Dyspepsia

Dyspepsia (from the Greek - dys-, "bad" or "difficult", and

pepsis"digestion"), also known as indigestion, is a condition of
impaired digestion.[1] It is a medical condition characterized by chronic or
recurrent pain in the upperabdomen, upper abdominal fullness and feeling
full earlier than expected when eating.[2] It can be accompanied
by bloating, belching, nausea, or heartburn. Dyspepsia is a common problem and is
frequently caused by gastroesophageal reflux disease (GERD) or gastritis.[3] In a
small minority it may be the first symptom of peptic ulcer disease (an ulcer of the
stomach or duodenum) and occasionally cancer. Hence, unexplained newly onset
dyspepsia in people over 55 or the presence of other alarming symptoms may
require further investigations.[4]
Functional dyspepsia (previously called nonulcer dyspepsia [5]) is dyspepsia "without
evidence of an organic disease that is likely to explain the symptoms". [6] Functional
dyspepsia is estimated to affect about 15% of the general population in western
countries.[5]
In most cases, the clinical history is of limited use in distinguishing between organic
causes from functional dyspepsia. A large systematic review of the literature was
recently performed to evaluate the effectiveness of diagnosing organic dyspepsia
by clinical opinion versus computer models in patients referred for upper
endoscopy. The computer models were based on patient demographics, risk factors,
historical items,and symptoms. The study showed that neither clinical impression
nor computer models were able to adequately distinguish organic from functional
disease
In a recent study, patients with peptic ulcer disease were compared with patients
with functional dyspepsia in an age and sex-matched study. Although the functional
dyspepsia group reported more upper abdominal fullness, nausea, and overall
greater distress and anxiety, almost all the same symptoms were seen in both
groups. Therefore, it is the clinicians challenging task to separate patients who may
have an organic disorder, and thus warrant further diagnostic testing, from patients
who have functional dyspepsia, who are given empiric symptomatic treatment.The
workup should be targeted to identify or rule out specific causes. Traditionally, highrisk patients have been identified by alarm features. However, the utility of these
features in identifying the presence of upper gastrointestinal malignancy has been
debated.A recent meta analysis looking at the sensitivity and specificity of alarm
features found a range of 080% and 4098%, respectively. However, there was
high heterogeneity between studies
The physical examination may elicit abdominal tenderness, but this finding is
nonspecific. A positive Carnett sign, or focal tenderness that increases with
abdominal wall contraction and palpation, suggests an etiology involving the
abdominal wall musculature. Cutaneous dermatomal distribution of pain may
suggest a thoracic polyradiculopathy. Thump tenderness over the right upper
quadrant may suggest chronic cholecystitis.[7]
Cause
Non-ulcer dyspepsia
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In about 50-70% of patients with dyspepsia, no definite organic cause can be

determined. In this case, dyspepsia is referred to as non-ulcer dyspepsia and its
diagnosis is established by the presence of epigastralgia for at least 6 months, in
the absence of any other cause explaining the symptoms.
Post-infectious dyspepsia
Gastroenteritis increases the risk of developing chronic dyspepsia. Post infectious
dyspepsia is the term given when dyspepsia occurs after an acute gastroenteritis
infection. It is believed that the underlying causes of post-infectious IBS and postinfectious dyspepsia may be similar and represent different aspects of the same
pathophysiology.[8]
Functional Dyspepsia This is the most common cause of chronic dyspepsia. Up to
three-fourths of patients have no obvious organic cause for their symptoms after
evaluation. Symptoms may arise from a complex interaction of increased visceral
afferent sensitivity, gastric delayed emptying or impaired accommodation to food,
or psychosocial stressors. Although benign, these symptoms may be chronic and
difficult to treat.
Diseases of the gastrointestinal tract
When dyspepsia can be attributed to a specific cause, the majority of cases
concern gastroesophageal reflux disease(GERD) and peptic ulcer disease. Less
common causes include gastritis, gastric cancer, esophageal cancer, coeliac
disease,food allergy, inflammatory bowel disease, chronic intestinal
ischemia and gastroparesis.
Liver and pancreas diseases
These include cholelithiasis, chronic pancreatitis and pancreatic cancer.
Food or Drug Intolerance
Acute, self-limited dyspepsia may be caused by overeating, eating too quickly,
eating high-fat foods, eating during stressful situations, or drinking too much alcohol
or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal antiinflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), diabetes
drugs (metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor
antagonists), antihypertensive medications (angiotensin converting enzyme [ACE]
inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin,
fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil,
rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake
inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine
oxidase [MAO]-B inhibitors),corticosteroids, estrogens, digoxin, iron, and opioids.[9]
Helicobacter pylori Infection
The role of H. pylori in functional dyspepsia is controversial, and no clear causal
relationship has been established. This is true for both the symptom profile and
pathophysiology of functional dyspepsia. Although some epidemiologic studies have
suggested an association between H. pylori infection and functional dyspepsia,
others have not. The discrepancy may stem in part from differences in methodology
and lack of adequate consideration of confounding factors such as past history
ofpeptic ulcer disease and socioeconomic status.[10] Controlled trials disagree about
whether or not H. pylori eradication is beneficial in functional dyspepsia, with
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roughly half of the trials showing improvement and the other half no
improvement.In a recent multicenter U.S.trial that randomized 240 patients to
treatment or placebo, and followed patients for 12 months, 28% of treated patients
versus 23% of those receiving placebo reported relief of symptoms at the 12-month
follow-up. Similarly, recent European trials have not shown significant differences in
symptoms after H pylori eradication as compared with controls. Systematic reviews
of eradication have been conducted, with varying results.A systematic review in the
Annals of Internal Medicine suggested no statistically significant effect, with an odds
ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.891.89;P=
0.18).Still,no effect was seen after adjusting for heterogeneity and for cure of H.
pylori. In contrast, the most recent update of a Cochrane Database review showed a
small but statistically significant effect in curing symptoms (H pylori cure vs
placebo, 36% vs 30%, respectively; relative risk reduction [RRR],8% [95% CI,3
18%],number needed to treat [NNT] = 18]). [11][12]
Systemic diseases
There is a number of systemic diseases that may involve dyspepsia and
include coronary disease, congestive heart failure,diabetes
mellitus, hyperparathyroidism, thyroid disease, chronic renal disease and adrenal
fatigue.[13]
Pathophysiology
Psychosomatic and cognitive factors are important in the evaluation of patients with
chronic dyspepsia. The psychiatric hypothesis holds that the symptoms of dyspepsia
maybe due to depression,increased anxiety,or a somatization disorder.
Epidemiologic studies suggest there is an association between functional dyspepsia
and psychological disorders. Symptoms of neurosis, anxiety, hypochondriasis, and
depression are more common in patients being evaluated for unexplained
gastrointestinal complaints than in healthy controls.Comparisons of functional and
organic dyspepsia have demonstrated that patients with functional dyspepsia are
less likely to have decreased stress or anxiety at 1-year follow-up after being
reassured of having no serious disease. This suggests that functional dyspepsia
symptoms are long-lasting, compared with those of organic dyspepsia,and that the
emotional ties are strong.[14]
Diagnosis
People under 55 years without alarm symptoms can be treated without
investigation. People over 55 years with recent onset dyspepsia or those with alarm
symptoms should be urgently investigated by upper gastrointestinal endoscopy.
This will rule out peptic ulcer disease, medication-related ulceration, malignancy
and other rarer causes.[4]
People under the age of 55 years with no alarm features do not need endoscopy but
are considered for investigation for peptic ulcer disease caused by Helicobacter
pylori infection. Investigation for H. pylori infection is usually performed when there
is a moderate to high prevalence of this infection in the local community or the
person with dyspepsia has other risk factors for H. pylori infection, related for
example to ethnicity or immigration from a high-prevalence area. If infection is
confirmed, it can usually be eradicated by medication.
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Medication-related dyspepsia is usually related to NSAIDs and can be complicated

by bleeding or ulceration with perforation of stomach wall.
Treatment
Functional and undifferentiated dyspepsia have similar treatments. Decisions
around the use of drug therapy are difficult because trials included heartburn in the
definition of dyspepsia. This led to the results favoring proton pump inhibitors (PPIs),
which are effective for the treatment of heartburn.
Traditional therapies used for this diagnosis include lifestyle modification,
antacids, H2-receptor antagonists (H2-RAs),prokinetic agents, and antiflatulents. It
has been noted that one of the most frustrating aspects of treating functional
dyspepsia is that these traditional agents have been shown to have little or no
efficacy.[15]
Pharmacological acid suppression
Antacids and sucralfate were found to be no better than placebo in a literature
review.[16] H2-RAs have been shown to have marked benefit in poor quality trials
(30% relative risk reduction[16]), but only a marginal benefit in good quality trials.
[15]
Prokinetic agents would empirically seem to work well since delayed gastric
emptying is considered a major pathophysiological mechanism in functional
dyspepsia.[15] They have been shown in a meta-analysis to produce a relative risk
reduction of up to 50%, but the studies evaluated to come to this conclusion used
the drug cisapride which has since been removed from the market (now only
available as an investigational agent)[17] due to serious adverse events such
astorsades, and publication bias has been cited as a potential partial explanation for
such a high benefit.[16] Modern prokinetic agents such as metoclopramide,
erythromycin and tegaserod have little or no established efficacy and often result in
substantial side effects.[16] Simethicone has been found to be of some value, as one
trial suggests potential benefit over placebo and another shows equivalence with
cisapride.[16] So, with the somewhat recent advent of the proton pump inhibitor (PPI)
class of medications, the question of whether these new agents are superior to
traditional therapy has arisen.
A 2002 systemic review of herbal products found that several herbs,
including peppermint and caraway, have anti-dyspeptic effects for non-ulcer
dyspepsia with "encouraging safety profiles". [18] A 2004 meta-analysis, pooling data
from three double-blind placebo-controlled studies, found the multiple herbal
extract Iberogast to be significantly more effective than placebo (p value = .001) at
treating patients with functional dyspepsia through the targeting of multiple
dyspeptic pathologies.[19] This German-made phytopharmaceutical was found to be
equivalent to cisapride and significantly superior to metoclopramide at reducing the
symptoms of functional dyspepsia over a four-week period. [20][21] Retrospective
surveillance of 40,961 children (12 years and under) found no serious side-effects.
[22]
Red pepper powder has also found to be promising. [23] Ginger and related
products made therefrom have been shown to have some positive alleviation of
symptoms, in particular for motion sickness and pregnancy-related nausea [24]
Currently, PPIs are, depending on the specific drug, FDA indicated for
erosive esophagitis, gastroesophageal reflux disease (GERD), Zollinger-Ellison
syndrome, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced
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ulcer healing and prevention, but not functional dyspepsia. There are, however,
evidence-based guidelines and literature that evaluate the use of PPIs for this
indication. A helpful chart summarizing the major trials is available from the
functional dyspepsia guidelines published in the World Journal of Gastroenterology
in 2006.[15]
The CADET study was the first to compare a PPI (omeprazole 20 mg daily) to both
an H2-RA (ranitidine 150 mg BID) as well as a prokinetic agent (cisapride 20 mg
BID) alongside placebo.[25] The study evaluated these agents in patients at 4 weeks
and 6 months and noted that omeprazole had a significantly better response at 6
months (31%) than cisapride (13%) or placebo (14%) (p = .001) while it was just
above the cutoff for being statistically significantly better than ranitidine (21%) (p =
.053). Omeprazole also showed a significant increase in quality of life scores over
the other agents and placebo in all but one category measured (p = .01 to .05).
The ENCORE study, which was a follow-up of patients from the OPERA study,
showed responders to omeprazole therapy had fewer clinic visits than nonresponders (1.5 vs 2.0) over a three-month period (p < .001). [26][27]
Acotiamide is a new drug approved in Japan im March 2013 for the treatment of
meal related symptoms of functional dyspepsia. It is an acetylcholinesterase
inhibitor.[citation needed]
1.

- "dyspepsia" at Dorland's Medical Dictionary

2.

- Talley NJ, Vakil N (October 2005). "Guidelines for the management of

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- Zajac, P; Holbrook, A; Super, ME; Vogt, M (MarchApril 2013). "An

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85.doi:10.1016/j.osfp.2012.10.005.

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^ Jump up to:a b National Institute for Health and Clinical

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^ Jump up to:a b Saad RJ, Chey WD (August 2006). "Review article:

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- van Kerkhoven LA, van Rossum LG, van Oijen MG, Tan AC, Laheij RJ,
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- Flier, SN; S, Rose (2006). "Is functional dyspepsia of particular

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8.

- Futagami S, Itoh T, Sakamoto C (2015). "Systematic review with

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- Ford, AC (2013). "Dysepsia". BMJ 29: 347.PMID 23990632. Retrieved

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- Laine L, Schoenfeld P, Fennerty MB (2001). "Therapy for Helicobacter

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- Moayyedi, P; Deeks, J; Talley, NJ (2003). "An update of the Cochrane

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12.

- Talley, NJ (2002). "Review article: Helicobacter pylori and nonulcer

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- Pajala, M; Heikkinen, M (2006). "A prospective 1-year follow-up study

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15.

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^ Jump up to:a b c d e Talley NJ, Vakil N (2005). "Guidelines for the

management of dyspepsia". Am. J. Gastroenterol. 100 (10): 2324
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- Melzer J, Rsch W, Reichling J, Brignoli R, Saller R (2004). "Metaanalysis: phytotherapy of functional dyspepsia with the herbal drug
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- Rsch W, Vinson B, Sassin I (2002). "A randomised clinical trial

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