Atchara Mahayosnond

Expanding the phenotypic spectrum of Caffey disease

Infantile cortical hyperostosis (ICH) is an inherited disorder characterized by hyperirritability, acute inflammation of soft tissues, and massive subperiosteal new bone formation. It typically appears in early infancy and is considered a benign self‐limiting disease. We report a three‐generation Thai family with ICH, the oldest being a 75‐year‐old man. A heterozygous mutation for a 3040C→T in exon 41 of COL1A1 was found in affected individuals, further confirming the autosomal dominance of Caffey disease that is caused by this particular mutation. The novel findings in our studies include short stature and persistent bony deformities in the elderly. The height mean Z‐score of the five affected individuals was −1.75, compared to 0.53 of the other seven unaffected individuals giving a p‐value of 0.008. Short stature may be partly due to progressive height loss from scoliosis, compression fractures of the spine and genu varus. These features, which have not previously been described, expand the phenotypic spectrum of the Caffey disease.

Possible cause of liver failure in patient with dengue shock syndrome.

To the Editor: We report a rare hepatic ultrasonograph finding for a patient with liver failure associated with dengue virus (DENV) infection. This finding might shed light on the pathogenesis of liver involvement in this disease. In March 2006, a 10-year-old previously healthy boy was hospitalized for a 3-day history of fever, headache, and nausea/vomiting. Fever subsided on the day of admission, but the patient was in shock (blood pressure 80/40 mm Hg) and had gastrointestinal bleeding and hematuria. Physical examination showed an obese, confused patient with generalized petechiae and hepatomegaly. The initial diagnosis was dengue shock syndrome (DSS). The patient was intubated and received intravenous fluid infusion, packed red blood cells, ceftriaxone, sodium bicarbonate, and ranitidine before being transferred to King Chulalongkorn Memorial Hospital in Bangkok. The patient’s blood pressure increased to 130/90 mm Hg after the initial fluid resuscitation (28 mL/kg free flow), and systolic pressure remained at ≈130 mm Hg until transfer. Laboratory examinations found 14,930 leukocytes/mm3, hemoglobin 16.4 g/dL, hematocrit 48.2%, platelet 18,000/mm3, blood urea nitrogen 33 mg/dL, creatinine 1 mg/dL, sodium 128 mEq/L, potassium 6.2 mEq/L, chloride 91 mEq/L, total CO2 5 mEq/L, total bilirubin 6.9 mg/dL, direct bilirubin 3.9 mg/dL, aspartate transaminase 3,507 IU/L, alanine transaminase 2,775 IU/L, prothrombin time 43 seconds (international normalized ratio 3.4), and partial thromboplastin time 93.5 s (control 28.7 s). Blood and urine cultures showed negative results. Serum was positive for IgM against DENV. Unfortunately, we did not investigate other viral causes of liver failure. DSS with liver failure was diagnosed and treated with intravenous fluid, sodium bicarbonate, omeprazole, fresh frozen plasma, platelet transfusion, vitamin K, and recombinant factor VIIa concentrate (NovoSeven; Novo Nordisk, Bagsvaerd, Denmark). Despite stable blood pressure over the next 6 days, liver enzymes continued to rise with progressive jaundice (Technical Appendix). Hepatic ultrasonograph on the second day after admission showed totally reversed direction of portal venous blood flow away from the liver (Figure, panel A), becoming bidirectional on the following day and, finally, reverting to normal direction (although with low velocity) 3 days later (Figure, panel B). Despite improved hemodynamic status, progressive encephalopathy and gastrointestinal bleeding developed and were unresponsive to treatment. Six days later, the patient died of pulmonary hemorrhage and progressive respiratory failure. Figure Ultrasonograph with Doppler image of the liver of a 10-year-old boy with liver failure associated with dengue virus infection. A) Day 2 of hospitalization, showing reversed direction of blood flow in the right branch of the portal vein (hepatofugal flow). ... DENV infection is one of the most prevalent emerging infectious diseases affecting children and one of the leading causes of liver failure in tropical countries (1,2). Although liver involvement in patients with dengue hemorrhagic fever is well known, the mechanism for DENV-induced liver injury is still a mystery. Liver autopsy specimens of terminal DSS patients generally showed massive or focal necrosis with little or no recruitment of polymorphonuclear cells or lymphocytes (3,4). Ultrasonograph images from patients with liver failure caused by acetaminophen poisoning or hepatitis B indicate increased portal vein flow and normal flow velocity to the damaged liver (5). Decreased portal vein flow velocity and reversal of the flow direction is seen in the terminal stage of hepatic cirrhosis and a few other conditions such as hepatic sinusoidal obstruction (hepatic veno-occlusive disease), arterioportal fistula, extrahepatic portal vein thrombosis, and hepatic venous outflow obstruction (6). This finding is unusual in other instances of toxin- or virus-induced liver failure and might contribute to the understanding of the mechanism of liver involvement in patients with DENV infection. We previously reported increased portal vein congestion during the toxic stage of DENV infection (7). At defervescence, the portal vein was dilated and blood flow velocity was decreased. This finding is usually observed for patients with high resistance in the hepatic sinusoidal capillary network, such as those with liver cirrhosis, and is correlated with the degree of portal venous hypertension (8). We postulate that DENV infection of the liver might affect the sinusoidal endothelial or Kupffer cells in a way that causes obstruction to the hepatic sinusoidal capillary lumen resulting in decreased portal venous blood velocity and flow to the liver and, when severe, shunting of portal blood away from the liver (hepatofugal flow). Because portal venous blood comprises 75% of total hepatic blood (6), this condition coupled with decreased hepatic arterial blood flow as a consequence of shock might have led to severe and irreversible liver damage in this patient. This hypothesis can be further supported by a pathology study of the skin in patients with DENV infection, which showed endothelial swelling and extrusion of its plasma membrane into the capillary lumen, resulting in narrowing of the capillary lumen (9). Of note are the similarities between clinical findings in patients with DENV infection and sinusoidal obstruction syndrome such as hepatomegaly, ascites, right pleural effusion, swelling of the gall bladder wall, and decreased velocity or reversed direction of portal blood flow (10). In conclusion, we report a case of liver failure from DENV infection with reversal of portal venous blood flow. We postulate that hepatic sinusoidal obstruction coupled with shock might be the underlying mechanism of liver failure in this disease. Technical Appendix: Clinical and laboratory data for patient with liver failure associated with dengue virus infection. Click here to view.(55K, pdf)

Spontaneous choledochal cyst rupture in a child

Dear Sir, Choledochal cysts represent an uncommon but important cause of jaundice in infants and of abdominal pain in children. The classic presentation of jaundice, abdominal pain, and right hypochondrial mass occurs in approximately 6–8% of affected children [1]. We would like to report a 20-month-old boy referred to Chulalongkorn Hospital because of fever, abdominal distention, and pale stools of a 4-week duration. There was no history of preceding abdominal trauma. Exploratory laparotomy performed at another hospital 2 weeks prior to referral revealed 500 ml of exudative ascites without evidence of intestinal perforation. Physical examination showed an irritable, febrile, and mildly jaundiced child. The abdomen was markedly distended and tender. There was evidence of massive ascites without palpable mass. The remainder of the physical examination was normal. The hematocrit value was 30.6%, and the white blood cell count was 12,070/mm with 59% polymorphonuclear cells. The alkaline phosphatase value was 2,417 U/l (39–117 U/l), serum alanine aminotransferase 27 U/l (0–38 U/l), and serum aspartate aminotransferase 41 U/l (0–38 U/l). Serum albumin was 3.4 g/dl (3.4–5.5 g/dl), globulin 2.9 g/dl (2–4 g/dl), total bilirubin 2.4 mg/dl ( £ 1 mg/dl), and amylase 205 U/l (0–220 U/l). Abdominal paracentesis revealed bilestained fluid with numerous red and white blood cells, bilirubin of 18.54 mg/dl, amylase of 968 IU/l, and lipase of 15,020 IU/l. Liver 99mTc-DISIDA showed common bile duct dilatation and leakage of the isotope into the peritoneal cavity without visualization of bowel activity (Fig. 1). The patient was treated for peritonitis with systemic antibiotic therapy. Subsequent exploratory laparotomy revealed 2,000 ml of bilious ascites and a loose fibrous band extending over the entire peritoneal cavity. Perioperative cholangiography revealed fusiform dilatation of the common bile duct 2 cm in diameter (type I choledochal cyst), with a perforation just below the cystic duct junction and minimal dilatation of the intrahepatic bile duct (Fig. 2). Excision of the cyst, cholecystectomy, and Roux-en-Y hepaticodochojejunostomy were performed. The child’s postoperative period was uneventful, and he has remained well for more than 4 years after surgery. Rupture of a choledochal cyst has been considered an uncommon complication. However, this complication has been reported to occur at rates as high as 18% [2]. In many cases, the cause of rupture is unknown and is considered spontaneous. The etiology of a perforation is assumed to be epithelial irritation of the biliary tract due to a reflux of pancreatic juice caused by pancreaticobiliary malunion associated with mural immaturity during infancy [3, 4]. However, only six of 26 patients with choledochal cyst perforation reported by Yamaguci displayed this malformation of the pancreaticobiliary system; thus, other factors are assumed to contribute to the perforation [5]. Ando et al. suggested that perforation of the common bile duct is related to an abrupt V. Chongsrisawat Æ Y. Poovorawan Department of Pediatrics, Faculty of Medicine, Chulalongkorn Hospital and University, Bangkok, Thailand

Accuracy of ultrasound in pediatric undescended testes

Abstract Background: The undescended testis represents a common condition affecting male infants with significant clinical implications such as infertility and testicular malignancy. There is controversy as to the diagnosis when a clinical examination fails to identify a testis. Objective: Investigate the value of ultrasound in the diagnosis of undescended testis, and evaluate the correlation between the preoperative ultrasonographic data and operative findings. Material and method: Thirty-nine boys (age: 3months -12 years) with undescended testes were examined between January 2003 and December 2007. All the boys had undergone a sonogram performed for localizing the undescended testes. Only 20 boys were sent for inguinal exploration, or other surgical procedures for localizing the undescended testes. We calculated specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of ultrasonographic diagnosis in boys with undescended testes. Results: Twenty-nine undescended testes were included in this study. Ultrasonography had a sensitivity of 82%, a specificity of 0%, PPV of 96%, NPV of 0%, and accuracy of 79% in the diagnosis of the undescended testis. Conclusions: The sensitivity and specificity including NPV of uetrasound had the unsatisfactory outcomes.