Gastroesophageal reflux disease (GERD), gastro-oesophageal reflux disease (GORD), gastric reflux disease, or acid reflux disease is defined as chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus.^[1]

This is commonly due to transient or permanent changes in the barrier between the esophagus and the stomach. This can be due to incompetence of the lower esophageal sphincter, transient lower esophageal sphincter relaxation, impaired expulsion of gastric reflux from the esophagus, or a hiatal hernia. Respiratory and laryngeal manifestations of GERD are commonly referred to as extraesophageal reflux disease (EERD).

[edit] Signs and symptoms

[edit] Adults

The most-common symptoms of GERD are:

• Heartburn
• Regurgitation
• Trouble swallowing (dysphagia)

Less-common symptoms include:

• Pain with swallowing (odynophagia)
• Excessive salivation (this is common during heartburn, as saliva is generally slightly basic^[2] and is the body's natural response to heartburn, acting similarly to an antacid)
• Nausea^[3]
• Chest pain

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

• Reflux esophagitis—necrosis of esophageal epithelium causing ulcers near the junction of the stomach and esophagus.
• Esophageal strictures—the persistent narrowing of the esophagus caused by reflux-induced inflammation.
• Barrett's esophagus—metaplasia (changes of the epithelial cells from squamous to columnar epithelium) of the distal esophagus.
• Esophageal adenocarcinoma—a rare form of cancer.^[3]

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:

• Chronic cough
• Laryngitis (hoarseness, throat clearing)
• Asthma
• Erosion of dental enamel
• Dentine hypersensitivity
• Sinusitis and damaged teeth^[4]

Some people have proposed that symptoms such as pharyngitis, sinusitis, recurrent ear infections, and idiopathic pulmonary fibrosis are due to GERD; however, a causative role has not been established.^[3]

[edit] Children

GERD may be difficult to detect in infants and children. Symptoms may vary from typical adult symptoms. GERD in children may cause repeated vomiting, effortless spitting up, coughing, and other respiratory problems. Inconsolable crying, failure to gain adequate weight, refusing food, bad breath, and belching or burping are also common. Children may have one symptom or many — no single symptom is universal in all children with GERD.

Common symptoms of Pediatric Reflux

• Irritability and pain, sometimes screaming suddenly when asleep. Constant or sudden crying or “colic” like symptoms. Babies can be inconsolable especially when laid down flat.
• Poor sleep habits typically with arching their necks and back during or after feeding
• Excessive possetting or vomiting
• Frequent burping or frequent hiccups
• Excessive dribbling or running nose
• Swallowing problems, gagging and choking
• Frequent ear infections or sinus congestion
• Babies are often very gassy and extremely difficult to “burp” after feeds
• Refusing feeds or frequent feeds for comfort
• Night time coughing, extreme cases of acid reflux can cause apnoea and respiratory problems such as asthma, bronchitis and pneumonia if stomach contents are inhaled.
• Bad breath – smelling acidy
• Rancid/acid smelling diapers with loose stool. Bowel movements can be very frequent or babies can be constipated.

Vomiting feeds

Possetting after a feed is quite normal with most infants. They gain weight, feed well and have no other symptoms, but still this can be upsetting for parents. As the child gets older the lower oesophageal sphincter becomes more competent so the vomiting should begin to show signs of improvement and eventually stop. Some babies suffer more with reflux and about 60% of these babies with persistent reflux may have weight gain issues. It is a very popular misconception though that all babies and children with reflux are underweight. This isn't always the case, some may comfort eat and feed very frequently and not all are sick. Many doctors advise that babies outgrow reflux once they can sit up, or once they stand. Many do, but some will not only fail to outgrow it, but will noticeably worsen with developmental milestones, teething episodes, viral illness and weaning.

Silent Reflux

Some babies with reflux do not vomit at all. This is actually more of a problem because the acidic stomach contents go up the throat and back down again, causing twice the pain and twice the damage.^{[citation needed]} There is no clear relationship between symptoms and the severity of reflux.

It is estimated that of the approximately 4 million babies born in the U.S. each year, up to 35% of them may have difficulties with reflux in the first few months of their life, known as spitting up.^[5] Most of those children will outgrow their reflux by their first birthday. However, a small but significant number of them will not outgrow the condition. This is particularly true where there is a family history of GERD present.

[edit] Barrett's esophagus

GERD may lead to Barrett's esophagus, a type of metaplasia which is in turn a precursor condition for carcinoma. The risk of progression from Barrett's to dysplasia is uncertain but is estimated at about 20% of cases.^[6] Due to the risk of chronic heartburn progressing to Barrett's, EGD every 5 years is recommended for patients with chronic heartburn, or who take drugs for chronic GERD.^{[citation needed]}

[edit] Diagnosis

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

A detailed historical knowledge is vital for an accurate diagnosis. Useful investigations may include ambulatory Esophageal pH Monitoring, barium 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. 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.^[7]

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)
• 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".

[edit] 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.

Another paradoxical cause of GERD-like symptoms is not enough stomach acid (hypochlorhydria). The valve that empties the stomach into the intestines is triggered by acidity. If there is not enough acid, this valve does not open, and the stomach contents are churned up into the esophagus. However, there is still enough acidity to irritate the esophagus.

Factors that can contribute to GERD:

• Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.^[8]
• Obesity: increasing body mass index is associated with more severe GERD.^[9]. 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.</ref>^[10]
• 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 cough, pulmonary fibrosis, earache, and asthma, even when not clinically apparent. These atypical manifestations of GERD is commonly referred to as extraesophageal reflux disease.

Factors that have been linked with GERD but not conclusively:

• Obstructive sleep apnea^[11][12]
• Gallstones, which can impede the flow of bile into the Duodenum, which can affect the ability to neutralize gastric acid

In 1999, a review of existing studies found that, on average, 40% of GERD patients also had H. pylori infection.^[13] The eradication of H. pylori can lead to an increase in acid secretion,^[14] 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.^[15]

[edit] Treatment

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

[edit] Lifestyle modifications

Dietary modification

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.^[16] A subsequent randomized crossover study showed benefit by avoiding eating two hours before bedtime.^[8]

The following may exacerbate the symptoms of GERD:

• Coffee and alcohol stimulate gastric acid secretion. Taking these before bedtime especially can cause evening reflux.
• Antacids based on calcium carbonate (but not aluminum 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.^[17]
• Foods high in fats and smoking reduce lower esophageal sphincter competence, so avoiding these may help. Fat also delays stomach emptying.
• Eating within 2–3 hours before bedtime.
• Large meals. Having smaller, more frequent meals reduces GERD risk, as it means there is less food in the stomach at any one time.
• Carbonated soft drinks with or without sugar.
• Chocolate and peppermint.
• Acidic foods: tomatoes and tomato-based preparations; citrus fruits and citrus juices.
• Cruciferous vegetables:cabbage, cauliflower, broccoli, and Brussels sprouts.
• Milk and milk-based products containing calcium^{[citation needed]} and fat, within 2 hours of bedtime.

Positional therapy

Sleeping on the left side has been shown to reduce nighttime reflux episodes in patients.^[18]

A meta-analysis suggested that elevating the head of bed is an effective therapy, although this conclusion was only supported by nonrandomized studies.^[16] 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, or a wedge or an inflatable mattress lifter that fits in between mattress and box spring. 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.

Other lifestyle modifications

• Avoidance of smoking.
• Weight reduction in overweight or obese people.
• Avoiding tight garments in those with abdominal obesity.

[edit] Medications

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

• Proton pump inhibitors (such as omeprazole, esomeprazole, pantoprazole, lansoprazole, 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 ranitidine, famotidine 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 of eight (8).^[19]
• 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 number needed to treat of four.^[19]
• 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 significant side effects called Tardive Dyskinesia/Dystonia.^[10] The United States Food and Drug Administration issued a Black Box Warning about Reglan in January 2009.
• 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.^[20]

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 6 months, and was achieved for 70% of patients in "step-down" versus 72% of patients in "step-up."^[21]

[edit] Surgical treatments

The standard surgical treatment is the Nissen fundoplication. In this procedure the upper part of the stomach is wrapped around the LES to strengthen the sphincter and prevent acid reflux and to repair a hiatal hernia. The procedure is often done laparoscopically.^[22] When compared to medical management laparoscopic fundoplication had better results at 1 year.^[23]

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 diaphragm by going through the esophagus.^[24]

[edit] Other treatments

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.

Another treatment that involved injection of a solution during endoscopy into the lower esophageal wall was available for about one year ending in late 2005. It was marketed under the name Enteryx. It was removed from the market due to several reports of complications from misplaced injections.

[edit] References

[edit] External links

• GERD patient information page at NIH
• Acid Peptic Disorders Overview from the Cleveland Clinic.