Canadian Medical Association Journal 1995; 153: 293-299
From earlier surveys the prevalence of dyspepsia has been estimated at 6%[15] and 30%[16] of the population. The latter figure includes people with heartburn, which is very common in its own right.[17,18] A survey of 8250 householders (with a 66% response rate) that used more restrictive criteria,11 found a prevalence of 2.6%, if dyspepsia caused by known structural disease is excluded.[19] On the basis of this prevalence, and excluding people with known ulcers, at least 760,000 Canadians have dyspepsia. This figure should be kept in mind in considering the costs of managing individual cases.
In 1985 the American College of Physicians (ACP), mindful of the costs of endoscopy, recommended that, in the absence of certain risk factors, patients with dyspepsia should receive a trial of anti-ulcer therapy, which then meant 6 to 8 weeks' treatment with histamine (H2)-receptor antagonists.[20] This recommendation predated the availability of omeprazole and the concept of Helicobacter pylori eradication to cure ulcers. Therefore, it is time to examine whether this policy is the correct one.
What is dyspepsia?
Most would agree that dyspepsia is a recurrent pain or discomfort
in the epigastrium. Some would add that it involves bloating,
nausea and belching. The symptoms often occur after eating.
Patients blame what they eat, but in fact, under controlled
conditions, specific foods are seldom implicated. The difficulty
is distinguishing what we understand as dyspepsia from other
well-characterized structural and functional entities that also
cause pain or discomfort in the epigastrium. The term
"indigestion" is even more confusing and should not be used.[21] It
is constructive to consider first what dyspepsia is not.
Dyspepsia is not caused by gallstones. The notion of "gallbladder dyspepsia" has no pathophysiologic or clinical basis. The pains associated with cholecystitis or biliary colic are acute, severe, unpredictable and self- limited, involving the epigastric area or right upper quadrant and radiating to the infrascapular area.[22,23] These pains are different from those associated with dyspepsia, which is no more common in patients with gallstones than in those without.[24-27]
Careful history taking should permit a physician to identify angina, which is related to exercise, or pancreatitis, which is characterized by episodic, severe abdominal and back pain. Irritable bowel syndrome may cause epigastric pain, but pain so caused is altered by defecation or followed by a change in the consistency and frequency of stools.[28,29] Pains in the chest or abdominal wall can be identified from the effect of movement and by examination.
The term "reflux-like dyspepsia" has been proposed.[13] However, this term describes heartburn, not dyspepsia at all. Heartburn is a retrosternal or high-epigastric burning discomfort provoked by eating (especially chocolate or large meals), worsened by bending and lying down, and relieved by taking antacids. One in 3 adults suffers heartburn, and 1 in 10 experiences it at least once a month.[17,18] Heartburn is due to gastroesophageal reflux disease, a syndrome distinct from dyspepsia that presents different diagnostic and treatment challenges.
Once these syndromes have been ruled out, patients with epigastric pain and discomfort may be said to have dyspepsia. The mechanism by which dyspeptic symptoms are generated are unknown. Even in those patients whose dyspepsia results from a peptic ulcer, the mechanism of the pain is uncertain,[30] and many ulcers are painless.[31-33] Attempts to relate nonulcer dyspepsia to faulty gastric motility have failed. Consensus groups have classified dyspepsia as ulcer-like and motility-like,[13,34] but these categories have no physiologic basis, and about half of patients with dyspepsia overlap both categories.[12,35,36] Therefore, such distinctions do not serve family physicians. The practical question is whether a patient with dyspepsia has an ulcer. This is why I suggest defining dyspepsia as "epigastric pain or discomfort that is chronic or recurrent (lasting more than 3 months), that suggests a peptic ulcer."
The discovery that infection with H. pylori causes chronic gastritis and peptic ulcers presents a new issue. This organism is very common in the community and thus, by chance, in patients with nonulcer dyspepsia. However, it does not follow that H. pylori causes nonulcer dyspepsia. Most patients with nonulcer dyspepsia do not harbour the organism, and the treatment of those who do would be very costly. So far, the relation between the organism and the nonulcer dyspepsia is unconvincing, and clinical trials of the benefits of eradication are conflicting and flawed.[37-40] Although H. pylori causes gastritis, many patients with the infection and gastritis have no symptoms. As well, older studies failed to find an association between histologic gastritis and symptoms.[41,42]
Ulcer or nonulcer dyspepsia?
Thus, the main question when a physician sees a patient with
dyspepsia is "ulcer or nonulcer?" An ulcer may lead to serious
complications, nonulcer dyspepsia will not; an ulcer can be
treated with drugs, nonulcer dyspepsia probably cannot be.[43,44]
It is arguable whether the physician needs to know that an ulcer
is present. To deal with this issue, let us assume (1) that the
patients in question have dyspepsia that is severe, or has not
responded to lifestyle changes and antacid therapy, and have
reached the point at which drug therapy would normally be
considered; and (2) that there is no convincing evidence to date
that treatment with anti-ulcer drugs - including antibiotics - is
effective in nonulcer dyspepsia.
Are ulcers and nonulcer dyspepsia a
continuum?
Spiro45 suggested in 1974 that ulcers and nonulcer dyspepsia are
the same disease, distinguished only by whether the disease
causes a hole in the mucosa. Both involve dyspepsia, have a
natural history of recurrence, appear to be related to stress,
affect patients of all ages and tend to respond to treatment with
a placebo. However, this hypothesis predates the effective
treatment of ulcers with antibiotics and anti-ulcer drugs and the
finding that nonulcer dyspepsia fails to respond to such
treatment.[43,46] Furthermore, patients with nonulcer dyspepsia
tend to remain free of ulcers.[47,48] In contrast with patients
with ulcers, the acid secretion[49] and genetic profiles[27] of
patients with nonulcer dyspepsia are similar to those of patients
without ulcers or dyspepsia. Although H. pylori is present in
most cases of duodenal ulcer not caused by nonsteroidal
anti-inflammatory drugs (NSAIDs), it is no more common in
patients with nonulcer dyspepsia than in the general
population.[50] Therefore, nonulcer dyspepsia is distinct from
peptic ulcer.
Which patients have an ulcer?
Although many studies involving computer analysis of data and
large patient cohorts have been conducted, none has produced a
clinical profile that permits family physicians to determine
which patients with dyspepsia have an ulcer.[2,23,51-53] Of course,
previous ulcers or a strong family history are compelling clues.
Nocturnal epigastric pain that is relieved by taking antacids is
statistically suggestive, but nocturnal pain alone is not.[2]
Abdominal tenderness does not predict an ulcer.[54] Therefore,
there is no reliable means, short of endoscopic examination or a
barium-contrast radiograph, of determining which patients with
dyspepsia have a peptic ulcer.
Studies involving patients with dyspepsia examined by endoscopy in specialist centres during the past 5 years show that about half of these patients have no ulcer or other pathologic condition[27,52,55-59] (Table 1 [not available]). However, the definition of dyspepsia is unclear in many of these studies. Inclusion of patients with heartburn in some studies results in a lower prevalence of ulcers.[12,57] The ratio of patients with nonulcer dyspepsia to those with dyspepsia caused by an ulcer seen in family practice is likely even greater than in these studies.[60]
Why not a trial of therapy?
What is the prognosis in dyspepsia?
The rate of recurrence of duodenal ulcers not caused by NSAIDs is
approximately 60% within 1 year of healing.61 This is true even
after 1 year of remission in patients taking a histamine
(H2)-receptor antagonist.[61] At least 5 years of therapy with
histamine (H2)-receptor antagonists are needed to alter the
natural history of peptic ulcer.[62] Otherwise, the disease has a
chronic and recurrent course over 10 years or more.[63,64] Nonulcer
dyspepsia also has a chronic, recurrent course, with 70% of
patients continuing to experience symptoms for 2 to 7
years.[27,47,48] Double-blind clinical trials have shown that 30%
to 50% of patients with ulcers or with nonulcer dyspepsia taking
placebo experience some improvement.[27] Therefore, how dyspepsia
responds to anti-ulcer medication is of little value in
diagnosis. Since both types of dyspepsia are likely to recur, so
is the dilemma. Does the patient have an ulcer or nonulcer
dyspepsia?
To 'scope or not to 'scope?
If a trial of therapy is therefore inappropriate and an
investigation should be conducted, which is the test of choice?
Endoscopy is more accurate[65-67] and cost-effective[68] and better
accepted by patients[69] than barium-contrast radiography, although
radiographic technique has recently improved. Other tests are of
little value in the investigation of dyspepsia.[52,70-72] Endoscopy
is therefore the diagnostic gold standard. It is very safe in
healthy patients[73-75] and permits biopsy to detect gastritis, H.
pylori infection or cancer.
Any analysis of the ACP policy must involve not only the initial cost of an endoscopic examination but also the long-term costs of patient visits, repeated drug therapy, absenteeism from work and reduced quality of life for patients with ulcers or nonulcer dyspepsia. Endoscopy is costly in some parts of the United States, but the cost is coming down.[76] In Ontario, the procedure costs only 60% more than a 2-month course of ranitidine and about the same as a 4-week course of omeprazole. The cost of an initial, precise diagnosis with the use of endoscopy in patients with dyspepsia is similar to that of antibiotic therapy to eradicate H. pylori, and may be lower if the adverse effects of the drugs are factored in[77,78] (Table 2 [not available]). In fact, the ACP policy may lead to costs greater than those of a precise, initial diagnosis, if one takes into account that half of patients with dyspepsia do not require drug therapy, that such patients are not identified by a trial of therapy, that initial therapy may even obscure the diagnosis, that the placebo effect may lead to continued use of drugs, that symptoms recur within a year in most patients and that a gastric tumour may be missed.
Several sources support this point of view. A Danish group studied 414 patients with "upper dyspepsia" who were considered eligible for therapy with histamine (H2)-receptor antagonists on the basis of symptoms.[60] They compared a trial of therapy with prompt endoscopic examination and denial of therapy to those who did not have an ulcer. In this study, general practitioners were permitted to bypass consultation and to have open access to endoscopy. Although the initial costs were lower in the group given treatment, 66% of these patients had a treatment failure or relapse of symptoms within a year, necessitating an endoscopic examination. When loss of employment and drug expenses over the year were taken into account, the costs in the treatment group were higher for patients of all ages. Moreover, initial therapy did not improve the selection of patients for endoscopic examination; the diagnostic profile of the 66% of patients given treatment who subsequently required an endoscopic examination was similar to that of the patients upon entry to the study. Despite later endoscopic examination, an estimated 40% of peptic ulcers in the group given therapy were missed after 1 year. There were two cases of gastric carcinoma in each group.
Silverstein, Petterson and Talley[79] employed a decision-analysis technique to compare the costs of initial therapy with those of endoscopic examination. As expected, initial therapy was cheaper at first, but after 1 year costs were about equal because of recurrences of dyspepsia. If endoscopy were less expensive, or drugs were more expensive, diagnosis would become the more cost-effective approach. Goulston and associates[58] compared strategies with and without endoscopic or radiographic confirmation of an ulcer before treatment with histamine (H2)-receptor antagonists. In both arms of the study, the patient's general practitioner prescribed drugs as he or she saw fit. The costs of the two strategies over 6 months were similar ($392 per patient with confirmation of an ulcer v. $406 without such confirmation). Now that H. pylori can be eradicated and ulcers can be cured, selection of patients to be treated may further improve the cost-effectiveness of an initial endoscopic examination.
Many people with dyspepsia do not seek medical help, but among those who do, psychosocial distress and fear of cancer are common.[80] For these patients, reassurance is a powerful therapeutic tool. A study conducted in England showed that patients with nonulcer dyspepsia had only one fifth the physician visits and prescriptions in the year following endoscopic examination as those who were not examined by endoscopy.[81] Another study found that endoscopic examination resulted in a 60% reduction in drug use and physician visits.[82] The Danish group discussed earlier compared patients with nonulcer dyspepsia 6 months before and 6 months after endoscopic examination.[83] After the examination, there were 41% fewer physician visits, and the number of prescriptions was reduced by 72%. A total of 52% of patients felt more reassured, and 66% of patients felt better and were more productive at work. A similar British study also showed that endoscopy reduced subsequent physician visits and drug use.[84] Hence, the positive effects of early diagnosis outweigh the stated benefits of a trial of therapy.
Factors affecting the decision to diagnose
the cause of dyspepsia
Primary care physicians' access to high-quality endoscopic or
radiographic services is essential to a strategy involving early
diagnosis. Endoscopic services are available without a
consultation in parts of Europe but not in Canada. Lower-cost,
more accessible endoscopy would prevent long-term, unnecessary
drug therapy and would better satisfy patients. The cost and
unwanted effects of drugs are also important issues. Under a
policy of offering a trial of therapy before diagnosis, many
patients without ulcers are treated needlessly, with no more
benefit than if they took a placebo. Even among patients with
ulcers, therapy may fail and diagnosis may eventually be
necessary; this is part of the cost of a trial of therapy.
If eradication of H. pylori is considered desirable in itself, then diagnosis of an ulcer is less relevant. Screening of the population for H. pylori infection, and treatment of those infected, would involve very many people, few of whom have dyspepsia. Such a policy would be very expensive, even if the diagnosis were made on the basis of blood tests. The results of this policy are difficult to predict; however, some organisms would be resistant to treatment and many people treated would experience side effects of antibiotics.
The decision to diagnose before treating would be influenced by evidence concerning the efficacy of eradicating H. pylori in alleviating nonulcer dyspepsia. We must insist upon well-conducted clinical trials to determine this. If H. pylori eradication in nonulcer dyspepsia has only marginal benefits or shows positive results in one of many parameters only by chance, this will not do as evidence of efficacy. Furthermore, even if H. pylori eradication proves to help some patients with functional dyspepsia, it would not help those who do not harbour the organism.
The best approach is to identify dyspepsia through careful history taking, rule out structural disease through physical examination and hemoglobin or hematocrit estimation and determine whether the dyspepsia is caused by an ulcer by endoscopic or radiographic examination. A US National Institutes of Health panel has recommended an anti-ulcer drug and combination antibiotic therapy for patients with a peptic ulcer who have a positive result of a test for H. pylori infection[85] (Table 2 [not available]). Therefore, if an ulcer is found, a suitable test for the organism is indicated.[85] For patients who do not have an ulcer, physicians should avoid drug therapy and, through reassurance and compassion, cure sometimes, ameliorate often and comfort always.
Conclusion
An endoscopic or high-quality radiographic examination is needed
to distinguish between an ulcer and nonulcer dyspepsia. This
approach is useful if the dyspepsia is consistent with an ulcer,
but not if the symptoms are those of irritable bowel syndrome,
gastroesophageal reflux or disease of the biliary tract and other
organs. Its usefulness also depends on physicians' conviction to
withhold drugs without proven benefit in diagnosed cases of
nonulcer dyspepsia. Therefore, in such cases, an initial
endoscopic diagnosis is the most cost-effective approach and the
most likely to improve the patient's quality of life. Careful
research is needed to discover the most cost-effective strategy
for treating and managing dyspepsia.[86] Meanwhile, an initial,
precise diagnosis of the cause of dyspepsia is fundamental to
rational use of therapy and is a sound investment.
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