Diagnostic Delay in Clinical Practice-A Case Report of Coeliac Disease

Once considered a gastrointestinal disease of childhood affecting mainly whites, Coeliac Disease is now recognized as a systemic disease that may affect persons of any age and many races and ethnic groups. In this paper we present a case of a 60-year-old woman presented with protein-losing enteropathy associated with partial villous atrophy on distal duodenal biopsy. In Coeliac enteropathy the changes in intestinal permeability is sufficient to cause excessive loss of protein into the gut leading to hypoproteinaemia. The patient had presented with peripheral oedema without liver or renal impairment. The case emphasizes that clinicians should have a heightened suspicion about the disease that may be present at any age in both sexes and in a wide variety of clinical circumstances.


Introduction:
Coeliac disease is a systemic immune-mediated disorder triggered by dietary gluten in genetically susceptible persons.Gluten is a protein complex found in wheat, rye and barley.Coeliac Disease is characterised by a broad range of clinical presentations, a specific serum autoanti body response and variable damage to the small-intestinal mucosa. 1 The frequency of the disease is increasing in many developing countries because of westernization of the diet, changes in wheat cosumption and increased awareness of the disease. 2 lts prevalence is I .5 to 2 times as high among women as among men and is increased among persons who have an affected first degree relative (l Oto 15%), type-1 diabetes (3 to 16%), Hashimoto's tbyroiditis (5%) or other autoim mune diseases (including autoimmune liver diseases, Sjogren's syndrome, IgA nephropathy), Down syndrome (5%), Turner's syndrome (3%), and IgA deficiency (9%).

Case Report:
In August, 2013, a 60-year-old woman presented to us with a 3-month history of swelling of both legs, fatigabil ity, significant loss of weight and appetite.She had also experienced several episodes of loose stool along with cramping abdominal pain three years ago which had lasted for two months, 5-6 times in a day, voluminous, semisolid, not mixed with blood or mucous.After that she visited many physicians and her condition improved witb general supportive measures.She had artluitis on both knee joints described as swelling, redness, raised tempera ture and painful movement.This had also been treated with intra articular steroid six month back.She had no significant family history.She was hypertensive and her blood pressure was controlled by losartan potassium and bydrochlorothiazide.She was non-diabetic.On initial assessment her pulse was 80 beats/min, blood pressure was 120/80 mmHg, temperature was normal, non-anaemic and non-icteric, a painless ulcer over the tongue, bilateral pitting ankle oedema extending to legs and lymph nodes were not enlarged.Examination of abdomen showed bepatomegaly, 5cm below the costal margin along the mid-clavicular line, firm in consistency, margin rounded, smooth surface, no bruit, upper border of liver dullness present on the right fifth intercostal space at the mid-clavicular line, no splenomegaly and no ascites.
Examination of other systems was unremarkable as well.
Complete blood count and urine routine microscopic examination and random blood sugar all were within normal range.24 hours urinary total protein showed, urinary total volume: l,7l}mllday, urinary total protein: O.2lgmlday (0.05-0.08gm/duy), serum albumin: 28 glL (35-50), S. creatinine: l11pmol/L, USG of whole abdomen revealed that liver is mildly enlarged with homogeneous echopattern.Chest X-ray (P/A) view and colonoscopy were normal.Endoscopy of upper GIT and tissue from duode- num for Histopathology showed: sections of duodenal  mucosa with slightly short villi and elongated crypts.Intra epithelial lymphocytes are increased (>30/100 enterocytes).The lamina propria contains many plasma cells, lymphocytes and small number of eosinophils.No malignant cells.Diagnosis was chronic duodenitis with partial villous atrophy.Tissue transglutaminase (tTG), IgA: 126.5 U/ml (Normal is upto 50U/m1).In the light of avallable history clinical and histopathological findings, and the presence of serological markers an uncommon diagnosis of coeliac disease was considered.

Discussion:
Coeliac Disease is a pernanent dietary disorder caused by an immunologic response to gluten, a storage protein found in certain grains that results in diffuse damage to the proximal small intestinal mucosa with malabsorption of nutrients.aThe aetiology of Coeliac disease is not known but environmental, immunologic and genetic factors appear to contribute to the disease.3 Gluten is a protein found in whe at, rye and barley.After being taken up by epithelial cells, gluten peptides are deamidated by the efizyme tissue transglutaminase in the subepithelial layer.
They are then able to fit the antigen-binding motif on HLA-DQ2 positive antigen presenting cells.Recognition by CD4+ T cells triggers a Thl immune response with generation of pro-inflammatory cytokines (L,, INF-y and TNF-o).Lymphocytes infiltrate the lamina propria and increased intraepithelial lymphocytes (IEL), crypt hyper- plasia and villous atrophy ensue.sThe villi become inflamed and flattened.The surface area available for digestion is therefore decreased and a person is unable to absorb nutrients from food effectively.
In adults, damage to the small intestine may be severe without symptoms being obvious or specific.This may make it difficult for Coeliac Disease to be identified.Manifestations of Coeliac Disease include-diarrhoea, weight loss, steatorrhea, anaemia, folate, vit-B,, deficiencies, fatigue and generaltzed weakness, calcium, edema due to low albumin, failure to thrive in infants.6When clinicians request serology, laboratories should use IgA tissue transglutaminase, (tTG) as the first choice test.This should result in the resolution of the infl antmation and restoration of the inner lining of the small bowel.
Medications to treat conditions such as aruaemLa and nutrient deficiencies Iron, folate, vit-B 12, ca.Lcium may be required.Dietary adherence can be monitored by serial tests for antibodies EMA and tTG.Patients should have pneumococcal vaccinations (because of splenic atrophy) once every 5 years."A determination of bone mineral density to asses for osteoporosis is recommended.CD treads to an increased risk of both adenocarcinoma (small intestine) and lymphoma (enteropathy associated T-cell lymphoma), ulcerative jejunitis and stricturing.

Conclusion:
In conclusion it can be said that, Coeliac Disease is often difficult to diagnose due to its non-specific symptoms and the long period of onset.Diagnosis is based traditionally on symptoms, positive serology and charucteristic histo- logical changes.Among these, biopsy remains the gold standard for establishing the diagnosis.There is compel- ling evidence that treatment of symptomatic Coeliac Disease results in substantial improvement in nutritional parameters.Compliance with life-long gluten free diet is likely protective against the development of non-Hodgkin's lymphoma and Dermatitis herpetiformis.

Fig- l :
Fig-l: Biopsy taken from proximal duodenum showing partial villous atrophy with increased intraepithelial lympho- cytes and inflammatory infiltrate in the lamina propria.
Intestinal biopsy in needed to confirn or exclude Coeliac disease to people with positive serological results from arry tTG or EMA test.7 Presence of IgA endomysial antibody and IgA tTG antibody tests both have >95o specificity andZ 90% sensitivity for the diagnosis.aThe finding of circulating IgA antibodies at the time of diagno- sis and their disapp earance following a gluten free diet added weight to the diagnosis.sThe ESPGAN recently proposed new criteria for the diagnosis of coeliac disease, it is stated that if IgA anti-tTG exceeds 10 times the upper limit of normal in patients with a clinical suspicion of coeliac disease, diagnosis of coeliac disease is possible by performing further other laboratory tests (endomysial antibodies and HLA typing) instead of duodenal biopsies.eAn important component of the disease is the intraepithe- lial lymphocyte that might become clonally expanded in refractory sprue and enterop athy associated T:cell lymphoma'oThe treatment for coeliac disease is the complete and life-long removal of gluten containing foods from the diet.