J.N. Leonard

The Oslo definitions for coeliac disease and related terms

Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.

Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology

A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.

Linear IgA disease in adults

A multi‐centre study is described in which thirty‐five adult patients with papillary IgA dermatitis herpetiformis (DH) were compared with forty‐two patients with linear IgA deposits, of whom thirty‐four had homogeneous‐linear (HL) and eight had granular‐linear (GL) IgA deposits.

Absence of Toxicity of Oats in Patients with Dermatitis Herpetiformis

BACKGROUND People with gluten sensitivity should avoid foods containing wheat, rye, and barley, but there has been debate about whether they should avoid oats. Although patients with celiac disease have recently been shown to tolerate oats, less is known about the effects of oats on patients with dermatitis herpetiformis. METHODS We studied seven men and three women (mean age, 58 years) with biopsy-confirmed dermatitis herpetiformis. They had followed a strict gluten-free diet for a mean of 15.8 years, which controlled their rash and enteropathy. The patients added oats that were not contaminated with gluten to their diets for 12 weeks (mean [+/-SD] daily intake, 62.5+/-10.8 g). RESULTS None of the patients had any adverse effects. Serologic tests for antigliadin, antireticulin, and antiendomysial antibodies were negative before oats were introduced into the diet and after they were discontinued. Villous architecture remained normal: the mean (+/-SE) ratio of the height of villi to the depth of crypts was 3.59+/-0.11 before the diet and 3.71+/-0.09 afterward (normal, 3 to 5), and the mean enterocyte heights were 31.36+/-0.58 microm and 31.75+/-44 microm, respectively (normal range, 29 to 34). Duodenal intraepithelial lymphocyte counts all remained within normal limits (mean, 13.8+/-1.03 per 100 enterocytes before the diet and 14.2+/-1.2 per 100 enterocytes afterward; normal range, 10 to 30). Dermal IgA showed no significant changes. CONCLUSIONS Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.

The effects of cyclosporin A on T lymphocyte and dendritic cell sub-populations in psoriasis

Sequential skin biopsies from six patients with severe psoriasis were studied during treatment with cyclosporin. Four of the patients cleared completely and the remaining two showed a marked improvement. A subset of dendritic cells, HLA‐DR+ but lacking the T6 antigen characteristically expressed by Langerhans cells (DR+ 6‐), was observed in lesional epidermis. They disappeared during treatment, before clinical improvement was apparent and at a rate which correlated with clearance of psoriasis. These cells were not found in normal or uninvolved psoriatic epidermis and their number in lesional skin appeared to be related to the clinical severity of the disease. Total numbers of CD4 and CD8, and HLA‐DR+ CD8 T cells were substantially reduced in both epidermis and dermis prior to clinical improvement. In contrast, there was generally no decrease in the number of HLA‐DR + CD4 T cells in the epidermis during resolution, whereas these cells were reduced by an average of 68% in the dermis. The beneficial effects of cyclosporin in psoriasis further support the hypothesis that T cells play a central role in the pathogenesis of psoriasis. The cellular changes observed in the skin during cyclosporin treatment may help to elucidate the effects of this drug on immunoregulatory mechanisms in man.

Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis.

A retrospective study of 487 patients with dermatitis herpetiformis showed that lymphoma developed in eight patients, the expected incidence being 0.21 (standardized registration ratio 3810). All lymphomas occurred in patients whose dermatitis herpetiformis had been controlled without a gluten‐free diet (GFD) or in those who had been treated with a GFD for less than 5 years. The results are suggestive of a protective role for a GFD against lymphoma in dermatitis herpetiformis and give further support for advising patients to adhere to a strict GFD for life.

Increased incidence of malignancy in dermatitis herpetiformis.

A retrospective study of 109 patients with dermatitis herpetiformis showed that malignant tumours had developed in seven patients, the expected incidence being 2.93, giving a relative risk of 2.38. In three of the seven patients the malignancy was a lymphoma, giving a relative risk of 100 for this tumour (expected incidence 0.03). In six of the seven patients who developed malignancies small-intestinal biopsy specimens were macroscopically abnormal, giving a relative risk of 4.22 in this group, which is similar to that reported in adult coeliac disease. Patients treated with a gluten-free diet appeared to have a reduced risk of developing malignancy compared with those taking a normal diet (relative risk with gluten-free diet 1.01 and with normal diet 3.09). A small subgroup of eight patients with linear IgA dermatitis herpetiformis were also studied: three developed malignant disease and in one the tumour was a lymphoma.

25 years' experience of a gluten‐free diet in the treatment of dermatitis herpetiformis

Gluten‐free diets have been used in the treatment of patients with dermatitis herpetiformis in our department since 1967. Of the 212 patients with dermatitis herpetiformis attending between 1967 and 1992, 133 managed to take the diet, and 78 of these achieved complete control of their rash by diet alone. Of the remaining 55 patients taking a gluten‐free diet, all but three were taking partial diets; over half of these patients managed to substantially reduce the dose of medication required. Of the 77 patients taking a normal diet, eight entered spontaneous remission, giving a remission rate of 10%; a further two patients who had been taking gluten‐free diets were found to have remitted when they resumed normal diets. Loss of IgA from the skin was observed in 10 of 41 (24%) patients taking strict gluten‐free diets. These patients had been taking their diets for an average of 13 years (range 5–24 years), and their rash had been controlled by diet alone for an average of 10 years (range 3–16 years).

Immunofluorescent studies in ocular cicatricial pemphigoid.

Twenty nine patients with cicatrizing conjunctivitis were studied; 17 with a clinical diagnosis of cicatricial pemphigoid, five with a clinical diagnosis of pseudopemphigoid caused by long‐term application of topical medication and seven who had a cicatrizing conjunctivitis from other causes. Biopsies from clinically uninvolved bulbar conjunctiva were taken for direct immunofluorescence and blood was taken for indirect immunofluorescence using normal human conjunctiva, oral mucosa and skin as substrates.

Linear IgA disease of adults: association with lymphoproliferative malignancy and possible role of other triggering factors

Seventy patients with linear IgA disease of adults were followed up for a mean of 8.5 years and all malignant diseases in this group were ascertained. There were three cases of lymphoproliferative malignancy, which constituted a significant excess over the 0.2 cases that would be expected by comparison with an age‐ and sex‐matched population using National Cancer Registry statistics. In contrast, the non‐lymphoid malignancy rate of 13% is almost identical to the expected 14%. A subgroup of 35 of the adult linear IgA disease patients were assessed with respect to the possible precipitating illnesses or drugs, as well as co‐existing medical conditions. Almost one‐third of patients described an event that was felt could possibly have triggered the linear IgA disease, the most frequent being non‐steroidal anti‐inflammatory or antibiotic drug therapy, trauma/burns and upper respiratory tract infections. However, it is difficult to determine how often the preceding event is coincidental, and how often, if at all, it is causal.