How many hospital visits does it take before celiac sprue is diagnosed?

Author Dickey W; McConnell JB

Address Department of Gastroenterology, Antrim Hospital, Northern Ireland.

Source J Clin Gastroenterol, 1996 Jul, 23:1, 21-3

 

Abstract We studied the hospital records of patients with celiac sprue in order to determine how frequently hospital specialists failed to make the diagnosis. Over a 7 1/2-year period, 39 patients were diagnosed, 49% within the last 18 months of the study period. Fourteen patients (39%) had been referred to the hospital a total of 30 times with features suggestive of celiac sprue, yet without being successfully diagnosed: the delay between initial referral and diagnosis was 6 years in nine of these patients. The diagnosis was made by gastroenterologists or other internists in 38 (97%) patients. Gastroenterologists had an 85% (33 of 39) diagnostic success rate, other internists 63% (five of eight), and surgeons 7% (one of 14). None of eight referrals to other specialists led to diagnosis. While a history of diarrhea was morel likely to lead to diagnosis, it was reported by only 59% (23 of 39) of patients at the time of diagnosis and at only 46% (32 of 69) of referrals; furthermore, it did not prompt correct diagnosis in 28% (nine of 32). Anemia was the sole manifestation of celiac sprue at 17 referrals, and correct diagnosis was made in only seven (41%), all by gastroenterologists. The perceived rarity of celiac sprue reflects its underdiagnosis. Diagnosis is still delayed even in patients with classic diarrhea, and there is still a failure to appreciate the possible manifestations of sprue, including anemia without gastrointestinal symptoms. Because patients may be referred to specialists other than gastroenterologists with symptoms arising from celiac sprue, a wider knowledge of its manifestations is called for.

Combining the lactulose/mannitol test with endomysial antibody testing

Vogelsang et al also reported on the use of GIT permeability measurements in relatives of celiac patients. (Am J Gastroenterol, 1995 Oct, 90:10, 1838-42) They stated that the relatives have a higher risk of getting diseases associated with celiac disease; a higher risk for malignancy and nutritional deficiencies.

 

Study report: " Lactulose/mannitol permeability is increased in untreated celiac patients and has been recommended to screen for celiac disease. We investigated the usefulness of a lactulose/mannitol home test kit for screening first-degree relatives home test kit for screening first-degree relatives of celiac patients. METHODS: The lactulose/mannitol test was performed at home by 111 first-degree relatives. These subjects received the test kit from celiac index patients, were instructed by an information sheet how to carry out the test, and were asked about their symptoms by questionnaire. When lactulose/mannitol permeability was abnormal, endomysial antibodies were tested by immunofluorescence. Any relatives with positive endomysial antibodies were then biopsied. To investigate the specificity of the lactulose/mannitol test for celiac disease, 40 patients with nonspecific gastrointestinal symptoms were tested. RESULTS: Lactulose/mannitol permeability was elevated in 34 (31%) relatives, but only nine (8%) of those relatives showed positive endomysial antibodies. Flat mucosa was found in all nine relatives after biopsy. The prevalence of celiac disease was much higher (42%) among 12 relatives who contacted the outpatient clinic themselves because of symptoms. Seventy-one percent of the remaining 21 relatives with elevated permeability demonstrated normal intestinal permeability at a control test1 yr.

Coeliac disease in adults.

Author Corazza GR; Gasbarrini G

Address University of L'Aquila, Italy.

Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 329-50

 

Abstract Coeliac disease is a chronic disease characterized by small bowel villous atrophy which impairs nutrient absorption and improves on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. Knowledge of the adult form of coeliac disease has greatly improved in recent years. Although this knowledge is not yet sufficiently widespread among referring clinicians, it has, over the past few years, allowed an increasing number of patients to be diagnosed with subclinical forms characterized by minor, transient or apparently unrelated symptoms. As a consequence, our views on the clinical and epidemiological aspects of this condition, the prevalence of which in the general population is believed to be close to 1 in 300, have changed and are still changing. Since it has been demonstrated that a strict gluten-free diet is protective against the complications of adult coeliac disease, it is important that even subclinical and silent forms are diagnosed and treated as early as possible. Non-invasive screening tests, such as anti-gliadin and anti-endomysium antibody estimation, should therefore be used systematically in groups considered to be at risk of coeliac disease. These include first-degree relatives of coeliac patients and patients with insulin-dependent diabetes mellitus, iron-deficiency anaemia, epilepsy with cerebral calcification, recurrent aphthous stomatitis and dental enamel hypoplasia. Other conditions will probably be identified in the near future.

Coeliac disease in childhood.

Author Littlewood JM

Address St. James's University Hospital, Leeds, UK.

Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 295-327

 

Abstract Coeliac disease usually presents in infancy or early childhood with diarrhoea, vomiting and interference with weight gain and growth. Withdrawal of dietary gluten is followed by resolution of the symptoms and signs and restoration of normal weight gain and growth; the characteristic subtotal villous atrophy of the jejunal mucosa also recovers. Later re-introduction of dietary gluten will lead to a return of the jejunal mucosal abnormality in the majority and to clinical relapse in many but not all. The severity and timing of both are variable and 5% of children initially considered on clinical, biopsy and gluten response evidence to have coeliac disease appear to develop permanent tolerance to gluten, although mucosal relapse may occur years after the re-introduction of dietary gluten in a minority, emphasizing the need for long-term follow-up. Although a diagnostic and subsequent follow-up jejunal biopsy are necessary to confirm the diagnosis, anti-gliadin IgA and IgG, anti-reticulum and anti-endomysium antibodies are now almost totally reliable in identifying children who have coeliac disease and are valuable in monitoring the adequacy of gluten withdrawal. Dietary compliance is frequently poor and regular supervision by a paediatric dietitian is needed; indeed, lifelong supervision to ensure gluten withdrawal is essential to reduce the chance of developing later gastrointestinal malignancy.

Gender and clinical presentation in adult celiac disease.

Author Ciacci C; Cirillo M; Sollazzo R; Savino G; Sabbatini F; Mazzacca G

Address Gastrointestinal Unit, Medical School, University Federico II of Naples, Italy.

Source Scand J Gastroenterol, 1995 Nov, 30:11, 1077-81

 

Abstract BACKGROUND: Celiac disease may present in various forms. This study aimed to investigate whether gender affects the clinical presentation of the disease in adult celiac patients from the Mediterranean area. METHODS: This study retrospectively analyzes data collected in all adult patients with celiac disease (n = 195) seen during the past 13 years at the Gastrointestinal Unit of the Federico II University of Naples, Italy. RESULTS: In these series of patients the ratio of women to men was 3.33. Age at diagnosis was lower in women that in men (p < 0.05). Except for asthenia, all signs and symptoms were more frequent in women than in men. Hypochromic anemia was the most commonest finding in women and was 40% more frequent in women than in men (p < 0.001). Dyspepsia was twice as frequent in women as in men (p < 0.05); genital disorders were reported by 44% of women and by no men. Recent weight loss or low body mass index was the commonest finding in men. About 60% of men and women reported diarrhea; among patients without diarrhea, the prevalence of hypochromic anemia differed between sexes (p < 0.05), occurring in about 80% of women. CONCLUSION: This study shows that the clinical presentation of celiac disease is not the same in men and women. The disease is not only more frequent in women than in men but is also more severe and more rapid. The data also suggest the need to look for celiac disease in patients with unexplained hypochromic anemia.

The major complications of coeliac disease.

Author Wright DH

Address University Department of Pathology, Southampton General Hospital, UK.

Source Baillieres Clin Gastroenterol, 1995 Jun, 9:2, 351-69

 

Abstract Neoplasms constitute the major complication of coeliac disease, and high-grade T-cell lymphoma of the small intestine (enteropathy-associated T-cell lymphoma) is the most common neoplasm in this category. HLA genotyping indicates that in patients with enteropathy-associated T-cell lymphoma have the coeliac disease associated DQA1*0501, DQB1*0201 phenotype, although additional HLA-DR/DQ alleles may represent risk factors for lymphoma development. Molecular biological and immunohistochemical studies have shown that the intestinal mucosa distant from the tumour contains clonal populations of small T cells, often of the same clone as the high-grade T-cell lymphoma. These findings suggest that enteropathy-associated T-cell lymphoma arises in the setting of coeliac disease and evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high-grade tumour, which is usually the cause of the presenting symptoms. Most cases of chronic ulcerative enteropathy (ulcerative jejunitis) are probably part of the same disease process. If the ulceration occurs at a time when the neoplastic T-cells are of a low grade, morphological recognition of tumour cells in the ulcers may be impossible. Carcinoma of the pharynx and oesophagus, and adenocarcinoma of the small intestine, are increased in frequency in patients with coeliac disease. The increased risk of carcinoma of the oesophagus may be related to vitamin A deficiency. A number of reports have indicated an increased prevalence of various types of chronic hepatitis in patients with coeliac disease, but no coherent view of the cause of this association has emerged. Similarly, patients with coeliac disease have been reported to have various forms of fibrosing lung disease of uncertain causation. In recent years, there have been several reports, mainly from Italy, of a syndrome of epilepsy and bilateral brain calcification occurring in coeliac patients. The pathogenesis of this condition is not known and its prevalence in other communities is uncertain. Splenic atrophy occurs frequently in patients with coeliac disease and is related to the severity of the disease and degree of dietary control. Splenic atrophy predisposes to infection with capsulated bacteria, although mortality studies indicate that infection with these organisms is not a major cause of death in patients with coeliac disease.

Non-malignant complications of coeliac disease.

Author Holmes GK

Address Department of Medicine, Derbyshire Royal Infirmary, Derby, UK.

Source Acta Paediatr Suppl, 1996 May, 412:, 68-75

 

Abstract Patients with coeliac disease are at increased risk of developing complications which increase morbidity and mortality. Emphasis on malignant complications has often overshadowed the non-malignant risks, which have received relatively little attention, although some of these can be very troublesome and even life-threatening. This article points out that a large population of unidentified or neglected coeliac patients is at potential risk. The challenge is to identify this group by case-finding or screening programmes in selected populations, so that they can be offered a gluten-free diet and other treatments which will not only improve general health but may also prevent or reduce the development of health problems. The non-malignant risks are outlined and bone and neuropsychiatric disturbances considered in more detail because of recent developments in these areas.

Bone remodeling indices and secondary hyperparathyroidism in celiac disease.

Author Keaveny AP; Freaney R; McKenna MJ; Masterson J; O'Donoghue DP

Address Department of Gastroenterology, St. Vincent's Hospital, Dublin, Ireland.

Source Am J Gastroenterol, 1996 Jun, 91:6, 1226-31

Abstract

OBJECTIVES: To determine the prevalence of hypovitaminosis D and secondary hyperparathyroidism (SHPT) and to assess bone turnover by using markers of bone formation and resorption in celiac disease (CD). METHODS: Forty-three patients with CD were investigated: group 1, newly diagnosed celiacs (n = 19); group 2, treated celiacs responding histologically to a gluten-free diet (n = 16); group 3, refractory celiacs, unresponsive to a gluten-free diet and immunosuppressive therapy (n = 8). Serum was drawn for intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], ionized calcium (Cai), total alkaline phosphatase (AP), and biochemical markers of bone formation: procollagen I carboxyterminal propeptide (PICP) and osteocalcin (Oc). Urinary indices of bone resorption, deoxypyridinoline (DPD), pyridinoline (PyD), and hydroxyproline (OHP), were measured in a 2-h fasting urine. In 22 patients, computerized tomographic scan for bone mineral density (BMD) was performed. RESULTS: The prevalence in groups 1, 2, and 3, respectively, of hypovitaminosis D (<50 nmol/L) was 58%, 25%, and 88%, and the prevalence of SHPT ( 5.4 pmol/L) was 25%, 19%, and 25%. Bone resorption markers were significantly elevated in all groups, and bone formation indices were elevated in the newly diagnosed celiacs compared with a group of healthy adults. Low BMD (T-score greater than -1 SD unit) was found in 68% of patients assessed; 36% of patients had a T-score greater than -2.5 SD units. CONCLUSIONS: Hypovitaminosis D and SHPT are common in newly diagnosed and refractory celiacs but are less common in those who respond to a gluten-free diet. Newly diagnosed patients have a high bone turnover state with elevation of both bone formation and resorption indices. Those with refractory disease demonstrate a remodeling imbalance with high bone resorption.

Body composition and bone mineral density in untreated and treated patients with celiac disease.

Author Gonz?lez D; Mazure R; Mautalen C; Vazquez H; Bai J

Address Secci?n Osteopat?as M?dicas, Hospital de Cl?nicas, Buenos Aires, Argentina.

Source Bone, 1995 Feb, 16:2, 231-4

 

Abstract Body composition and bone mineral density (BMD) were studied by X-ray absorptiometry in 20 untreated and 12 treated women with celiac disease, as well as in 85 age-matched control women. Untreated patients had a significantly lower body weight, fat mass, lean tissue mass and BMD at the lumbar spine and total skeleton compared to controls (p < 0.001 for all parameters). Treated patients had also a significantly lower body weight (p < 0.01) fat mass (p < 0.05) and bone mineral density at lumbar spine and total skeleton (p < 0.05) compared with controls, but lean tissue mass was not diminished. However, treated patients had a significantly higher body weight, fat mass and BMD of the total skeleton compared with untreated celiac patients (p < 0.01 for all parameters). Serum alkaline phosphatase levels were increased in untreated patients but serum 250HD was normal. In conclusion, celiac disease causes a global and almost universal reduction of fat mass and BMD. The results of this cross-sectional study suggest that osteopenia does not seem to be completely restored by adequate treatment. Alteration of vitamin D metabolism was not the cause of osteopenia in the majority of patients.

Neurological complications of celiac disease

Author Muller AF; Donnelly MT; Smith CM; Grundman MJ; Holmes GK; Toghill PJ

Address University Hospital, Nottingham, England.

Source Am J Gastroenterol, 1996 Jul, 91:7, 1430-5

 

Abstract Neurological complications are a recognized but unusual manifestation of celiac disease. We present here our experiences with four current cases. Age of patients at presentation with neurological signs varied from 7 to 67 yr. In one patient, the neurological disability developed before the diagnosis of celiac disease, whereas, in the other three, it occurred from months to 16 yr after the diagnosis had been established. One patient died of rapidly progressive neuromyopathy. The other three patients had combinations of cerebellar and posterior and lateral column abnormalities. All four patients developed neurological complications despite a strict gluten-free diet. In three of four patients, there was no improvement in duodenal histology on this diet. Treatment with vitamin B12, folic acid, or vitamin D failed to reverse the changes. No other nutritional deficiencies were found. Vitamin E levels were normal in two of three patients. One patient had no response to treatment with immunosuppressive drugs. The mechanisms responsible for these neurological complications are poorly understood, although patients whose duodenal histology fails to improve on a gluten-free diet may be at greater risk. There have been no real advances in the understanding of this condition since the original description nearly 30 yr ago.

Celiac disease and type I (insulin-dependent) diabetes mellitus in childhood: follow-up study.

Author Lorini R; Scotta MS; Cortona L; Avanzini MA; Vitali L; De Giacomo C; Scaramuzza A; Severi F

Address Department of Paediatrics, University of Pavia, Policlinico San Matteo I.R.C.C.S., Italy.

Source J Diabetes Complications, 1996 May-Jun, 10:3, 154-9

 

Abstract To ascertain the specificity of IgA and IgG antigliadin (IgA-AGA, IgG-AGA), IgA-antireticulin (R1-ARA), and antiendomysial (AEA) antibodies for the diagnosis of celiac disease, we evaluated 133 type I diabetic children aged 1.4-28.4 years (mean 14.1 +/- 6.6), with diabetes from onset to 20.5 years. Fifty-three patients were considered at onset and 49 of these also during follow-up. IgA-AGA and IgG-AGA were determined by enzyme-linked immunosorbent assay (ELISA), R1-ARA and AEA by indirect immunofluorescence. IgA-AGA were positive in 20 of 133 (15%), IgG-AGA were positive in seven of 133 (5.26%), while R1-ARA and AEA were positive in three patients. At the onset of disease we found elevated IgA-AGA in 17 of 53 (32%) patients, IgG-AGA in four (7.55%) patients, three of them with IgA-AGA as well; R1-ARA and AEA were present in three (5.66%) patients, all with high IgA-AGA levels. During 1-10 year follow-up IgA-AGA decreased to within the normal range in 13 patients, with elevated IgA-AGA at onset but without R1-ARA and AEA; in four patients with high IgA-AGA at onset, IgA-AGA remained constantly elevated as did R1-ARA and AEA in three of them; and two patients, without IgA-AGA, R1-ARA, and AEA at onset, became positive for all three antibodies. Intestinal biopsy confirmed a diagnosis of celiac disease in five of these with IgA-AGA, R1-ARA, and AEA, but not in one patient with persistent IgA-AGA but no AEA and R1-ARA, suggesting that R1-ARA and AEA are more reliable markers for the screening of celiac disease in type I diabetic patients.

Clinical aspects of coeliac disease in children with insulin-dependent diabetes mellitus.

Author Lorini R; Scaramuzza A; Vitali L; d'Annunzio G; Avanzini MA; De Giacomo C; Severi F

Address Department of Pediatrics, University of Pavia, Italy.

Source J Pediatr Endocrinol Metab, 1996 Mar, 9 Suppl 1:, 101-11

 

Abstract Coeliac disease (CD) is heterogeneous in its clinical presentation and pathological expression. Silent, latent and potential forms represent the submerged part of the so-called "coeliac iceberg". The association of insulin-dependent diabetes mellitus (IDDM) and CD has been widely reported. For the screening of CD in diabetic patients, anti-reticulin R1 (ARA-R1) and anti-endomysium (AEA) antibodies are more reliable markers than anti-gliadin (AGA) antibodies. Recent studies have reported an increased prevalence of CD in children with IDDM. In our experience intestinal biopsy confirmed a diagnosis of CD in 6 out of 172 diabetic patients, with a prevalence of 3.5%. Only occasionally does CD precede the onset of IDDM; more often CD is diagnosed shortly or sometimes years after the onset of diabetes. Typical gastrointestinal complaints of CD (such as diarrhoea, abdominal distension) are rare in IDDM patients, while atypical isolated signs or symptoms of CD are more common, in particular sideropenic anemia, short stature, delayed puberty, epilepsy, hypertransaminasemia, dyspeptic symptoms, herpetiform dermatitis, and recurrent aphthous stomatitis. It is recommended that all diabetic children, even those asymptomatic, should be screened yearly for CD, using a combination of AGA plus ARA-R1 and AEA.

Gluten-sensitive enteropathy in patients with insulin-dependent diabetes mellitus.

Author Rensch MJ; Merenich JA; Lieberman M; Long BD; Davis DR; McNally PR

Address Fitzsimons Army Medical Center, Aurora, Colorado, USA.

Source Ann Intern Med, 1996 Mar 15, 124:6, 564-7

 

Abstract OBJECTIVE: To determine the prevalence of celiac disease in a cohort of patients with insulin-dependent diabetes mellitus and to describe the clinical characteristics of patients with coexistent disease. DESIGN: Prospective cohort study. SETTING: U.S. Army medical center. PATIENTS: 47 patients with insulin-dependent diabetes mellitus. MEASUREMENTS: Antiendomysial antibody testing was used to screen for celiac disease. The diagnosis of celiac disease required histologic evidence of villous atrophy and crypt hyperplasia and a positive antiendomysial antibody test result. In patients identified as having coexistent disease, complete blood counts, multiphasic biochemical testing, D-xylose absorption testing, and bone mineral density estimates were done. RESULTS: 3 of 47 patients with insulin-dependent diabetes mellitus (6.4%; 95% CI, 1.4% to 17.5%) had positive antiendomysial antibody test results and small-bowel biopsy specimens consistent with celiac disease. The 95% CI lies entirely above the estimated prevalence of celiac disease expected in the general U.S. population, which ranges from 0.02% to 0.1%. Mean bone mineral densities were 0.8 and 1.1 SD below age-, ethnicity-, and sex-matched controls in each of the 2 antiendomysial antibody-positive patients tested. Small bowel absorption was abnormal in 1 of the 2 patients tested by D-xylose. Anemia and hypoalbuminemia were not detected in any of the patients with coexistent disease. Only 1 of the 3 patients had symptoms of diarrhea. All patients were at or above their ideal body weights. CONCLUSIONS: Celiac disease appears to be more common among patients with insulin-dependent diabetes mellitus than in the general U.S. population (p less than 0.001). Two of the three patients with coexistent disease in this study had subclinical or latent celiac disease.

Polymyositis, arthritis, and proteinuria in a patient with adult celiac disease.

Author Evron E; Abarbanel JM; Branski D; Sthoeger ZM

Address Department of Internal Medicine, Kaplan Hospital, Rehovot, Israel.

Source J Rheumatol, 1996 Apr, 23:4, 782-3

 

Abstract A 37-year-old woman developed polymyositis and arthritis concomitantly with proteinuria and watery diarrhea. Repeated duodenal biopsies and serological evaluation established the diagnosis of adult celiac disease. Treatment with gluten-free diet resolved all clinical and laboratory abnormalities.

The arthritis of coeliac disease: prevalence and pattern in 200 adult patients.

Author Lubrano E; Ciacci C; Ames PR; Mazzacca G; Oriente P; Scarpa R

Address Rheumatology Unit, Federico II University, Naples, Italy.

Source Br J Rheumatol, 1996 Dec, 35:12, 1314-8

 

Abstract Arthritis has often been alluded to as an extra-intestinal clinical manifestation of coeliac disease, but definitive data regarding its prevalence are still lacking. We therefore evaluated the overall prevalence of articular involvement in 200 consecutive adult coeliac patients attending routine gastroenterology follow-up and in 40 controls, and determined whether the prevalence and pattern of articular involvement varied according to the dietary status. An arthritis was present in 26% of patients and in 7.5% of controls, prevalences ranging from 41% in patients on a regular diet to 21.6% in patients on a gluten-free diet (P < 0.005). Arthritis was peripheral in 19 patients, axial in 15 and an overlap of both in 18 subjects. These data suggest that arthritis is much more common than previous reports have indicated, particularly in patients receiving an appropriate dietary regimen, and support the need for combined gastrointestinal and rheumatological follow-up in coeliac patients.

Prevalence of celiac disease in patients with juvenile chronic arthritis.

Author Lepore L; Martelossi S; Pennesi M; Falcini F; Ermini ML; Ferrari R; Perticarari S; Presani G; Lucchesi A; Lapini M; Ventura; A

Address The Clinica Pediatrica and the Laboratorio di Immunologia, Istituto perl'Iinfanzia di Trieste, Italy.

Source J Pediatr, 1996 Aug, 129:2, 311-3 

Abstract We estimated the prevalence of celiac disease in children with juvenile chronic arthritis (JCA), using antiendomysium antibodies as the screening test to select patients for intestinal biopsy. We studied 119 children with JCA and found four patients with antiendomysium antibodies. In three of these patients (2.5%), intestinal biopsy revealed villous atrophy; in the fourth the intestinal mucosa was normal. We conclude that the prevalence of celiac disease is increased in patients with JCA.

Adult celiac disease is frequently associated with sacroiliitis.

Author Usai P; Boi MF; Piga M; Cacace E; Lai MA; Beccaris A; Piras E; La Nasa G; Mulargia M; Balestrieri A

Address Istituto di Medicina Interna, University of Cagliari, Italy.

Source Dig Dis Sci, 1995 Sep, 40:9, 1906-8

 

 Abstract No data are available on the presence and frequency of peripheral or central joint disease, routinely determined by bone scintigraphy with 740 MBq of [99mTc]MDP, in adult celiac disease. Bone scintigraphy was carried out to detect early acute inflammatory lesions in 22 adult celiac patients (15 females and seven males; mean age 36.72 years, range 17-63). Bone scintigraphy was positive for sacroiliitis in 14 cases (63.6%). Except in the case of one patient suffering from rheumatoid arthritis, laboratory data were normal. Our data suggest that as in other chronic intestinal diseases, celiac disease in adults, is frequently associated with central joint disease. This high incidence of sacroiliitis, the joint disease most frequently found in our patients, has not been previously reported in other series. We believe, therefore, this difference could be explained by the different methodology used for the screening of joint disease.

Celiac disease and alopecia areata: report of a new association.

Author Corazza GR; Andreani ML; Venturo N; Bernardi M; Tosti A; Gasbarrini G

Address Department of Internal Medicine, University of L'Aquila, Italy.

Source Gastroenterology, 1995 Oct, 109:4, 1333-7

 

Abstract Celiac disease is frequently associated with other autoimmune disorders but has never been reported in association with alopecia areata. In a routine clinical practice, 3 patients with such an association were observed. In one of the patients, celiac disease was diagnosed after the occurrence of malabsorption symptoms. In the youngest patient, a 14-year-old boy, gluten-free diet resulted in complete regrowth of scalp and body hair. A prospective screening program for celiac disease using antigliadin and antiendomysial antibodies was therefore set up in 256 consecutive outpatients with alopecia areata. Three patients, all completely asymptomatic for intestinal diseases, were found to be positive and underwent biopsy. Histological analysis showed a flat intestinal mucosa consistent with the diagnosis of celiac disease. The results show that alopecia areata may constitute the only clinical manifestation of celiac disease and that the association between these two conditions is a real one because the observed frequency of association is much greater than can be expected by chance. It is suggested that antigliadin and antiendomysial antibodies should be included in the work-up of patients with alopecia areata.

Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge.

Author Chowers Y; Marsh MN; De Grandpre L; Nyberg A; Theofilopoulos AN; Kagnoff MF

Address Department of Medicine, University of California, San Diego, La Jolla 92093-0623, USA.

Source Clin Exp Immunol, 1997 Jan, 107:1, 141-7

 

Abstract Activation of T cells in the intestinal mucosa in response to gluten exposure is thought to play a key role in the pathogenesis of coeliac disease. Moreover, the response of the rectal mucosa to gluten challenge has been considered a useful predictor of gluten sensitivity in coeliac disease. In the present study, we assessed early changes in the expression of proinflammatory cytokine genes and the T cell receptor (TCR) Vbeta repertoire in the rectal mucosa of coeliac disease patients following experimental gluten challenge. Cytokine gene expression was assessed in rectal mucosal biopsies from coeliac disease subjects and controls before and after rectal gluten challenge using quantitative reverse transcription polymerase chain reaction analysis, and the TCR Vbeta repertoire was characterized using a multiprobe RNase protection assay. Marked up-regulation of expression of the C-X-C chemokine IL-8, the proinflammatory cytokine IL-1beta, and the C-C chemokine monocyte chemotactic protein-1 occurred within 24 h of rectal gluten challenge in coeliac disease subjects, but not in controls. Furthermore, these changes occurred in the absence of parallel changes in the expressed repertoire of TCR Vbeta genes in the rectal mucosa. Thus, an increased expression of proinflammatory cytokine genes precedes the expansion of antigen-specific T cell populations in the early period following experimental exposure of the rectal mucosa of coeliac disease patients to gluten. These findings provide new insights into pathways that may be involved in the activation or reactivation of coeliac disease.

Infertility and coeliac disease.

Author Collin P; Vilska S; Heinonen PK; H?llstr?m O; Pikkarainen P

Address Department of Medicine, University of Tampere, Finland.

Source Gut, 1996 Sep, 39:3, 382-4

 

Abstract BACKGROUND: Coeliac women may suffer from gynaecological and obstetric complications. It is possible that these complications are the first symptom of coeliac disease. AIMS: To investigate the occurrence of subclinical coeliac disease in patients with infertility or recurrent miscarriages. SUBJECTS: Women of reproductive age who were attending the hospital because of either primary or secondary infertility, or two or more miscarriages. Women undergoing sterilisation served as control subjects. METHODS: The diagnostic investigation for infertility included the endocrine status, diagnostic laparoscopy, investigation of tubal patency, postcoital test, and semen analysis of the partner. Circulating antibodies against IgA class reticulin and gliadin were used in screening for coeliac disease. In positive cases, the diagnosis was confirmed by small bowel biopsy specimens. RESULTS: Four (2.7%) of 150 women in the infertility group, and none of the 150 control subjects were found to have coeliac disease (p = 0.06). All four women with coeliac disease suffered from infertility of unexplained origin. Altogether 98 women had no discoverable reason for infertility. Thus, in this subgroup the frequency of coeliac disease was 4.1% (four of 98), the difference from the control group being statistically significant (p = 0.02). None of the coeliac women had extensive malabsorption, but two had iron deficiency anaemia. One women with coeliac disease has had a normal delivery. None of the 50 women with miscarriage had coeliac disease. CONCLUSION: Patients having fertility problems may have subclinical coeliac disease, which can be detected by serological screening tests. Silent coeliac disease should be considered in the case of women with unexplained infertility.

 

Incidence of familial dermatitis herpetiformis.

Author Reunala T

Address Department of Dermatology, University of Helsinki, Finland.

Source Br J Dermatol, 1996 Mar, 134:3, 394-8

 

Abstract Dermatitis herpetiformis (DH) and coeliac disease (CD) are gluten-sensitive diseases which have a common immunogenetic background, with the histocompatibility locus antigen (HLA) alleles DQ A1*0501 and B1*0201 in the short arm of chromosome 6. CD is well known to cluster in families whereas DH has not been generally regarded as a familial disease. To study the familial incidence of DH, a prospective study was started in 1969 at the Department of Dermatology of Helsinki University Hospital and in 1976 at the Department of Dermatology of Tampere University Hospital. A total of 1018 patients with DH were diagnosed and questioned for positive family histories. Of the 999 unrelated DH patients, 105 (10.5%) had one or several affected first-degree relatives. The disease in the relatives was either DH (4.4%) or CD (6.1%). Analysis of the 105 families showed that 13.6% of parents, 18.7% of siblings and 14.0% of children were affected, a segregation pattern which fits well to a dominant mode of Mendelian inheritance. Gender may also be important because the first-degree relatives affected with DH were more often females and those affected with CD twice as often females as males. In contrast, there were more males among the 105 propositi with DH and also among the 894 DH patients with no affected relatives. The present study clearly shows that DH is a familial disease in which the first-degree relatives can be affected both with DH and CD, presumably because of a common genetic background. The environmental factors which could cause the rather high penetrance of DH and CD in the first-degree relatives of DH patients remain unknown.

IgA and IgG binding components of wheat, rye, barley and oats recognized by immunoblotting analysis with sera from adult atopic dermatitis patients.

Author Varjonen E; Kalimo K; Savolainen J; Vainio E

Address Department of Dermatology, Helsinki University Central Hospital, Finland.

Source Int Arch Allergy Immunol, 1996 Sep, 111:1, 55-63

 

Abstract IgA and IgG antibody response of adult atopic dermatitis patients against neutral/ acidic fractions of wheat, rye, barley and oats was analyzed utilizing an immunoblotting method. Moreover, the antibody response against ethanol-soluble fraction of wheat was examined with serum pools of healthy donors, atopic dermatitis patients and patients with dermatitis herpetiformis or adult celiac disease. All patient sera revealed polymorphic IgA and IgG binding to cereal peptides with molecular weights of 11-97 kD. The antibody staining was essentially identical with atopic dermatitis patients and controls. Patients with dermatitis herpetiformis or celiac disease showed more intensive staining with the ethanol extract of wheat and showed more IgA-stained bands in immunoblotting. It seems that the presence of IgA and IgG antibodies to different cereal antigens is a result of natural exposure and in atopic dermatitis displays little diagnostic significance, in contrast to antigliadin antibody response in dermatitis herpetiformis and celiac disease.

Celiac disease and hypoparathyroidism: cross-reaction of endomysial antibodies with parathyroid tissue.

Author Kumar V; Valeski JE; Wortsman J

Address IMMCO Diagnostics, Inc., Buffalo, NY 14223, USA.

Source Clin Diagn Lab Immunol, 1996 Mar, 3:2, 143-6

 

Abstract Celiac disease (CD) is a gluten-sensitive enteropathy characterized by the presence of serum antibodies to endomysial reticulin and gliadin antigens. CD has been associated with various autoimmune endocrine disorders, such as diabetes. We report a rare case of idiopathic hypoparathyroidism with coexistent CD characterized by the presence of serum autoantibodies. Studies were conducted to determine the specificities of these autoantibodies and to localize the antibody binding sites by indirect immunofluorescence and immunoelectron microscopy. Sera from a patient with idiopathic hypoparathyroidism and CD and from two patients with CD alone were tested by indirect immunofluorescence for autoantibodies to parathyroid and endomysial antigens. The specificities of the antibody reactions were determined by testing the sera before and after absorption with monkey stomach tissue. In addition, immunoelectron microscopic studies were performed to determine the localization of the endomysial antigen. Indirect-immunofluorescence studies on the patient's serum were positive with the parathyroid as well as the endomysial substrate. Similar reactions were also observed with the sera of endomysial antibody-positive patients with CD. Absorption of the sera with monkey stomach powder, which is known to have the endomysial antigen, abolished the antibody activities on both the endomysial substrate and the parathyroid tissue. Immunoelectron microscopic studies showed that endomysial antibody activity was associated with antigens localized on the myocyte plasma membrane and in the intercellular spaces. Thus, reactions of the patient's serum with the parathyroid tissue were due to endomysial antibodies and were not parathyroid specific as in patients with idiopathic hypoparathyroidism who did not have coexistent CD. In conclusion, indirect-immunofluorescence tests on parathyroid tissue detect not only tissue-specific antibodies but also cross-reactive antibodies, and this should be taken into consideration when these tests are performed.

Serum soluble interleukin-2 receptor, soluble CD8 and soluble intercellular adhesion molecule-1 levels in Crohn's disease, celiac disease, and systemic lupus erythematosus.

Author Srivastava MD; Rossi TM; Lebenthal E

Address Department of Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Source Res Commun Mol Pathol Pharmacol, 1995 Jan, 87:1, 21-6

 

Abstract We investigated soluble interleukin-2 receptor (sIL-2R), soluble CD8 (sCD8) and soluble intercellular adhesion molecule-1 (sICAM-1) levels in the sera of patients with non-malignant diseases believed to have an autoimmune or immunosuppressive component, Crohn's disease, celiac disease, and systemic lupus erythematosus (SLE). Sera of healthy blood donors served as controls. All samples were analyzed by commercial ELISA kits for sIL-2R, sCD8, and sICAM-1. Our control level of sIL-2R (x +/- S.D) was 395 +/- 84 units/ml, sCD8 (x +/- S.D.) 263 +/- 90 units/ml and sICAM-1 405 +/- 118 ng/ml. The 8 Crohn's disease patients had an average sIL-2R level of 920 +/- 329 units/ml, and an average sCD8 level of 355 +/- 91 units/ml, and sICAM-1 952 +/- 329 ng/ml. The four celiac disease patients had an average sIL-2R concentration of 1740 +/- 1071 units/ml, a sCD8 level of 460 +/- 320 units/ml and sICAM-1 1221 +/- 720 ng/ml. The three systemic lupus erythematosus patients had an average sIL-2R of 1023 +/- 123 units/ml, and an average sCD8 of 395 +/- 69 units/ml, and sICAM-1 1153 +/- 219 ng/ml. Thus, sIL-2R and sICAM-1 were significantly elevated over control levels in all 3 patient groups, and sCD8 was mildly elevated. These results indicate enhanced immune activation which may be a common feature in the onset and/or progression of these idiopathic illnesses.

Premalignant conditions of the small intestine.

Author Ryan JC

Address Gastroenterology Section, University of California San Francisco, USA.

Source Semin Gastrointest Dis, 1996 Apr, 7:2, 88-93

 

Abstract Cancer of the small intestine is rare compared with other sites in the gastrointestinal tract. Of the four major primary small-bowel tumors (adenocarcinomas, lymphomas, carcinoid, and leiomyosarcomas), adenocarcinomas and lymphomas are associated with diseases that seem to increase the risk of developing these malignancies. In the case of immunoproliferative small intestinal disease and celiac disease, both of which are thought to predispose patients to the development of primary lymphoma, treatment of the predisposing conditions seems to decrease the risk of developing subsequent malignancy. Recognition of the increased risk associated with other conditions, such as immunodeficiency syndromes, nodular lymphoid hyperplasia, Crohn's disease, the gastrointestinal polyposis syndromes, hereditary nonpolyposis colon cancer, neurofibromatosis, long-standing ileostomy, and urinary diversion procedures, may lead to early diagnosis and improved survival.

Reversal of osteopenia with diet in adult coeliac disease.

Author Valdimarsson T; L?fman O; Toss G; Str?m M

Address Department of Internal Medicine, University Hospital of Link?ping, Sweden.

Source Gut, 1996 Mar, 38:3, 322-7

 

Abstract 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.

Detection of low bone mineral density by dual energy x ray absorptiometry in unsuspected suboptimally treated coeliac disease.

Author

Walters JR; Banks LM; Butcher GP; Fowler CR

Address

Department of Medicine, Hammersmith Hospital, Royal Postgraduate Medical School, London.

Source

Gut, 1995 Aug, 37:2, 220-4

Abstract

Patients with coeliac disease may present with calcium malabsorption but it is unclear whether this results in longterm impairment of bone mineralisation. Dual energy x ray absorptiometry (DXA) was used to study bone mineral density in 34 asymptomatic coeliac disease patients, treated with a gluten free diet for at least two years, and also in 10 newly diagnosed or untreated patients. As expected, untreated patients had low bone mineral density in all regions. In the 29 treated female coeliac disease patients, overall mean values for age adjusted bone mineral density expressed as Z scores were normal although there were many patients with low values, particularly of the lumbar spine and total body. Scores in the postmenopausal patients were significantly worse than in the premenopausal patients and low mean Z scores were found in the five treated male patients. The subjects who had reduced bone mineral density could not be predicted clinically but, despite being asymptomatic, were more likely to have subtotal or partial villous atrophy on small intestinal biopsy (p < 0.0275). In conclusion, although many treated coeliac disease patients have normal bone mineral density, suboptimally treated and newly diagnosed or untreated patients have osteopenia. To reduce the risk of osteoporotic fractures, it is recommended that bone mineral density be measured in all treated coeliac disease patients and those with osteopenia have a repeat intestinal biopsy to assess disease activity.

Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them?

Author Dickey W; McMillan SA; Collins JS; Watson RG; McLoughlin JC; Love AH

Address Department of Medicine, Queen's University of Belfast, Northern Ireland.

Source J Clin Gastroenterol, 1995 Jun, 20:4, 290-2

 

Abstract We prospectively measured serum alkaline phosphatase (ALP), aspartate and alanine transaminase (AST/ALT), and tested sera for antinuclear, smooth-muscle, and antimitochondrial antibodies (ANA, SMA, AMA) in our patients with celiac sprue to determine the prevalence of associated liver abnormalities and its relevance to clinical management. Of 129 patients, ALP was the only elevated enzyme in 12 (9%) and in most cases was not thought to reflect significant liver disease. Seventeen (13%) had elevated AST and/or ALT with normal ALP. Levels normalized in 15 patients after dietary gluten exclusion and remained elevated in 2 noncompliers. Two patients (2%) with elevated AST, ALT, and ALP underwent further investigation: one had negative autoantibodies, liver biopsy, and endoscopic retrograde cholangiography and the other had ANA-positive chronic active hepatitis; enzymes in both cases improved with a gluten-free diet. There was no significant association between elevated AST/ALT and positive ANA/SMA; no patient had AMA. Abnormalities in liver enzymes are common in celiac sprue, but usually respond to dietary gluten exclusion. We propose that there is no need for invasive liver investigation in these patients unless there is more specific evidence of primary liver disease or failure of dietary response.

Recommendations Alpha Nutrition is gluten-free and is recommended as the diet revision strategy for anyone with diagnosed celiac disease, or any person with symptoms suggestive of gluten allergy.

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