"Block-and-replace" treatment in Graves' disease: experience in a cohort of pediatric patients.

PURPOSE: The "block-and-replace" (BR) method involves the use of a high dose of antithyroid drugs (ATD) with levothyroxine (L-T4). Its use in the management of Graves' disease (GD) is still debated mainly because the frequency of side effects of ATD is dose dependent. We retrospectively studied the effect of medium dose of ATD with L-T4 versus monotherapy with ATD in pediatric patients with unstable GD. METHODS: 28 pediatric patients with GD with unstable response to ATD were treated with L-T4 and medium dose of ATD. We compared the rate of euthyroidism, hypothyroidism and hyperthyroidism episodes observed during treatment with methimazole alone with those observed during the BR approach. We evaluated the occurrence of side effects and the rate of remission in patients treated with ATD + L-T4 therapy and the efficacy of combination therapy to postpone a definitive treatment (radioiodine and thyroidectomy). RESULTS: Patients showed a better control of thyroid function during the BR therapy, presenting fewer episodes of hyperthyroidism and hypothyroidism. No serious side effects during the BR approach were observed. Only one patient went into remission with the ATD + L-T4 therapy. Fifteen patients required a definitive therapy (4 radioiodine, 11 thyroidectomy). The use of BR method has delayed radioiodine treatment for 4.9 years and surgery for 2.9 years. CONCLUSIONS: The BR method does not increase the remission rates. It may be useful to combine L-T4 with a medium dose of methimazole when GD is difficult to manage with methimazole alone. It may represent a therapeutic option to postpone definitive treatments to a suitable age.

Celiac disease and bone health: just gluten free diet?

Not available.

[Acute liver failure due to human herpesvirus 6 in an infant]. / Insufficienza epatica acuta da Human Herpesvirus 6 in un lattante.

We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

[Celiac disease and "gluten sensitivity"]. / Malattia celiaca e "gluten sensitivity".

It is known that celiac disease is characterized by a huge variety of clinical forms ranging from classical ones to silent forms, potential ones and to an increased number of cases of gluten-sensitivity. The latter is an abnormal non-allergic sensibility to gluten. Clinical manifestations can be very different without a severe intestinal damage (Marsh/Oberhuber 0-I) and this condition seems to benefit from a gluten free diet. Cases of gluten-sensitivity appear very interesting in the search of histological markers with elevated specificity, which are able to identify slight and early gluten dependent enteropathy, especially in at risk patients for celiac disease even before classical autoantibodies appear: for instance, this is the case of intraepithelial lymphocytes T-cell receptor gamma delta and mucosal deposits of class IgA anti transglutaminase antibodies. Other studies are investigating transglutaminase isoenzimes (different from tissue one), that can be identified in patients with gluten dependent symptoms without classical autoantibodies. Forms of gluten allergy have a different pathogenesis from celiac disease and are represented by "backer's asthma" or by classical allergy to wheat proteins. Clinical manifestations can vary from anaphylactic reactions to dermatological, respiratory and intestinal symptoms. Also in these cases the therapeutic approach is based on gluten free diet.

Respiratory disorders and hospitalization rates during the second RSV season in preterm infants who received palivizumab prophylaxis during their first RSV season.

This prospective study evaluated the frequency and severity of respiratory symptoms during the second respiratory syncytial virus (RSV) season in an italian cohort of preterm infants (< or = 35 weeks) who had received palivizumab prophylaxis in their first year of life (October 2004-April 2005) and who had not previously been hospitalized for RSV-induced lower respiratory tract infection (LRTI). infants were evaluated at enrolment (May-September 2005), in October/November 2005 and in April 2006. The occurrence of any respiratory episode, the rate of hospitalization for respiratory-related LRTI, total length of stay in hospital, physician-documented recurrent wheezing (>or = 3 physician-documented episodes of wheezing) and use of airway medication/antibiotics were recorded during follow-up. All infants had prior palivizumab prophylaxis during their first RSV season. In the total evaluable population (n=260), 32.3% of infants experienced at least one respiratory episode, 3.8% required short hospitalization because of LRTI, 8.5% had physician-documented recurrent wheezing, and 48.8% required airway medications/antibiotics during follow-up. in this study the rate of airway morbidity, hospitalization and physician-documented recurrent wheezing during the second RSV season was low among preterm infants who had received prior palivizumab prophylaxis.

Optical coherence tomography in pediatric patients: a feasible technique for diagnosing celiac disease in children with villous atrophy.

BACKGROUND AND AIM: Celiac disease is a common condition with many atypical manifestations, where histology serves as the "gold standard" for diagnosis. A useful new technique, optical coherence tomography, can depict villous morphology in detail, using light waves. This study examined the correlation between the sensitivity and specificity of optical coherence tomography in pediatric patients undergoing esophago-gastro-duodenoscopy for the diagnosis of celiac disease. MATERIALS AND METHODS: A total of 134 children were prospectively enrolled, 67 with a serological suspicion of celiac disease (group 1) and 67 with negative histology for celiac disease (group 2). During a diagnostic esophago-gastro-duodenoscopy we acquired multiple images and films in the four quadrants of the second part of the duodenum, and biopsies were taken in the area where optical coherence tomography had been done. Three patterns of villous morphology were considered: pattern 1=no atrophy (types 0, 1 or 2 of the Marsh classification); pattern 2=mild atrophy (type 3a or 3b); pattern 3=marked atrophy (type 3c). RESULTS: The diagnosis of celiac disease was histologically confirmed in all 67 children with positive antiendomysium and/or antitransglutaminase antibodies. Optical coherence tomography correlated with pattern 1 histology in 11/11 cases, pattern 2 in 30/32 (93.8%) and pattern 3 in 22/24 (91.6%). Sensitivity and specificity were 82% and 100%. In the control group there was 100% concordance between optical coherence tomography and histology. The overall concordance between optical coherence tomography and histology in determining patchy lesions was 75%. CONCLUSION: Optical coherence tomography could be a helpful diagnostic tool in children with mild or marked villous atrophy for diagnosing celiac disease during upper gastrointestinal (GI) endoscopy, avoiding biopsies. However, duodenal biopsies are mandatory if the optical coherence tomography shows normal villous morphology in patients with positive antibodies.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Antibodies to recombinant human tissue-transglutaminase in coeliac disease: diagnostic effectiveness and decline pattern after gluten-free diet.

BACKGROUND/AIMS: To assess the sensitivity and specificity of IgA and IgG tissue-transglutaminase antibodies assay, the pattern of antibody decline after gluten withdrawal and their modifications with reference to dietary compliance. SUBJECTS: We studied sera from 143 untreated coeliac children and adolescents (8.8+/-6.1 years), 212 sera from 97 of those patients after gluten withdrawal, and 64 control subjects with non-coeliac intestinal disorders (6.8+/-4.8 years). METHODS: Samples were tested for IgA and IgG class tissue-transglutaminase antibodies by radiobinding assay, using human-derived tissue-transglutaminase, and for IgA anti-endomysium antibodies by indirect immunofluorescence on monkey oesophagus. RESULTS: Untreated coeliac patients had significantly higher titres of IgA and IgG tissue-transglutaminase antibodies than controls (p<0.00001); the diagnostic sensitivity was 95.8% and 99.3%, respectively, and the specificity was 95.3%. Three patients with selective IgA deficiency were positive for IgG tissue-transglutaminase antibodies. The concordance rate between IgA tissue-transglutaminase antibodies and anti-endomysium antibodies was 98.1%. Patients on gluten-free diet showed a significant decrease in IgA and IgG tissue-transglutaminase antibodies with respect to untreated patients (p<0.0001). Tissue-transglutaminase was more sensible than anti-endomysium antibodies to detect small amounts of gluten intake when the compliance was poor. CONCLUSIONS: The recombinant human tissue-transglutaminase antibodies assay is a highly sensitive and specific test for diagnosis of coeliac disease, and it is useful in monitoring the compliance to gluten-free diet.

A prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease.

OBJECTIVE: Because osteopenia is a frequent complication of celiac disease, we evaluated the impact of a long-term gluten-free diet (GFD), initiated during childhood, on bone density. study design: Patients with celiac disease (n = 19; mean age, 14.2 +/- 2.6 years) were studied after 4.3 +/- 0.6 years of GFD. Bone density had been measured at diagnosis and after 1 year of GFD. We also studied 211 healthy children as a control group. Bone mineral density was measured by dual-energy x-ray absorptiometry. Intact parathyroid hormone (PTH) and bone-specific alkaline phosphatase (BALP) levels were measured in serum, and N-terminal telopeptide of type I collagen (NTx) was measured in urine. RESULTS: Although at diagnosis bone mineral content, bone area, and bone mineral density were significantly lower than in control subjects, the 3 measurements were normal after GFD. None of the patients on a GFD showed elevated values of PTH. Patients on a GFD had BALP (110.2 +/- 67.2 U/L) and NTx levels (261.9 +/- 187.8 nmol bone collagen equivalents/mmol creatinine) that were significantly higher than those of control subjects. The levels of BALP and NTx were significantly higher in patients with good compliance with the GFD, compared with patients with poorer compliance. CONCLUSIONS: This study shows that bone mineral content, bone area, and bone mineral density improve significantly with a GFD.

Macroamylasemia attributable to gluten-related amylase autoantibodies: a case report.

BACKGROUND: Macroamylasemia (MA) is a benign condition caused by circulating macroamylase complexes of pancreatic or salivary amylase bound to plasma proteins, which cannot be cleared by the renal glomeruli. In most cases, the macromolecular amylase represents a complex of normal amylase and either immunoglobulin A or G and may be a specific antigen-antibody complex. Celiac disease (CD) is a permanent intolerance to ingested gluten that results in immunologically mediated inflammatory damage of the small intestinal mucosa. Several recent population-based serologic surveys have shown CD to be a common disorder, possibly affecting 1 in 200 to 250 individuals in most countries studied, including the United States, where overt CD is rare, indicating a high proportion of subclinical disease. The diagnosis of CD currently rests on the histological demonstration of the characteristic lesion in the small intestine and the subsequent clinical response to the introduction of a gluten-free diet. MA associated with CD has been described in adult patients, and in a few cases, MA decreased or resolved after a strict gluten-free diet. A few single cases of MA have been described in childhood, but no association with CD has been reported so far. We report a girl with CD, autoimmune thyroiditis, and MA, in whom CD-related antibodies to amylase and to exocrine pancreas tissue resolved with a gluten-free diet. CASE REPORT: An 11-year-old girl was referred for chronic abdominal pain and growth retardation associated with persistent hyperamylasemia and suspected chronic pancreatitis. We confirmed elevated serum amylase, normal serum lipase, and very low 24-hour urine amylase and amylase clearance/creatinine clearance ratio, consistent with MA. Serologic tests for CD were positive, and the diagnosis was confirmed by small bowel biopsy showing subtotal villous atrophy. Thyroid function tests showed a pronounced hypothyroidism, associated with high titers of thyroid microsomal and thyroglobulin antibodies. Screening for other autoantibodies-including antinuclear, islet cell, glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen 512, adrenal gland, and cytoplasmic neutrophil granulocyte antibodies-was negative. A diagnosis of CD, MA, and hypothyroidism attributable to autoimmune thyroiditis was made. A gluten-free diet and oral replacement with L-thyroxine was started with clinical improvement. Serum amylase and amylase clearance/creatinine clearance ratio normalized, consistent with resolution of MA. STUDY DESIGN AND METHODS: The patient's serum samples were obtained at the time of CD diagnosis and at 3 and 12 months after instituting a gluten-free diet. Serum samples from 10 consecutive untreated celiac children were disease controls, and 39 participants with no gastrointestinal symptoms and no family history of CD served as healthy controls. The origin of MA as determined by complexes of amylase with circulating immunoglobulins was tested by the measurement of amylase on supernatants after precipitation of immune complexes with either protein A Sepharose or polyethylene glycol. The precipitation of >60% of amylase activity was consistent with the presence of MA. Immunoglobulin G (IgG) and immunoglobulin A (IgA) circulating autoantibodies to amylase were measured using recently developed enzyme-linked immunosorbent assay (ELISA), using porcine amylase as antigen. Results were expressed as arbitrary units (AUs). Statistical analysis was performed by Student's t test for unpaired data. IgA and IgG antibodies to exocrine pancreas tissue were detected by indirect immunofluorescence on human pancreas cryosections. RESULTS: Serum immunoprecipitation with either protein A Sepharose or polyethylene glycol reduced amylase activity from 1698 to 89 U/L (94.8%) and to 75 U/L (95.6%), with only marginal reduction in control serum samples. The ELISA for autoantibodies to amylase detected high values, both IgA (3531 AU) and IgG (1855 AU), in the serum sample from the patient at CD diagnosis. IgA autoantibodies (mean +/- standard deviation) were 3.4 +/- 2.5 AU in healthy controls, and 2.1 +/- 1.2 AU in celiac controls; IgG autoantibodies were 10 +/- 4.8 AU in healthy controls and 8.5 +/- 3.2 AU, respectively. Autoantibodies to exocrine pancreas tissue were documented in patient sera at the time of CD diagnosis, both IgA and IgG, but not in control groups. Preincubation of patient's serum with excess of alpha-amylase specifically inhibited antibody binding to coated amylase in the ELISA, and partially inhibited immunoreactivity to exocrine pancreas. Autoantibodies to alpha-amylase and to exocrine pancreas declined in CD patients after institution of a gluten-free diet. CONCLUSIONS: Few cases of MA have been described in children, and in all amylase determination was part of the clinical investigation for abdominal pain or trauma. (ABSTRACT TRUNCATED)

Body composition in children with celiac disease and the effects of a gluten-free diet: a prospective case-control study.

BACKGROUND: Celiac disease is the most common cause of malnutrition in children of Western countries. OBJECTIVE: The objective was to measure body composition in children at the time celiac disease was diagnosed and after consumption of a gluten-free diet (GFD). DESIGN: We assessed body composition by dual-energy X-ray absorptiometry in 29 children and adolescents with a mean (+/-SD) age of 9.5 +/- 3.4 y at the time celiac disease was diagnosed and in a subset of 20 patients after 1.2 +/- 0.2 y of a GFD. We also studied 23 patients aged 21.2 +/- 4.6 y who consumed a GFD for 10.6 +/- 4.5 y. Each patient was matched with a healthy control subject of the same age and sex. RESULTS: Untreated patients weighed less than control subjects (P = 0.04). Fat mass and bone mineral content were lower in the patients than in the control subjects (P < 0.01), as was lean mass of the limbs (P = 0.0013). After approximately 1 y of the GFD, there were no significant differences in body-composition values between patients and control subjects. Similarly, body-composition values of celiac disease patients who consumed the GFD long term were comparable with those of healthy subjects. CONCLUSIONS: Remarkable abnormalities in body composition were found in children at the time of diagnosis of celiac disease. Appropriate dietary treatment reverses body-composition abnormalities quickly and the beneficial effects of gluten withdrawal are persistent. Because these results are harder to achieve if celiac disease is first diagnosed in adulthood, efforts to encourage early diagnosis of celiac disease should be made.

Severe and protracted diarrhea: results of the 3-year SIGEP multicenter survey. Working Group of the Italian Society of Pediatric Gastroenterology and Hepatology (SIGEP).

BACKGROUND: The spectrum of severe and protracted diarrhea (SPD), previously defined as intractable diarrhea, has changed during the past several decades. Despite recent advances in determining the cause of SPD and in treatment, this syndrome still represents a challenge and is becoming a major problem affecting health care resources. This study was conducted to characterize the epidemiology, spectrum of causes, and the outcome of SPD in Italy in recent years. METHODS: All the SPD cases seen at the major centers of pediatric gastroenterology in Italy during a 3-year period (1993-1996) were recruited in this multicenter, prospective survey. RESULTS: Thirty-two children (26 boys and 6 girls; median age at the onset of SPD, 40 days) were enrolled in this study by 9 of 26 participating centers. Twelve were newly diagnosed cases, with an estimated SPD incidence rate in Italy of 0.64 to 0.92 x 10(-5) infants per year. The most common causes were autoimmune enteropathy (n = 8) and ultrastructural abnormalities of the enterocyte (n = 7), whereas food intolerance and postenteritis syndrome were less frequent (3 and 2 cases, respectively). Two children with autoimmune enteropathy fulfilled the criteria for the X-linked variant of this condition. At the end of the study period, 9 of 31 patients had recovered, 15 still had diarrhea, and 7 had died. CONCLUSIONS: Severe and protracted diarrhea is a rare but challenging problem in Italy. Because parenteral nutrition or intestinal transplantation are the only options in a subset of cases (e.g., ultrastructural abnormalities of the enterocyte), infants with SPD should be referred to specialized centers where advanced diagnostic and therapeutic facilities are available.

Comparison of tissue transglutaminase-specific antibody assays with established antibody measurements for coeliac disease.

Tissue transglutaminase C has recently been identified as one of the auto-antigens of endomysial antibodies found in coeliac disease. In this study we have cloned the human autoantigen and developed immunoassays measuring antibodies to transglutaminase in order to compare their diagnostic performance to that of established markers of the disease. A radiobinding assay using in vitro transcribed and translated 35S-methionine-labelled transglutaminase detected IgG antibodies in 110 and IgA antibodies in 109 of 112 patients at diagnosis of coeliac disease and in three and four of 92 control subjects, respectively. A radiobinding assay measuring both IgG and IgA transglutaminase antibodies identified 111 (99.1%) of the patients and 4 (4.3%) control subjects. Concordance of this assay with the IgA endomysial antibody test was found in 108 patients and 89 control subjects: two patients who had IgA deficiency and a third patient without IgA deficiency were only detected in the radiobinding assay; one patient had weak IgA endomysial antibodies only, and three of the control subjects with weak transglutaminase antibodies by radiobinding assay were undetectable in the IgA endomysial antibody assay. IgA and IgG ELISA using guinea pig transglutaminase and commercial ELISA measuring anti-gliadin antibodies had lower sensitivity and specificity than the radiobinding assays or the IgA endomysial antibody assay. This study confirms tissue transglutaminase C as a major autoantigen in coeliac disease and describes novel radiobinding assays for large scale testing to identify cases of coeliac disease.

Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients.

OBJECTIVES: Osteoporosis and alterations of bone metabolism are frequent complications of celiac disease. We evaluated the impact of long-term gluten-free diet (GFD) initiated during childhood and adolescence on bone mineralization and bone metabolism. METHODS: We studied 30 celiac patients on GFD for > or = 5 yr. The mean age at diagnosis was 11.4+/-5.0 yr, and the mean duration of GFD was 10.7+/-4.3 yr. Results were compared with those obtained in 240 healthy controls. Bone mineral density (BMD) was measured in the lumbar spine and in the whole skeleton by dual-energy x-ray absorptiometry. Serum levels of bone-specific alkaline phosphatase (BALP) and N-terminal propeptide of type I procollagen (PINP) were measured as bone formation indices, and urine levels of N-telopeptide of type I collagen (NTx) as bone resorption index. RESULTS: BMD measurements of celiac patients (lumbar spine: 1.131+/-0.121 g/cm2; total body: 1.145+/-0.184 g/cm2) did not differ from those of control subjects (lumbar spine: 1.131+/-0.184 g/cm2; total body: 1.159+/-0.118 g/cm2). The levels of BALP, PINP, and NTx of celiac patients did not differ from those of controls. Patients who started GFD before puberty had BMD and bone metabolism measurements comparable to those of patients who started GFD during puberty. CONCLUSIONS: Our data show that long-term dietary treatment ensures normal mineralization and bone turnover.

Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease.

Osteoporosis is a common finding in adult celiac disease patients; however, there are still few data regarding children and adolescents. In the present study we measured the bone mineral density (BMD) in children and adolescents at diagnosis of celiac disease and after approximately 1 y of a gluten-free diet. BMD was measured at the lumbar spine and in the whole skeleton by dual-energy X-ray absorptiometry in 44 celiac disease patients aged 2.58-20.42 y at diagnosis. BMD was also measured in a subset of 25 patients after 1.4 +/- 0.04 y of a gluten-free diet. BMD was compared with that of 177 healthy control subjects aged 1.52-20.99 y. Lumbar spine and whole-body BMD values at diagnosis of celiac disease were significantly lower than in control subjects (P = 0.015 and P = 0.0001, respectively) after differences in age and anthropomorphic variables were controlled for. The subjects studied after the gluten-free diet had BMD values not significantly different from those of control subjects. In conclusion, children and adolescents with celiac disease have remarkably reduced lumbar spine and whole-body bone density. A gluten-free diet promotes a rapid increase of BMD that leads to a complete recovery of bone mineralization. These results emphasize the need for an early diagnosis and treatment in patients with celiac disease to obtain an adequate peak bone mass at the end of puberty.

Effect of gluten-free diet on bone mineral content in growing patients with celiac disease.

Osteoporosis is a complication of celiac disease in adulthood, but little is known about the influence of the disease on bone mineralization in children. In the present study we evaluated radial bone mineral content (BMC) in celiac children and adolescents at diagnosis and after they consumed a gluten-free diet (GFD). The BMC values of 33 celiac patients at diagnosis were significantly lower than those of 255 control subjects (P < 0.001). There was no difference between diabetic and non-diabetic celiac patients. In 14 patients the BMC increased significantly (P < 0.05, ANCOVA) after 1.28 y of GFD. In these patients the mean annual BMC increment was 0.07 g/cm, significantly greater (P < 0.05) than the increment of normal growing children (0.05 g.cm-1.y-1). Our data indicate that although osteoporosis complicates celiac disease during childhood and adolescence, GFD alone is able to remarkably improve bone mineralization.

Screening of diabetic children for coeliac disease with antigliadin antibodies and HLA typing.

IgA and IgG antigliadin antibodies were measured in 498 patients with insulin dependent diabetes mellitus and no history of intestinal malabsorption. Thirty patients had abnormal concentrations of antigliadin antibodies; 22 of these had an intestinal biopsy carried out and 16 of the 22 had subtotal villous atrophy suggestive of coeliac disease (prevalence 3.2%). There were no significant differences between patients with coeliac disease and diabetes and diabetic patients with normal IgA antigliadin antibodies in any of the nutritional variables measured, duration of diabetes, and mean insulin requirement. The mean age of onset of diabetes and attainment of expected height for age were both significantly lower in the patients with both diseases. Typing HLA classes I and II was done in 242 patients. The incidence of HLA-B8, DR3, and DQW2, which are commonly associated with both the diseases, is increased when both are present.