*Division of Pediatric Immunology, Taiwan
†Gastroenterology, Department of Pediatrics, Taiwan
‡Radiology, Taichung Veterans General Hospital, Taichung, Taiwan.
Received 11 September, 2010
Accepted 28 December, 2010
Address correspondence and reprint requests to Jiaan-Der Wang, MD, Department of Pediatrics, Taichung Veterans General Hospital, No. 160, Sec. 3, Chung-Kang Rd., Taichung 40705, Taiwan (e-mail: email@example.com).
The authors report no conflicts of interest.
Budd-Chiari syndrome (BCS), characterized by hepatic venous outflow tract obstruction, is a rare disorder in children (1). There is a wide variety of predisposing causes, including inferior vena cava (IVC) webs and thrombotic, inflammatory, or neoplastic processes (2). BCS associated with eosinophilia has been reported, and the pathogenesis is considered to be related to the toxic protein released from eosinophils (3). Clinical presentation of the disease depends on the extent and rapidity of hepatic vein occlusion and on whether a venous collateral circulation has developed. Abdominal pain, hepatomegaly, and ascites are present in almost all patients (2). Eosinophilic gastroenteritis (EGE) is not an uncommon disorder in pediatric population. Approximately two-thirds of the patients have eosinophilia. In addition, abdominal pain and ascites can occur in patients with EGE with serosal involvement (4). Therefore, eosinophilia-associated BCS may mimic EGE, leading to difficulty in diagnosis. However, early diagnosis has the best possible outcome by providing the opportunity of reestablishing native hepatic venous outflow tract (3). We herein report that a child with eosinophilia-associated BCS occurring after the resolution of serosal-type EGE was diagnosed by multidetector computed tomography (MDCT) study and successfully treated with percutaneous transhepatic angioplasty and montelukast.
A previously healthy 10-year-old boy presented with a 1-week history of progressive abdominal fullness and pain. It was not associated with fever, vomiting, or diarrhea. No medication history was noted before the illness. On initial physical examination, there was distended abdomen with shifting dullness, but no palpated liver or spleen. Neither skin rash nor lymphoadenopathy was noticed. Laboratory data disclosed a total white cell count of 9 × 103/μL with 15% eosinophils (total eosinophil count: 1350/μL), a hemoglobin level of 12.3 g/dL, and a platelet count of 179 × 109/L. No degranulation or vacuolation of the eosinophil was noted on morphology. Biochemistry analysis showed glutamate oxaloacetate transaminase of 52 (8–38 IU/ L), glutamate pyruvate transaminase of 49 (4–44 IU/L), bilirubin (total/direct) of 1.0/0.2 mg/dL, γ-glutamyl transpeptidase of 195 (4–28 U/ L), albumin of 4.2 (3.5–5.0 g/dL), creatinine of 0.7 mg/dL (0.7–1.4), and total immunoglobulin E of 8.5 (normal <196 KU/L). Surveys for hepatitis B and C virus infections were both negative. The anti-nuclear antibody titer and complement factors 3 and 4 were within normal limits. Urinalysis showed no proteinuria or hematuria, and stool examination was negative for occult blood, parasites, and ova. Abdominal echogram showed normal liver size and echogenicity, patent hepatic vein outflow, but marked ascites. Diagnostic abdominal tapping revealed yellowish ascites and the analysis disclosed a total white cell count 110 /μL with 14% eosinophils; glucose 101 g/dL; and albumin 3.2 g/dL. Cytological examination of the ascites disclosed numerous eosinophils and a few mesothelial cells, but no malignant cells in the cellular cytospin preparation. Panendoscopy showed erythematous mucosa change from antrum to upper jejunum, and the results of biopsy demonstrated prominent infiltration of eosinophils over mucosal and submucosal layers of jejunum (Fig. 1), compatible with the diagnosis of EGE. Pulse therapy with methylprednisolone (30 mg · kg−1 · day−1) for 3 days followed by oral prednisolone (1 mg · kg−1 · day−1) was administered, and the abdominal distention greatly improved by 1 week.
Six months later the patient experienced a relapse with the same abdominal symptoms later despite maintenance treatment with 0.5 mg · kg−1 · day−1 prednisolone. Abdominal echogram revealed not only recurrent ascites but also increased liver echogenicity and moderate hepatomegaly with the absence of visualized hepatic venous flow. Repeat panendoscopy showed resolution of mucosa change, but occurrence of esophageal varices. At that time, a total white cell count was 12 × 103/μL with 8% eosinophils (total eosinophil count 960 /μL). Liver function tests showed mild elevation of glutamate pyruvate transaminase and glutamate oxaloacetate transaminase, 45 and 44 IU/L, respectively, but normal bilirubin and albumin levels. Coagulation studies including prothrombin time, activated partial thromboplastin time, protein C, protein S, and antithrombin III were within normal limit. MDCT study demonstrated hepatic lobar low-attenuated lesions (Fig. 2A), hepatic veins thrombosis (Fig. 2B), and moderate stenosis over intrahepatic portion of IVC (Fig. 3). Based on the above-mentioned features, eosinophilia associated with BCS was confirmed. Further percutaneous transhepatic angioplasty successfully resolved IVC stenosis. Thereafter, the patient was started on montelukast 10 mg orally daily. During the 1-year follow-up period, there was no recurrence of ascites, hepatomegaly, or IVC stenosis.
BCS is characterized by hepatic venous outflow tract obstruction with resultant increased sinusoidal pressure and portal hypertension, which can be accompanied by marked hepatomegaly and ascites (2). A few reports have been published regarding the association between BCS and idiopathic hypereosinophilic syndrome (3). Although many cases may not fulfill the criteria of idiopathic hypereosinophilic syndrome (eosinophilia >1500/μL persisting for more than 6 months), eosinophilia can be associated with tissue eosinophilic infiltration and organ damage, which mainly include skin, the gastrointestinal system, lung, and the cardiovascular system (5). The vascular damage of eosinophils may lead to thrombosis, stenosis, and outflow obstruction (6). The major mechanism is thought to be mediated by toxin proteins from eosinophils, which consist of eosinophilic cationic protein, peroxidase, eosinophil-derived neurotoxin, major basic protein, and platelet-activating factor (7,8).
Considering the above-mentioned components, massive eosinophil infiltration would lead to damage to the endothelium and the hypercoagulable state in vessels. Thus, the association between eosinophilia and BCS is thought to be related to the eosinophilic infiltration of the walls of IVC and/or hepatic veins. The reported case with hepatic venous outflow tract obstruction caused by eosinophilia-induced thrombosis and stenosis was clearly demonstrated by an MDCT study. Moreover, eosinophilic infiltration can be demonstrated on computed tomography by the presence of lower attenuated hepatic lobar, segmental, or subsegmental low-attenuated lesions. This presence may be related to damage of the liver parenchyma with associated portal phlebitis (9).
The rarity of BCS diagnosis in children often means that the disease is diagnosed in its later stage. Prompt management can prevent irreversible pathological process (1). In our case, corticosteroid was initially used to treat EGE and the patient responded well. However, recurrent ascites and hepatomegaly were observed during follow-up. An MDCT examination confirmed the diagnosis of BCS; thereafter, aggressive management with angioplasty and other potential medicine could be started. Because eosinophils are potent sources of leukotrienes known to induce eosinophil chemotaxis and mucosal injury, montelukast, a leukotriene receptor antagonist, has been shown to be useful as steroid-sparing agent in patients with the serosal form of EGE (10). Although surgical intervention or angioplasty plays an important role in the treatment of the disorder, our reported case disclosed that a leukotriene receptor antagonist may be beneficial in preventing eosinophilia-associated liver and vascular damage.
EGE is not an uncommon disorder in the pediatric population, characterized by an eosinophil-predominant inflammatory process in gastric and/or small intestinal mucosa. Although the most common presentations are abdominal pain, vomiting, and diarrhea, ascites has been reported in patients with serosal involvement (4). Importantly, other possible causes of gastrointestinal eosinophilia, including parasitic infections, allergy disorder, and drug-induced causes, must have been ruled out before the diagnosis of EGE is established. In addition, some cases with eosinophilia may have eosinophilic infiltration initially localized to the gastrointestinal tract alone; therefore, close observation of other organ involvement is required (4).
In summary, eosinophilia may cause multiple organ damage. In spite of its rarity, further abdominal imaging studies should be considered in patients with eosinophilia and persistent ascites for the presence of BCS.
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