Bone mineral density and growth in children with coeliac disease on a gluten free-diet.

BACKGROUND/AIM: To evaluate changes in growth and bone metabolism during consumption of a gluten-free diet (GFD) in children with coeliac disease (CD). MATERIALS AND METHODS: Thirty-seven children with CD (mean age of 8.8 ± 4.6 years, 21 girls) were enrolled. Anthropometric measurements, bone mineral density (BMD) in lumbar 2-4 vertebrae, and serum alkaline phosphatase, calcium, and phosphorus levels at diagnosis and at follow-up were recorded. RESULTS: The mean follow-up period was 3.5 ± 2.3 years. The BMD of patients was significantly lower than that of control subjects at the time of diagnosis but not after 1 year of the GFD. Incidence of low BMD with respect to z-scores for chronological age (CA) was significantly higher than z-scores for height age (HA) (P = 0.006). At the first year of GFD, BMD, BMD z-score, height-for-age z-scores, and weight-for-age z-scores were significantly increased compared with the baseline, but not after 1 year of the GFD. CONCLUSION: In CD, the first year of GFD is important in weight gain, linear growth, and improvement of BMD. A considerable relation of low BMD in children with CD, with respect to z-scores for CA, may be a result of misinterpretation of low BMD due to short stature.

Mesalamine Intolerance in Three Children with Crohn's Disease.

OBJECTIVE: To present the mesalamine-induced acute exacerbation of symptoms and inflammatory markers in children with Crohn's disease (CD). CLINICAL PRESENTATION AND INTERVENTION: Three children who presented with CD had acute exacerbation of colitis symptoms or elevated inflammatory markers when mesalamine was added to treatment while tapering/ceasing steroid treatment. While on steroid treatment, the patients maintained clinical and laboratory remission, but with the initiation of mesalamine treatment, they had abdominal pain and bloody mucoid diarrhoea and/or elevation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. Bacterial pathogens were excluded from the urine, throat and blood cultures, parasites with stool examination, viral pathogens with serology. Within 3-7 days after the mesalamine treatment had been stopped, the patients showed improvement of colitis symptoms and normalisation of white blood cell count, C-reactive protein level and erythrocyte sedimentation rate. CONCLUSION: In this study mesalamine mimicked CD relapse in children with CD while tapering or after stopping steroid treatment. Awareness of this side effect of mesalamine could prevent a misdiagnosis of steroid dependency.

Celiac disease and autoimmune thyroid disease in children with type 1 diabetes mellitus: clinical and HLA-genotyping results.

OBJECTIVE: Increased prevalence of celiac disease (CD) and autoimmune thyroid disorders (ATD) in patients with Type 1 diabetes mellitus (T1D) has been widely reported. Such an association may lead to adverse effects on the growth, bone metabolism and fertility, and response to therapy may become difficult. The aim of this study was to evaluate the clinical findings and HLA typing results in patients with T1D associated with CD or ATD. METHODS: The association of CD and ATD was evaluated in 38 children with T1D aged 1.5-16.8 years who had been followed for 48.3±28 months. Diagnosis of CD was based on positivity for serum endomysial IgA antibody and histopathological findings of intestinal biopsy specimens. Thyroid autoimmunity was assessed by antithyroglobulin and antithyroid peroxidase antibodies and with diagnostic ultrasonographic findings. RESULTS: ATD was detected in 31.5%, and CD-in 7.8% of T1D patients. Subjects with CD showed either no symptoms or suggestive problems such as short stature, hepatosteatosis, pubertal delay and difficulties in the control of diabetes. Patients with ATD had no clinical symptoms. DQ8 was the most prominent finding in CD. CONCLUSIONS: It is essential that patients with T1D, regardless of presence or absence of symptoms, should be investigated for CD and ATD.

Effect of interferon therapy on glucose metabolism in children with chronic hepatitis B.

The aim of this study was to investigate the effect of interferon (IFN)-alpha treatment on glucose metabolism in children with chronic hepatitis B (CHB). Forty children with CHB received IFN 10 MU/m2 for six months. Oral glucose tolerance test, anti-insulin and anti-glutamic acid decarboxylase (GAD) antibody, fasting plasma C-peptide and insulin (FPI), postprandial insulin, homeostasis model assessment of insulin resistance (HOMA-IR), HOMA-cell, and glucose/insulin ratio (G/I) were measured before and after treatment. The last four parameters were also evaluated in healthy controls (n=42). In patients, fasting plasma glucose (FPG) and HOMA-IR levels were significantly lower than in controls (p = 0.001 and p = 0.020, respectively). There was a strong correlation between degree of liver disease and FPG. Two patients had hyperinsulinemia. HOMA-IR was suppressed in 7 patients enough to indicate increased sensitivity. FPI of 13 patients and HOMA-cell of 9 patients were lower than the minimum level of controls, features compatible with beta-cell hypofunction. Frequency of glucose metabolism abnormalities was not different before and after therapy. After therapy, only 1 patient developed anti-GAD antibody, and FPI of 8 children and HOMA-cell level of 9 children were lower than the minimum level of controls. Hyperinsulinemia was persistent in the same patients. We demonstrated that HBV-infected children had insulin sensitivity; however, no adverse effects of IFN on glucose homeostasis were seen.

Efficacy of combined interferon alpha and long-term lamivudine therapy in children with chronic hepatitis B.

The aim of this study was to evaluate the efficacy of interferon alpha (IFN-alpha) and long-term lamivudine therapy in children with chronic hepatitis B and to determine the optimal duration of lamivudine therapy. Thirty-eight HBeAg-positive children simultaneously received IFN-alpha2a 5 MU/m2 to 10 MU/m2 for six months and lamivudine (4 mg/kg/day). Lamivudine was administered until anti-HBe seroconversion and was continued for six months in responders. During the five-year study period, we evaluated the efficacy of treatment, occurrence of YMDD mutants and adverse effects. During the study period, alanine aminotransferase (ALT) normalization, clearance of hepatitis B virus (HBV) DNA, HBeAg/anti-HBeAb, HBsAg/anti-HBsAb seroconversion, and histological response were noted in 27 (71.1%), 14 (36.8%), 13 (34.2%), 2 (5.2%) and 10 (47.9%) patients, respectively. Complete response was determined in 34.2% (13/38), and in 69.2% of these responders, response was achieved within 18 months. Breakthrough and YMDD mutant rates were 65.8% and 55.2%, respectively. Breakthrough time was a median 24 months and was associated with low baseline ALT level (p < 0.01). In conclusion, although lamivudine was used for a longer period, the response rate was not higher than in previous reports. We suggest that 18 months' duration of lamivudine treatment is sufficient for combination therapy.

Celiac disease: presentation of 109 children.

PURPOSE: The clinical features of patients with celiac disease (CD) are variable. In the present study, clinical and laboratory features of 109 patients with CD were retrospectively evaluated. MATERIALS AND METHODS: In all cases, diagnosis of CD was made by European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria and clinical and laboratory findings, including hematological and biochemical analyses, immunoglobulin levels, autoantibodies [antinucler antibody (ANA), antidouble stranded DNA (dsDNA), antimitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), liver kidney antibody (LKM-1), anti thyroid peroxidase (TPO), anti thyroglobulin (Tg)], bone mineral density (BMD), and electroencephalogram were evaluated. The type of CD was recorded. RESULTS: Of 109 patients with CD, 66 (60.6%) were classical type, 41 (37.6%) were atypical type and 2 (1.8%) were silent type. The mean age was 8.81 +/- 4.63 years and the most common symptom was diarrhea (53.2%) followed by failure to thrive, short stature, and abdominal pain. Paleness (40.4%), underweight (34.8%), and short stature (31.2%) were the most common findings. Iron deficinecy anemia (81.6%), zinc deficiency (64.1%), prolonged prothrombin time (35.8%), and elevated transaminase levels (24.7%) were the most common laboratory findings. Eight percent of patients had at least 1 autoantibody, and 28 of 52 patients had low BMD. Four of 38 patients had abnormalty in electroencephalograms. The prevalance of selective immunoglobulin (Ig) A deficiency was 9.1%. Histocompatibility antigen HLA-DQ and/or DQ8 genotypes were found in 91% of patients. Abdominal distention, iron deficiency, prolonged prothrombine time, hypoalbuminemia, and elevated transaminase levels were more significantly frequent in the classical type than atypical type (p < 0.005). CONCLUSION: Although classical CD was seen in most patients in the present study, clinical variability of the condition should be kept in mind.

A rapid lateral flow stool antigen immunoassay and (14)C-urea breath test for the diagnosis and eradication of Helicobacter pylori infection in children.

Our aim was to evaluate diagnostic accuracy of rapid immunochromatographic stool antigen test (Rapid HpSA; LINEAR Chemical, Barcelona, Spain) and a practical low-dose (14)C urea breath test (UBT) (Heliprobetrade mark) test before and after eradication therapy. One hundred nine children with abdominal symptoms (age range, 5-17 years; mean, 12.1) underwent endoscopy, (14)C-UBT, and Rapid HpSA. Patients were defined as Hp infected when histology was positive for Hp. Forty children (36.6%) were Hp infected. The sensitivity of Rapid HpSA and (14)C-UBT was 65% and 92.5% (P = 0.0003), respectively; the specificity of Rapid HpSA and (14)C-UBT was 92.3% and 85.5% (P = 0.180), respectively. After eradication therapy endoscopy, (14)C-UBT and Rapid HpSA were repeated. The eradication rate was 70.5%. After eradication, the sensitivity of Rapid HpSA and (14)C-UBT was 60% and 100%, respectively; the specificity of Rapid HpSA and (14)C-UBT was 100%. (14)C-UBT was more reliable than the Rapid HpSA test for the diagnosis and for confirming eradication of Hp infection.

An unusual presentation of Wilson's disease in childhood: nodular fatty infiltration in liver.

Wilson's disease is a rare inherited disorder characterized by progressive accumulation of copper in the body tissues. Liver and brain are the most commonly involved organs and the disease is presented predominantly by hepatic manifestations in childhood. Histopathological findings of hepatic involvement may vary from steatosis to end stage cirrhosis. Although diffuse fatty infiltration is a typical finding of Wilson's disease, it can very rarely present in nodular pattern. We report the first case with Wilson's disease who presented with nodular fatty infiltration in the liver in childhood.

Crohn's disease of the vulva in a 10-year-old girl.

Crohn's disease may involve all parts of the gastrointestinal tract and may often involve other organs as well. These non-intestinal affections are termed extraintestinal manifestations. Vulval involvement is an uncommon extraintestinal manifestation of Crohn's disease, and it is very rare in children. Patients with vulval CD typically present with erythema and edema of the labia majora, which progresses to extensive ulcer formation. Vulval Crohn's disease can appear before or after intestinal problems or it may occur simultaneously. We present a 10-year-old girl with intestinal Crohn's disease complicated with perianal skin tags and asymptomatic unilateral labial hypertrophy. The course of her lesion was independent of the intestinal disease and responded significantly to medical treatment including azathioprine and topical steroid. We emphasize that although vulval involvement in childhood is uncommon, Crohn's disease must be considered in the differential diagnosis of nontender, red, edematous lesions of the genital area.

Successful living-related liver transplantation in a child with familial yellow nail syndrome and fulminant hepatic failure: report of a case.

An 11-yr-old boy with familial YNS and FHF and who underwent LRLT is presented. LRLT was performed from his father with YNS. The findings of hepatic failure resolved immediately after LRLT, but severe respiratory complications and chylous ascites were observed during the follow-up. At 12 months after successful LT, the patient has good graft function, but findings of YNS including chronic cough, lymphedema and yellow nails are still present. To the best of our knowledge, this is the first case of YNS who underwent LRLT for FHF.

Human tissue transglutaminase antibody screening by immunochromatographic line immunoassay for early diagnosis of celiac disease in Turkish children.

BACKGROUND/AIMS: Celiac disease has a large prevalence worldwide. There are a limited number of comparable epidemiological data for celiac disease in Turkey. The aim of this preliminary study was to determine the prevalence of celiac disease in a sample of 1000 Turkish children by a novel, simple, and visual one-step immunoassay screening test. METHODS: This prospective study consisted of 1000 serum samples from apparently healthy children and children with disorders other than celiac disease aged between 2-18 years who presented as outpatients at Ankara University, Faculty of Medicine, Department of Pediatrics. Sera were tested for IgA-class antibodies against human tissue transglutaminase and gliadin by rapid immunochromatographic line immunoassay. Endomysial antibody IgA against human tissue transglutaminase and AGA IgA/IgG were also tested by ELISA as a second step when the result of the screening test was positive. Small bowel biopsy was recommended to all the children with positive anti-tissue transglutaminase and/or endomysial antibody results. RESULTS: Ten of the 1000 individuals (1%) had positive antibody screening test to human tissue transglutaminase. All tissue transglutaminase-positive samples revealed good correlation with endomysial antibody by ELISA method. Subsequently small bowel biopsy was performed in all serology-positive cases. Biopsy results confirmed a diagnosis of celiac disease in nine cases. The prevalence of biopsy- proven celiac disease was 1:111 (0.9%). CONCLUSIONS: Determination of anti-tissue transglutaminase antibodies by simple visual system for celiac disease appeared to be as reliable as the ELISA system. It is easy to perform and interpret, cost-effective, and rapid, as pointed out in other previous studies, as a screening test in large population-based studies. The prevalence of celiac disease in the overall sample of Turkish children (1:111 or 0.9%) in this preliminary study is similar to that reported in European and Middle Eastern countries and the United States.

Is there an association between familial Mediterranean fever and celiac disease?

Familial Mediterranean fever (FMF) and celiac disease (CD) shares some clinical features such as abdominal pain, diarrhea, arthralgia, and arthritis. Furthermore, both diseases are related to several inflammatory disorders. Based on these analogies, we have investigated whether there is any relationship between CD and FMF. The study had two groups. Group I: 50 children with FMF were questioned and examined for the evidence of CD, serum immunoglobulin A (IgA) levels, antigliadin antibodies (AGA) IgA, AGA IgG, and anti-endomysial antibodies (EMA) IgA were tested, and intestinal biopsy was performed when necessary. Group II: 17 children with CD were evaluated for the presence of clinical and laboratory features of FMF and mutation analysis for MEFV gene was performed to all of them. Six predominant mutations (p.M694V, p.M680I, p.M694I, p.V726A, p.K695R, p.E148Q) in the MEFV gene were studied. The results were as follows-group I: three patients had diarrhea, six had abdominal pain, one had positive AGA IgA, six had AGA IgG, and one had EMA IgA. Intestinal biopsy was performed in one patient who was normal, so none of the patients with FMF were diagnosed as CD and group II: none of the patients with CD had complaints consistent with FMF. Four of the 17 patients (23.5%) were found to carry MEFV mutations. Three of them had heterozygous p.E148Q mutation and one of them had heterozygous p.M680I mutation. None of the FMF patients had CD. MEFV mutation frequency in patients with CD was similar to the normal population in Turkey. Our study did not reveal any association between CD and FMF.

HLA types in Turkish children with celiac disease.

The aim of this study was to assess the distribution of human leukocyte antigen (HLA) groups in Turkish children with celiac disease (CD) and to investigate the association of HLA types and clinical manifestations of CD. Seventy-five children with CD were evaluated in two groups: Group I consisted of 45 classical celiac patients (15 males, 6.7+/-3.8 years); Group II consisted of 30 atypical celiac patients (9 males, 9.3+/-4.3 years). The control group consisted of 100 healthy renal transplantation donors. HLA typing was made serologically using standard lymphocytotoxicity techniques. HLA A29, B51, CW5, DR14, DR16, and DQ1 were the most common antigens in the control group. Frequency of HLA B13, CW7, B8, DR7, DR17 and DQ2 was higher in CD patients than in the control group (p<0.005, <0.05, <0.001, <0.001 and <0.001, respectively). The relative risks for HLA DQ2, B8, DR17 and B13 were 14.9, 13.6, 7.1 and 3.6, respectively. Frequency of HLA B35, DR11 and DQ7 was higher in classical CD than atypical CD, while a positive association was found between HLA B8 and atypical CD. A positive association was found between HLA B13, CW7 and DR17 in Turkish celiac patients in addition to HLA B8, DR7 and DQ2. This study also suggested that a correlation may exist between genotype and clinical manifestations.

Liver histology of children with chronic hepatitis treated with interferon-alpha alone or in combination with lamivudine.

AIM: To evaluate histological changes with interferon monotherapy or interferon plus lamivudine combination therapy in children with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. PATIENTS AND METHODS: 31 children aged 2-13 years were randomly treated with interferon (IFN) (group 1, n = 16) or IFN plus simultaneously started lamivudine (group 2, n = 15). IFN-alpha 2a was given 9 MU/m2 3 times per week for 6 months in each group; lamivudine was given 4 mg x kg(-1) x day(-1) for 24 months. Liver biopsy specimens were evaluated according to the Knodell score before therapy and after 24 months of therapy. Histological response was defined as a decrease in the histological activity index (HAI) score by at least 2 points. Efficacy of therapy was evaluated at 24 months of therapy in all children. RESULTS: Alanine aminotransferase normalization, HbeAg, and hepatitis B virus DNA clearance were not different. Complete response and histological response were 37.5%/62.5% and 40%/46.7% in groups 1 and 2, respectively (P = NS). At baseline and at 24 months of therapy, total HAI and components of HAI were not different in the 2 groups. In comparison with baseline, a significant decrease in scores of periportal +/- bridging necrosis was observed in group 1 (P = 0.01); periportal +/- bridging necrosis, intralobular degeneration, focal necrosis, and necroinflammation scores significantly decreased in group 2 (P = 0.04 and P = 0.02) at 24 months of therapy. CONCLUSIONS: The addition of lamivudine to IFN-alpha did not increase the effectiveness of the treatment in terms of complete and histological responses. Both therapies seemed to be effective in the regression of periportal +/- bridging necrosis. In addition, combination therapy was also effective in the regression of intralobular degeneration, focal necrosis, and necroinflammatory activity index.

The influence of interferon-alpha and combination interferon-alpha and lamivudine therapy on height and weight in children with chronic hepatitis B infection.

AIM: To evaluate the height and weight patterns of children with chronic hepatitis B (CHB) with and without treatment. METHODS: Thirty-four patients with immunoactive CHB randomly assigned to receive interferon-alpha2a (IFN) (5 mIU/m2, 6 months, group I) or IFN (same dose and duration) plus lamivudine (4 mg/kg/day, 24 months) (group II). Fifteen immunotolerant patients (group III) were followed without any treatment. Height (Ht-SDS), weight (Wt-SDS) and growth velocity (GV-SDS) standard deviation scores were monitored for a total of 36 months. RESULTS: Ht-SDS was significantly lower in group II than in group I one year after completion of IFN treatment (p < 0.05). Wt-SDS was significantly higher in group I than the other groups two years after completion of IFN treatment (p < 0.05). In groups I and II, the percentage of children showing abnormal GV-SDS decreased once treatment was completed (p < 0.05). CONCLUSION: CHB does not have deleterious effects on height and weight. Although IFN treatment temporarily compromises weight gain and growth velocity, lamivudine does not have any additional adverse effect.

The incidence and evolution of thyroid dysfunction during interferon-alpha therapy in children with chronic hepatitis B infection.

AIM: To assess the effect of interferon-alpha (IFN-alpha) therapy on thyroid functions in children with chronic hepatitis B infection (CHB). METHODS: Sixty-eight children (7.8 +/- 3.6 years) were treated with 5 (n = 37, group I) or 10 MU/m2 (n = 31, group II) IFN for 6 months. Thyroid hormones, thyrotropin, thyrotropin-releasing hormone stimulation test, thyroid peroxidase and thyroglobulin autoantibodies were evaluated. RESULTS: Baseline features were not different in the two groups. After therapy, thyroid dysfunction was 27% and 41.9% in groups I and II (n.s.). Subclinical hypothyroidism was 17.9%/ 29%, subclinical hyperthyroidism 5.4%/12.9%, hypothyroidism 2.7%/-, and thyroid antibody positivity 2.7%/- in groups I and II (n.s.). Thyroid dysfunction was 33.8% in the whole group (p = 0.001). Predictors of IFN induced-thyroid dysfunction were female sex and age < 6 years. Thyroid dysfunction resolved within median 6 months in all but three children. CONCLUSION: Although IFN-induced thyroid dysfunction is mostly subclinical and reversible, this side effect should be kept in mind.

Membranoproliferative glomerulonephritis in a patient with Wilson's disease.

Wilson's disease is an autosomal recessive disorder of hepatobiliary copper metabolism. Glomerular diseases can ensue during the course of Wilson's disease and membranous nephropathy is the eventual pathology in the majority of these cases. Membranoproliferative glomerulonephritis (MPGN) has rarely been reported in patients with Wilson's disease. Further, in this report, we present a patient with Wilson's disease who had developed MPGN during follow-up due to D-penicillamine therapy. This case is presented to draw attention to the rare association of Wilson's disease and MPGN and to discuss the possible underlying causes.

Inflammatory bowel disease in exclusively breast-fed infants.

Inflammatory bowel disease is uncommon in infants. We present the clinical, endoscopic and pathologic findings for two exclusively breast-fed infants with a diagnosis of inflammatory bowel disease. We emphasize that although inflammatory bowel disease is rare in infants, chronic bloody diarrhea must be a sufficiently alarming symptom to consider a differential diagnosis of inflammatory bowel disease in young infants is considered, even when they are exclusively breast-fed.