STUDY OBJECTIVE: To estimate the incidence rate of newly diagnosed cases of coeliac disease in Italy. DESIGN: This was a descriptive study of coeliac disease incidence in the period 1990-91. SETTING: During 1990-91 newly diagnosed cases of coeliac disease were signalled by several sources including diagnostic records of departments of paediatrics, general medicine and gastroenterology, national health service records for the supply of gluten free diets and the archives of the Italian Coeliac Society. PATIENTS: Altogether 1475 cases were flagged throughout Italy, 478 of whom were selected, corresponding to 270 individual patients from a target population resident in four areas: Provices of Turin and Cuneo (Piedmont Region, northern Italy); Province of Brescia (Lombardia Region, northern Italy); Umbria Region (central Italy) and Sardinia Region (insular Italy). Only for these areas were patients flagged from several sources and the reference population was identifiable. MAIN RESULTS: The overall crude incidence rates for all ages per 100,000 residents per year were 2.4, 2.7, 1.5, and 1.7 in the four areas, respectively. The childhood cumulative incidence rates (aged < or = 15 years) per 100,000 live births were 143, 141, 72, and 80 respectively. The mean ages at diagnosis were similar for both childhood and adult cases throughout the areas--these were around 4 and 34 years respectively. For each area, the incidence rate was constantly higher in the main city than elsewhere. Using the capture-recapture method, an estimated completeness of case archives of 0.84 was obtained, whereas this figure was only 0.47 for hospital sources. CONCLUSIONS: This population based study on the incidence of coeliac disease shows that several information sources should be used to avoid underestimation. The incidence rate of coeliac disease in Italy was among the highest in Europe, and was widely variable showing highest figures in Piedmont and Lombardia and the lowest in Umbria and Sardinia. This trend was not due to different age at diagnosis, which suggests variable diagnostic awareness of the disease rather than different environmental patterns affecting the clinical presentation.
Evidence suggests that many coeliac disease patients suffer from persistent clinical symptoms and reduced health-related quality of life despite a strict gluten-free diet. We aimed to find predictors for these continuous health concerns in long-term treated adult coeliac patients.
In a nationwide study, 596 patients filled validated Gastrointestinal Symptom Rating Scale and Psychological General Well-Being questionnaires and were interviewed regarding demographic data, clinical presentation and treatment of coeliac disease, time and place of diagnosis and presence of coeliac disease-associated or other co-morbidities. Dietary adherence was assessed by a combination of self-reported adherence and serological tests. Odds ratios and 95% confidence intervals were calculated by binary logistic regression.
Diagnosis at working age, long duration and severity of symptoms before diagnosis and presence of thyroidal disease, non-coeliac food intolerance or gastrointestinal co-morbidity increased the risk of persistent symptoms. Patients with extraintestinal presentation at diagnosis had fewer current symptoms than subjects with gastrointestinal manifestations. Impaired quality of life was seen in patients with long duration of symptoms before diagnosis and in those with psychiatric, neurologic or gastrointestinal co-morbidities. Patients with persistent symptoms were more likely to have reduced quality of life.
There were a variety of factors predisposing to increased symptoms and impaired quality of life in coeliac disease. Based on our results, early diagnosis of the condition and consideration of co-morbidities may help in resolving long-lasting health problems in coeliac disease.
Coeliac disease; Symptoms; Quality of life; Gluten-free diet; Adults
Primary hyperparathyroidism may present with non‐specific symptoms, and this may be one reason why patients with coeliac disease fail to improve despite compliance with a gluten‐free diet. Seven case reports of primary hyperparathyroidism due to sporadic adenoma occurring in a series of 310 patients with coeliac disease are presented, highlighting the importance of looking for this condition in this population group. A prevalence of primary hyperparathyroidism of 2.3% in this series suggests a significant association between hyperparathyroidism and coeliac disease; most studies have indicated a prevalence of 3 in 1000 in the general population, although one study found that it may be as high as 21 in 1000 in women aged 55–75 years. The average age of patients in our series was 59 years and all but one were women. Further studies are needed to establish a possible association between primary hyperparathyroidism and coeliac disease.
primary hyperparathyroidism; coeliac disease; autoimmune disease
BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.
A significant proportion of patients with coeliac disease are ‘nonresponsive’ to gluten withdrawal. Most cases of nonresponsive coeliac disease are due to persisting gluten ingestion. Refractory coeliac disease (RCD) is currently defined by persistent symptoms and signs of malabsorption after gluten exclusion for 12 months with ongoing intestinal villous atrophy. Primary (without initial response to diet) and secondary (relapse following response to diet) RCD is recognized. RCD is further classified as type I or type II based on the absence or presence of a population of aberrant intestinal lymphocytes. Quality of dietetic advice and support is fundamental, and lack of objective corroboration of gluten exclusion may result in over-identification of RCD I, particularly in those cases with persisting antibody responses. Over-reliance on lymphocyte clonality similarly may result in over-diagnosis of RCD II which requires careful quantification of aberrant lymphocyte populations. Management of RCD should be undertaken in specialist centres. It requires initial intensive dietary supervision, strict gluten exclusion and subsequent re-evaluation. There is currently insufficient evidence to recommend specific treatments. Steroids are often used in both RCD I and II (albeit with little objective evidence of benefit in RCD II), and azathioprine as steroid-sparing therapy in RCD I. There is growing evidence for the use of cladribine in RCD II with autologous stem cell transplantation in nonresponders, but this requires further multicentre evaluation. There remains considerable controversy regarding the diagnosis, treatment and surveillance of RCD: international consensus in these areas is urgently required to facilitate future therapeutic advances.
coeliac disease; diet; gluten; management
Previous retrospective studies of intestinal mucosal mast cells in coeliac disease have given divergent results, and we have recently reported that inappropriate methodology could account for these discrepancies. In this prospective study, mucosal mast cell counts were performed in Carnoy fixed, peroral jejunal biopsy specimens from patients with coeliac disease, both untreated and treated with a gluten-free diet; and from controls (mainly irritable bowel syndrome). Mean mucosal mast cell count in 27 control subjects was 146/mm2, SD 29. Significantly higher values were obtained in untreated coeliac disease (mean 243, SD 41, p less than 0.001) returning to the normal range in coeliacs treated with a gluten-free diet with normal jejunal biopsy morphology. In seven patients mucosal mast cell counts were performed in multiple jejunal biopsies, and these showed that mucosal mast cell distribution was not patchy. There was no evidence of degranulation of intestinal mucosal mast cells under the conditions of routine biopsy (overnight fast). An increase in mucosal mast cells in untreated coeliac disease may be one explanation for the high number of IgE positive stained cells in the intestinal mucosa that has been reported by some authors.
AIMS: To determine the frequency of abnormal pancreolauryl tests in untreated and treated adults with coeliac disease and to see whether abnormalities in treated coeliac patients correlate with the degree of recovery of intestinal morphology or brush border enzyme activity. METHODS: Pancreolauryl tests were performed in a study population of 57 adult coeliac patients (25 on gluten containing diets and 32 on gluten free diets), 59 symptomatic controls, and eight patients with pancreatic disease. Brush border enzyme activity and morphological assessment were performed on small intestinal biopsies in 27 of the treated coeliac patients. RESULTS: Forty per cent of untreated coeliac patients and 18% of treated coeliac patients had abnormal tests. In treated coeliac patients, no significant correlation was detected between the pancreolauryl test result and either brush border enzyme activity or morphological parameters. CONCLUSION: Abnormal pancreolauryl test results are common in untreated and treated adult coeliac disease patients. Abnormalities in treated coeliac patients do not correlate with the degree of recovery of small intestinal morphology or brush border enzymes.
By accurate morphometry the length of the rough endoplasmic reticulum (RER) was estimated in electron micrographs of a population of jejunal plasma cells in biopsies obtained from normal volunteers, untreated coeliac disease patients, and coeliac disease patients treated for one year on a gluten free diet. Increase in length or hypertrophy of the endoplasmic reticulum is an indication of increased protein synthesis of the cell (Ghadially, 1977). An increase compared with normal length was demonstrated in the mean length of the plasma cell rough endoplasmic reticulum in plasma cells obtained from both groups of coeliac patients. This estimate of increased protein production--in this case immunoglobulin--indicates an increase in the immunological activity of plasma cells even after treatment and suggests not only a reaction to dietary gluten but probably to other antigens also.
A small fraction of coeliac disease (CD) patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD) patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII). Pathogenesis of active CD (ACD) has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of the TH2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05). In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02). IL-13 secretion correlated with other TH2 as well as TH1 cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.
BACKGROUND—Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are markedly increased in coeliac mucosa, and are thought to play a crucial role in the generation of villous atrophy in coeliac disease (CD). However, the mechanisms by which they mediate the killing of enterocytes in this condition are still poorly characterised.
AIM—We investigated Fas mediated cytotoxicity and apoptosis of both LPLs and IELs, isolated from 10 untreated coeliac patients, 10 coeliac patients on a gluten free diet, and 10 biopsied controls.
METHODS—Fas and Fas ligand expression were assessed by flow cytometry and immunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat cells was determined by the Jam test. The effect of the antagonist ZB4 anti-Fas antibody on apoptotic activity exerted by coeliac lymphocytes against enterocytes was analysed. Lymphocyte apoptosis was assessed by oligonucleosome ELISA.
RESULTS—LPLs and IELs showed increased apoptotic activity and higher levels of Fas ligand expression in untreated CD compared with treated CD patients and controls. Enterocyte apoptosis observed after coculturing coeliac lymphocytes and enterocytes in the presence of ZB4 antibody was reduced. In active CD, LPLs manifested increased apoptosis whereas IELs showed decreased apoptosis.
CONCLUSIONS—Our results support the involvement of the Fas/Fas ligand system in CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to downregulate mucosal inflammation whereas decreased IEL apoptosis could be responsible for autoimmune and malignant complications of CD.
Keywords: apoptosis; coeliac disease; cytotoxicity assay; Fas/Fas ligand system; intraepithelial lymphocytes; lamina propria lymphocytes
Background—Selective immunoglobulin A (IgA)
deficiency (SIgAD) is associated with coeliac disease (CD).
Aim—To make a retrospective study of the
association of SIgAD with CD in Italy.
Methods—Hospital medical records of 2098 patients
consecutively diagnosed as having CD were reviewed.
Results—Of 2098 patients with CD, 54 (2.6%) had
SIgAD, representing a 10-16-fold increase over that in the population
in general. This increase was not influenced by age or geographical
factors. Patients with SIgAD had a higher incidence of silent forms
(7/54, 13%), recurrent infections (16/54, 29.6%), and atopic diseases (7/54, 13%) than those without. The association with autoimmune and
malignant diseases and the outcome after eating a gluten free diet were
similar in patients with or without SIgAD. In all patients with SIgAD,
antibodies for IgA gliadin and endomysium were absent, but serum levels
of IgG anti-gliadin antibodies were high in almost all of them (51/54).
Conclusions—Serum IgA should be measured in order
to be able to interpret negative results for IgA anti-gliadin
antibodies and anti-endomysial antibodies in patients being screened
for CD. Since some patients with CD and SIgAD may be negative for IgG
anti-gliadin antibodies, an intestinal biopsy should be performed in
all suspected cases.
coeliac disease; IgA deficiency
A migration inhibition test was used to assess sensitisation of blood leucocytes, and thus cell-mediated immunity, to gluten fraction III in controls and patients with coeliac disease. Migration indices were significantly less (indicating sensitisation) in untreated and in treated patients than in controls, and significantly less in treated patients than in untreated patients. At a concentration of 1 mg/ml gluten fraction III, 13% of untreated patients and 54% of treated patients had migration indices in the sensitised range. At 2 mg/ml gluten fraction III, sensitisation was demonstrated in 8% of untreated patients and 48% of treated patients. After starting a gluten free diet, migration indices fell into the sensitised range in all patients followed. After at least nine months on a gluten free diet, migration indices were significantly higher in those patients with a normal interepithelial lymphocyte count than in those patients with a raised interepithelial lymphocyte count. Cell-mediated immunity to gluten fraction III can be detected in the peripheral blood of certain patients with coeliac disease. Detectable sensitivity is related to the time on a gluten free diet, and the interepithelial lymphocyte count.
To assess the incidence and effects of continuing gluten ingestion in coeliac disease 51 adult coeliac patients were studied after four to 132 (mean 63) months on a prescribed gluten-free diet. Each patient completed a prospective dietary questionnaire, underwent a repeat jejunal biopsy, and gave serum for gluten antibody estimation. Altogether 65% of patients were still ingesting gluten, often inadvertently. Direct questioning on dietary habits had failed to uncover most of this consumption. The gluten antibody test proved a useful screening test for detecting continuing gluten ingestion and patients with both persistent subtotal villous atrophy and gluten antibodies were almost certain to be taking large amounts ( more than 2 g/day). The presence of persistent partial villous atrophy was found, however, to be an unreliable guide to gluten intake.
To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.
Villous atrophy, changes in the surface epithelium, mucosal thickening, and glandular hypertrophy were a feature of all the mucosal biopsies from the small intestine obtained from eight coeliac children. No histological differences were observed between the children previously treated with intermittent gluten-free diets and the untreated children. Serial biopsy studies were carried out on one coeliac child before and after treatment with a gluten-free diet over a period of two years. On the whole they confirmed the irreversible nature of the observed histopathological changes but minor improvements could not be excluded. Mucosal abnormalities in coeliac disease are the same as in adult idiopathic steatorrhoea, where they are observed in patients with or without a response to a gluten-free diet. It is concluded that the elimination of gluten from the diet has little if any influence on the histopathological abnormalities observed in coeliac disease.
Monoclonal antibodies were used to determine the relative numbers of T lymphocyte subsets in 61 jejunal biopsies and in peripheral blood of 35 children with coeliac disease, and of 13 healthy controls. The T cell numbers in the lamina propria were unaffected by a change from gluten-free to gluten containing diet in the patients. The number of intraepithelial lymphocytes (where the CD8 cells predominated) were significantly raised in patients taking gluten. Ten to 20% of the patients' intraepithelial CD3 (mature T) cells expressed neither CD8 nor CD4 surface antigens. This CD4 8 T cell population persisted through gluten elimination and challenge. The circulating lymphocyte subsets showed little variation with the diet although there was a marked increase in the proportion (14.9%) of CD4 8 T cells in patients during gluten elimination. In the histologically normal jejunal mucosa from control subjects, the age of the subject showed a positive correlation with villus intraepithelial CD3+ and CD8+ cells, and crypt intraepithelial CD4+ cells. No clear cut effect of age was observed on lamina propria lymphocyte counts of the controls, or on the lymphocyte counts in jejunal mucosa of the coeliac patients. The observed CD3+4-8- lymphocytes may represent activated cells unable to present their surface antigens, or they may be gamma delta-receptor bearing T cells, which could have a significant role in the pathogenesis of coeliac disease.
Thirty-five children, in whom coeliac disease had been diagnosed on inadequate grounds and who had been on a gluten-free diet for one to 10 years, were challenged with gluten in accordance with a standardised procedure. All children were admitted to hospital for 48 hours for general assessment, two one-hour blood xylose tests, and the introduction of gluten. Thirty children underwent a pre-challenge peroral jejunal mucosal biopsy; the specimens were either normal or showed slight non-specific abnormalities. Gluten powder 20 g/day was given in addition to an otherwise gluten-free diet. The children were reassessed as outpatients every two weeks, when a one-hour blood xylose test was performed. Repeat biopsy was performed when xylose absorption fell or after three months. Seventeen children had abnormal post-challenge biopsy appearances compatible with coeliac disease in relapse; 14 of these children completed their challenge within eight weeks. Seventeen children had completely normal biopsy appearances at the end of three months and were returned to a normal diet. One to two years later eight underwent repeat biopsies, which showed nothing abnormal. In only one child, the oldest in the series, were the histological findings equivocal. In the 17 children in whom coeliac disease was confirmed the duration of gluten challenge was not related to age, duration of gluten-free diet, histological findings on the pre-challenge biopsy, or HLA status.
BACKGROUND—Up to 50% of women with untreated coeliac disease experience miscarriage or an unfavourable outcome of pregnancy. In most cases, after 6-12 months of a gluten free diet, no excess of unfavourable outcome of pregnancy is observed. The prevalence of undiagnosed coeliac disease among pregnant women is not known.
AIM—To determine the prevalence of untreated coeliac disease among women attending the obstetrics-gynaecological department.
METHODS—Endomysial antibodies, which are specific and sensitive for coeliac disease, were evaluated in all women attending the obstetrics-gynaecology department of a large city hospital over a 90 day period.
RESULTS—Of 845 pregnant women screened, 12 were identified as having coeliac disease. Three had previously been diagnosed but were not following a gluten free diet. The remaining nine underwent a small intestinal biopsy, which confirmed the diagnosis. The outcome of pregnancy was unfavourable in seven of these 12 women. Six healthy babies were born with no problems after the women had been on a gluten free diet for one year.
CONCLUSIONS—Overall, 1 in 70 women was affected by coeliac disease, either not diagnosed (nine cases) or not treated (three cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for coeliac disease should be included in the battery of tests prescribed for pregnant women. Coeliac disease is considerably more common than most of the diseases for which pregnant women are routinely screened. Unfavourable events associated with coeliac disease may be prevented by a gluten free diet.
Keywords: coeliac disease; screening; pregnancy; miscarriage; gluten free diet
A small bowel enema was performed in patients with non-responsive coeliac disease, in coeliac patients on a normal diet (untreated) and those who had shown a good response to a gluten free diet, and in control subjects to determine whether there were any specific radiological features of the non-responsive state. A significant reduction in the average number of jejunal folds and an increase in the number of ileal folds (reversal of the jejunoileal fold pattern) was found in eight of nine non-responsive coeliac patients, one of seven untreated coeliac patients, and in none of the good responders or control subjects. This pattern identifies coeliac patients with a poor response to a gluten free diet who are likely to suffer major complications.
The subclass distribution of IgG-producing immunocytes was studied by two colour immunohistochemistry with monoclonal antibodies in jejunal biopsy specimens from 10 adults with untreated coeliac disease, 11 coeliac disease patients on a gluten free diet, and seven patients with established food allergy. Paired immunofluorescence staining was performed with subclass specific murine monoclonal antibodies in combination with polyclonal rabbit antibody reagent to total IgG; the proportion of cells belonging to each subclass could thereby be determined. The ratio of IgG2 immunocytes was significantly higher (p less than 0.05) in untreated coeliac disease patients (median, 35.2%; range, 26.7-65.2%) than in those on a gluten free diet (median, 7.3%; range, 0-31.9%) or those having food allergy (median, 12.5%; range, 0-36.5%). The disparity in the local IgG2 response between patients with untreated coeliac disease and those with food allergy might be due to differences in the nature of the antigenic stimuli, dissimilar genetic 'make-up' of the subjects, or both.
Serum lysozyme activities were measured in 34 control subjects, 13 untreated adult coeliac patients, 21 adult coeliac patients on gluten-free diet, and eight coeliac patients with a histiocytic lymphoma. Serum lysozyme activities were raised in three untreated patients, three patients treated with a gluten-free diet, and in only two patients with coeliac disease and lymphoma. Serum lysozyme estimations cannot be recommended as an aid to the diagnosis of lymphoma in patients with coeliac disease.
Coeliac disease is a chronic intestinal inflammatory disorder due to an aberrant immune response to dietary gluten proteins in genetically predisposed individuals. Mucosal immune response through IgA secretion constitutes a first line of defence responsible for neutralizing noxious antigens and pathogens. The aim of this study was the characterization of the relationships between immunoglobulin-coated bacteria and bacterial composition of faeces of coeliac disease (CD) patients, untreated and treated with a gluten-free diet (GFD) and healthy controls.
IgA-coated faecal bacterial levels were significantly lower in both untreated and treated CD patients than in healthy controls. IgG and IgM-coated bacterial levels were also significantly lower in treated CD patients than in untreated CD patients and controls. Gram-positive to Gram-negative bacteria ratio was significantly reduced in both CD patients compared to controls. Bifidobacterium, Clostridium histolyticum, C. lituseburense and Faecalibacterium prausnitzii group proportions were less abundant (P < 0.050) in untreated CD patients than in healthy controls. Bacteroides-Prevotella group proportions were more abundant (P < 0.050) in untreated CD patients than in controls. Levels of IgA coating the Bacteroides-Prevotella group were significantly reduced (P < 0.050) in both CD patients in comparison with healthy controls.
In CD patients, reduced IgA-coated bacteria is associated with intestinal dysbiosis, which altogether provide new insights into the possible relationships between the gut microbiota and the host defences in this disorder.
Plasma enteroglucagon was measured before and during three hours after a standard meal in 21 untreated adult patients with suspected coeliac disease who all had villous atrophy of the small intestinal mucosa and malabsorption, and in nine control subjects. In 11 of these patients the diagnosis of coeliac disease was confirmed and 10 were again investigated on a gluten free diet. The coeliac patients had higher basal (37 +/- 9 pmol/l, mean +/- SE, p less than 0.05) and postprandial (70 +/- 9 pmol/l, p less than 0.005) mean plasma enteroglucagon concentrations than the control subjects (basal 14 +/- 4 pmol/l, postprandial 25 +/- 5 pmol/l). The 10 coeliac patients on gluten free diet for five to 20 months had a basal mean plasma enteroglucagon concentration not significantly lower than before treatment (25 +/- 5 pmol/l) but significantly lower postprandial enteroglucagon concentrations than before treatment (40 +/- 7 pmol/l, p less than 0.025). Postprandial plasma enteroglucagon concentration after 90 minutes in untreated patients correlated positively to the faecal fat excretion (r = 0.58, p less than 0.02). It correlated negatively to the urinary five hour D-xylose excretion after an oral load of 165 mmol D-xylose (r = -0.71, p less than 0.01). Thus, the postprandial plasma enteroglucagon concentrations in untreated coeliac disease were related to the degree of malabsorption and they normalised during treatment with a gluten free diet.
Arthritis is a recognized complication of untreated coeliac disease. Symptoms and signs usually respond to the institution of a gluten-free diet. We report a case of occult coeliac disease presenting as a monoarthritis. Severe and progressive erosive damage has occurred in his talo-navicular joint despite a response to the institution of a gluten-free diet.
Cell kinetics in the proximal jejunal epithelium were studied by the methods of Cairnie et al. and Wright et al. Seventeen children with untreated malabsorption syndrome and cow's milk protein intolerance (CMI) and 12 of these on a cow's milk free diet were compared with 47 children with untreated coeliac disease, with 15 of these on a gluten free diet, and with 15 controls. The total number of cells in the crypts of the patients with CMI was 1.8 times (P less than 0.001) and in patients with coeliac disease 2.4 times (P less than 0.001) that seen in the controls. During the elimination diet the total number of cells in the crypts returned to the level seen in the controls. The mitotic indices, both crude and corrected, were significantly higher (P less than 0.001) in untreated patients with CMI and those with coeliac disease than in the controls. During dietary treatment the indices fell, but not quite to the level of the controls. These small differences between the two groups may be due to the difference in the causative agents or to the different ages of the patients.