeptidase, 152 U/l; lipase, 26 U/l; amylase, 22 U/dl; and erythrocyte sedimentation rate, 43 mm/hr. Blood cultures and urinalysis were obtained. Abdominal ultrasound demonstrated a normal-appearing gallbladder and appendix but identified a thrombus in the portal vein. The blood culture grew Gram-negative rods on Giemsa stain, subsequently identified as Bacteroides fragilis.
At admission, physical examination showed the patient to be a well-developed adolescent in no distress. Temperature was 98.6°F; heart rate, 70 beats/minute; respiratory rate, 18 breaths/minute; blood pressure, 130/62 mmHg; weight, 66.5 kg (75th percentile); and height, 171 cm (50th percentile). His lungs were clear to auscultation except for decreased breath sounds over the right base, and there was a grade II-VI systolic ejection murmur along the left sternal border. His abdomen was nontender, nondistended, without hepatosplenomegaly or mass. There were normal bowel sounds. There was no intrarectal tenderness or mass, and the stool was heme negative.
Intravenous ampicillin, gentamicin, and metronidazole were initiated. His stool was positive for Clostridium difficile toxin B at the time of admission, for which he received a 2-week course of oral vancomycin therapy. A chest roentgenogram was normal. A second abdominal ultrasound with Doppler study was performed that revealed a normal liver, gallbladder, pancreas, and kidneys. The spleen was mildly enlarged at 13.1 cm, without any focal abnormality. A focus of increased echogenicity was present within the proximal main portal vein at the confluence of the superior mesenteric vein and splenic vein, consistent with a nonocclusive thrombus, in that flow was seen surrounding these structures (Fig. 1). There were several lymph nodes in the aortocaval region, and the right lower quadrant had a tubular, noncompressible retrocecal structure greater than 1 cm in diameter, consistent with a dilated appendix. An abdominal-pelvic computed tomographic scan identified a thrombus centrally in the portal vein, extending into the left portal vein and the distal portal branches of the left lobe of the liver. Hypodensity was seen in the superior mesenteric vein, suggesting a partial thrombosis (Fig. 2). The spleen appeared slightly enlarged. There were prominent vessels surrounding the hilum that appeared to be varices, and there was evidence of portal hypertension. A 1-cm diameter, tubular structure with an enhancing wall was identified in the right lower quadrant, which was thought to be a dilated appendix with minimal focal surrounding inflammation and no inflamed adjacent fat (Fig. 3). Free fluid was present within the pelvis. His lung bases were clear.
The patient was administered a heparin infusion to maintain his prothrombin time at 60 to 80 seconds. Further evaluation included another complete blood count CBC, amylase, lipase, blood cultures, erythrocyte sedimentation rate, antinuclear antibody, antinuclear cytoplasmic antibody, protein S, protein C, antithrombin III, chest roentgenogram, and echocardiogram, all of which produced normal findings. An upper gastrointestinal series with small bowel follow-through revealed a small retrocecal collection most suggestive of a perforated retrocecal appendix without evidence of inflammatory bowel disease or intrinsic bowel obstruction (Fig. 4). After 10 days of antibiotic and anticoagulation therapy an abdominal ultrasound with Doppler study showed a decrease in the extent of the superior mesenteric vein thrombus. The portal vein was patent without thrombus.
At laparotomy, an abnormal distal one third of his appendix was observed, with periappendiceal inflammation but no phlegmon or abscess. Gross examination revealed a 6.7-cm long, swollen appendix that was covered by a yellow-green exudate and was 0.5 cm at the surgical margin but was distended to 1.4 cm and clearly perforated at the tip. Histologic examination demonstrated extensive acute inflammation that traversed the edematous wall and extended to the peritoneal surface. The mucosa was partially ulcerated, and the muscularis propria was disrupted, allowing extravasation of mucus into the surrounding tissue where it elicited a foreign body giant cell reaction.
The patient had an uneventful postoperative course during which his antibiotic therapy was discontinued and converted to warfarin without further complications. Another ultrasound of his portal-mesenteric venous system revealed resolution of his thrombi after 3 months of therapy (Fig. 5). His anticoagulation medication was discontinued after 6 months.
Ascending superior mesenteric or portal vein pylephlebitis with thrombi is a rare occurrence in pediatric patients with appendicitis. There are five reports of portal vein thrombosis in children and two of superior mesenteric vein thrombosis (2,8). These complications are caused by the venous drainage of the affected bowel that empties directly into the superior mesenteric vein and subsequently into the portal system (9). Before the advent of antibiotics, portal vein thrombosis and liver abscess were complications in 50% of cases of appendicitis, diverticulitis, and other inflammatory bowel conditions (6). Since the routine administration of antibiotics and early surgical intervention, the incidence of ascending infectious portal thrombophlebitis is 0.05% for acute appendicitis and 3% for a ruptured appendix (10).
Portal vein thrombosis is caused by inflammatory conditions such as pancreatitis, appendicitis or inflammatory bowel disease (11); infectious causes such as intraabdominal abscess, perforated appendicitis, and cholecystitis; space-occupying lesions such as neoplasm or biliary dilation; and vascular anomalies such as congenital stenosis or cavernous transformation of the portal vein (Table 1). The clinical symptoms associated with an infected portal vein include spiking fevers, variable abdominal pain (predominantly right upper quadrant), anorexia, weight loss, and malaise. These findings are usually subtle in children (12). Portal vein thrombosis unrelated to an intra-abdominal infectious process typically does not cause fever, but may appear as splenomegally or abdominal pain (5,13). Ascites usually occurs in the early stages of the thrombosis while collateral blood vessels are forming (2).
Treatment for pylephlebitis and thrombosis in the portal venous system includes intravenous hydration, intravenous antibiotics, and anticoagulation therapy (12). In appendicitis, intraabdominal abscess, or diverticulitis, an exploratory laparotomy may be warranted, with particular attention directed to the area of bowel drained by the thrombosed vasculature.
At admission, this patient's physical examination did not suggest portal vein thrombosis-superior mesenteric vein thrombosis. The history was consistent with but not suggestive of a ruptured retrocecal appendicitis. The positive anaerobic blood cultured indicated a significant occult intra-abdominal process. The radiologic studies, however, clearly demonstrated the full extent of the associated disorders and proved to be invaluable in making this patient's diagnoses. The underlying diagnosis in this case was ultimately made by pathologic confirmation of the surgically resected appendix. These comorbidities required a brief course of intravenous antibiotic therapy, surgery to remove the primary disease focus, and warfarin anticoagulation medication for 6 months. The patient did not develop further complications, such as liver abscesses or intestinal compromise.
The patient's clinical course and disease substantiated the diagnosis of pylephlebitis, secondary to a ruptured appendix resulting in thrombosis of both the superior mesenteric vein and portal vein. However, a recent Epstein-Barr viral infection could have explained the original hepatitis and in turn could have contributed to decreased portal blood flow and resulted in thrombi. The positive findings of C. difficile B toxin may have contributed to the diarrhea or may have been an incidental finding; 10% of adolescents carry asymptomatic C. difficile(14). There is no literature, however, to implicate Epstein-Barr virus or to support the notion that the virus or C. difficile causes portal vein thrombosis-superior mesenteric vein thrombosis.
It is difficult to speculate on the need for anticoagulation treatment in the setting of a ruptured appendix with portal vein thrombosis-superior mesenteric vein thrombosis, because it is a rare occurrence, and there are few reported studies (15,16). However, despite initial antibiotic intervention for appendicitis, there are several reports describing outcomes of variable degrees of portal vein thrombosis resulting in portal hypertension and associated morbidity (2,3,5-7,11). Although one must consider that superior mesenteric vein thrombosis may be clinically asymptomatic, there is still an overall reported mortality rate of 32% (12). Because of the high mortality rate and the data reported by Boley et al. (13), which showed that administration of heparin decreased the recurrence rate of superior mesenteric vein thrombosis, anticoagulation therapy was used in our patient.
The exact proportion of patients with appendicitis who have an ultrasound or computed tomographic imaging study to evaluate the portal vein before surgery is unknown. For more than a decade, however, ultrasonography has been used to assist the clinician with the diagnosis of appendicitis or ruptured appendix; recently, computed tomography has also been shown to be efficacious and cost effective for this diagnosis (17-27). Even in one report in which color Doppler ultrasound was used, no reference was made to the status of the portal vein. (28) Therefore, it would be important to determine further the incidence of symptomatic and asymptomatic portal vein thrombosis-superior mesenteric vein thrombosis in a ruptured appendix. Although a controlled, prospective trial of anticoagulation for portal vein thrombosis-superior mesenteric vein thrombosis would undoubtedly be useful, the complications of untreated portal vein thrombosis-superior mesenteric vein thrombosis could be catastrophic.
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