FUNCIONAL DYSPEPSIA (FD)

EPIDEMIOLOGY

Globally, the prevalence of uninvestigated dyspepsia (UD) varies between 7% - 45%, depending on definition used and geographical location, whilst the prevalence of FD has been noted to vary between 11% - 29.2%. It is clear that dyspepsia and FD in particular are common conditions globally, affecting most populations, regardless of location.⁽¹⁾

There is a lack of data regarding prevalence of dyspepsia in Pakistan.

PATHOPHYSIOLOGY

The main pathophysiological mechanisms proposed for FD are motor dysfunction, visceral sensory abnormalities, and psychosocial factors. Several motor abnormalities have been documented in adults and children with FD. These include delayed gastric emptying, impaired initial distribution of a meal within the stomach, impaired accommodation, antral hypomotility, gastric dysrhythmia (tachygastria, bradygastria, and mixed dysrhythmia), and altered duodenojejunal motility.⁽²⁾ Abnormal gastric emptying or electogastrography abnormality is found in up to 70% of children with FD.^(3,4) Abnormal sensory perception has also been noted in FD. In particular, hypersensitivity to gastric distension, labeled as “irritable stomach syndrome,” has been seen in FD but not in organic dyspepsia and is thought to be akin to rectal hypersensitivity in irritable bowel syndrome — an entity that is often associated with FD.⁽⁵⁾ Finally, psychosocial factors have a significant impact on FD. The comorbidity between anxiety and FD is high. FD patients with gastric hypersensitivity were noted to have a significant negative correlation between anxiety level and threshold for pain and discomfort.⁽⁶⁾

NATURAL HISTORY

Dyspepsia, is a condition of impaired digestion. People may experience feeling full earlier than expected when eating. Dyspepsia is a common problem and is frequently caused by gastroesophageal reflux disease (GERD) or gastritis. In a small minority it may be the first symptom of peptic ulcer disease (an ulcer of the stomach or duodenum) and occasionally cancer.

SIGNS AND SYMPTOMS

Children with FD complain of one or more of the following symptoms:

• bothersome postprandial fullness
• early satiety
• epigastric pain
• epigastric burning
• Nausea and vomiting after eating may also occur.

Children having problem of early satiety may not be able to finish a normal sized meal. The feeling of fullness usually occurs much earlier than pain after the meal.

Alarm symptoms in Children with FD

• Persistent right upper- or right lower-quadrant pain
• Dysphagia
• Significant vomiting
• Gastrointestinal blood loss
• Family history of inflammatory bowel disease
• Unexplained fever
• Nocturnal diarrhea
• Perirectal disease
• Involuntary weight loss
• Deceleration of liner growth
• Delayed puberty

DIAGNOSTIC TEST

History and physical examination: Dyspepsia is a common symptom having either an organic or a functional cause. A thorough history and examination is useful to screen for organic cause.

Radionuclide gastric emptying test: History of a viral illness may be present in post-infectious gastroparesis, which can present with symptoms of FD.⁽⁷⁾ A radionuclide gastric emptying test may be helpful in such cases.

Breath hydrogen tests: Breath hydrogen tests may be used to evaluate symptoms of bloating or pain with or without dairy intake to screen for lactose intolerance or bacterial overgrowth.

Testing for H.Pylori: History of unexplained refractory iron deficiency anemia or first-degree relatives with gastric cancer should raise suspicion for Helicobacter pylori.^(8,9) The test for initial diagnosis of H. pylori should preferably be histopathology and rapid urease test or culture, and the use of serology either for initial diagnosis or for test of eradication is discouraged.⁽¹⁰⁾ Of note, there is inadequate evidence to support a causal relation between H. pylori gastritis and abdominal pain in the absence of ulcer; therefore, abdominal pain alone does not justify testing for H. pylori.^(10,11)

Testing for celiac disease: Testing for celiac disease may be considered with positive family history, history of weight loss or stunting, or autoimmune endocrine diseases.

Other Tests:

History of discrete, acute episodic pain associated with food intake or localized to the right upper or periumbilical regions may prompt testing of serum amylase, lipase, and obtaining an abdominal ultrasound.

History of severe abdominal pain or recurrent vomiting may prompt consideration of an upper-GI series to rule out an anatomical anomaly or mechanical obstruction, such as malrotation or duodenal web.

Symptoms suggestive of gastroesophageal reflux disease (GERD) may be treated empirically; however, a pH probe or impedance test may be useful in case of abdominal pain in the absence of classic symptoms of GERD (e.g. heartburn, waterbrash).

Role of endoscopy: Esophagogastroduodenoscopy (EGD) is helpful in identifying mucosal lesions, including erosive esophagitis, eosinophilic esophagitis, peptic ulcer, and H. pylori infection, among others. However, mucosal abnormalities do not preclude a diagnosis of FD. In fact, mild histologic gastritis or duodenitis without macroscopic lesions on endoscopy, and in the absence of NSAIDs intake, may be consistent with a diagnosis of FD. The majority of patients with dyspepsia do not have mucosal lesions on endoscopy. In one prospective study of children with dyspepsia symptoms, 44% had an EGD at a mean of 39 days from initial exam, and 62% of the EGDs were normal.⁽¹²⁾ Only 9% of the EGDs were notable for H. pylori. Hence the “test and treat” strategy (performing a non-invasive test for H. pylori and administering treatment), which has been validated in adults, is not encouraged in children.⁽¹³⁾

Differential Diagnosis

• Gastroesophageal reflux
• Eosinophilic esophagitis
• Gastroparesis
• Abdominal migraine
• Gastric or duodenal ulcer with or without helicobacter pylori
• Eosinophillic gastroenteritis
• Infection: Giardia, bacterial overgrowth
• Celiac disease
• Inflammatory bowel disease
• Pancreatitis
• Hepatitis
• Biliary dyskinesia
• Henoch-Schonlein purpura
• Malrotation with or without volvulus
• Duodenal web
• Ureteropelvic junction obstruction
• Psychogenic vomiting
• Eating disorder

TREATMENT OPTIONS

Medications: A trial of acid suppression and / or prokinetic therapy may be worthwhile, particularly if the symptoms have a burning component. Other medicines used include tramadol, gabapentin, pregabalin and duloxetine. Antacids, bismuth and sucralfate do not appear to be effective in functional dyspepsia.

1. pylori eradication H. pylori infection can cause functional dyspepsia. Eradication regimens (7 days treatment with Esomeprazole, amoxycillin and clarithromycin) may provide modest symptomatic benefit. Eradication also reduces the risk of future peptic ulcer disease.

Acid suppression Acid suppression involves treatment with a proton pump inhibitor (PPI) or a H2 -receptor antagonist, with some evidence that H2 -blockers have a greater benefit than PPIs for functional dyspepsia.

PPIs include:

• Esomeprazole
• Lansoprazole
• Omeprazole
• Pantoprazole
• Rabeprazole

H2 -receptor antagonists (H2 -blockers) include:

• Cimetidine
• Famotidine
• Nizatidine
• Ranitidine

Treatment at full doses of PPIs for 4 to 8 weeks may relieve symptoms, and allow stepping down to intermittent use or short courses. Long term use of PPIs has many adverse effects including vitamin B12 deficiency, enteric gut infections (Clostridium difficile), pneumonia, fractures, myopathy, skin reactions, and acute interstitial nephritis. If the main symptom is a burning epigastric pain, the Therapeutic Guidelines recommends a PPI once daily, half an hour before food. If a PPI fails to resolve symptoms after an adequate treatment period, a H2 -receptor antagonist could be trialed.

Domperidone: If the main symptom is a feeling of discomfort and bloating, domperidone 10 to 20 mg, 3 to 4 times daily before meals is recommended in the Therapeutic Guidelines.

Tricyclic antidepressants (TCA): If PPIs or domperidone are not effective, a trial of a low-dose tricyclic antidepressant (TCA) may be helpful.

Amitriptyine has been used in the treatment of FD. In a multicenter, randomized clinical trial in children, low-dose amitriptyline (10mg for weight < 35 kg and 20 mg for weight > 35 kg) was not superior to placebo; however, both amitriptyline and placebo had excellent therapeutic responses, underscoring the power of placebo in pediatric functional GI disorders.⁽¹⁴⁾ Based on this study, it seems reasonable to reserve TCAs for anxious children with FD who fail non-pharmacological therapy or are unwilling to consider it.

Botulinum toxin A, which has been used for treating spasticity in cerebral palsy, can be injected intrapylorically for treatment of gastroparesis. It has been used in children for treating gastroparesis refractory to medical therapy.⁽¹⁵⁾ It was found to be safe and effective in treating symptoms of nausea, vomiting, abdominal pain, and distension.

Prokinetics⁽¹⁶⁾

Prokinetic drugs that stimulate gastric smooth muscle contractions are widely used in patients with FD.

Cisapride, the first prokinetic used in FD and gastroparesis, accelerates gastric emptying by stimulating 5-hydroxytryptamine-4 (5-HT4) receptors and releasing acetylcholine in the myenteric plexus. The drug has been withdrawn due to cardiac safety concerns.

Tegaserod, a partial 5-HT4 receptor agonist, accelerates gastric emptying and enhances gastric accommodation in FD. The drug was generally well tolerated, but was withdrawn for a putative increased risk of cardiovascular ischemic events.

Mosapride is a new 5-HT4 receptor agonist that also exhibits 5-HT3 receptor antagonist properties. The drug is commercially available in several Asian countries.

Domperidone is a butyrophenone derivative that exerts antidopaminergic effects on peripheral dopamine2 receptors (D2).

Itopride is a mixed dopamine D2 antagonist and acetycholinesterase inhibitor. It has prokinetic effects and probably also modulates gastric accommodation and hypersensitivity. One trial shows that after a 4 week treatment period with itopride 50 mg three times daily, 75% of patients who fulfilled Rome III criteria for FD reported improvement in the total symptom score compared to baseline.

Non-Pharmacological Therapy

There is increasing literature to support the use of non-pharmacologic therapy in pediatric functional GI disorders. Cognitive behavior therapy is useful when there is history of anxiety. Guided imagery and progressive relaxation have been shown to be effective in pain-related functional GI disorders.⁽¹⁷⁾ Biofeedback-assisted relaxation training, or BART, is a promising adjunctive tool to medications.⁽¹⁸⁾

Dietary Interventions and Supplements: Ginger root and STW5 (an herbal preparation containing iberis, peppermint, and chamomile) have been shown in adult studies to be effective for relief of dyspepsia symptoms.^(19,20)

Non pharmacological therapy of functional dyspepsia also includes eating small meals and altering the time of the main meal of the day (i.e. to lunchtime). Reduced fat intake may improve symptoms, as fat can slow gastric emptying. Reducing anxiety is often helpful, and cognitive behavioural therapy or psychotherapy has been shown to be effective.

GOALS OF THERAPY

The goal of therapy is to provide symptom relief and prevent disease progression

GUIDELINES

To view, “Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders”, please click on below link:

http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf

To view, “American Family Physician - Update on the Evaluation and Management of Functional Dyspepsia”, please click on below link:

http://www.aafp.org/afp/2011/0301/p547.html

To view, “National Institute for Health and Care Excellence (NICE) guideline - Dyspepsia and gastro-oesophageal reflux disease: investigation and management of dyspepsia, symptoms suggestive of gastro-oesophageal reflux disease, or both”, please click on below link:

https://www.nice.org.uk/guidance/cg184/documents/dyspepsiagord-nice-guideline2

To view “American College of Gastroenterology guidelines for the management of Dyspepsia”, please click on following link:

https://gi.org/guideline/management-of-dyspepsia

PRECAUTIONS

Offer following prevention to child’s guardian:

Change child eating habits

• It's best to feed several small meals instead of two or three large meals to your child. Do not skip meal of your child.
• Instruct child to eat slowly and chew food thoroughly. This will prevent excessive air swallowing (aerophagia) and pronounced distension of the stomach.
• After taking meal, allow child to wait for 2 to 3 hours before child lie down. Late-night snacks aren't a good idea.
• Avoid chocolate, mint, and alcohol, they can make dyspepsia worse.
• Spicy foods, foods that have a lot of acid (like tomatoes and oranges), and coffee can make dyspepsia worse in some children. If child symptoms are worse after he/she eat a certain food, stop giving that food and check if child symptoms get better.
• Keep a food diary to identify trigger foods which can make your child dyspepsia worse. These trigger foods should then be avoided or minimized.
• Make a habit of your child to walk after eating. This can assist with gastric emptying and may also help with symptoms of reflux.

Protect from your child from second hand smoke.

If child get dyspepsia at night, raise the head of bed 6 to 8 inches by putting the frame on blocks or placing a foam wedge under the head of mattress. (Adding extra pillows does not work.)

Do not dress tight clothing around child abdomen.

Losing weight can help if your child is overweight. It's important to lose weight safely and steadily through regular exercise and by eating a healthy, balanced diet.

Manage stress effectively with relaxation techniques that prove to be helpful. Physical activity like sports may have multiple benefits when it comes to functional dyspepsia.

REFERENCES

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