Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Gastroesophageal reflux with children requiring adenotonsillectomy.

BACKGROUND: Our aim is to determine the incidence of reflux in children older than 3 years requiring adenotonsillectomy and relationship between GER and diagnostic tests. METHODS: Forty-four patients, who were listed for adenoidectomy/tonsillectomy at Pediatric Ear Nose Throat department due to severe hypertrophy, were evaluated for accompanying GER (Group 1). GER was diagnosed as having at least one positive GER test result (including esophagitis or pH monitoring). Twenty children without reflux symptoms were used as healthy control group (Group 2) and LPR was held. RESULTS: Reflux was detected in 32 children requiring adenotonsillectomy (72.7%). LPR score was negative in all patients in Group 2. There was no correlation between pH monitoring and histopathological evaluation of esophagus. There was a correlation between the LPR score and histological esophagitis in the proximal esophagus. CONCLUSIONS: GER was high in patients with adenotonsillary hypertrophy. LPR score and the history of patients are as effective as invasive techniques like pH monitorization and endoscopy in determining GER disease.

Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey.

BACKGROUND/AIMS: A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations. MATERIALS AND METHODS: The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart. RESULTS: In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas. CONCLUSION: After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.

A rare cause of refractory ascites in a child: familial Mediterranean fever.

Familial Mediterranean fever (FMF) is hereditary episodic febrile syndrome characterized by acute attacks of fever and serosal inflammation, generally lasting 1-3 days and resolves spontaneously. Apart from abdominal pain, patients may present with variety of abdominal manifestations such as acute peritonitis, mechanical intestinal obstruction, diarrhea, bowel infarction, amyloidosis and small amounts of peritoneal fluid during the acute attacks. A 6-year-old boy was admitted with massive ascites. After extensive laboratory investigations, no causative agent could be identified. On subsequent days, he developed fever and skin eruptions. Acute-phase reactants were increased. A second tomography revealed cystic fluid collection near the anterior side of spleen that invades the stomach. An exploratory was performed and histopathological examination of the all resected specimens revealed mix inflammatory cell infiltrate associated with severe myofibroblast proliferation suggesting chronic inflammatory process on the mesenteric region. A diagnosis of FMF was suspected based on the clinical, laboratory and histopathological findings, and a trial of colchicine therapy initiated. Ascites and other serosal inflammations improved within 1 week without any recurrence during the next 12-month period on colchicine treatment. Atypical presentations of FMF have been increasingly reported. Pediatricians should keep FMF in mind in the differential diagnosis of massive ascites especially in regions where hereditary inflammatory disease are common.

A rare complication of central catheter in an infant with intestinal failure.

OBJECTIVE: To report the successful percutaneous transcatheter removal of a snapped intracardiac fragment of the central vein catheter in an infant. CLINICAL PRESENTATION AND INTERVENTION: A 3-month-old infant with short bowel syndrome who required long-term parenteral nutrition via portacath central catheter was hospitalized. Two months after the insertion of the second catheter, the distal tip of the catheter snapped and became tangled in the heart. The catheter fragment was removed by a percutaneous femoral vein approach using a 10-mm diameter snare-loop catheter (Amplatz). The procedure was performed under fluoroscopy; the fragment was removed after being released into the right ventricle by pulling the proximal tip with a pigtail catheter. No complications were observed and the patient was transported back to the intensive unit in stable condition. CONCLUSION: Central catheter-related complications may cause difficulties in patients with short bowel syndrome prior to intestinal transplantation. The percutaneous retrieval of the fragmented catheter using a snare-loop catheter is a safe and reliable technique and may be used instead of surgery especially in small infants.

Trigonocephaly and Wilson's disease in two siblings.

Trigonocephaly and Wilson's disease (WD) are two different entities. The former is a type of craniosynostosis that occurs because of fusion of the metopic suture and the latter, also called hepatolenticular degeneration, is caused by an accumulation of copper in tissues all over the body because of failure of copper excretion. No single gene has been identified for trigonocephaly whereas the ATP7B gene has been shown to be responsible for Wilson's disease. Here we present two siblings born to nonconsanguineous parents who both presented with trigonocephaly, Wilson's disease and facial dysmorphism. In addition, the female has renal agenesis and the male has a history of undescended testis. Karyotypes were normal and no mutation of the ATP7B gene has been identified in the patients or their parents.

Effect of long-term lamivudine in chronic hepatitis B virus-infected children.

OBJECTIVE: To evaluate, retrospectively, biochemical, serological and histological responses in chronic hepatitis B (CHB)-infected children who received combination therapy and continued with prolonged treatment with lamivudine (3TC). PATIENTS AND METHODS: CHB infection was defined as the presence of hepatitis B surface antigen (HBsAg), hepatitis Be antigen (HBeAg) and hepatitis B virus (HBV) DNA in serum screened at 3-month intervals for at least 1 year, serum alanine aminotransferase (ALT) levels >1.5 times the normal limit and CHB with histological activity index (HAI) >5 by liver biopsy. A total of 99 children with CHB infection were treated with IFN-alpha (three times a week, 5 MU/m2) and 3TC (4 mg/kg/d) orally for 6 months. End of therapy response (CR) was defined as ALT normalization, HBV-DNA clearance and e seroconversion. Partial responders (PR) were defined as patients who had ALT normalization and HBV-DNA clearance, but who had not had e seroconversion. Forty-five children with PR at the end of the sixth month continued to receive 3TC alone thereafter. Breakthrough infection was determined as re-emergence of HBV DNA in serum after its clearance. The response rate, side effects and the breakthrough infection rate were examined on prolonged 3TC treatment. Liver biopsy was held in 29 patients at median 32 (14-66) months of 3TC; pre- and post-treatment liver histology was compared. RESULTS: Pre- and post-treatment evaluation was carried out in 45 children [mean age: 11+/-4.2 years, 31 males (69%), 14 females (31%)] with PR at the end of the sixth month of combination therapy. The initial mean ALT values and HAI scores were 75.6+/-60 IU/l and 8+/-3.3, respectively. 3TC was continued for median 33 (14-66) months and CR was achieved in 15.6% (7/45) and 5.6% (2/36) at the end of first and second year, and 0% (none) at the end of third and fourth year, respectively. Breakthrough incidence was detected in six (13.3%) cases at 12 months and increased to 69.4% (n=25) and 82.4% (n=14) at the end of the second and third years, respectively. Patients with breakthrough continued to receive 3TC. Seroconversion and CR of the mutant virus was achieved in one patient (2.9%) at month 46 of treatment with 3TC. Liver biopsy was held in 29 cases at median 32 (14-66) months of 3TC. Pre- and post-treatment mean HAI scores were 8+/-3.3 and 3.9+/-2.1, respectively (P=0.000). Mean necrosing scores were not different at the beginning and end of therapy (P=1.0). Inflammation, bridging and fibrosis scores decreased to 0.8+/-0.6, 1.3+/-1.2 and 0.6+/-0.8, respectively (P=0.000, P=0.002, P=0.000). CONCLUSION: The long-term 3TC usage in children with PR does not induce complete response and is associated with high breakthrough incidence. However, histological improvement is achieved and/or sustained even in children with HBV DNA breakthrough.

Regenerative nodule mimicking hepatocellular carcinoma in a cirrhotic child due to hepatitis B: an imaging dilemma.

Viral hepatitis B, post-hepatitic cirrhosis and hepatocellular carcinoma (HCC) is the classical sequence of events in hepatitis B virus (HBV) infected children and serum Alpha-fetoprotein (AFP) and ultrasound (USG) screening is recommended during follow up. We present a 13-yr-old girl with cirrhosis related to chronic HBV infection with normal AFP level and a 4 cm mass appearance by USG. Contrast spiral evaluation computed tomography (CT) study demonstrated a single mass located at 8th segment of the liver. Pre-contrast CT and portal venous phase studies showed heterogeneous liver parenchyma without mass appearance. HCC was suspected based on strong arterial enhancement. Two mediastinal lymphadenopathies, 1 cm under the xyphoid and 2 cm above the pericardium, were detected by thorax CT. Mediastinal exploration was undertaken with living related liver transplant donor in a second operating room. She was transplanted with the right lobe of her ABO compatible mother after evaluation of the lymph nodes revealed reactive histology by frozen section. Histologic evaluation of the explant liver documented cirrhosis with a cirrhotic nodule without histologic malignant evidence. False negative results from screening methods are familiar in the literature; however false positivity of a contrast CT study is rare. The significance of screening methods is discussed.

Comparison of antiviral effect of lamivudine with interferon-alpha2a versus -alpha2b in children with chronic hepatitis B infection.

AIM: To compare additive efficacy of combination therapy including interferon (IFN)-alpha2a+lamivudine (3TC) to IFN-alpha2b+3TC in children with chronic hepatitis B virus (HBV) infection. MATERIAL AND METHODS: Chronic hepatitis B infection was determined by presence of HBsAg, HBeAg and HBV DNA in serum screened at 3 months intervals for at least 1 year, serum alanine transaminase (ALT) levels more than 1.5-times the upper normal limit and chronic hepatitis with histological activity index (HAI) more than 6 by liver biopsy. Sixty-three children with chronic hepatitis B infection were treated randomly with thrice-weekly subcutaneous injections of 5 MU/m2 recombinant IFN-alpha2a (n=29) or recombinant IFN-alpha2b (n=34) with the same dose, intervals for 6 months. Patients also received 3TC (4 mg/kg/day, max 100 mg/day) orally daily combined with IFN and continued for 12 months. End of therapy response was defined as ALT normalization, HBV DNA clearance and HBe/anti-HBe seroconversion. Breakthrough infection was determined as re-emergence of HBV DNA in serum after its clearance. Response rate, incidence of side effects and breakthrough infection were compared between IFN-alpha2a+3TC- and IFN-alpha2b+3TC-treated patients. RESULTS: Response rate was 44.8% (n=13) with IFN-alpha2a+3TC and 47.1% (n=16) with IFN-alpha2b+3TC (P=1.0). No significant difference was found in respect to the DNA clearance (P=0.32), anti-HBe (P=1.0), anti-HBs (P=0.09) seroconversion and response rates (P=1.0) between the groups. Breakthrough infection was detected in 1 (3.4%) case on IFN-alpha2a and none of the cases on IFN-alpha2b (P=0.46). All of the patients experienced flu-like symptoms, malaise and fatigue; however, side effect interfering with therapy was not encountered. CONCLUSION: No significant difference was found in response rates achieved by combination therapies based on IFN-alpha2a and IFN-alpha2b. Clinical efficacy of 3TC and two different IFN subtypes was found similar.

Celiac disease in children with Down syndrome: importance of follow-up and serologic screening.

BACKGROUND: Celiac disease, also known as gluten-sensitive enteropathy, is a chronic inflammation disease of the small intestinal mucosa. Detection of Ig-A antigliadin antibodies (AGA) and antiendomysial antibodies (EMA) in serum is important in the diagnosis and screening for celiac disease. Antiendomysial antibodies have greater sensitivity compared to antigliadin antibodies. It has been reported that the prevalence of celiac disease is higher in children with Down syndrome than the other autoimmune conditions. The aim of the present study was to investigate the incidence of celiac disease in children with Down syndrome, to assess the availability of Ig-A AGA and EMA for serologic screening, and to highlight the importance of follow-up for children with Down syndrome. METHODS: Forty-seven children with Down syndrome without known celiac disease were tested for total blood count, thyroid function tests, immunoglobulin values, Ig-A AGA and EMA. Duodenal biopsy was performed on eight patients who showed at least one serologically positive marker. RESULTS: The ages of the children with Down syndrome ranged from 2 to 18 years (30 boys/17 girls). The mean age was 6.55 +/- 3.88. Total blood count and immunoglobulin values were normal. Eleven of the 47 patients (23.40%) were found to be serologically positive, 10 (21.28%) having antigliadin antibody concentrations above normal; and six (12.77%) being positive for antiendomysial antibody. In five patients (10.64%), both Ig-A AGA and EMA concentrations were high and positive. Duodenal biopsies of three of eight cases (37.50%) revealed villous atrophy, lymphocyte infiltration and crypt hyperplasia. Three cases with abnormal biopsy results (100%) were below the 10th percentile for weight and height. Hypo-thyroidism was detected in one of 11 cases where at least one serologic marker was positive. CONCLUSION: Children with Down syndrome should be carefully examined in their follow up, and celiac disease should be considered in cases with growth retardation. Ig-A antigliadin antibodies and EMA are non-invasive, cheap and readily available serologic screening tests for celiac disease, and the positivity of both markers gives the most reliable result.