Functional Dyspepsia and IBS: One Disease or Two?
Dyspepsia is a highly prevalent disorder that affects up to 25% of the general population. Dyspepsia affects men and women equally and occurs independently of race, religion, and socioeconomic status. Symptoms of dyspepsia include epigastric pain and/or discomfort, early satiety, postprandial fullness, bloating, and nausea. Dyspeptic symptoms may develop due to an organic process (peptic ulcer disease, gastritis, occult acid reflux); however, most patients with dyspeptic symptoms are ultimately diagnosed as having functional dyspepsia (FD).1 Functional dyspepsia is diagnosed after an appropriate diagnostic evaluation fails to identify an organic etiology to explain the patient’s symptoms. Similar to IBS, FD is a chronic disease for many patients, as approximately 50% of patients remain symptomatic over a 5-year follow-up period.2 Contrary to many patients’ beliefs, however, FD is not a risk factor for gastric cancer or peptic ulcer disease.
In an effort to incorporate new information about symptom expression and pathophysiology, the Rome criteria were recently revised (Rome III). Functional dyspepsia is now defined as the presence of symptoms thought to originate in the gastroduodenal region in the absence of any organic, systemic, or metabolic disease likely to explain the symptoms.3 The Rome committee also introduced two new subcategories to help further differentiate the FD population—postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS; Table 23-1).
Epigastric pain or discomfort is a hallmark symptom in patients with FD. The word discomfort is important to emphasize, as many patients will not complain of pain, but rather state that they have a burning feeling, or pressure, or fullness in the epigastric area. Other common symptoms include early satiety, postprandial fullness and nausea, belching, bloating, and nausea. Frustratingly, symptoms of FD do not consistently predict underlying pathophysiology and do not reliably guide therapy.
The precise etiology of FD is unknown; although there are limited data to suggest that genetics, a prior infection, and environmental factors all play a role in symptom expression. Preliminary studies have demonstrated that patients with the GNß3 CC genotype are more likely to suffer from dyspepsia. This gene is involved in cell signaling, although the exact mechanisms by which alterations in this gene can produce symptoms of dyspepsia are not known. Similar to data from IBS studies, there is evidence demonstrating that a prior gastrointestinal infection may be the cause of FD symptoms in up to 20% of cases. Although H. pylori infection may produce dyspeptic symptoms in a small subset of patients, there are few data to support this pathogen as a cause of symptoms in a majority of FD patients. Finally, psychological factors (stress, anxiety, somatization, depression) may modulate symptom expression in some FD patients.
Functional dyspepsia is a heterogeneous disorder, and no single pathophysiologic abnormality can explain the multiple symptoms expressed by FD patients. Research over the past 2 decades has identified a number of different pathophysiologic processes that may disturb normal gastric motor and sensory function in the upper gastrointestinal tract of FD patients. Abnormal gastric accommodation may account for symptoms of epigastric fullness and pressure in some patients and is present in approximately 40% of FD patients.1 Antral hypomotility and delayed gastric emptying are present in other patients with FD, with several studies showing that approximately onethird of FD patients have a mild delay in gastric emptying. Similar to many IBS patients, FD patients are characterized by visceral hypersensitivity. Balloon distension studies have demonstrated that up to twothirds of patients with FD have heightened gastric perception, although this does not correlate with any specific symptom. Other patients with FD may have gastric electrical dysrhythmias, abnormalities of duodenal motor or sensory function, or disordered feedback from the proximal small intestine as the cause of their symptoms.
Why Might FD and IBS Overlap?
There are several plausible theories to explain why FD and IBS might overlap. One, they are both common medical disorders. The prevalence of IBS is 12% to 15% in the United States, while the prevalence of FD is approximately 10%. Given the high prevalence of both disorders, it would not be uncommon for some patients to suffer from both disorders. Two, the proposed etiologies of FD seem remarkably similar to those of IBS (see Chapter 13). A number of research studies have shown that, for both conditions, a genetic predisposition may exist (Figure 23-1). For FD symptoms to develop, however, the GI tract must be exposed or subjected to some type of insult. This may be the result of a viral or bacterial infection (ie, postinfectious FD), an inflammatory process (ie, medications), or stress (eg, mental, physical, emotional, financial, sexual). Symptoms of IBS and/or FD may then develop, and these are generally mild. However, symptoms may become severe if psychological factors are present and burdensome (ie, anxiety, depression, somatization, catastrophization, poor coping skills, ongoing stress). Three, both FD and IBS are linked by similar pathophysiology. As mentioned above, twothirds of patients with FD have evidence of visceral hypersensitivity, demonstrated during balloon distention studies. Thus, it is easy to think of FD as nothing more than IBS pathophysiology expressed in the upper gastrointestinal tract. Finally, IBS and FD are similar in that they both respond, in part, to treatments for visceral hypersensitivity and visceral pain4 (see below).
Figure 23-1. Proposed pathway for the development of FD and IBS.
What Treatment Options Are Available for My Patient With FD?
Most patients with FD have symptoms associated with the ingestion of food.5 There are limited data to suggest that dietary fat may increase gastric sensitivity to distension and cause dyspeptic symptoms. I recommend that patients with FD focus on low-fat meals and smaller, more frequent meals.
Eradication of H. pylori
Testing and treating for H. pylori (if present) is often recommended as the first step in the management of younger patients with uncomplicated dyspeptic symptoms. Although safe, this strategy is unlikely to improve symptoms of FD. In fact, a recent analysis found only a small benefit above placebo, with a number needed to treat of 14.
Histaminereceptortype2antagonists (H2RAs) are marginally better than placebo at improving epigastric pain, although they do not improve other dyspeptic symptoms. Most providers thus use a proton pump inhibitor (PPI) as firstline treatment for FD. This is not an unreasonable course of action, as shortterm risks of PPIs are low, and this may provide relief of symptoms in a small number of people, many of whom may have had silent acid reflux. Overall, however, PPIs are only approximately 10% better than placebo at improving dyspeptic symptoms with a number needed to treat (NNT) of 9. In addition, longterm use of PPIs can be expensive, and there are emerging data that long-term PPI use may place patients at increased risk for Clostridium difficile colitis, communityacquired pneumonia, and hip fractures.
FD patients with symptoms of early satiety, epigastric fullness, and postprandial discomfort may respond to the use of prokinetic agents. Metoclopramide and domperidone are now the most commonly employed agents. Although individual patients may respond to prokinetic medications, there are conflicting data in the literature regarding their utility, with one systematic review showing prokinetic agents were somewhat better than placebo, while a metaanalysis did not show any benefits compared to placebo. In addition, metoclopramide is associated with a variety of side effects (anxiety, drowsiness, decreased libido, breast tenderness) and as of February 2009 carries a blackbox warning. Domperidone is not readily available in the US and is difficult to obtain for most providers.
Tricyclic antidepressants (TCAs) may improve symptoms of dyspepsia in patients who have failed H2RAs, PPIs, or prokinetic agents. Although the precise mechanism is unknown, they may improve symptoms of visceral hypersensitivity and reduce intragastric pressure. In general, lower doses of TCAs are used to treat FD than depression. Selective serotonin reuptake inhibitors (SSRIs) have not been well-studied for the treatment of FD, although a recent trial of venlafaxine failed to show any benefits over placebo.
Hypnotherapy and Psychological Therapies
Hypnotherapy may improve dyspeptic symptoms in some patients, and a recent study found that hypnotherapy was better than medical therapy and supportive therapy at improving quality of life and symptom scores (see Chapter 45). Although not well studied, psychological therapies, including cognitive behavioral therapy, may relieve symptoms of dyspepsia by reducing coexisting stress and anxiety (see Chapter 46).
Managing patients with IBS and FD can be a challenging and frustrating process for clinicians. Currently, these two common functional gastrointestinal disorders are thought of as completely separate disorders. Because many patients have overlapping symptoms of IBS and dyspepsia, maintaining two separate diagnoses leads to separate, but often parallel, processes of evaluation and treatment. Unfortunately, this results in redundant laboratory tests, duplication of diagnostic studies, frequent office visits, and the use of multiple medications.
As discussed, IBS and FD are remarkably similar. Injury to the enteric nervous system likely serves as the unifying link in the generation and expression of the typical symptoms found in IBS and FD. Some patients will manifest the abnormal pathophysiology that develops as a result of ENS injury with primarily upper GI tract symptoms (epigastric fullness and discomfort, bloating, nausea), while others will manifest primarily lower GI symptoms (abdominal pain and disordered defecation).
The recognition that symptom expression in IBS and FD reflects different manifestations of the same disorder should help eliminate repetitive diagnostic testing, minimize office visits, and improve our ability to target therapy at the common link. Treatment options for IBS and FD should be directed at modulating both peripheral and central pain mechanisms, with the goal of improving symptoms, improving quality of life, and minimizing the economic burden to society.6
1. Tack J, Caenepeel, P, Fischler B, et al. Symptoms associated with hypersensitivity to gastric distention in functional dyspepsia. Gastroenterology. 2001;121:526-535.
2. Talley NJ, Dennis EH, Schettler-Duncan VA, et al. Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol. 2003;98:2454-2459.
3. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:
4. Saad RJ, Chey WD. Review article: current and emerging therapies for functional dyspepsia. Aliment Pharmacol Ther. 2006;24:475-492.
5. Bisschops R, Karamanolis G, Arts J, et al. Relationship between symptoms and ingestion of a meal in functional dyspepsia. Gut. 2008;57:1495-1503.
6. Lacy BE, Cash BD. Clinical cornerstone. A 32 year old woman with abdominal pain. JAMA. 2008;299:555-565.