Complicated Pylephlebitis Secondary to Perforated Appendicitis in an Adolescent.

Septic thrombophlebitis of the portal vein or pylephlebitis is a rare cause of morbidity and mortality in children. The common causes include infective intra-abdominal pathology (acute appendicitis or diverticulitis) or inflammatory conditions (acute pancreatitis and inflammatory bowel disease). Management involves a multidisciplinary team approach for favorable outcome. We present a case report of pylephlebitis secondary to perforated appendicitis with incomplete resolution of thrombosis. Copyright:

INTRODUCTION

Pylephlebitis, resulting from appendicitis, is an uncommon life-threatening condition in children.[1] Due to its rarity, the overall incidence is unknown in children; however, adult studies estimate 2.7 per 100,000 person-years.[23] The diagnosis relies on clinical features, imaging of the portal system and underlying abdominal pathology, and positive blood/tissue cultures.[1234] Prompt treatment with antibiotics with anticoagulation and surgical management is essential for patient survival.[1]

CASE REPORT

A 12-year-old boy presented with a high fever with chills and abdominal pain for 10 days. His abdominal pain was periumbilical in location initially but later localized to the right side. There was no significant past or family history. An ultrasound (USG) Doppler on the 10th day of disease showed thrombosis in the main portal vein, while no other abnormal pathology was found.

On examination, he was febrile and sick. Abdominal examination revealed tenderness in the right side of the abdomen and hepatomegaly. Investigations revealed that Hb was 11.1 g/dl; platelet count was 560 × 103/mm3; white blood cell count was 12.06 × 103/mm3 with 75% neutrophils, erythrocyte sedimentation rate (ESR) was 80 mm/h and C-reactive protein (CRP) 31 mg/l, procalcitonin was 2.33 ng/mL, aspartate aminotransferase was 45 U/l, and alanine aminotransferase was 51 U/l. USG of the abdomen showed heterogeneous liver echotexture and splenomegaly; portal vein showed a thrombus without cavernoma formation. The patient was treated with broad-spectrum antibiotics (piperacillin–tazobactam).

An abdominal contrast-enhanced computed tomography (CT) revealed perforated appendicitis and portal venous thrombosis [Figure 1].

Figure 1

Computed tomography of the abdomen on admission: Appendicitis and extraperitoneal rupture. Altered attenuation of the right lobe and portal venous thrombosis involving the main portal vein, superior mesenteric vein, left branch of the portal vein, and occluded right portal vein

He underwent an urgent laparotomy and appendectomy on the 2nd day of hospitalization. The adjacent bowel showed no ischemia. He was started on low-molecular weight heparin (LMWH), and metronidazole was added. The pus culture revealed Escherichia coli. He showed clinical improvement in the next 24 h and laboratory parameters normalized. The child was discharged after 2 weeks of hospital stay. Antibiotics were continued for 4 weeks, and LMWH was replaced with an oral factor Xa inhibitor (apixaban) that was continued for 12 months. He was reviewed periodically for 12 months using USG Doppler. On follow-up, CT of the abdomen showed an incomplete resolution of thrombus and resulting complication [Figure 2]. Liver chemistry and synthetic functions remained within normal limits.

Figure 2

Computed tomography of the abdomen on follow-up: Recanalization in the main portal vein, superior mesenteric vein, and left portal vein; the right portal vein showing total occlusion and attenuation of intrahepatic portal vein branches with right lobe atrophy and left lobe compensatory hypertrophy. The right hepatic vein is attenuated with peripheral veno-venous collaterals

Screening for underlying prothrombotic predisposition (activated protein C resistance, protein C and S, and antithrombin III) was normal. There was a heterozygous mutation detected in 1298 A > C MTHFR gene, while no mutations were found in prothrombin (G20210A) Factor II, Factor V (G1619 A), or 677 C > T MTHFR genes.

DISCUSSION

Very few case reports of pylephlebitis secondary to undiagnosed perforated appendicitis in children exist in literature. Other known etiologies include umbilical vein catheterization, necrotizing enterocolitis, acute and chronic pancreatitis, liver abscess, and inflammatory bowel diseases.[3]

The diagnosis of septic pylephlebitis was delayed by 12 days in this case. Yoon et al.[3] reported a delay in diagnosis of few days to 6 weeks, and the main reason was attributed to the nonspecific presentation. Clinical features in children usually include fever, abdominal pain, jaundice, and generalized weakness. The clinical features may be a mild form or severe with septic shock and death. Reported mortality in pediatric series is up to 50%.[13]

Typical blood investigations show leukocytosis and elevated inflammatory markers such as thrombocytosis, ESR, CRP, or procalcitonin, similar to this case. Deranged liver biochemistry such as hyperbilirubinemia or transaminitis may be seen in some cases. Blood culture in pylephlebitis is most commonly polymicrobial in nature and may be seen in 23% to 88% of cases.[13] With the correction of surgical pathology, these abnormalities normalized before discharge.

Classical features of portomesenteric thrombosis on Doppler sonography include a flow defect and dilation or absent compressibility of the portal venous system, while CT and magnetic resonance imaging commonly show a central hypodense venous thrombosis.[2] The ease of USG Doppler makes it the initial investigation of choice. However, contrast-enhanced CT scan reveals the filling defect in the portal vein and its tributaries, in addition to the underlying pathology (appendicitis, liver abscess, or pancreatitis), similar to our case.[3]

The first episode of deep-vein thrombosis or a life-threatening thrombotic event in a child warrants an evaluation of the underlying thrombotic condition.[1] Yoon et al. did not report an associated thrombophilic condition in most cases of portomesenteric thrombosis in their review.[3] In this case, we found a heterozygous mutation in (A > C) MTHFR gene that may have contributed to the extension of the thrombotic event.

The most important therapy of pylephlebitis is the eradication of the initial infectious process with appropriate broad-spectrum antibiotics. In our case, the initial blood culture was sterile because of early antibiotics treatment, but pus culture grew E. coli. The ideal duration of antibiotic therapy is unclear, but 4–6 weeks' duration is recommended. Both interval appendectomy and urgent laparotomy with appendectomy have been reported in treating acute appendicitis with pylephlebitis.[1]

The exact role of anticoagulation and duration in the management of septic pylephebitis is controversial.[1234] It prevents thrombus extension, improves recanalization, and reduces the risk of bowel ischemia. The usual recommended period is 4–6 months; however, prolonged anticoagulation may be needed in children with underlying thrombotic conditions. We initiated LMWH immediately after surgery and replaced it with oral apixaban (oral nonvitamin K anticoagulant) post discharge that has an adequate safety profile.[3] We decided to continue it for 12 months because of an associated thrombotic predisposition.

The most common complication of pylephlebitis is cavernomatous transformation, leading to portal hypertension and variceal bleeding.[5] We noted a complete resolution of thrombosis in mean platelet volume, left portal vein, and superior mesenteric vein; however, recanalization in the right portal vein did not occur. Subsequently, the right lobe of the liver showed atrophy and peripheral scarring. It resulted in right hepatic vein occlusion and veno-venous collateral formation. The patient remained asymptomatic because of involvement of a single hepatic vein.[6] In conclusion, septic pylephlebitis in a setting of acute appendicitis requires a high index of suspicion and careful evaluation. Close follow-up is essential in children with added complications.

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Conflicts of interest

There are no conflicts of interest.