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Nutrients Apr 2020The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and...
The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and barley should be strictly avoided, but the role of oats is more controversial. This study aimed to investigate the safety and long-term quality of life and health effects of oat consumption in 312 long-term treated DH patients. Baseline data were gathered from patient records and follow-up data from questionnaires or interviews, and validated questionnaires were used to assess quality of life. We found that altogether 256 patients (82%) were consuming oats as part of their GFD at the follow-up. Long-term follow-up data showed that there were no differences in the presence of long-term illnesses, coeliac disease complications or the usage of medication between those consuming and not consuming oats. However, oat consumers had a better quality of life and reported ongoing gastrointestinal symptoms less frequently (4% vs 19%, = 0.004) at the follow-up than those not consuming oats. The study established that oats are safe for DH patients and in the long-term seem to improve the quality of life of DH patients.
Topics: Adult; Avena; Celiac Disease; Cohort Studies; Dermatitis Herpetiformis; Diet, Gluten-Free; Female; Follow-Up Studies; Humans; Male; Middle Aged; Quality of Life; Safety
PubMed: 32290504
DOI: 10.3390/nu12041060 -
Journal of Dermatological Science May 2018Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate... (Review)
Review
Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate immunity that result in overlapping patterns of dermal and epidermal inflammation with hyperkeratosis. For such conditions, the umbrella term "autoinflammatory keratinization diseases" (AIKD) has been proposed. AIKD encompasses diseases with mixed pathomechanisms of autoinflammation and autoimmunity, and includes IL-36 receptor antagonist (IL-36Ra)-related pustulosis, CARD14-mediated pustular psoriasis, pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Mechanistically, the entities include generalized pustular psoriasis (GPP) without psoriasis vulgaris, impetigo herpetiformis and acrodermatitis continua, which are IL-36Ra-related pustuloses caused by loss-of-function mutations in IL36RN; GPP with psoriasis vulgaris and palmoplantar pustular psoriasis which are CARD14-mediated pustular psoriasiform dermatoses with gain-of-function variants of CARD14; PRP type V which is caused by gain-of-function mutations in CARD14; and, familial KLC in which mutations in NLRP1, an inflammasome sensor protein predominantly expressed in skin, have been identified. It is likely that further inflammatory keratinization disorders will also fall within the concept of AIKD, as elucidation of novel pathogenic mechanisms of inflammatory keratinization diseases emerges. A better understanding of the pathophysiology of AIKD is likely to lead to innovative, targeted therapies that benefit patients.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Autoimmune Diseases; CARD Signaling Adaptor Proteins; Dermatitis; Guanylate Cyclase; Humans; Immunity, Innate; Interleukins; Membrane Proteins; Mutation; NLR Proteins; Skin; Skin Diseases, Papulosquamous
PubMed: 29422292
DOI: 10.1016/j.jdermsci.2018.01.012 -
Health Technology Assessment... Oct 2022Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to...
BACKGROUND
Coeliac disease is an autoimmune disorder triggered by ingesting gluten. It affects approximately 1% of the UK population, but only one in three people is thought to have a diagnosis. Untreated coeliac disease may lead to malnutrition, anaemia, osteoporosis and lymphoma.
OBJECTIVES
The objectives were to define at-risk groups and determine the cost-effectiveness of active case-finding strategies in primary care.
DESIGN
(1) Systematic review of the accuracy of potential diagnostic indicators for coeliac disease. (2) Routine data analysis to develop prediction models for identification of people who may benefit from testing for coeliac disease. (3) Systematic review of the accuracy of diagnostic tests for coeliac disease. (4) Systematic review of the accuracy of genetic tests for coeliac disease (literature search conducted in April 2021). (5) Online survey to identify diagnostic thresholds for testing, starting treatment and referral for biopsy. (6) Economic modelling to identify the cost-effectiveness of different active case-finding strategies, informed by the findings from previous objectives.
DATA SOURCES
For the first systematic review, the following databases were searched from 1997 to April 2021: MEDLINE (National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, the Netherlands), Cochrane Library, Web of Science™ (Clarivate™, Philadelphia, PA, USA), the World Health Organization International Clinical Trials Registry Platform ( WHO ICTRP ) and the National Institutes of Health Clinical Trials database. For the second systematic review, the following databases were searched from January 1990 to August 2020: MEDLINE, Embase, Cochrane Library, Web of Science, Kleijnen Systematic Reviews ( KSR ) Evidence, WHO ICTRP and the National Institutes of Health Clinical Trials database. For prediction model development, Clinical Practice Research Datalink GOLD, Clinical Practice Research Datalink Aurum and a subcohort of the Avon Longitudinal Study of Parents and Children were used; for estimates for the economic models, Clinical Practice Research Datalink Aurum was used.
REVIEW METHODS
For review 1, cohort and case-control studies reporting on a diagnostic indicator in a population with and a population without coeliac disease were eligible. For review 2, diagnostic cohort studies including patients presenting with coeliac disease symptoms who were tested with serological tests for coeliac disease and underwent a duodenal biopsy as reference standard were eligible. In both reviews, risk of bias was assessed using the quality assessment of diagnostic accuracy studies 2 tool. Bivariate random-effects meta-analyses were fitted, in which binomial likelihoods for the numbers of true positives and true negatives were assumed.
RESULTS
People with dermatitis herpetiformis, a family history of coeliac disease, migraine, anaemia, type 1 diabetes, osteoporosis or chronic liver disease are 1.5-2 times more likely than the general population to have coeliac disease; individual gastrointestinal symptoms were not useful for identifying coeliac disease. For children, women and men, prediction models included 24, 24 and 21 indicators of coeliac disease, respectively. The models showed good discrimination between patients with and patients without coeliac disease, but performed less well when externally validated. Serological tests were found to have good diagnostic accuracy for coeliac disease. Immunoglobulin A tissue transglutaminase had the highest sensitivity and endomysial antibody the highest specificity. There was little improvement when tests were used in combination. Survey respondents ( = 472) wanted to be 66% certain of the diagnosis from a blood test before starting a gluten-free diet if symptomatic, and 90% certain if asymptomatic. Cost-effectiveness analyses found that, among adults, and using serological testing alone, immunoglobulin A tissue transglutaminase was most cost-effective at a 1% pre-test probability (equivalent to population screening). Strategies using immunoglobulin A endomysial antibody plus human leucocyte antigen or human leucocyte antigen plus immunoglobulin A tissue transglutaminase with any pre-test probability had similar cost-effectiveness results, which were also similar to the cost-effectiveness results of immunoglobulin A tissue transglutaminase at a 1% pre-test probability. The most practical alternative for implementation within the NHS is likely to be a combination of human leucocyte antigen and immunoglobulin A tissue transglutaminase testing among those with a pre-test probability above 1.5%. Among children, the most cost-effective strategy was a 10% pre-test probability with human leucocyte antigen plus immunoglobulin A tissue transglutaminase, but there was uncertainty around the most cost-effective pre-test probability. There was substantial uncertainty in economic model results, which means that there would be great value in conducting further research.
LIMITATIONS
The interpretation of meta-analyses was limited by the substantial heterogeneity between the included studies, and most included studies were judged to be at high risk of bias. The main limitations of the prediction models were that we were restricted to diagnostic indicators that were recorded by general practitioners and that, because coeliac disease is underdiagnosed, it is also under-reported in health-care data. The cost-effectiveness model is a simplification of coeliac disease and modelled an average cohort rather than individuals. Evidence was weak on the probability of routine coeliac disease diagnosis, the accuracy of serological and genetic tests and the utility of a gluten-free diet.
CONCLUSIONS
Population screening with immunoglobulin A tissue transglutaminase (1% pre-test probability) and of immunoglobulin A endomysial antibody followed by human leucocyte antigen testing or human leucocyte antigen testing followed by immunoglobulin A tissue transglutaminase with any pre-test probability appear to have similar cost-effectiveness results. As decisions to implement population screening cannot be made based on our economic analysis alone, and given the practical challenges of identifying patients with higher pre-test probabilities, we recommend that human leucocyte antigen combined with immunoglobulin A tissue transglutaminase testing should be considered for adults with at least a 1.5% pre-test probability of coeliac disease, equivalent to having at least one predictor. A more targeted strategy of 10% pre-test probability is recommended for children (e.g. children with anaemia).
FUTURE WORK
Future work should consider whether or not population-based screening for coeliac disease could meet the UK National Screening Committee criteria and whether or not it necessitates a long-term randomised controlled trial of screening strategies. Large prospective cohort studies in which all participants receive accurate tests for coeliac disease are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42019115506 and CRD42020170766.
FUNDING
This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 44. See the NIHR Journals Library website for further project information.
Topics: United States; Adult; Child; Male; Humans; Female; Celiac Disease; Longitudinal Studies; Prospective Studies; Skin Neoplasms; Immunoglobulin A; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36321689
DOI: 10.3310/ZUCE8371 -
The Journal of Investigative Dermatology Jun 2017Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal... (Review)
Review
Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lübeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases. Considerable advances have been made in describing incidences and prevalences of these diseases and linking comorbidities with autoantibody reactivities and clinical variants, for example, dipeptidyl peptidase-IV inhibitor-associated noninflammatory bullous pemphigoid. Although new entities are still being described, diagnosis of most autoimmune blistering diseases can now be achieved using standardized and widely available serological test systems. Various experimental mouse models of pemphigus and pemphigoid disease are increasingly being used to understand mechanisms of central and peripheral tolerance and to evaluate more specific treatment approaches for these disorders, such as molecules that target autoreactive T and B cells and anti-inflammatory mediators, that is, dimethyl fumarate, phosphodiesterase 4, and leukotriene B4 inhibitors in pemphigoid disorders, and chimeric antigen receptor T cells in pemphigus. Very recent experimental data about the immunopathology and the determinants of autoantibody formation and keratinocyte susceptibility in pemphigus were discussed. With regard to cellular mechanisms leading to the loss of cell-cell adhesion, new ideas were shared in the field of signal transduction. Major steps were taken to put the various partly contradictory and controversial findings about the effects of pemphigus autoantibodies and other inflammatory mediators into perspective and broaden our view of the complex pathophysiology of this disease. Finally, two investigator-initiated multicenter trials highlighted doxycycline and dapsone as valuable medications in the treatment of bullous pemphigoid.
Topics: Animals; Autoantibodies; Autoimmune Diseases; Consensus; Female; Germany; Humans; Male; Mice; Pemphigoid, Bullous; Pemphigus; Prognosis; Risk Assessment
PubMed: 28390814
DOI: 10.1016/j.jid.2017.01.028 -
Nutrients Dec 2023Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including... (Review)
Review
Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including damage to cutaneous and connective tissue. We report a rare case of chronic severe dermatitis involving connective tissue and cutaneous vascular vessels as the main clinical presentation of undiagnosed seronegative gluten disorder. A gluten-free diet dramatically improved the intestinal and cutaneous clinical damage in the patient. Pitfalls and the steps of differential diagnosis are described. We also review the literature regarding studies of CD and connective tissue diseases to extend the knowledge of these rare associations. We propose a practical diagnostic approach in suspected CD in autoimmune cutaneous disorders.
Topics: Humans; Celiac Disease; Skin Diseases; Dermatitis; Glutens; Autoimmune Diseases
PubMed: 38201912
DOI: 10.3390/nu16010083 -
JAMA Dermatology Dec 2020This survey study describes the frequency of dermatitis herpetiformis among patients included in the iCureCeliac network as well as the demographics of patients with...
This survey study describes the frequency of dermatitis herpetiformis among patients included in the iCureCeliac network as well as the demographics of patients with dermatitis herpetiformis and underlying celiac disease.
Topics: Adult; Celiac Disease; Counseling; Dermatitis Herpetiformis; Diet, Gluten-Free; Female; Humans; Male; Middle Aged; Prevalence; Surveys and Questionnaires; Young Adult
PubMed: 33026427
DOI: 10.1001/jamadermatol.2020.3431 -
Nutrients Feb 2020Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits....
Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.
Topics: Adult; Aged; Autoantibodies; Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Female; GTP-Binding Proteins; Glutens; Humans; Intestinal Mucosa; Intestine, Small; Male; Middle Aged; Plasma Cells; Protein Glutamine gamma Glutamyltransferase 2; Transglutaminases
PubMed: 32069794
DOI: 10.3390/nu12020467 -
Cureus Sep 2021Background and objective Celiac disease is an autoimmune multisystem disorder that is triggered by dietary gluten sensitivity in genetically susceptible individuals. It...
Background and objective Celiac disease is an autoimmune multisystem disorder that is triggered by dietary gluten sensitivity in genetically susceptible individuals. It presents with extraintestinal cutaneous manifestations including dermatitis herpetiformis (DH), atopic dermatitis, psoriasis, urticaria, and alopecia areata. Due to the insufficient availability of data, this study aimed to estimate the frequency of cutaneous manifestation in a Pakistani population with celiac disease. Methods This cross-sectional study was conducted from January 2020 to July 2021, and 300 patients with a confirmed diagnosis of celiac disease were enrolled in the study from the internal medicine department of a tertiary care hospital in Pakistan. Celiac disease was confirmed by the presence of immunoglobulin A (IgA) endomysial antibody and IgA tissue transglutaminase antibody. The presence of cutaneous manifestations was assessed with the assistance of a qualified dermatologist and noted in a self-structured questionnaire. Results Overall, the most common cutaneous manifestation was DH (16.0%), whereas the second most common cutaneous manifestation was psoriasis (13.8%). DH was most commonly found among males (18.9%), while psoriasis was more common among females (14.12%). Conclusion Among the various cutaneous presentations in patients with celiac disease, the most common dermatological manifestation was DH. Therefore, patients with cutaneous manifestations should undergo screening for celiac disease.
PubMed: 34703686
DOI: 10.7759/cureus.18148 -
Annals of Gastroenterology 2017Microscopic enteritis (ME) is characterized by abnormal infiltration of intraepithelial lymphocytes in intestinal mucosa. It was described as duodenal lymphocytosis or... (Review)
Review
Microscopic enteritis (ME) is characterized by abnormal infiltration of intraepithelial lymphocytes in intestinal mucosa. It was described as duodenal lymphocytosis or lymphocytic duodenitis until the dedicated Consensus Conference of 2015. ME represents a common feature of several gluten-mediated and non-gluten related diseases; therefore, it is an umbrella term embracing several conditions. The most frequent causes of ME are gluten-related disorders (celiac disease, non-celiac gluten sensitivity, wheat allergy), infection and drug-related damages. Less frequently, ME may be secondary to inflammatory bowel disease, some autoimmune conditions, immunoglobulin deficiencies, blood malignancies, infections and irritable bowel syndrome. Therefore, the differential diagnosis of ME may be challenging. The diagnosis of ME needs to be driven by predominant symptoms and patient history. However, it is often difficult to achieve an immediate identification of the underlying condition, and a broad variety of diagnostic tests may be required. Ultimately, long-term surveillance is needed for a final diagnosis in many cases, since a hidden or quiescent condition may be disclosed after a period of latency. In any case, strict collaboration between the clinician and the pathologist is pivotal. The treatment of ME should be personalized, depending on the underlying disease. For gluten-related conditions (celiac disease, gluten sensitivity, wheat allergy, dermatitis herpetiformis), a gluten-free diet may be proposed. For other conditions, a targeted etiologic treatment is necessary. In conclusion, ME represents a novel entity that is attracting increasing interest. The growing epidemiologic trend confirms that it will become a common condition in clinical practice.
PubMed: 28655974
DOI: 10.20524/aog.2017.0165 -
JAMA Dermatology Nov 2021Dermatologists submit direct immunofluorescence (DIF) biopsies on a daily basis, using an assay detecting immunoreactant deposition with a panel that has traditionally...
IMPORTANCE
Dermatologists submit direct immunofluorescence (DIF) biopsies on a daily basis, using an assay detecting immunoreactant deposition with a panel that has traditionally comprised immunoglobulin (Ig) G, IgA, IgM, C3, and fibrin, with or without albumin antibodies.
OBJECTIVES
To evaluate and compare the frequency of immunoreactants in DIF biopsies submitted over an 8-year period and assess use by dermatologists based on clinical impression.
DESIGN, SETTING, AND PARTICIPANTS
A quality improvement study was conducted in a community outreach reference laboratory associated with a large academic medical center. Results of 2050 consecutive DIF skin biopsies submitted to the laboratory between April 1, 2012, and June 12, 2020, were analyzed by final pathologic diagnosis and antibody subtype positivity, in comparison with clinical impression. Biopsies in which the submitting physician had not performed the biopsy were excluded.
MAIN OUTCOMES AND MEASURES
Histopathologic findings and the results of DIF biopsies using the standard 6-antibody panel were evaluated in correlation with the submitted clinical diagnosis to assess immunoreactivity of the assay.
RESULTS
Of 2050 DIF biopsies submitted, 367 (17.9%) were positive; IgG, IgA, and C3 alone identified all primary immunobullous disease cases (pemphigoid, pemphigus, linear IgA, and dermatitis herpetiformis), and IgA, C3, and fibrin antibodies alone identified all vasculitis cases. A panel of IgG, IgA, IgM, and fibrin identified all cases of lupus erythematosus. DIF results were positive in less than half of cases of hematoxylin and eosin biopsy-confirmed lupus erythematosus (23 of 47 [49%]). A total of 247 biopsies were submitted for clinical diagnoses not optimally supported on DIF: lichen planus, porphyria, and connective tissue disease.
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that there is a knowledge gap among dermatologists relating to the opportunity for high-value, cost-conscious use of DIF. The practice of reflexive antibody testing using a 6-antibody panel for all DIF biopsies is likely unnecessary. DIF protocols tailored to the clinical diagnosis may enhance cost-effectiveness without loss of test sensitivity or specificity.
Topics: Fluorescent Antibody Technique, Direct; Humans; Linear IgA Bullous Dermatosis; Pemphigus; Skin; Skin Diseases
PubMed: 34613346
DOI: 10.1001/jamadermatol.2021.3892