Coeliac disease

In coeliac disease there is an abnormality of the intestinal mucosa which is caused by ingesting gluten. The intestinal lesion affects predominantly the proximal small intestine and the ileum is either normal or less severely involved than the jejunum. In some cases adaptive changes occur in the ileum, producing enhanced absorption in that region when there is malabsorption in the jejunum. The characteristic absorptive abnormality in coeliac disease is therefore jejunal malabsorption and ileal hyperabsorption. When such a situitation develops it is possible that an indivisual with a flat jejunal mucosa may develop no symptoms of the disease, since the adaptive changes in the ileum compensate for the jejunal lesion. This may explain why in Western society there are probably more cases of coeliac disease undiagnosed in the community that have been treated by their doctors. The basic lesion in coeliac disease appears to be genetically determined and it is likely to be a failure to clear antigen which normally enters the lamina propria of the gut resulting in the formation of immune complexes with complement fixation at gut level.     

Coeliac disease in the adult

Coeliac disease can by defined as a chronic disease characterized by a typical mucosal lesion of the small intestine and an impaired nutrient absorption which improves on withdrawal of gluten from the diet. The prevalence rate has increased over the last decades and just 1/3 of cases are diagnosed in childhood. There is a striking association with class II histocompatibility antigens, HLA-DR3 and HLA-DQ2. Cellular immune response mediated by intraepithelial and lamina propria lymphocytes is the primary event in the small intestine damage. Up to 50% of adult coeliac patients don't present intestinal symptoms being more frequent subclinic forms. The immunological markers of coeliac disease are antigliadin, antireticulin and antiendomysial antibodies, being the last one the most specific. Mortality of coeliac patient is increased mainly for malignancies, being the most frequent the intestinal T lymphoma.     

Intestinal absorption in Saudi Arabia: an evaluation of the one hour blood xylose test

The screening value of the one-hour blood xylose test, corrected for body surface area, was prospectively studied in Saudi Arabian adults and children under investigation for suspected intestinal malabsorption. Sensitivity of discrimination between patients with and without upper small bowel disease was 91%, compared to 85% for the five-hour urine xylose test. Primary small bowel disorder was rare. In a three-year review, no cases of adult coeliac disease or tropical sprue were found. The most common causes of malabsorption were intestinal tuberculosis, abdominal lymphoma and immunoproliferative small intestinal disease. Despite its acceptability as an index of proximal small bowel function, the blood xylose test alone is an inadequate screening test for any of these conditions.     

Adaptive response in embryogenesis: I. Dose and timing of radiation for reduction of prenatal death and congenital malformation during the late period of organogenesis

BACKGROUND: Coexistent primary biliary cirrhosis (PBC) and coeliac disease has been recorded but the association has not been systematically studied. AIMS: To determine relative prevalences of PBC and coeliac disease in a defined population over a 12 year period. PATIENTS AND METHODS: All patients with PBC or coeliac disease in a stable population of 250,000 in South Wales were identified from a clinical register and laboratory records. RESULTS: Sixty seven patients with PBC and 143 patients with coeliac disease have been diagnosed and followed over a median of 86 (4-135) months; point prevalences in 1996 were 20 per 100,000 for PBC and 54 per 100,000 for coeliac disease. PBC in patients with coeliac disease was sought by investigating abnormal liver function tests. Ten (7%) had persistent abnormalities and three had PBC. Coeliac disease in patients with PBC was sought by investigating malabsorption, haematinic deficiency, positive antigliadin antibody, or coeliac disease family history. Eleven patients underwent duodenal biopsy revealing one further coeliac disease case. Four patients (three women have both conditions giving a point prevalence for patients with both conditions of 1.6 per 100,000 (95% confidence limits 0.44 to 4.1 per 100,000). Prevalence of PBC in patients with coeliac disease was 3% and of coeliac disease in patients with PBC was 6%. CONCLUSION: A 12 year study of a stable 250,000 population revealed a relative prevalence of PBC in 3% of 143 patients with coeliac disease and of coeliac disease in 6% of 67 patients with PBC. PBC and coeliac disease are therefore associated. Screening for PBC in patients with coeliac disease using antimitochondrial antibody testing and screening for coeliac disease in patients with PBC with antigliadin antibody testing or duodenal biopsy are recommended.     

The role of small bowel follow-through examination in the diagnosis of coeliac disease

A retrospective study of 105 barium follow-through examinations on 102 patients suspected of having malabsorption syndrome has been carried out to assess the usefulness of this technique in the diagnosis of coeliac disease. Comparison with histological and biochemical data has been made. Of the 34 examinations on 31 patients with a proven diagnosis of coeliac disease, 30 examinations showed both abnormal X-ray and biopsy findings, two examinations showed normal X-ray appearance but abnormal jejunal biopsy and two showed normal jejunal histology but abnormal X-ray findings. There were two cases with sensitivity, non-invasive nature, ease and cheapness of the technique, barium follow-through examination is suggested as the initial investigation in patients suspected of coeliac disease.     

Sodium hyaluronate eyedrops enhance tear film stability

Coeliac disease, also known as gluten-sensitive enteropathy or non-tropical sprue, is a relatively uncommon condition. The dietary presence of gliadin, an alcohol-soluble subfraction of gluten, in immunologically susceptible hosts will lead to small intestinal mucosal inflammation and subsequent mucosal villous atrophy which results in nutrient and vitamin malabsorption. The symptomatic presentations of patients with coeliac disease are related to this malabsorption process which can be reversed in the vast majority of patients with a gluten-free diet.     

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.     

Coeliac disease: frequent occurrence after clinical onset of insulin-dependent diabetes mellitus. Childhood Diabetes in Finland Study Group

Coeliac disease was searched for in a series of 776 children with newly diagnosed IDDM. During the follow-up of 2 to 3 years from diagnosis, reticulin and gliadin antibodies were measured, and a jejunal biopsy was performed in those cases with high levels of antibodies; 19 children were identified with coeliac disease, giving the prevalence of 2.4%. In only one case had coeliac disease been diagnosed before IDDM. Nine patients with proven coeliac disease were negative for antibodies when IDDM was diagnosed, but became positive within 24 months. All patients found to have coeliac disease were positive for IgA reticulin antibodies, but only 12 of 18 (67%) showed a high level of IgA gliadin antibodies. Of the 18 patients genotyped for HLA DR locus, 14 (78%) were positive for DR3 and 10 (56%) were positive for DR4. DQB1*0201 allele was present in 17 of 18 patients (94%). Coeliac disease in children with IDDM tends to develop soon after diabetes is diagnosed. Routine screening for coeliac disease is recommended repeatedly during the first years after the diagnosis of IDDM.     

Ovarian neoplasms in children

OBJECTIVE: To review the clinical presentation, treatment, and outcome in a series of children with ovarian neoplasms. DESIGN: A retrospective review of the medical records in a case series of 29 girls with ovarian neoplasms. The length of follow-up ranged from 6 months to 7 1/2 years and averaged 3.0 years in the girls with malignant tumors. SETTING: The patients were treated at a large referral children's hospital. PATIENTS: Twenty-nine girls with ovarian neoplasms were treated from 1976 to 1992. The average age of the patients was 10 years and ranged from 2 to 16 years. MAIN OUTCOME MEASURES: The principal outcomes examined were mortality and surgical morbidity. RESULTS: The most common presenting symptoms for these ovarian tumors in pediatric patients included chronic abdominal pain, an abdominal mass, or distention. Three girls presented with precocious puberty or hirsutism. In 27 cases, the tumor was a primary ovarian lesion. In two patients, the ovarian mass was the presenting finding for a stage IV non-Hodgkin's lymphoma. Seventeen tumors were benign and 12 were malignant. Tumors originating from the germ-cell line predominated (n = 17). Seven of the 10 ovarian malignant neoplasms were stage I at the time of diagnosis. All but one of the girls with malignant tumors received either adjunctive radiation therapy or multiple-agent chemotherapy. Two girls with sex cord/stromal cell tumors who presented with stage I disease ultimately developed widespread metastases. Both girls with large epithelial tumors survived. All of the girls with benign tumors and seven (70%) of 10 with malignant lesions survived. CONCLUSION: Ovarian tumors are unusual lesions in the pediatric population. Unlike in adults, such neoplasms generally originate from the germ-cell line. Whereas most ovarian tumors in girls are benign, some children have malignant tumors that are very aggressive and do not respond well to adjuvant therapy. In particular, malignant sex cord/stromal cell tumors, even when they present at an early stage, may behave unpredictably.     

Diagnosis of gluten-sensitive enteropathy: is exclusive reliance on histology appropriate?

OBJECTIVE: Coeliac disease is a prevalent disorder but frequently remains undiagnosed because of varied modes of clinical presentation. In this study, methods for the detection of coeliac disease were evaluated in a clinical practice setting. METHODS: Small intestinal histology, IgA anti-endomysial and IgG anti-gliadin antibody tests were performed on 441 unselected, consecutive patients under investigation for small intestinal disease. Response to treatment and other clinical events were monitored over the ensuing years. RESULTS: Untreated coeliac disease was diagnosed in 97 patients and was excluded in 344. At clinical presentation, the endomysial antibody test was positive in 84 of the 97 untreated coeliac patients (sensitivity 87%) and negative in 340 of the 344 non-coeliac patients (specificity 99%). A typical histological lesion was found in 83 of the 97 coeliac patients (sensitivity 86%) but was absent in all 344 non-coeliacs (specificity 100%). The sensitivity of the gliadin antibody test was 69% and the specificity was 71%. CONCLUSIONS: In unselected patients attending a gastroenterology clinic, small bowel histology and endomysial antibody serology show similar predictive value in the diagnosis of coeliac disease. These results emphasize that a combination of clinical, histological and serological criteria are required for effective diagnosis of this disorder. Exclusive reliance on histology or serology will result in failure to make a diagnosis in a significant proportion of patients.     

Coeliac disease in Galway, Ireland 1971-1990

Recent studies have reported changes in the incidence of coeliac disease and in its presentation. We carried out a retrospective study looking at the incidence and clinical features of coeliac disease in Galway children over a 20 year period. The study period was divided in two parts. (I) Patients diagnosed between 1971 and 1980 and (II) between 1981 and 1990. Comparison was made between demographic and clinical data in these two periods. There were 97 cases of coeliac disease diagnosed in children resident in Galway over the 20 year period. 71 patients were diagnosed in period I and 26 in period II. The median age at diagnosis in period I was 1.41 years and 4.95 years in period II. There were more females diagnosed in period I. Growth data, histology and enzyme levels were similar in both groups. Diarrhoea and vomiting were the major presenting symptoms in both periods but more patients presented with wasting or abdominal protuberance in the latter period. Our data support the concept that coeliac disease in childhood is declining, and is presenting at a later age.     

Long-term followup of patients with Sj?gren's syndrome

OBJECTIVE: To assess long-term outcome in patients with isolated keratoconjunctivitis sicca (KCS), primary Sj?gren's syndrome (SS), and secondary SS. METHODS: In 112 patients referred because of dry eyes, an ophthalmologic diagnosis of KCS was made based on results of the Schirmer I test, the tear fluid lysozyme concentration, and rose bengal staining. Subsequent assessments, including sublabial salivary gland biopsy, were performed. Followup assessments were performed 10-12 years after initial diagnosis. RESULTS: Six patients were excluded because no biopsy specimen was available. Seventy-three percent of the remaining 106 patients were female, with a mean age of 53.5 years and a mean symptom duration of 3.9 years. Application of the 1987 classification criteria of Daniels and Talal revealed a diagnosis of isolated KCS in 56 patients, primary SS in 31, and secondary SS in 19. At baseline, 2 of 56 patients with isolated KCS and 8 of 31 with primary SS exhibited mild features of organ-specific autoimmune disease. At followup, 2 of 38 patients with isolated KCS and 4 of 21 with primary SS had developed new features related to autoimmune disease, not necessitating treatment with corticosteroids; none of the patients developed major glandular complications. Three of 30 patients with primary SS died of malignant lymphoma. In 1 of these patients, the possibility could not be excluded that sicca symptoms and infiltrates seen on sublabial salivary gland biopsy had occurred concomitantly with early stages of lymphoma. Malignant lymphoma did not develop in any of the patients with isolated KCS or secondary SS. CONCLUSION: Primary Sj?gren's syndrome is characterized by a stable and rather mild course of glandular and extraglandular manifestations, in marked contrast to the increased risk of development of malignant lymphoma in these patients. Since patients with isolated KCS do not have an increased risk for development of malignant lymphoma, a presumptive diagnosis of primary SS should be confirmed in patients with sicca syndrome.     

Simultaneous enucleation of a pulmonary melanoma metastasis and myocardial revascularization

BACKGROUND: The incidence of late, recurrence of malignant melanoma, is a well known, but very rare clinical experience. CASE REPORT: We report a case of simultaneous myocardial revascularisation and resection of pulmonary melanoma metastasis. In 1963 an enucleation of the right eye was necessary due to an ocular melanoma. In 1993 the patient suffered acute left heart failure and a 3-vessel disease with severe reduced left ventricular function was diagnosed. Chest X-ray examination revealed a singular pulmonary lesion in the right lower lobe with a diameter of 5.5 cm. Myocardial revascularisation and resection of the pulmonary focus was performed simultaneously without complication. The histological examination documented a pulmonary late recurrence of malignant melanoma. Up to this time (3 years later) the patient is free of cardiac symptoms and there is no evidence of further late recurrence of malignant melanoma. CONCLUSION: The appreciable number of patients who, after a disease-free interval of 10 to 20 years, develop a late recurrence of a malignant melanoma, and in particular-as in the present case-a choroidal melanoma, is powerful evidence for a need to keep these patients under lifelong surveillance.     

Melanoma arising from the mucosal surfaces of the head and neck

Oral mucosal malignant melanoma is a rare disease. We reviewed 30 years of data from a tumor registry and identified 65 patients who had head and neck melanomas. Two thirds (43) of the 65 patients were identified as male, with the mean age in the sixth decade. Of the 65 patients, only 6 had melanoma that arose from the oropharyngeal mucosa. Of the lesions involving the oral mucosa, each lesion manifested itself as a mass or was associated with symptoms of discomfort; only one third (2) of the lesions were pigmented. The clinician must carefully examine the head, neck, and oral cavity, and any pigmented lesion that is not recognized as a specific entity, such as amalgam tattoo, should be biopsied. The more common presentation of amelanotic malignant melanoma requires a high index of suspicion for masses identified in the mouth and requires biopsy for definitive diagnosis. The prognosis for oral mucosal malignant melanoma is poor.     

Changing clinical features of coeliac disease

The classical clinical picture of coeliac disease includes prolonged diarrhoea with failure to thrive. During the past two decades this type of active presentation of coeliac disease has decreased in many European countries, giving the impression that coeliac disease is a disappearing disease. However, this is not true. The disease can be found in older children with a more or less silent presentation. Silent coeliac disease can be detected by active screening with serological tests. Coeliac disease can be suspected in children suffering from mild gastrointestinal symptoms, such as abdominal pain, and in those with signs of nutritional deficiencies, as well as in children of first-degree relatives of already diagnosed coeliacs, patients with IgA-deficiency, patients suffering from dental enamel hypoplasia or dermatitis herpetiformis, and patients with some other disease known to be associated with coeliac disease, such as diabetes mellitus. According to the fundamental criteria of coeliac disease, the intestinal mucosa is flat when the individual is eating gluten-containing foods. However, this is not strictly true. Intolerance to gluten is obviously variable and the intestinal mucosa may be normal. This type of latent coeliac disease can be detected by analysing genetic markers, measuring antibodies in intestinal fluid or counting the density of intra-epithelial gamma/delta T cells which are increased greatly even in the latent phase of coeliac disease. Thus the general concept of the natural history of coeliac disease is changing.     

Dopamine receptor D2 Ser/Cys311 variant associated with disorganized symptomatology of schizophrenia

AIMS: To investigate the prevalence of lymphocytic gastritis in patients with coeliac disease. METHODS: Gastric biopsies from 70 patients with coeliac disease were examined by light microscopy for the presence of lymphocytic gastritis, defined as 25 or more intraepithelial lymphocytes/100 gastric columnar epithelial cells. RESULTS: Lymphocytic gastritis was found in seven cases. Positive cases had a mean of 32.1 intraepithelial lymphocytes/100 columnar cells, compared with a mean of 13.9 in negative cases, and 5.15 in noncoeliac controls. No differences were found for age, sex, gastric corpus or antrum, or degree of inflammation in the gastric lamina propria. All intraepithelial lymphocytes were of T cell lineage. Cases not showing lymphocytic gastritis did however show significantly increased gastric intraepithelial lymphocytes compared with non-coeliac controls. Eighteen of 70 cases were positive for Helicobacter pylori, and four of seven cases of lymphocytic gastritis were H pylori positive; no significant difference was observed between H pylori positive and negative patients. Three cases had concomitant ulcerative enteritis, of which none showed lymphocytic gastritis, while five cases had concomitant enteropathy associated T cell lymphoma, of which one showed lymphocytic gastritis. CONCLUSIONS: Lymphocytic gastritis occurred in 10% of patients with coeliac disease. Cases without lymphocytic gastritis nevertheless showed increased gastric intraepithelial lymphocytes. Coeliac disease may on occasion be a diffuse lymphocytic enteropathy occurring in response to gluten. Lymphocytic gastritis outside coeliac disease may involve an immune response to luminal antigens, such as H pylori, not unlike the response to gluten in patients with coeliac disease.     

Dental enamel hypoplasia in a group of celiac disease patients. Clinico-epidemiologic correlations

BACKGROUND: The aim of present study was to carry out a personal clinical-epidemiological research concerning a possible correlation between coeliac disease and enamel hypoplasia. MATERIALS AND METHODS: Forty-five patients of Cam-pania, aged between 2 and 26 years old, with a diagnosis of coeliac disease (diagnosis in accordance with recent protocol ESPGAN), were subjected to a careful dental examination: at the same time a control-group formed by 105 healthy subjects, of the same province, age- and sex-matched with coeliac patients was examined. RESULTS: The finding of enamel hypoplasias was more significant in coeliac patients (11 cases with a percentage of 2.4%) than in controls (5 cases with a percentage of 4.7%). CONCLUSIONS: The percent rate, if on the one hand is lower than in Finnic studies, on the other hand fundamentally reflects the results of studies on the same topic carried out by other Italian groups. Furthermore also in this research the involvement of milk-teeth is observed as reported by other authors. This appears to confirm a clear association between coeliac disease and dental hard tissues alterations.     

Netherton syndrome revisited

Because coeliac disease often presents atypically it is underdiagnosed. It is suggested that the detection rate may be increased by 12% if serology is used to identify cases of occult enteropathy. All adults noted incidentally to be R1 anti-reticulin antibody (ARA) positive in the course of routine autoantibody testing of 6532 sera over one year were followed. None of the eight patients with seropositive serum was suspected of having coeliac disease. All eight had high titres of IgA anti-gliadin and IgA anti-endomysial antibodies, neither of which is detected in a routine autoantibody test, in addition to IgA R1-ARA. On clinical review coeliac disease was considered probable in only one patient, but because of the strong serological evidence of gluten sensitivity, jejunal biopsy was advised in all eight. Seven agreed and all had villous atrophy and crypt hyperplasia in keeping with coeliac disease. Six of the seven presented initially with vague symptoms such as tiredness or arthralgia. These symptoms disappeared after several weeks of gluten withdrawal. Forty two sera showing reticulin staining patterns other than R1 were used as controls. Low titre IgA anti-gliadin was noted in two of 42 but none had IgA anti-endomysial antibody. These 42 cases were not recommended for biopsy. During our study 58 other new adult cases of coeliac disease were diagnosed, primarily on clinical rather than serological grounds, at the four hospitals that request autoantibody studies. Occult coeliac disease detected serologically thus increased the overall incidence of coeliac disease by 12% from 58 to 65 cases. R1-ARA, even in the absence of the expected symptoms and signs of coeliac disease, is an indication for jejunal biopsy and is a reliable indicator of occult coeliac disease.     

Sequence analysis of DNA randomly amplified from the Saccharomyces cerevisiae genome

OBJECTIVES: To report the features of malignancies responsible for a chest wall mass and involving the sternum, the sternocostal and/or sternoclavicular joints, the chondrocostal junction and/or the adjacent soft tissues. METHODS: The medical records of patients with a chest wall mass due to malignant disease were reviewed retrospectively. The following data were abstracted from each record: characteristics of the pain and mass, constitutional symptoms, physical findings, laboratory test results, findings from imaging studies (plain radiographs, computed tomography and magnetic resonance imaging of the chest, radionuclide bone scan), histologic features of the biopsy specimen from the chest wall mass and origin of the mass. RESULTS: Seven men and three women with a mean age of 53.1 years were included in the study. A single patient had a history of malignant disease (lymphoma); in the remaining nine patients the chest wall mass was the first manifestation of the malignancy. All ten patients had pain with a mixed time pattern. The mass was located on the sternum in half the patients and in a parasternal location in the other half. Erythrocyte sedimentation rate elevation was found in seven patients, an increased serum level of lactate dehydrogenase in one and a monoclonal immunoglobulin in three. Sternal lesions were visible on plain radiographs in four patients. Computed tomography of the chest consistently disclosed sternal or sternocostal lytic lesions with spread to the adjacent soft tissues; in five cases, enlarged lymph nodes were visible in the anterior part of the mediastinum. Magnetic resonance imaging of the chest did not add to the information provided by computed tomography. Radionuclide uptake on the bone scan was increased, decreased, or normal at the site of the lesion. The cause was Hodgkin's disease in two cases, non-Hodgkin's lymphoma in three, metastatic bone disease in two (from an adenocarcinoma of the lung and a hepatocarcinoma, respectively), multiple myeloma in one, and solitary plasmacytoma in two. CONCLUSION: A chest wall mass can be caused by a known or as yet undiagnosed malignancy. Chest wall involvement due to malignant disease in rare, however. The specific features of sternal metastases, lymphomas involving the sternum, and sternal plasmacytomas are discussed. Nonmalignant chest wall lesions that can manifest as a bulging or swelling of the chest wall are reviewed.     

Coeliac disease in primary care: case finding study

OBJECTIVES: To provide evidence of underdiagnosis of coeliac disease and to describe the main presenting symptoms of coeliac disease in primary care. DESIGN: Case finding in a primary care setting by testing for coeliac disease by using the endomysial antibody test. SETTING: Nine surgeries in and around a market town in central England, serving a population of 70 000. PARTICIPANTS: First 1000 patients screened from October 1996 to October 1997. OUTCOME MEASURES: Determination of endomysial antibody titre of patients fulfilling the study criteria, followed by small intestine biopsy of those with positive results. RESULTS: The 30 patients (out of 1000 samples) with positive results on the endomysial antibody test all had histological confirmation on small intestine biopsy. The commonest mode of presentation (15/30) was anaemia of varying severity. Most patients (25/30) presented with non-gastrointestinal symptoms. Specificity of the endomysial antibody test was 30/30. CONCLUSIONS: Underdiagnosis and misdiagnosis of coeliac disease are common in general practice and often result in protracted and unnecessary morbidity. Serological screening in primary care will uncover a large proportion of patients with this condition and should be made widely available and publicised. Coeliac disease should be considered in patients who have anaemia or are tired all the time, especially when there is a family history of the disease.