CASE 1.

‘Nothing Is Working for Me . . . ’

Miranda Clark, a 30-year-old administrator, presents to her general practitioner because
she is suffering from cramps in her left lower quadrant abdomen, bloating and loose
bowel motions for the last 2 weeks. The pain is recurrent, and she has had similar pain
since childhood. The pain frequently occurs after meals. It is sometimes relieved by def-
ecation, and at other times, passing stools makes it worse. She admits that she gets anxious
and is always worried about minor issues at work or home. Mrs Clark has no family
history of coeliac disease or colon cancer. She gives no history of anaemia, weight loss,
loss of appetite, fever, bleeding per rectum or vomiting. On examination, her vital sign
readings are within normal range. Abdominal examination showed tenderness of the left
lower quadrant but no guarding or rigidity. Per rectum examination was normal.

CASE DISCUSSION
Q1. On the basis of Mrs Clark’s presentation, what is your diagnosis?
Q2. What is your differential diagnosis?
Q3. What are the key clinical features of this disease? What are the scientific bases for
these features?
Q4. What is the pathophysiology underlying these changes?
Q5. What are your management goals and management options?

ANSWERS
1. The findings of a long history of recurrent abdominal pain since childhood together
with loose bowel motions, bloating, anxiety and the absence of warning signs such as
anaemia, weight loss, fever, bleeding per rectum, loss of appetite and vomiting as well
as the absence of family history of coeliac disease and colon cancer are suggestive of
the diagnosis of irritable bowel syndrome (IBS).
2. The differential diagnosis of IBS:
• Coeliac disease
• Microscopic colitis
• Collagen colitis
• Crohn disease
• Amoebic dysentery
• Chronic diarrhoea

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The following are essential for the diagnosis of IBS:

• The Roma IV criteria for IBS are currently the basis for the diagnosis. These
criteria comprise the following:
– The patient has recurrent abdominal pain .1 day per week, on average, in
the previous 3 months with an onset of .6 months before diagnosis.
– The abdominal pain is associated with at least two of the following three
symptoms: (i) pain related to defecation, (ii) change in the frequency of stool
and (iii) change in the form or appearance of stool.
– The patient has none of the warning signs or ‘alarm features’, e.g. anaemia,
nocturnal pain or nocturnal symptoms, weight loss and family history of
colorectal cancer, ovarian cancer or inflammatory bowel disease (the whole
list is discussed later).
3 . Symptoms and signs:
• Abdominal pain caused by defecation is present.
• Bloating occurs.
• There occur changes in bowel habits.
• There occur changes in the form of stools.
• The warning signs or ‘alarm features’ are absent.
• The diagnosis is usually based on the clinical presentation and not on biochemical
or histological examination.
• The diagnosis is based on the Roma IV criteria and is not reached by exclusion.
• However, in the primary care, the doctor may need to order basic tests to exclude other
related conditions (e.g. coeliac disease, tropical sprue, inflammatory bowel disease).
• Four types (categories) of IBS have been identified: (i) Constipation-predominant
(IBS-C), (ii) diarrhoea-predominant (IBS-D), (iii) mixed bowel pattern (IBS-M)
and (iv) unclassified (IBS-U).
• On making the diagnosis, the ‘alarm features’ should be excluded. The presence
of any of the following features makes the diagnosis of IBS unlikely:
(1) Anaemia
(2) Rectal bleeding
(3) Unintentional and unexplained weight loss
(4) Abdominal mass
(5) Rectal mass
(6) Presence of inflammatory markers for inflammatory bowel disease
(7) A family history of colorectal cancer, ovarian cancer or inflammatory bowel
disease
(8) Nocturnal symptoms
(9) Appearance of symptoms of changes in bowel habits for the first time in a
male over the age of 50
4. Investigations:
• Full blood count and blood film
• C-reactive protein or erythrocyte sedimentation rate
 ‘Nothing Is Working For Me …’ 79

• Blood urea/creatinine and electrolytes

• Coeliac antibodies
• Faecal calprotectin
More investigations are needed in patients who have ‘alarm features’ to make a final
diagnosis. These investigations may include the following:
• Sigmoidoscopy
• Colonoscopy/barium enema
• Microscopic examination of stools for ova and parasite test
• Thyroid function tests
Pathology and pathogenesis:
In IBS, biochemical tests are expected to be normal. The exact pathophysiology
of IBS is not known. The key pathophysiological processes underlying IBS can
be summarised as follows:
(1) Gut dysmotility: This includes delayed gastric emptying, increased small
bowel mobility and increased colonic motility in response to a meal.
(2) Intestinal hypersensitivity: It is responsible for the chronic abdominal dis-
comfort and pain. Tissue damage and inflammation n release of inflam-
matory mediators n sensitivity and excitability of nociceptor terminals n
perceived as hyperalgesia or discomfort.
(3) Postinfectious gastrointestinal IBS: Acute gastroenteritis could trigger ongo-
ing inflammation and the development of IBS symptoms. This is not related
to a particular organism but Shigella, Campylobacter and Salmonella infections
have been reported.
Postinfectious IBS could be related to inflammatory changes, release of
inflammatory mediators, changes in or increased permeability from weak
tight junctions and alterations in ion channels (sodium and type 2 chloride
channels).
(4) Stress response and IBS: Patients with IBS report more negative life events
than do matching controls. Stress is mediated via the hypothalamic–
pituitary–adrenal axis n release of corticotrophin-releasing factor (CRF)
from the hypothalamus n stimulates the release of adrenocorticotrophic
hormone (ACTH) from the anterior pituitary n cortisol release from the
adrenal gland. Both the stimulation of the autonomic nervous system and the
increased secretion of cortisol are responsible for the changes and symptoms
of IBS.
5. Management goals:
• Support and reassurance
• Ameliorating the patient’s symptoms
• Improvement of the quality of life
• Educating the patient
However, the management of IBS is challenging and the patient’s symptoms are
often recurrent and resistant to therapy.
80 Clinical cases in internal medicine

Therapeutic options include exercise, dietary changes, antispasmodics, increased

fibre in diet, laxatives (IBS-C), antidiarrhoeals (IBS-D), serotonin agonists (5-HT4) and
serotonin antagonists (5-HT3), antibiotics, probiotics and the use of guanylate cyclase
C agonists.

BACK TO BASIC SCIENCES

Q1. Briefly discuss the role of psychological factors in the pathogenesis of IBS.
• A range of disturbances may be present in patients with IBS including anxiety,
depression, neurosis and panic attacks.
• Patients may also have reduced coping abilities, increased stress, past exposure to
childhood abuse or psychological difficulties.
• The mechanism related to stress and IBS could be explained on the basis of stimula-
tion of the hypothalamic–pituitary–adrenal axis and stimulation of the autonomic
nervous system (review earlier discussion).
• This relationship and the role of CRF from the hypothalamus could explain the role of
corticotrophin-releasing factor-1 receptor (CRF-1) antagonist in the treatment of IBS.

Q2. What are the essential laboratory tests that you may order in a patient
with IBS?
Usually the diagnosis of IBS is based on the clinical presentation and the application of
Roma IV criteria. However, some basic tests may be ordered to exclude coeliac disease
and inflammatory bowel disease. These tests are (i) full blood count and blood film; (ii)
C-reactive protein or erythrocyte sedimentation rate; (iii) blood urea, creatinine and
electrolytes; (iv) coeliac disease; and (v) faecal calprotectin.

Q3. What are the ‘alarm features’ in IBS?

1. Anaemia
2. Rectal bleeding
3. Unintentional and unexplained weight loss
4. Abdominal mass
5. Rectal mass
6. Presence of inflammatory markers for inflammatory bowel disease
7. A family history of colorectal cancer, ovarian cancer or inflammatory bowel disease
8. Nocturnal symptoms
9. Appearance of symptoms of changes in bowel habits for the first time in a male over
the age of 50

Q4. What is the role of guanylate cyclase C agonists in the management of IBS?
Guanylate cyclase C agonists (e.g. linaclotide) are recommended in managing IBS-C.
The therapy comprises a minimally absorbed 14–amino acid peptide n activation
of guanylate C n stimulation of the production of cyclic guanosine monophosphate
 ‘Nothing Is Working For Me …’ 81

n stimulation of bicarbonate and chloride secretion via the cystic fibrosis transmem-
brane conductance regulator n increased intestinal motility and stool softness.

REVIEW QUESTIONS
Q1. Which one of the following symptoms is not consistent with the diagnosis of IBS?
A. Abdominal pain is related to defecation.
B. Abdominal pain is associated with changes in the frequency of stool.
C. Abdominal pain is associated with a change in the form of stool.
D. Abdominal pain awakens the patient from sleep.

Q2. Which one of the following laboratory tests may you order for a patient presenting
with IBS-D or IBS-M?
A. Hydrogen breath test
B. Coeliac antibodies
C. Serum albumin
D. Faecal calprotectin

Q3. Which one of the following is recommended in the management of IBS?

A. Test for food allergy.
B. Ask the patient to have a food diary.
C. Increase soluble fibre in diet.
D. Prescribe polyethylene glycol to relieve abdominal pain.

Q4. Which one of the following does not reduce abdominal pain in IBS?
A. Rifaximin
B. Antispasmodics
C. Probiotics
D. Loperamide
E. Antidepressants

ANSWERS
A1. D. The abdominal pain in IBS does not awaken the patient from sleep. This finding
in the history should direct the attention to the possibility of other organic disorders.
Also, abdominal pain associated with anorexia, weight loss or bleeding per rectum is
not consistent with IBS.
A2. B. Routine testing for coeliac disease in patients with IBS-D or IBS-M should
always be considered. Coeliac antibody test is recommended in these patients.
A3. B. There is no evidence that testing for food allergies will help in the management
of IBS. Also there is no evidence that increasing soluble or insoluble fibre in diet in
82 Clinical cases in internal medicine

patients with IBS has a beneficial effect over placebo for improving pain or other symp-
toms (for further reading, check Ruepert et al., 2011). Polyethylene glycol is prescribed
for patients with constipation, not IBS. There is no solid evidence that its use helps in
reducing symptoms in IBS (for further reading, check Khoshoo et al., 2006). However,
there is evidence that the use of a food diary can help the patient to identify food that
could trigger his/her symptoms.
A4. D. Loperamide, a synthetic opioid, is used as an antidiarrhoeal. Studies showed that
it is effective in decreasing stool frequency and enhancing stool consistency. However, it
did not improve abdominal pain (Lesbros-Pantoflickova et al., 2004). Antibiotics such as
rifaximin or neomycin for 2 weeks were found to improve bloating, abdominal pain and
stool consistency in IBS (Pimentel et al., 2011). Antispasmodics were effective in reduc-
ing abdominal pain. Antidepressants also reduced abdominal pain in IBS. Probiotics
reduced IBS symptoms including abdominal pain and flatulence (Moayyedi et al., 2010).

TAKE-HOME MESSAGE
• The diagnosis of IBS is based on the Roma IV criteria.
• Diagnosis is based on the finding of recurrent abdominal pain related to defecation
or in association with a change in stool frequency or form. Bloating is common.
• Symptoms are chronic such as abdominal pain at least once per week, on average, in the
previous 3 months, or altered bowel habits for at least 6 months as per Roma IV criteria.
• No obvious structural or biochemical abnormalities are found in IBS (no fever, no
raised C-reactive protein or erythrocyte sedimentation rate, normal haemoglobin,
normal serum albumin, negative tests for coeliac disease, etc.).
• The ‘alarm features’ include anaemia, unexplained loss of body weight, bleeding per
rectum, abdominal mass, rectal mass, family history of colorectal cancer, ovarian cancer,
inflammatory bowel disease and presence of markers for inflammatory bowel disease;
development of symptoms in a male patient after the age of 50 should be carefully
considered before making a final diagnosis.These features indicate that IBS is less likely.
• Coeliac antibody test and faecal calprotectin, full blood count and C-reactive protein
may be needed.
• The pathogenesis of IBS is explained on the following bases: (i) gut dysmotility,
(ii) intestinal hypersensitivity, (iii) postinfectious IBS and (iv) stress response in IBS.
• The management of IBS aims at the following: (i) support and reassurance,
(ii) ameliorating the patient’s symptoms, (iii) improvement of the quality of life and
(iv) patient education.

FURTHER READINGS
Dimidi E, Rossi M, Whelan K. Irritable bowel syndrome and diet: where are we in 2018? Curr Opin Clin
Nutr Metab Care. 2017;20(6):456-463.
Ford AC, Lacy BE, Talley NJ. Irritable bowel syndrome. N Engl J Med. 2017;376(26):2566-2578. Review.
 ‘Nothing Is Working For Me …’ 83

Khoshoo V, Armstead C, Landry L. Effect of a laxative with and without tegaserod in adolescents with
constipation predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2006;23(1):191-196.
Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum AL. Meta-analysis: the treatment of irritable
bowel syndrome. Aliment Pharmacol Ther. 2004;20(11-12):1253-1269.
Moayyedi P, Ford AC, Talley NJ, et al. The efficacy of probiotics in the treatment of irritable bowel
syndrome: a systematic review. Gut. 2010;59(3):325-332. Review.
Pimentel M, Morales W, Chua K, et al. Effects of rifaximin treatment and retreatment in nonconstipated
IBS subjects. Dig Dis Sci. 2011;56(7): 2067-2072.
Ruepert L, Quartero AO, de Wit NJ, van der Heijden GJ, Rubin G, Muris JW. Bulking agents, antispas-
modics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev.
2011;(8):CD003460.
Simrén M, Törnblom H, Palsson OS, Whitehead WE. Management of the multiple symptoms of irritable
bowel syndrome. Lancet Gastroenterol Hepatol. 2017;2(2):112-122.
Sultan S, Malhotra A. Irritable bowel syndrome. Ann Intern Med. 2017;166(11):ITC81-ITC96. Review.
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SECTION 2

Cardiovascular and
Respiratory Systems

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