Celiac disease

Original Article

Vol. 3 nº 3 - Jul/Sep - 2006
Pages:52-
56

Celiac disease

Authors:

Celiac disease is an enteropathy that affects the small intestine of genetically predisposed children and adults; it is also known as celiac sprue, non-tropical sprue or gluten-sensitive enteropathy (a protein found in wheat, barley, rye and oats). This clinical entity was first characterized in the late 19th century, when it referred to a group of specific diseases that were only identified and correctly named over time. A good example of this occurred in 1938, when cases of cystic fibrosis with pancreatic involvement were identified. These cases were correctly diagnosed and distinguished from the celiac group. Thanks to the spectacular scientific and technological developments at the end of the last century, medicine can increasingly base medical diagnoses on precise and specific facts. Celiac disease, like so many others, is a result of this virtuous process. Therefore, today, this clinical entity thus known refers to a specific disease with a defined etiopathogenesis, namely, an abnormal tissue inflammatory reaction in the mucosa of the digestive tract, especially in the small intestine, with a cellular (T-lymphocyte-dependent) and humoral (B-lymphocyte-dependent) immunological basis, when it is exposed to the presence of prolamins and glutenins, proteins that structure gluten. Syndromically, it can be considered in the group of food allergies, malabsorptions or also protein-losing gastroenteropathies. In this article, we will present some notes that will update topics of recent developments in the epidemiology, pathophysiology, diagnosis and prognosis of this disease, which is so complex in its generating and maintaining mechanisms, but so unique in its treatment. WHAT’S NEW IN THE EPIDEMIOLOGY OF CELIAC DISEASE Currently, and differently from the notion of a few decades ago, celiac disease is not rare or infrequent, nor does it affect only white children in developed countries. Some specialized publications inform us, for example, that there are approximately 2.18 million people with the disease in the United States. Other projections conservatively estimate that there are almost 25 million people with celiac disease worldwide, a calculation based on a conservative prevalence estimate of 1:250 (cases/inhabitants) in which at least 60% of cases will be diagnosed in adults. Thus, another concept has emerged in recent years: the disease is not exclusive to children or adolescents, and can affect individuals of any age group, which has changed our perception of this diagnostic possibility in cases with malnutrition or equivalent, diarrheal or not. In countries with consistent and reliable statistics, at least 20% of new cases of celiac disease are diagnosed in people aged 60 or over. Furthermore, even greater emphasis should be given to information from research with children who were refugees from political and ethnic conflicts in Saharan Africa and who had severe nutritional deficiencies associated with dysentery and diarrhea. For example, in 989 refugee children camped in Tindouf, Algeria, a prevalence of celiac disease of 5.6% was found—five to ten times higher than that reported in developed countries. The clinical challenge in making this diagnosis lies in the spectrum of signs and symptoms presented by these children. In comparison with other children with potentially suspicious complaints, in addition to malnutrition and impaired growth, we see that only abdominal pain and distension were more common in celiac children ( p < 0.05), and diarrhea was as frequent in these children as in controls (50% of cases). The greatest challenge we still face is in the context of food intake for its treatment, since in the research of their 24-hour food intake recall, 88% and 63% ate bread and rice, respectively. RECENT PROGRESS IN GENETIC MARKERS OF THE DISEASE Celiac disease is genetic and autoimmune, and its symptoms can vary from person to person. The mere possibility of defining it as such is its greatest recent progress. Several genes contribute to the genetic predisposition to the anomalous reaction to gluten ingestion (immune, dependent on the activation of T lymphocytes). The most important genetic factors were identified on the short arm of chromosome 6, at position 21 (6p21), in the major histocompatibility complex (HLA) of the genes encoding DQ ₂ or DQ ₈ (95% and 5%, respectively). It appears that genes outside the HLA system also contribute to people’s (genetically determined) susceptibility to celiac disease, but these relationships are still poorly understood. The implications of this knowledge for the pathophysiological understanding of the disease are undeniable and, from a practical point of view, increasingly allow us to identify population subgroups at risk. HOW TO CLINICALLY SUSPECT AND DIAGNOSE CELIAC DISEASE Since 1888, with celiac disease in English children returning from trips to the tropics (and it must have been tropical sprue!), through intestinal infantilism that affected adults in 1908, until the 1950s, with jejunal biopsy and the introduction of the gluten-free diet to treat these people, when the concept that idiopathic steatorrhea in adults was, in fact, celiac disease in this age group, we have seen continuous progress in the knowledge of this disease, to the point that, today, even histopathology of the intestinal mucosa is dispensable for the definitive diagnosis of the disease. What progress! In this brief condensed review, three aspects that have revolutionized diagnosis deserve to be highlighted. First, when should I consider this diagnosis in a patient? Let us forget the classic syndrome with steatorrhea, growth and development deficiency in children and adolescents, with anemia and protruding abdomen; this will occur in a minority of cases. Today it is a diagnostic possibility for any type of abdominal (digestive) discomfort, with its varied spectrum of complaints. In irritable bowel syndrome, for example, at least 3% of adult patients are celiac and will greatly benefit from an appropriate diet (treatment). On the other hand, much more is known today about the association of several other diseases, autoimmune or not, with gluten intolerance: attention deficit hyperactivity disorder (ADHD), autism, nodular lymphoid hyperplasia of the digestive tract, chronic fatigue syndrome, Addison’s disease, type 1 diabetes, depression, Down syndrome, fibromyalgia, infertility, miscarriages, arthritis, migraines, multiple sclerosis, cardiomyopathies, autoimmune hepatitis, psoriasis, sarcoidosis, Sjögren’s, thrombocytopenic purpura, thyroiditis (lymphocytic?), mouth ulcers. It is worth remembering that dermatitis herpetiformis is the cutaneous manifestation of gluten intolerance. Secondly, after identifying a possible case, what should be done to confirm (or rule out) this diagnosis? The answer is straightforward: serological and histopathological tests. And the interpretation of the latter currently represents, as we will see, the third major recent advance in celiac disease. Let us separate our cases into those in which our clinical suspicion is low and those in which it is high. In the first group, low suspicion, we should arrange for the measurement of the anti-endomysium antibody (the connective tissue surrounding the smooth muscle) or, if available, the anti-transglutaminase antibody (the specific epitope of the immunological reaction that determines the disease). Do not forget, in addition, to measure the total serum immunoglobulin A to rule out its deficiency as the cause of the symptoms. If the specific test(s) are positive, ideally an intestinal biopsy should be indicated, which is now safely performed endoscopically and by removing fragments of the duodenal mucosa as distally as possible. If the blood test is negative, the diagnosis of celiac disease is ruled out in this patient. In the other subgroup, that of high clinical suspicion, it is recommended to initially combine the two tests, the serological and the histopathological. If both results are positive, there is no doubt: it is celiac disease. Obviously, if both are negative, it cannot be celiac disease. There is still the possibility that the results are conflicting. What should be done then? It is simple: if the blood test is positive and the histopathology is negative, confirm and monitor the patient; if the disease persists, repeat the biopsy after some time (one year, for example). If the situation is the opposite, negative blood and positive tissue, consider other causes for the patient’s disease. If there is no other possibility, treat as celiac: strict diet. Histopathological aspects constitute, as we said before, the third major recent advance, not only as a diagnostic criterion for celiac disease, but also, more importantly, as a qualified tool for better understanding the tissue dynamics of the evolution (natural history) of the disease. Just to mention, there are four defined stages of microscopic tissue injury named classes I to IV, with class III being subdivided into three subclasses: IIIa, IIIb and IIIc. In class I, we have exclusive lymphocytic infiltration; in class II, crypt hyperplasia is added; in class III, varying degrees of atrophy are added (partial, subtotal and total); class IV, in which atrophy is total, with large deposition of collagen in the mucosa and submucosa (collagenous sprue), generally consists of patients refractory to treatment and in whom possible lymphomatous transformation seems to occur more frequently. In this regard, immunohistochemical possibilities allow us to identify the subpopulation of celiac patients most likely to develop lymphomatous transformation over time: those who mark for CD8, CD30 and CD103 (associated with the mucosa). CHANGES IN ATTITUDE RESULTING FROM ADVANCES IN CELIAC DISEASE The conceptual evolution of celiac disease that has occurred in recent years presents us with professional challenges that were unimaginable just a few decades ago. Based on some of these advances, our change in attitude converges towards a single, priority action – early diagnosis. Advances in genetics and epidemiology and the technological simplicity for the definitive diagnosis of the disease, associated with the availability of dietary products necessary for its correct treatment, require us to actively seek out cases. How should we do this? There are clearly two types of strategy: the identification of cases in people at risk and the actions known as mass screening . For the second strategy, no country has developed any proposal and it should still be considered a remote possibility. However, in the case of active screening in people who are known to be at greater risk than the general population of being asymptomatic carriers of the disease[1], we have some indicators that justify its mandatory recommendation. The risk of celiac disease in the general population is estimated at 1%; in people with HLA-DQ2 or DQ8 it rises to 2%-3%; for first-degree relatives of patients with the disease it is already 10%-15% and 20%-30% if the relative is DQ2 or DQ8+. The iceberg metaphorThis recommendation is easy to understand because we know that in Europe, for every diagnosed case, there are an estimated five to 13 undiagnosed cases. A risk analysis for first- and second-degree relatives of celiac patients estimates a prevalence of the disease of 1:10 and 1:39, respectively. In other groups of symptomatic people, including those on the extensive list of diseases associated with or most common in celiac patients, this estimated prevalence is 1:56. Otherwise, this attitude will have positive repercussions, not only on the quality of life of these patients but also on the possibility of avoiding, in these cases, many of the deleterious and known evolutionary complications of untreated celiac disease. Among these we highlight intestinal lymphoma, small intestine neoplasms, oropharyngeal and esophageal tumors, colon adenocarcinoma, infertility, osteoporosis, growth retardation and some autoimmune diseases. Genetic counseling as a primary prevention strategy for new cases and even for genetic intervention in the future are currently open possibilities. The dissemination of information about this new knowledge about such an ancient disease mainly benefits its sufferers. In the specialized literature in English, an acronym was even created with the six commandments for the good treatment of patients:

C onsultation with a skilled dietitian, Education about the disease, Long -term adherence to a gluten-free diet, I dentification and treatment of nutritional deficiencies, Access to an advocacy group, and Continuous long-term follow-up with a multidisciplinary team!

In conclusion, we know that every synthesis is perverse because it cannot contemplate the synthesized universe. We refer the reader to a short list of recommended readings where it will be possible to find the complementary information necessary for a better understanding of this text and its bibliographical support.

References

1. Bai J, Zeballos E, Fried M, et al. WGO-OMGE Practice Guideline. Celiac Disease, February 2005. Available at:. 2. Bingley PJ, Williams AJK, Norcross AJ, et al. Undiagnosed celiac disease at age seven: population-based prospective birth. BMJ 2004;328:322-3. 3. Busschots GV, Vallee PA, Guandalini S. Sprue. eMedicine. Available at:. 4. Mulder C, Cellier C (editors). Coeliac disease. Best Pract Res Clin Gastroenterol 2005;19(3):311-487. Available at:. 5. National Institutes of Health. NIH Consensus Development Conference on Celiac Disease. Consensus Conference Statement. June 28-30, 2004. Available at:. 6. Rätsch IE, Catassi C. Celiac disease: a potentially treatable health problem of Saharawi refugee children. Bulletin of the World Health Organization 2001;79:541-5. Available at:. 7. Rostom A, Dubé C, Cranney A, et al. Celiac Disease. Summary, Evidence Report/Technology Assessment No. 104. AHRQ Publication No. 04-E029-1. Rockville, MD: Agency for Healthcare Research and Quality. June 2004. Available at:. 8. Sanders DS, Patel D, Stephenson TJ, et al. A primary care cross-sectional study in undiagnosed adult coeliac disease. Eur J Gastr Hep 2003;15:407-15. 9. Utiyama SR, Reason IJ and Kotze LM. Genetic and immunopathogenic aspects of celiac disease: current view. Arq Gastroenterol 2004;41(2):121-8. 1. Full professor of clinical medicine at the School of Medical Sciences of the State University of Rio de Janeiro (FCM/UERJ); director of the Center for Studies on Adolescent Health (NESA/UERJ); full member of the National Academy of Medicine (ANM). [1] An asymptomatic patient is a philosophical impossibility of the medical art, since only those who feel discomfort can be sick; science opens up this possibility for us, a contemporary paradox of development.