The known about the disease until 20th century.

The firstmention about coeliac disease is in the second century, but not much was knownabout the disease until 20th century. Coeliac disease is also knownas “gluten sensitive enteropathy”.

  Theskin condition from which coeliac patients suffer from is known as “dermatitisherpetiformis” or “Durhing’s disease”. Gluten ataxia is the generalmanifestation of coeliac disease. Non-coeliac gluten sensitivity and coeliacdisease were considered same but without HLA similarity because of the similarsymptoms and treatment. But recently it was discovered that gluten sensitivityis a different condition from coeliac disease (1).In 1888,Samuel Gee conducted a clinical study of children and adults in the GreatOrmond Street hospital for Children, the place he worked and presented thestudy.  In the study Gee stated that, “toregulate the food is the main part of the treatment.

The allowance of farinaceousfoods must be small, but if the patient can be cured at all, it must be bymeans of diet”. Dr. Willem Karel Dicke discovered the link between coeliacdisease and the role of wheat. He might have observed the clinical improvementof his patients during the Dutch famine and this later might have contributedto his discovery. His observation was that when bread was short there was asignificant drop in death rate among children who were diagnosed with coeliacdisease from 35% to zero and it rose after the famine when wheat was againavailable for the children. Later in 1954 the British Physician John.W. Paulleydiscovered villous atrophy on intestinal samples taken at his surgery whichlater led to endoscopic biopsy.

Most of the features of coeliac disease wereelucidated in the 60’s like the hereditary character of coeliac disease wasdiscovered in 1965 and dermatitis herpetiformis in 1966 was recognized as linkedto gluten sensitivity (2).MANIFESTATIONS OF COELIAC DISEASE3Thedifferent manifestations of coeliac disease has been classified according tothe symptoms that each condition shows. They are1.     TypicalCoeliac disease- It is characterized by gastrointestinal symptoms such asweight loss, recurrent mouth ulcers, chronic diarrhoea, bulky and pale stools,constipation and abdominal distension.2.

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     AtypicalCoeliac disease- The major symptoms are extra-intestinal and may have somegastrointestinal symptoms. It can also cause haematological disorders,neurological disorders, osteoporosis, irritable bowel syndrome, abnormal liverfunction, joint and muscle pain. Research show that most atypical coeliacdisease is characterized by extra-intestinal comorbidities. 3.

     Silentcoeliac disease- It affects a large group of individuals mostly within familymembers. These individuals will be asymptomatic and are discovered only when amember of their family is screened.PATHOPHYSIOLOGYUnlikeother autoimmune diseases, in coeliac disease the trigger factor is uniquelyidentifiable as gluten.

The main causative agents of the disease are dominantHLA and autoantibodies against Thyroglobulin which was detected in more than95% of individuals in coeliac disease4.Thepathogenesis of coeliac disease is proposed to be by different pathways whichleads to destruction of epithelium and villous atrophy caused by gluten whichis the storage protein found in wheat, barley and rye. Gliadin is aglycoprotein extract from gluten that causes the overexpression of IL-5 in theintestine that is considered to be toxic to enterocyte. It also upregulates theMIC-A stress molecule on the surface of enterocytes and NKG2D receptor on theinfiltrating intraepithelial lymphocytes thus promotes a lymphocyte-mediatedcytotoxic response towards the enterocytes which depends on IL-15.

TG has apivotal role in the pathogenesis of coeliac disease, gliadin is ingested intoenzyme crosslinks causing specific deamidation of glutamine into glutamic acidwithin the gliadin peptides. This deamidation process makes the gliadinpeptides more open to the gliadin -reactive CD-4 T cells in context of MHC-DQ2molecule thus increasing immunogenicity. Gliadin is believed to be lessimmunogenic and might not stimulate T cells efficiently without TG. Gliadin isvery rich proline residues which is resistant to digestion in the intestine andbinds with DQ2 molecules. The absorption of these large intact peptides ofgliadin is believed to initiate immunogenic response 5.TG playsan important role in the molecular level as in involved in deamidation ofgliadin and crosslinking, but there is very little evidence to support thetheory that TG has an immunologic role. The TG autoantibodies are believed toform by antigen presenting cells targeting the toxic gliadin peptides taking upTG-gliadin complexes resulting in immune reaction against gliadin and TG.

Thegeneration of gliadin-reactive T cells are a combined effect of adaptive andinnate immune system, leading to a cytotoxic response and antibody formation5. DIAGNOSIS OF COELIAC DISEASEAccordingto the British Society of Gastroenterology, coeliac disease is diagnosed byserology and duodenal biopsy while the patient is on gluten containing diet.Biopsy is an essential method for diagnosis for coeliac disease in adultscompared to serology. Villous atrophy is a definite diagnosis of coeliacdisease, but villous atrophy with lesser damage with positive IgA-EMA orIgA-tTG also represent coeliac disease. In such circumstance a gluten free dietcan be considered to support the diagnosis of coeliac disease.Serologicaltesting depends on the presence of specific antibodies known as endomysialantibodies and Immunoglobulin A anti-tissue transglutmaninase antibodies.Immunoglobulin G is used in patients deficient in IgA. HLA (human leucocyteantigen) status is also used in diagnosis, but the predictive value of HLA forcoeliac disease susceptibility is low as a large group of people carry HLA-DQ2and HLA-DQ8 without coeliac disease6.

TREATMENT FOR COELIAC DISEASEAccordingto guidelines the only treatment available for coeliac disease is a strictlifetime gluten free diet. The Codex Alimentarus by European Union definesgluten free diet as food which contains less than 20 part per million ofgluten. A little of 500mg of gluten a day can cause harm in a patient who hasbeen diagnosed for coeliac disease. The diet should eliminate wheat, rye,barley and any of their derivatives. The patient should be made aware thatgluten is ubiquitous in any commercially available food products6. Thepatients should be assessed for any mineral and vitamin deficiencies whichincludes folic acid, vitamin B12, Iron and calcium as there is chances ofmalabsorption due to villous atrophy. It is advised that all coeliac patientsshould be referred to a dietitian for educating, monitoring and assessing thenutritional status of the patient. The recommendations also include thatcoeliac patients should be tested for osteoporosis as it is prevalent incoeliac patients6.

  A completeadherence to a gluten free diet is essential in a coeliac patient as themucosal recovery will take months and years to recover; on the other handgluten free diet will lead to recovery or clinical improvement within days orweeks. However a gluten free diet is expensive and has a negative impact on thequality of life of a patient as a complete avoidance of gluten in diet is avery difficult task. Evidences shows that well informed patients and patientswho are adherent to gluten free diet are more compliant. The adherence togluten free diet affects the social life of the patient as it is very difficultto find gluten free meals while out dining with friends and family. Thepatients experiences a considerable amount of stress due to the economic andthe non-availability of gluten free diet7.  PRESENTATION OF THE CASEMiss B wasinitially presented to the GP with general fatigue and weight loss which arenot specific symptoms of coeliac disease. Weight loss is one of the many symptomsof coeliac disease but not observed in all cases.

Her BMI was 17 which isslightly below the normal range 18.5 – 24.9 known as the healthy weight range,thus she can be categorized as belonging to the underweight range. This loss ofBMI can be due to coeliac disease due to malabsorption or occultgastrointestinal bleeding. Her initial blood test showed low haemoglobin, lowferretin and low vitamin B12 levels8. The low haemoglobin andferretin can be due to iron deficiency due to malabsorption of dietary iron asthere is no diarrhoea and steatorrhea9. It is rarely caused due tooccult gastrointestinal bleeding as all coeliac disease patients might not havegastrointestinal bleeding.

So after first presentation she is was given dietaryadvice and vitamin replacement as the GP failed to detect coeliac disease inMiss B. According to the study done by Davidet.al in March 2012 out of 112 patients in the study 12 patients did nothave coeliac disease11.  Afterone month Miss B represented with no improvement in her condition and she hasdeveloped diarrhoea, mouth ulcers and bloating. Serological sample tests weredone on Miss B which turned out to be positive.

The two test that there weredone on Miss B are Immunoglobulin A class anti-tissue transglutaminaseantibodies (IgA tTG) test and Immunoglobulin A endomysial antibodies (IgA EMA)test. The IgA tTG is an enzyme linked immunosorbent assay test with a sensitivityof 93%, it is a preferred screening method and has a specificity of 98%. TheEMA- IgA test has an accuracy rate of 99%, measured by indirectimmunofluorescent assay. It is an adjunctive test routine to tTG-IgA test andthis test confirms coeliac disease.

But the results came out as a weak positivefor IgA-tTG and a positive IgA EMA. The weak IgA-tTG is because the test isless sensitive in patients with mild coeliac disease. Its performance dependson the degree of intestinal damage10. Thus it is clear that Miss Bis having a mild coeliac disease and is in the beginning stages of the disease. SYMPTOMS OBSERVEDThefollowing symptoms were observed in Miss B·       Fatigue·       Weightloss·       Lowhaemoglobin·       LowVitamin B12 levels·       Diarrhoea·       Bloating·       Mouthulcers·       VillousatrophyThese aregeneral clinical manifestations of coeliac disease in adults12.

Inthe UK, women are diagnosed more with coeliac disease than men. It is estimatedthat 70% of the coeliac diagnosed population in the UK are women. Women aremostly asymptomatic of coeliac disease than men. Almost 1% of the totalpopulation of the UK suffers from coeliac disease, out of this 8% of the womensuffer from infertility or amenorrhea along with hormonal problems.

Thehormonal problem mostly develops due to lack of nutrition13. PHARMACEUTICAL CARE PLAN 14Miss. B’ssymptoms (fatigue, weight loss, anaemia, diarrhoea, bloating and recurrentmouth ulcers) are due to coeliac disease.

These symptoms are characteristicsshown by atypical coeliac disease and considering her symptoms thepharmaceutical care plan will be focused on coeliac disease and the underlyingcomorbidities will be focussed accordingly.According toMiss B’s presenting complaints there are three goals are discussed with Miss B,·       Symptomrelief·       Timefor intestine to heal·       Nutritionand reversing deficienciesMiss B’ssymptoms can be managed by the following fundamental steps in managing coeliacdisease:1. Life-time adherence to acomplete gluten free diet There is no medication or treatment forcoeliac disease. The only treatment strategy available for coeliac disease iscomplete avoidance of gluten in the diet.

This is achieved by giving thepatient a gluten free diet (GFD). Thus GFD is the cornerstone treatment forcoeliac disease. The patient need to maintain a gluten free diet which can beachieved by constant education of the patient by doctors and dietitians. Thelocal health and support groups like community pharmacies, volunteers andclinics can be instruments of support and information.2.Educating her about the diseaseMiss Bshould be educated by healthcare professionals about the disease as data hasproved that educating the patient about the disease ensures adherence to agluten-free diet.

3.Treatment of deficienciesMiss B hasan iron and vitamin B12 deficiency due to malabsorption but this might getnormal after adhering to a gluten free diet as the mucosal membrane heals. Butshe might need supplements for a short term to improve her condition.4.

Frequent visits or consulting a qualified dietitianFrequentcounselling by a qualified dietitian who has a good knowledge about the diseasewill give Miss B a better knowledge about her disease and diet. The dietitianshould re-emphasize the importance of a gluten-free diet. She should also bewarned about taking gluten as she might feel asymptomatic but it does not meanthat harm will not happen.5.

Joiningthe national coeliac groupMiss Bshould be motivated to join a support group so she can access information aboutthe disease and get to know the disease and novel developments.6. Followup by a multidisciplinary teamHealthcare providers should motivate her to remain in a gluten-free diet and afollow-up schedule should be provided so that Miss B will receive collaborativeinformation from health care professionals.CO-MORBIDITIES PRESENT1. Fatigueand weight loss- The fatigue and weight loss of Miss B can be treated only by astrict gluten free and supplements.

Miss B can be supplied with gluten freediet by the pharmacy and educating her about what type of food she should betaking17.2. Anaemia-It is estimated that 46% of coeliac patients develop iron deficiency anaemia,the most common cause this anaemia is due to malabsorption of iron from gut. Thehaemoglobin levels are expected to rise when she is provided with supplementsand a healthy diets. She can be giving infusion but she is in initial stages ofcoeliac disease so dietary advice and supplements are expected to meet herrequirements. Regular blood tests can be done to know the levels of haemoglobin17.3.

Mouthulcers- Mouth ulcers occur due to malabsorption of vitamins which usual incoeliac disease. She can be given mouth ulcer creams to help with the pain andcan be aided with topical corticosteroids17.4. Villousatrophy- In Miss B’s case the intestine has not completely deteriorated. Theintestine is expected to heal in 6 months if the patient is on a strictgluten-free diet. Endoscopy can be done to monitor the intestine17.FUTURE HEALTH NEEDS AND PRECAUTIONS1.

Psychological effects of coeliac diseaseAccordingto a latest study done on patients who are newly diagnosed with coeliac diseaseit was revealed that the disease affects patients psychologically and has aserious negative impact on the social relationships as well as their families.Thus it is important that Miss B needs psychological assistance for bettercompliance and quality of life. Even though this evidence is not wellsupported, it puts some light into the importance of psychosocial support thatMiss B should receive to improve her condition. Miss B should be motivated andguided in such a way that she will pay less attention to the social awkwardnessof her disease and live her life with family and friends.

Health care providersshould make sure that she does not live in isolation and make her believe thatit is a curable disease. Her close family members should also be well informedabout her condition and the consequence of non-adherence to gluten free diet15.2.

Glutenin MedicationGluten ispresent in daily use items like lipstick, toothpaste and in pharmaceuticalproducts. Health professionals like doctors and pharmacists should be carefulwhen giving medication or supplements to the patient as some medications cancontain gluten. The inactive ingredients of some medications can contain glutenwhich can be changed by the manufacturers without prior warning as there is noregulations regarding formulation of the inactive ingredients components of amedication. The questionable ingredients are vegetable gum and food starch usedin medications can have gluten.

The pharmacist should also warn the patientabout non-prescription medicines that they should consult the pharmacist beforetaking any medication over the counter as it might contain gluten. The lack ofexpertise among health care professionals regarding coeliac disease and absenceof labels on food products have raised a significant challenge to newlydiagnosed coeliac disease14.3.HyposplenismMiss B asa coeliac patient has high potential to suffer from hyposplenism. Hyposplenismis a condition that make her vulnerable to encapsulated bacteria. Miss B can beoffered vaccination against Pneumococcus bacteria to avoid infection in thefuture14. 4.

OsteoporosisMiss B hasa chance to develop osteoporosis due to malabsorption of vitamins and calcium.She should be assessed according to guidelines after two years of gluten freediet. Miss B should be advised that she should adhere to gluten free diet sothat absorption improves. She can be offered a DEXA scan if symptoms persist orany non-adherence to gluten free diet14.PHARMACEUTICAL CARE PLAN TEMPLATE INTRODUCTION: Miss B is a 25 year old female complaining with fatigue and weight loss.

HPI: Her BMI is 17 and her blood test results show that her haemoglobin is 10g/dL with low ferretin and low vitamin B12 levels. After one month she represented with diarrhoea, bloating and recurrent mouth ulcers. Serology and endoscopy showed minor villous atrophy.

The diagnosis was Coeliac disease. Past medication history:   N/A Medications:   N/A Health Priorities:   Actual health needs 1.Managing coeliac disease 2.Treatment of deficiencies 3.Treatment of mouth ulcers 4.

Management of weight loss 5.Villous atrophy Potential Future needs 1.Psychological support 2.Hidden gluten sources 3.Hyposplenism 4.Osteoporosis   Assessment Plan Patient presented with fatigue and weight loss with no abnormalities. The blood results showed low ferretin and vitamin B12 levels. Serological testing for tTG and EMA came out positive.

Endoscopic biopsy showed villi still intact but shortened. Coeliac disease resulted in villi shortening and malabsorption of nutrients. If left untreated the patient will lose weight and develop numerous complications like complete villous atrophy, osteoporosis, infertility and autoimmune disorders.

  Goals of therapy: •           Symptom relief •           Time for intestine to heal •           Nutrition and reversing deficiencies Drug therapy: Iron complex: 18mg Vitamin complex: 24 mcg Antidiarrheal. Oral corticosteroids for mouth ulcers.   1.Life-long adherence to gluten free diet which should result in improvement of Miss B’s condition 2.Regular visits to a qualified dietitian: The dietitian should educate Miss B about the importance of keeping a gluten free diet and check for any non-adherence 3. Frequent GP visits and blood tests to check blood levels of haemoglobin, ferretin and vitamin B12. 4. Miss B should be motivated to join the national coeliac group so that she will receive novel information about the disease, sources of gluten free diet and socialize with people who got the similar condition.

5. Follow up by a multi-disciplinary team and monitor weight, compliance, education, etc. and scheduled visits.