When To Consult A Doctor

Description: 

Following things should be considered  for follow up if a patient is having diagnosed celiac diseases: 

A few patients do not improve on a strict diet and are said to have non-responsive coeliac disease. Many of these patients are still ingesting gluten. A few of the others may have concomitant problems, e.g. microscopic colitis, IBD, small bowel bacterial overgrowth or lactase deficiency.

A very small percentage will have the rare complication of refractory coeliac disease (RCD). In type 1 RCD, the lymphocytes are normal and the T cell receptors are polyclonal, whilst in type 2 there are abnormal clonal lymphocytes with loss of CD8 and CD3 surface markers. The 5-year survival rates are 93% and 40–60% respectively.

T cell lymphoma (EATCL)  or ulcerative jejunitis can occur as part of a spectrum of neoplastic T cell disorders. Small bowel adenocarcinoma is also increased in coeliac disease which are associated with weight loss and bleeding per rectum.

Ulcerative jejunitis presents with fever, abdominal pain, perforation and bleeding.

Diagnosis for these conditions is with MRI or barium studies but laparoscopy with full-thickness small bowel biopsies is often required. Steroids and immunosuppressive agents, e.g. azathioprine, are used in ulcerative jejunitis.

Carcinoma of the oesophagus as well as extragastrointestinal cancers are also increased in incidence. Malignancy seems to be unrelated to the duration of the disease but the incidence is reduced by a gluten-free diet.

Celiac Disease and Diabetes Melllitus

Description:

Celiac disease and TIDM both share common genetic patttern i,e sharing common HLA pattern including HLA-DQ2 and/or DQ8, TNF-α-308A. MYO9B polymorphism is also documented in both disorders.
Both diseases are immune-regulated and associated with autoimmune thyroiditis and rheumatoid arthritis.These diseases are associated with organ-specific autoantibodies: AIT with thyroid peroxidase (TPO) and thyroglobulin autoantibodies (TG), CD with endomysial (EMA) and transglutaminase (TTG) autoantibodies, and AD with adrenal autoantibodies.
Viral infections like rotavirus,coxsackievirus B etc cause disruption of intestinal permeability have also been documented to share role in both celiac disease and TIDM.Celiac disease associated with diabetes is usually silent, showing no signs and symptoms, such as abdominal pain, gas, bloating,malabsorption, weight loss, and abnormal liver function tests can be seen and easily confused with poor glucose control of TIDM.Untreated celiac disease can be associated with irregular blood glucose swings on screening.so it should be investigated.
Females have a higher risk of having both CD and T1DM than males.
Patients with CD and TIDM can show same symptoms like extremehunger,irritability
,weightloss,early fatigue,growth failure particularly in children.

Celiac Disease and Genetics

Celiac Disease and Obesity

Description:

Exact mechanism of correlation between celiac disease and obesity is not clearly understood but it seen clinically and experiments has shown favour to these observations.

Celiac disease center in the University of Columbia  conducted a study  from 1981 to 2007 duration, examined 369 patients who were diagnosed cases of celiac disease. Many testing procedures were performed. The study showed that malnutrition was a common condition in both , especially in females with high incidence of diarrhea as a symptom of celiac disease. But at the same time, it was also found that  a huge percentage of the celiac patients – mostly male – were obese. When  gluten free diet was followed, it was seen that while those patients with low BMI attained the normal range, 50% of those who were obese also attained normal BMI.

 A paper was published in the American Journal of Gastroenterology by dr.Willium Dickey in 2006. In this paper, he found that of all the celiac patients he tested; only five percent were underweight. This same study found that 39% of these patients were overweight and 13% were obese of all celiac disease patients. Hence, it can be said that obesity is far more common in celiac patients than malnutrition.

This linkage stresses that weight maintenance counselling should be an integral part of celiac dietary education.

Managment

Description:

Replacement minerals and vitamins, e.g. iron, folic acid, calcium, vitamin D, may be needed initially to replace body stores.

 Gluten-free diet for life is recommended so far. Dietary elimination of wheat, barley and rye usually produces a clinical improvement within days or weeks. Morphological improvement often takes months, especially in adults. Oats are tolerated by most coeliacs, but must not be contaminated with flour during their production. Meat, dairy products, fruits and vegetables are naturally gluten free and are all safe.

Gluten-free products can be expensive, unless subsidized by national health services. Patient support organizations such as The Coeliac Society are valuable as information sources and for advice about diet, recipes and gluten-free processed foods. Despite advice, many patients do not keep to a strict diet but maintain good health. The long-term effects of this low gluten intake are uncertain but osteoporosis can occur even in treated cases.

The usual cause for failure to respond to the diet is poor compliance. Dietary adherence can be monitored by serial tests for endomysial antibody (EMA) and tissue transglutaminase (tTG). If clinical progress is suboptimal then a repeat intestinal biopsy should be taken. If the diagnosis is equivocal on the diagnostic mucosal biopsy, or if the patient has already started on a gluten-free diet, then a gluten challenge, i.e. reintroduction of oral gluten, with evidence of jejunal morphological change, can confirm the diagnosis.

Patients should have pneumococcal vaccinations (because of splenic atrophy) once every 5 years

Diagnosis

Main Points

Description:

Small bowel biopsy is  considered ‘gold standard’ for positive diagnosis, and is therefore desirable in all but the most clear-cut cases, because treatment involves a life-long diet that is both expensive and socially limiting. However with the increasing accuracy of serological tests, it is no longer necessary to take duodenal biopsies for suspected celiac disease in patients without antibodies. For example in patients being endoscoped for iron deficiency anaemia with negative celiac serology, the pretest value of small bowel histology is <0.03%.

If biopsies are to be taken, because the disease is sometimes patchy and it can be difficult to orientate endoscopic biopsies for histological section, four to six forceps biopsies should be taken from the second part of the duodenum. Endoscopic signs including absence of mucosal folds, mosaic pattern of the surface and scalloping of mucosal folds are often present; however, their absence is not conclusive because they are markers of relatively severe disease.

Histology: Histological changes are of variable severity and, though characteristic, are not specific. Villous atrophy can be caused by many other conditions, but celiac disease is the commonest cause of subtotal villous atrophy.

Histological examination shows crypt hyperplasia with chronic inflammatory cells in the lamina propria, and villous atrophy. The enterocytes become cuboidal with an increase in the number of intraepithelial lymphocytes. In the lamina propria there is an increase in lymphocytes and plasma cells. The most severe histological change with mucosal atrophy and hypoplasia is seen in patients who do not respond to a gluten-free diet.

In mild cases, the villous architecture is almost normal but there are increased numbers of intraepithelial lymphocytes.

Serology. Persistent diarrhoea, folate or iron deficiency, a family history of celiac disease and associated autoimmune disease are indications for serological testing.

The most sensitive tests are for endomysial and anti-tissue transglutaminase antibodies. The sensitivity of these tests is >90% though both are not always positive in the same subject. Titres of either correlate with the severity of mucosal damage so they can be used for dietary monitoring. Standard tests use IgA class antibodies. Selective IgA deficiency occurs in 2.5% of celiac disease patients but only 0.25% of normals and renders these tests falsely negative. All patients should have concomitant IgA levels tested and if deficient, IgG-based tests should then be used.

HLA typing. HLA-DQ2 is present in 90–95% of CD patients and HLA-DQ8 in about 8%, i.e. most of the rest. The absence of both alleles has a high negative predictive value for celiac disease. HLA typing may occasionally be useful for risk assessment, e.g. in patients already on a gluten free diet.

Other investigations

• Haematology. Mild or moderate anaemia is present in 50% of cases. Folate deficiency is common, often causing macrocytosis. B₁₂ deficiency is rare. Iron deficiency due to malabsorption of iron and increased loss of desquamated cells is common. A blood film may therefore show microcytes and macrocytes as well as hypersegmented polymorphonuclear leucocytes and Howell–Jolly bodies due to splenic atrophy.
• Biochemistry, liver biochemistry and function. In severe cases, biochemical evidence of osteomalacia may be seen (low calcium and high phosphate) and hypoalbuminaemia.
• Radiology. A small bowel follow-through may show dilatation of the small bowel with slow transit. Folds become thicker and in severe disease total effacement is seen. Radiology is mainly used when a complication, e.g. lymphoma, is suspected.
• Bone densitometry (DXA) should be performed on all patients because of the risk of osteoporosis.
• Capsule endoscopy is used to look for gut abnormalities when a complication is suspected.

Signs and Symptoms

MAIN POINTS:

DESCRIPTION:

Celiac disease can present at any age. In infancy patients mostly present from 6 month to 2nd year of life. The peak period for diagnosis in adults is in the 5th decade, with a female preponderance. Many patients are asymptomatic (silent) and come to attention because of routine blood tests, e.g. a raised MCV, or iron deficiency in pregnancy. The symptoms are very variable and often nonspecific, e.g. tiredness and malaise often associated with anaemia.

GI symptoms may be absent or mild. Celiac disease should be tested for in all patients with symptoms suggestive of IBS. Diarrhoea or steatorrhoea, abdominal pain and weight loss suggest more severe disease. Mouth ulcers and angular stomatitis are frequent and can be intermittent. Infertility and neuropsychiatric symptoms of anxiety and depression occur.

Rare complications include tetany, osteomalacia or gross malnutrition with peripheral oedema. Neurological symptoms such as paraesthesia, ataxia (due to cerebellar calcification), muscle weakness or a polyneuropathy occur; the prognosis for these symptoms is variable. There is an increased incidence of atopy and autoimmune disease, including thyroid disease, type 1 diabetes and Sjögren’s syndrome. Other associated diseases include inflammatory bowel disease, primary biliary cirrhosis, chronic liver disease, interstitial lung disease and epilepsy. IgA deficiency is more common than in the general population. Long-term problems include osteoporosis which occurs even in patients on long-term gluten-free diets.

Physical signs are usually few and nonspecific and are related to anaemia and malnutrition

PICTOGRAM:

Prevalence

Up to 1% of many populations are affected, though most have clinically silent disease.
In disorders of small intestine causing malabsorption like dermatitis herpetiformis, tropical sprue, bacterial over growth, whipple's disease, radiation enteropathy, parasitic infestation, celiac disease is at the top.

Possible Culprits

Description:

Hygiene Hypothesis says that modern environment is so clean that the immune system has little to attack and turns on itself and gets autogenic and is increasing incidence of autoimmune diseases like celiac disease,hashimoto thyroiditis,addison disease etc.
21st century diet is also possible culprit.Although overall wheat consumption hasn't increased, the ways wheat is processed and eaten have changed dramatically.it can make our body immune system predisposed newer ingredients percentage made things which are newer to our inbuilt system.Many of the processed foods we eat were not in existence 50 years ago as said by hypothesis creator,Dr.Murray.He is of the opinion that modern wheat also differs from older strains because of hybridization techniques variability.

Pathology

Pathology

Celiac disease is a condition in which there is inflammation of the mucosa of the upper small bowel that improves when gluten is withdrawn from the diet and relapses when gluten is reintroduced.It is Also called Gluten sensitive enteropathy.

Prolamins which are part of gluten,(gliadin from wheat, hordeins from barley, secalins from rye) are damaging factors. These proteins are resistant to digestion by pepsin and chymotrypsin because of their high glutamine and proline content and remain in the intestinal lumen triggering immune responses.

Gluten containing plants taxonomy is as follows

Immunology. Gliadin peptides pass through the epithelium (para- and/or intracellularly) and are deaminated by tissue transglutaminase which increases their immunogenicity. Gliadin peptides then bind to antigen-presenting cells which interact with CD4⁺ T cells in the lamina propria via HLA class II molecules DQ2 or DQ8. These T cells produce pro-inflammatory cytokines, particularly interferon-γ. CD4⁺ T cells also interact with B cells to produce endomysial and tissue transglutaminase antibodies. Gliadin peptides also cause release of interleukin-15 from enterocytes, activating intraepithelial lymphocytes with a natural killer cell marker. This inflammatory cascade releases metalloproteinases and other mediators that contribute to the villous atrophy and crypt hyperplasia which specify the disease.

The mucosa of the proximal small bowel is predominantly affected, the mucosal damage decreasing in severity towards the ileum as gluten is digested into smaller ‘non-toxic’ fragments.

Genetic factors. There is an increased incidence of celiac disease within families 10–15% of 1st-degree relatives will have the condition, although it may be asymptomatic. The concordance rate in identical twins is about 70%.

HLA-DQ2 and HLA-DQ8  are associated with CD. Over 90% of patients will have HLA-DQ2, compared with 20–30% of the general population.HLA genes are responsible for <50% of the genetic cause of the disease. Many unaffected people also have these genes, so other factors must also be involved. Non-HLA genes may also contribute to celiac disease, e.g. chromosome regions 19p13.1, 11q, 5q31-33 and 6q21-22. The CD28/CTLA4/ILO5 gene cluster has also shown linkage with celiac disease.

Environmental factors. Breast-feeding,age of introduction of gluten into the diet and rotavirus infection in infancy also increases the risk, and adenovirus-12 which has sequence homology with α-gliadin has been suspected as a causative agent.