Causes
Celiac’s disease, previously also known as sprue, is an autoimmune disorder associated with the ingestion of gluten, a protein present in wheat, rye and barley, in genetically predisposed individuals. Incompletely digested gluten, or more specifically the gliadin protein portion, leads to inflammatory reactions predominantly in the small intestine. This process may be enhanced by factors increasing the leakiness of the intestinal lining (increased intestinal permeability), such as infections. Possible protective factors may be breast-feeding and the introduction of gluten only after the age of 7 months, at the time of weaning.
Frequency in population
Approximately 1% of the population has celiac’s disease, as detected by screening methods, most of whom are asymptomatic. The incidence may be even higher in 1st (5-22%) and 2nd degree (2-15%) relatives of individuals with manifest celiac’s disease, as well as patients with diabetes mellitus type 1 (2-8%), autoimmune thyroiditis (2-7%), liver disease (2-9%), Down’s (5%) and Turner’s (6%) syndromes, unexplained infertility (4%), and especially a skin disease known as dermatitis herpetiformis (100%). Both children and adults are affected by celiac’s disease and almost all patients have certain genetic markers (HLA-DQ2 or HLA-DQ8). Negative markers virtually exclude the disease, but positive markers also occur in over 40% of unaffected individuals. Twenty-five percent of patients with newly diagnosed celiac’s disease are now over 60 years old.
Symptoms
Symptoms and signs of celiac’s disease range from unspecific, such as fatigue, anemia, osteoporosis, malabsorption of vitamins and minerals, dental enamel malformations, skin, thyroid or liver disease, growth retardation in children, possibly infertility or miscarriages, and neurologic symptoms, to classic gastrointestinal, including diarrhea or constipation, bloating / abdominal distension, flatulence, increased intestinal sounds, abdominal pain and cramps, vomiting and weight loss. Diverse rheumatologic and autoimmune disorders, as well as depression are associated with celiac’s disease and there is an increased incidence of small bowel cancer in inadequately managed disease. Over 35% of patients with subsequently diagnosed celiac’s disease had earlier received a diagnosis of irritable bowel syndrome. Inflammation in the small intestine due to celiac’s disease is a common reason for so-called secondary lactose (milk sugar) intolerance (see Lactose intolerance), unexplained iron deficiency or anemia and osteoporosis.
Testing and diagnosis
Diagnosis is possible using tissue samples from the small intestine taken during upper endoscopy and with blood tests for specific antibodies (antitransglutaminase, aTGA) and genetic markers. Both children and adults are affected by celiac’s disease and almost all patients have certain genetic markers (HLA-DQ2 or HLA-DQ8). Negative markers virtually exclude the disease, but positive markers also occur in over 40% of unaffected individuals. Twenty-five percent of patients with newly diagnosed celiac’s disease are now over 60 years old. Exclusion of vitamin and other deficiencies, as well as associated diseases should be part of the diagnostic procedure.
See Tests.
Management
Treatment is via meticulous and life-long dietary exclusion of gluten. This requires long-term expert dietary advice, support and medical surveillance. Wheat, rye and barley must be excluded from the diet and they occur in hidden form in many processed foods, beverages and medicines (see Food tables). Oats are gluten-free, but can be gluten-contaminated due to processing procedures. They are tolerated by most patients. A wide range of gluten-free foods are now offered in many countries and patient support organizations offer useful support and resources (See Links below). The term ‘gluten-free’ actually implies gluten levels below a certain limit, as defined by governments. Some governments subsidize the special dietary needs. Various novel therapies are undergoing evaluation, including the development of cereals free of the offending proteins by genetic modification, induction of immune tolerance and ingestion of supplements digesting the offending dietary proteins.
Repeated and long-term follow-up is required in this multi-organ disease. Adherence to the gluten-free diet and disease regression should be periodically assessed using blood antibody tests (e.g. anti-transglutaminase antibody), or small intestinal biopsies. With strict adherence and a good clinical response, many of the potential disease complications can be prevented. However, due to an increased incidence of some cancers and other autoimmune disorders, follow-up at reasonable intervals is recommended. Vitamin and mineral supplements are often necessary. Improvement in symptoms can occur within 2 weeks of beginning the diet and antibodies can revert to normal within 3-12 months. Lactose intolerance often resolves naturally with time. Inadequate responses to a gluten-free diet are most commonly due to dietary errors, although about 5% of patients do not respond despite strict dietary adherence (‘refractory celiac disease”). In the latter case further diagnostic workup is required. Refractory celiac’s disease may respond to steroids or immunosuppressive drugs.
Currently contentious issues include the necessity of a gluten-free diet in asymptomatic individuals testing positive for celiac’s disease, the maximum amount of gluten permitted in foods labeled as ‘gluten-free” and interpretation of cereal or gluten sensitivity without evidence of celiac’s disease. It should be noted not all intolerances to grains constitute celiac’s disease, but that in case of symptoms other cereal allergies and intolerances should also be considered. One such differential diagnosis is wheat allergy, which is IgE-mediated and often exercise induced (see Food allergies).
See Food tables.
Links to literature, including support organizations:
www.celiac.org
www.gluten.net
www.americanceliac.org
www.celiac.com
www.csaceliacs.org
www.celiachealth.org
http://celiac.nih.gov
http://www.celiaccentral.org
http://www.glutenfreepassport.com/refcenter/links/associations.html
http://gflinks.com
www.coeliac.org.au
Gluten-free drugs
http://www.glutenfreedrugs.com/
and
http://healthsystem.virginia.edu/internet/digestive-health/nutritionarticles/PlogstedArticle.pdf