Gastroesophageal Reflux Disease

From Wikipedia

Gastroesophageal reflux disease (GERD), gastro-oesophageal reflux disease (GORD), gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus.[1] A typical symptom is heartburn.

GERD is usually caused by changes in the barrier between the stomach and the esophagus, including abnormal relaxation of the lower esophageal sphincter, which normally holds the top of the stomach closed; impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia. These changes may be permanent or temporary (“transient”).

Another kind of acid reflux, which causes respiratory and laryngeal signs and symptoms, is called laryngopharyngeal reflux (LPR) or “extraesophageal reflux disease” (EERD). Unlike GERD, LPR is unlikely to produce heartburn, and is sometimes called silent reflux.

 

Signs and symptoms

The most-common symptoms of GERD are:

Less-common symptoms include:

GERD sometimes causes injury of the esophagus. These injuries may include:

Several other atypical symptoms are associated with GERD, but there is good evidence for causation only when they are accompanied by esophageal injury. These symptoms are:

Some people have proposed that symptoms such as sinusitis, recurrent ear infections, and idiopathic pulmonary fibrosis are due to GERD; however, a causative role has not been established.[2

Main article: Barrett’s Esophagus

 

Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach. This is a complication of chronic gastroesophageal reflux disease and can be a cause of dysphagia or difficulty swallowing.

 

Diagnosis

A detailed historical knowledge is vital for an accurate diagnosis. Useful investigations may include ambulatory Esophageal pH Monitoringbarium swallow X-rays,esophageal manometry, and Esophagogastroduodenoscopy (EGD).

The current gold standard for diagnosis of GERD is esophageal pH monitoring. It is the most objective test to diagnose the reflux disease and it also allows to monitor GERD patients in regards of their response to medical or surgical treatment. One practice for diagnosis of GERD is a short-term treatment with proton pump inhibitors, with improvement in symptoms suggesting a positive diagnosis. According to a systematic review, short-term treatment with proton pump inhibitors may help predict abnormal 24-hr pH monitoring results among patients with symptoms suggestive of GERD.[7] In this study, the positive likelihood ratioof a symptomatic response detecting GERD ranged from 1.63 to 1.87, with sensitivity of 0.78 though specificity was only 0.54.

In general, an EGD is done when the patient either does not respond well to treatment or has alarm symptoms including dysphagia, anemia, blood in the stool (detected chemically), wheezing, weight loss, or voice changes. Some physicians advocate either once-in-a-lifetime or 5/10-yearly endoscopy for patients with longstanding GERD, to evaluate the possible presence of dysplasia or Barrett’s esophagus, a precursor lesion for esophageal adenocarcinoma.[8]

Esophagogastroduodenoscopy (EGD) (a form of endoscopy) involves insertion of a thin scope through the mouth and throat into the esophagus and stomach (often while the patient is sedated) in order to assess the internal surfaces of the esophagus, stomach, and duodenum.

Biopsies can be performed during gastroscopy and these may show:

  • Edema and basal hyperplasia (non-specific inflammatory changes)
  • Lymphocytic inflammation (non-specific)
  • Neutrophilic inflammation (usually due to reflux or Helicobacter gastritis)
  • Eosinophilic inflammation (usually due to reflux). The presence of intraepithelial eosinophils may suggest a diagnosis of eosinophilic esophagitis (EE)if eosinophils are present in high enough numbers. Less than 20 eosinophils per high-power microscopic field in the distal esophagus, in the presence of other histologic features of GERD, is more consistent with GERD than EE.[9]
  • Goblet cell intestinal metaplasia or Barretts esophagus
  • Elongation of the papillae
  • Thinning of the squamous cell layer
  • Dysplasia or pre-cancer
  • Carcinoma

Reflux changes may be non-erosive in nature, leading to the entity “non-erosive reflux disease”.

 

Pathophysiology

GERD is caused by a failure of the cardia. In healthy patients, the “Angle of His“—the angle at which the esophagus enters the stomach—creates a valve that prevents duodenal bile, enzymes, and stomach acid from traveling back into the esophagus where they can cause burning and inflammation of sensitive esophageal tissue.

Factors that can contribute to GERD:

  • Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.[10][11]
  • Obesity: increasing body mass index is associated with more severe GERD.[12] In a large series of 2000 patients with symptomatic reflux disease, it has been shown that 13 % of changes in esophageal acid exposure is attributable to changes in body mass index.[13]
  • Zollinger-Ellison syndrome, which can be present with increased gastric acidity due to gastrin production.
  • Hypercalcemia, which can increase gastrin production, leading to increased acidity.
  • Scleroderma and systemic sclerosis, which can feature esophageal dysmotility.
  • The use of medicines such as prednisolone.
  • Visceroptosis or Glénard syndrome, in which the stomach has sunk in the abdomen upsetting the motility and acid secretion of the stomach.

GERD has been linked to a variety of respiratory and laryngeal complaints such as laryngitis, chronic coughpulmonary fibrosisearache, and asthma, even when not clinically apparent. These atypical manifestations of GERD is commonly referred to as laryngopharyngeal reflux or as extraesophageal reflux disease (EERD).

Factors that have been linked with GERD, but not conclusively:

In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection.[16] The eradication of H. pylori can lead to an increase in acid secretion,[17] leading to the question of whether H. pylori-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.[18]

Prevention

GERD is largely preventable through changes in lifestyle, which are also used as treatment (see below).

Sleep on the left side, or with your upper body raised.
Relief is often found by raising the head of the bed, raising the upper body with pillows, or sleeping sitting up.[19] The upper body must be raised, not just the head; pillows that only raise the head do little for heartburn and put strain on the neck. Sleeping on the left side also keeps gravity working for you, keeping your stomach below your esophagus.[20]
Eat smaller meals.
Eating a big meal causes excess stomach acid production, so attacks can be minimized by eating smaller meals. It is also important to avoid eating shortly before bedtime.[11]
Lose weight.
Gaining even a few pounds increases your risk of heartburn.[19] Exactly why isn’t clear, but the leading theory is that more body fat puts more pressure on the stomach, which can cause highly acidic stomach contents to reflux to the lower esophageal sphincter. For the same reason, tight clothing around the abdomen can also increase the risk of heartburn.
Avoid acidic and rich foods.
Though less well supported by evidence,[19] a sufferer may benefit from avoiding foods that trigger their symptoms. These commonly include acidic fruit or juices, fatty foods, coffee, tea, onions, peppermint, chocolate, especially shortly before bedtime.
[21]

Treatment

Three types of treatments exist for GERD. These include lifestyle modifications, medications, and surgery.

[edit]Lifestyle

[edit]Diet

Certain foods and lifestyle are considered to promote gastroesophageal reflux, but a 2006 review suggested that evidence for most dietary interventions is anecdotal; only weight loss and elevating the head of the bed were supported by evidence.[19] A subsequent randomized crossover study showed benefit by avoiding eating two hours before bedtime.[11]

The following may exacerbate the symptoms of GERD:

  • Antacids based on calcium carbonate (but not aluminium hydroxide) were found to actually increase the acidity of the stomach. However, all antacids reduced acidity in the lower esophagus, so the net effect on GERD symptoms may still be positive.[22]
  • Smoking reduces lower esophageal sphincter competence, thus allowing acid to enter the esophagus.

[edit]Position

Sleeping on the left side has been shown to reduce nighttime reflux episodes in patients.[20]

meta-analysis suggested that elevating the head of the bed is an effective therapy, although this conclusion was only supported by nonrandomized studies.[19] The head of the bed can be elevated by plastic or wooden bed risers that support bed posts or legs, a therapeutic bed wedge pillow, a wedge or an inflatable mattress lifter that fits in between mattress and box spring or a hospital bed with an elevate feature. The height of the elevation is critical and must be at least 6 to 8 inches (15 to 20 cm) to be at least minimally effective to prevent the backflow of gastric fluids. Some innerspring mattresses do not work well when inclined and may cause back pain; some prefer foam mattresses. Some practitioners use higher degrees of incline than provided by the commonly suggested 6 to 8 inches (15 to 20 cm) and claim greater success.

[edit]Medications

A number of drugs are approved to treat GERD, and are among the most prescribed medication in Western countries.

  • Proton pump inhibitors (such as omeprazoleesomeprazolepantoprazolelansoprazole, and rabeprazole) are the most effective in reducing gastric acid secretion. These drugs stop acid secretion at the source of acid production, i.e., the proton pump.
  • Gastric H2 receptor blockers (such as ranitidinefamotidine and cimetidine) can reduce gastric secretion of acid. These drugs are technically antihistamines. They relieve complaints in about 50% of all GERD patients. Compared to placebo (which also is associated with symptom improvement), they have a number needed to treat (NNT) of eight (8).[23]
  • Antacids before meals or symptomatically after symptoms begin can reduce gastric acidity (increase pH).
  • Alginic acid (Gaviscon) may coat the mucosa as well as increase pH and decrease reflux. A meta-analysis of randomized controlled trials suggests alginic acid may be the most effective of non-prescription treatments with a NNT of four.[23]
  • Prokinetics strengthen the lower esophageal sphincter (LES) and speed up gastric emptying. Cisapride, a member of this class, was withdrawn from the market for causing long QT syndrome. Reglan (metoclopramide) is a prokinetic with a better side-effect profile.
  • Sucralfate (Carafate) is also useful as an adjunct in helping to heal and prevent esophageal damage caused by GERD, however it must be taken several times daily and at least two (2) hours apart from meals and medications.
  • Mosapride citrate is a 5-HT4 receptor agonist used outside the United States largely as a therapy for GERD and dyspepsia.[24]
  • Baclofen is an agonist of GABAB receptor. In addition to its skeletal muscle relaxant properties, it has also been shown to decrease transient lower esophageal sphincter relaxations at a dose of 10mg given four times daily. Reductions in esophageal relaxation clinically reduce episodes of reflux.[25]

Clinical trials which compare GERD treatments head-to-head provide physicians with critical information. Unfortunately most pharmaceutical-company sponsored studies are conducted versus placebo and not an active control. However, the DIAMOND has shown rough equivalence of efficacy between a “step-up” approach to therapy (antacids, followed by histamine antagonists, followed by PPIs) and a “step-down” approach (the reverse). The primary endpoint of the study was treatment success after six months, and was achieved for 70% of patients in “step-down” versus 72% of patients in “step-up.”[26]

[edit]Surgery

The standard surgical treatment is the Nissen fundoplication. In this procedure the upper part of the stomach is wrapped around the lower esophageal sphincter (LES) to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia. The procedure is often done laparoscopically.[27] When compared to medical management laparoscopic fundoplication had better results at 1 year.[28] In addition, laparoscopic fundoplication may reduce SF-36 score (quality of life questionnaire) among patients with gastro-esophageal reflux disease as compared to medical management according to a Cochrane systematic review of randomized controlled trials.[29] There were statistically significant improvements in quality of life at 3 months and 1 year after surgery compared to medical therapy, with an SF-36 general health score mean difference of -5.23 in favor of surgery (95%CI = -6.83 to -6.82).

An obsolete treatment is vagotomy (“highly selective vagotomy”), the surgical removal of vagus nerve branches that innervate the stomach lining. This treatment has been largely replaced by medication.

Another treatment is transoral incisionless fundoplication (TIF) with the use of a device called Esophyx, which allows doctors to rebuild the valve between the stomach and the esophagus by going through the esophagus.[30]

[edit]Other

In 2000 the U.S. Food and Drug Administration (FDA) approved two endoscopic devices to treat chronic heartburn. One system, Endocinch, puts stitches in the LES to create little pleats that help strengthen the muscle. However, long-term results were disappointing, and the device is no longer sold by Bard. Another, the Stretta Procedure, uses electrodes to apply radio frequency energy to the LES. The long-term outcomes of both procedures compared to a Nissen fundoplication are still being determined.

Subsequently the NDO Surgical Plicator was cleared by the FDA for endoscopic GERD treatment. The Plicator creates a plication, or fold, of tissue near the gastroesophageal junction, and fixates the plication with a suture-based implant. The company ceased operations in mid 2008, and the device is no longer on the market.