mention about coeliac disease is in the second century, but not much was known
about the disease until 20th century. Coeliac disease is also known
as “gluten sensitive enteropathy”. The
skin condition from which coeliac patients suffer from is known as “dermatitis
herpetiformis” or “Durhing’s disease”. Gluten ataxia is the general
manifestation of coeliac disease. Non-coeliac gluten sensitivity and coeliac
disease were considered same but without HLA similarity because of the similar
symptoms and treatment. But recently it was discovered that gluten sensitivity
is a different condition from coeliac disease (1).
Samuel Gee conducted a clinical study of children and adults in the Great
Ormond Street hospital for Children, the place he worked and presented the
study. In the study Gee stated that, “to
regulate the food is the main part of the treatment. The allowance of farinaceous
foods must be small, but if the patient can be cured at all, it must be by
means of diet”. Dr. Willem Karel Dicke discovered the link between coeliac
disease and the role of wheat. He might have observed the clinical improvement
of his patients during the Dutch famine and this later might have contributed
to his discovery. His observation was that when bread was short there was a
significant drop in death rate among children who were diagnosed with coeliac
disease from 35% to zero and it rose after the famine when wheat was again
available for the children. Later in 1954 the British Physician John.W. Paulley
discovered villous atrophy on intestinal samples taken at his surgery which
later led to endoscopic biopsy. Most of the features of coeliac disease were
elucidated in the 60’s like the hereditary character of coeliac disease was
discovered in 1965 and dermatitis herpetiformis in 1966 was recognized as linked
to gluten sensitivity (2).
MANIFESTATIONS OF COELIAC DISEASE3
different manifestations of coeliac disease has been classified according to
the symptoms that each condition shows. They are
Coeliac disease- It is characterized by gastrointestinal symptoms such as
weight loss, recurrent mouth ulcers, chronic diarrhoea, bulky and pale stools,
constipation and abdominal distension.
Coeliac disease- The major symptoms are extra-intestinal and may have some
gastrointestinal symptoms. It can also cause haematological disorders,
neurological disorders, osteoporosis, irritable bowel syndrome, abnormal liver
function, joint and muscle pain. Research show that most atypical coeliac
disease is characterized by extra-intestinal comorbidities.
coeliac disease- It affects a large group of individuals mostly within family
members. These individuals will be asymptomatic and are discovered only when a
member of their family is screened.
other autoimmune diseases, in coeliac disease the trigger factor is uniquely
identifiable as gluten. The main causative agents of the disease are dominant
HLA and autoantibodies against Thyroglobulin which was detected in more than
95% of individuals in coeliac disease4.
pathogenesis of coeliac disease is proposed to be by different pathways which
leads to destruction of epithelium and villous atrophy caused by gluten which
is the storage protein found in wheat, barley and rye. Gliadin is a
glycoprotein extract from gluten that causes the overexpression of IL-5 in the
intestine that is considered to be toxic to enterocyte. It also upregulates the
MIC-A stress molecule on the surface of enterocytes and NKG2D receptor on the
infiltrating intraepithelial lymphocytes thus promotes a lymphocyte-mediated
cytotoxic response towards the enterocytes which depends on IL-15.TG has a
pivotal role in the pathogenesis of coeliac disease, gliadin is ingested into
enzyme crosslinks causing specific deamidation of glutamine into glutamic acid
within the gliadin peptides. This deamidation process makes the gliadin
peptides more open to the gliadin -reactive CD-4 T cells in context of MHC-DQ2
molecule thus increasing immunogenicity. Gliadin is believed to be less
immunogenic and might not stimulate T cells efficiently without TG. Gliadin is
very rich proline residues which is resistant to digestion in the intestine and
binds with DQ2 molecules. The absorption of these large intact peptides of
gliadin is believed to initiate immunogenic response 5.
an important role in the molecular level as in involved in deamidation of
gliadin and crosslinking, but there is very little evidence to support the
theory that TG has an immunologic role. The TG autoantibodies are believed to
form by antigen presenting cells targeting the toxic gliadin peptides taking up
TG-gliadin complexes resulting in immune reaction against gliadin and TG. The
generation of gliadin-reactive T cells are a combined effect of adaptive and
innate immune system, leading to a cytotoxic response and antibody formation5.
DIAGNOSIS OF COELIAC DISEASE
to the British Society of Gastroenterology, coeliac disease is diagnosed by
serology and duodenal biopsy while the patient is on gluten containing diet.
Biopsy is an essential method for diagnosis for coeliac disease in adults
compared to serology. Villous atrophy is a definite diagnosis of coeliac
disease, but villous atrophy with lesser damage with positive IgA-EMA or
IgA-tTG also represent coeliac disease. In such circumstance a gluten free diet
can be considered to support the diagnosis of coeliac disease.
testing depends on the presence of specific antibodies known as endomysial
antibodies and Immunoglobulin A anti-tissue transglutmaninase antibodies.
Immunoglobulin G is used in patients deficient in IgA. HLA (human leucocyte
antigen) status is also used in diagnosis, but the predictive value of HLA for
coeliac disease susceptibility is low as a large group of people carry HLA-DQ2
and HLA-DQ8 without coeliac disease6.
TREATMENT FOR COELIAC DISEASE
to guidelines the only treatment available for coeliac disease is a strict
lifetime gluten free diet. The Codex Alimentarus by European Union defines
gluten free diet as food which contains less than 20 part per million of
gluten. A little of 500mg of gluten a day can cause harm in a patient who has
been diagnosed for coeliac disease. The diet should eliminate wheat, rye,
barley and any of their derivatives. The patient should be made aware that
gluten is ubiquitous in any commercially available food products6.
patients should be assessed for any mineral and vitamin deficiencies which
includes folic acid, vitamin B12, Iron and calcium as there is chances of
malabsorption due to villous atrophy. It is advised that all coeliac patients
should be referred to a dietitian for educating, monitoring and assessing the
nutritional status of the patient. The recommendations also include that
coeliac patients should be tested for osteoporosis as it is prevalent in
adherence to a gluten free diet is essential in a coeliac patient as the
mucosal recovery will take months and years to recover; on the other hand
gluten free diet will lead to recovery or clinical improvement within days or
weeks. However a gluten free diet is expensive and has a negative impact on the
quality of life of a patient as a complete avoidance of gluten in diet is a
very difficult task. Evidences shows that well informed patients and patients
who are adherent to gluten free diet are more compliant. The adherence to
gluten free diet affects the social life of the patient as it is very difficult
to find gluten free meals while out dining with friends and family. The
patients experiences a considerable amount of stress due to the economic and
the non-availability of gluten free diet7.
PRESENTATION OF THE CASE
Miss B was
initially presented to the GP with general fatigue and weight loss which are
not specific symptoms of coeliac disease. Weight loss is one of the many symptoms
of coeliac disease but not observed in all cases. Her BMI was 17 which is
slightly 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 of
BMI can be due to coeliac disease due to malabsorption or occult
gastrointestinal bleeding. Her initial blood test showed low haemoglobin, low
ferretin and low vitamin B12 levels8. The low haemoglobin and
ferretin can be due to iron deficiency due to malabsorption of dietary iron as
there is no diarrhoea and steatorrhea9. It is rarely caused due to
occult gastrointestinal bleeding as all coeliac disease patients might not have
gastrointestinal bleeding. So after first presentation she is was given dietary
advice and vitamin replacement as the GP failed to detect coeliac disease in
Miss B. According to the study done by David
et.al in March 2012 out of 112 patients in the study 12 patients did not
have coeliac disease11. After
one month Miss B represented with no improvement in her condition and she has
developed diarrhoea, mouth ulcers and bloating. Serological sample tests were
done on Miss B which turned out to be positive. The two test that there were
done on Miss B are Immunoglobulin A class anti-tissue transglutaminase
antibodies (IgA tTG) test and Immunoglobulin A endomysial antibodies (IgA EMA)
test. The IgA tTG is an enzyme linked immunosorbent assay test with a sensitivity
of 93%, it is a preferred screening method and has a specificity of 98%. The
EMA- IgA test has an accuracy rate of 99%, measured by indirect
immunofluorescent assay. It is an adjunctive test routine to tTG-IgA test and
this test confirms coeliac disease. But the results came out as a weak positive
for IgA-tTG and a positive IgA EMA. The weak IgA-tTG is because the test is
less sensitive in patients with mild coeliac disease. Its performance depends
on the degree of intestinal damage10. Thus it is clear that Miss B
is having a mild coeliac disease and is in the beginning stages of the disease.
following symptoms were observed in Miss B
Vitamin B12 levels
general clinical manifestations of coeliac disease in adults12. In
the UK, women are diagnosed more with coeliac disease than men. It is estimated
that 70% of the coeliac diagnosed population in the UK are women. Women are
mostly asymptomatic of coeliac disease than men. Almost 1% of the total
population of the UK suffers from coeliac disease, out of this 8% of the women
suffer from infertility or amenorrhea along with hormonal problems. The
hormonal problem mostly develops due to lack of nutrition13.
PHARMACEUTICAL CARE PLAN 14
symptoms (fatigue, weight loss, anaemia, diarrhoea, bloating and recurrent
mouth ulcers) are due to coeliac disease. These symptoms are characteristics
shown by atypical coeliac disease and considering her symptoms the
pharmaceutical care plan will be focused on coeliac disease and the underlying
comorbidities will be focussed accordingly.
Miss B’s presenting complaints there are three goals are discussed with Miss B,
for intestine to heal
and reversing deficiencies
symptoms can be managed by the following fundamental steps in managing coeliac
1. Life-time adherence to a
complete gluten free diet
There is no medication or treatment for
coeliac disease. The only treatment strategy available for coeliac disease is
complete avoidance of gluten in the diet. This is achieved by giving the
patient a gluten free diet (GFD). Thus GFD is the cornerstone treatment for
coeliac disease. The patient need to maintain a gluten free diet which can be
achieved by constant education of the patient by doctors and dietitians. The
local health and support groups like community pharmacies, volunteers and
clinics can be instruments of support and information.
Educating her about the disease
should be educated by healthcare professionals about the disease as data has
proved that educating the patient about the disease ensures adherence to a
Treatment of deficiencies
Miss B has
an iron and vitamin B12 deficiency due to malabsorption but this might get
normal after adhering to a gluten free diet as the mucosal membrane heals. But
she might need supplements for a short term to improve her condition.
Frequent visits or consulting a qualified dietitian
counselling by a qualified dietitian who has a good knowledge about the disease
will give Miss B a better knowledge about her disease and diet. The dietitian
should re-emphasize the importance of a gluten-free diet. She should also be
warned about taking gluten as she might feel asymptomatic but it does not mean
that harm will not happen.
the national coeliac group
should be motivated to join a support group so she can access information about
the disease and get to know the disease and novel developments.
up by a multidisciplinary team
care providers should motivate her to remain in a gluten-free diet and a
follow-up schedule should be provided so that Miss B will receive collaborative
information from health care professionals.
and weight loss- The fatigue and weight loss of Miss B can be treated only by a
strict gluten free and supplements. Miss B can be supplied with gluten free
diet by the pharmacy and educating her about what type of food she should be
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. The
haemoglobin levels are expected to rise when she is provided with supplements
and a healthy diets. She can be giving infusion but she is in initial stages of
coeliac disease so dietary advice and supplements are expected to meet her
requirements. Regular blood tests can be done to know the levels of haemoglobin17.
ulcers- Mouth ulcers occur due to malabsorption of vitamins which usual in
coeliac disease. She can be given mouth ulcer creams to help with the pain and
can be aided with topical corticosteroids17.
atrophy- In Miss B’s case the intestine has not completely deteriorated. The
intestine is expected to heal in 6 months if the patient is on a strict
gluten-free diet. Endoscopy can be done to monitor the intestine17.
FUTURE HEALTH NEEDS AND PRECAUTIONS
Psychological effects of coeliac disease
to a latest study done on patients who are newly diagnosed with coeliac disease
it was revealed that the disease affects patients psychologically and has a
serious negative impact on the social relationships as well as their families.
Thus it is important that Miss B needs psychological assistance for better
compliance and quality of life. Even though this evidence is not well
supported, it puts some light into the importance of psychosocial support that
Miss B should receive to improve her condition. Miss B should be motivated and
guided in such a way that she will pay less attention to the social awkwardness
of her disease and live her life with family and friends. Health care providers
should make sure that she does not live in isolation and make her believe that
it is a curable disease. Her close family members should also be well informed
about her condition and the consequence of non-adherence to gluten free diet15.
present in daily use items like lipstick, toothpaste and in pharmaceutical
products. Health professionals like doctors and pharmacists should be careful
when giving medication or supplements to the patient as some medications can
contain gluten. The inactive ingredients of some medications can contain gluten
which can be changed by the manufacturers without prior warning as there is no
regulations regarding formulation of the inactive ingredients components of a
medication. The questionable ingredients are vegetable gum and food starch used
in medications can have gluten. The pharmacist should also warn the patient
about non-prescription medicines that they should consult the pharmacist before
taking any medication over the counter as it might contain gluten. The lack of
expertise among health care professionals regarding coeliac disease and absence
of labels on food products have raised a significant challenge to newly
diagnosed coeliac disease14.
Miss B as
a coeliac patient has high potential to suffer from hyposplenism. Hyposplenism
is a condition that make her vulnerable to encapsulated bacteria. Miss B can be
offered vaccination against Pneumococcus bacteria to avoid infection in the
Miss B has
a chance to develop osteoporosis due to malabsorption of vitamins and calcium.
She should be assessed according to guidelines after two years of gluten free
diet. Miss B should be advised that she should adhere to gluten free diet so
that absorption improves. She can be offered a DEXA scan if symptoms persist or
any non-adherence to gluten free diet14.
PHARMACEUTICAL CARE PLAN TEMPLATE
Miss B is a 25
year old female complaining with fatigue and weight loss.
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.
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.
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
Goals of therapy:
• Symptom relief
• Time for intestine to heal
• Nutrition and reversing
Drug therapy: Iron
Vitamin complex: 24
corticosteroids for mouth ulcers.
adherence to gluten free diet which should result in improvement of Miss B’s
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
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