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Chronic Abdominal Pain New thoughts on the sensitive gut John T. Boyle, M.D. Educational Objectives Learn an algorithm for evaluation of chronic abdominal pain Define diagnostic criteria for functional abdominal pain Review current concepts of pathophysiology Establish goals of therapy Evaluate current treatment options Ambiguity of Terms Chronic abdominal pain • In clinical practice, it is generally believed that abdominal pain that exceeds 1 or 2 months can be considered chronic • In population studies, chronic abdominal pain is reported to occur in 10-15% of all children Recurrent abdominal pain (Seminal definition by Apley in 1958 • Paroxysmal abdominal pain in children between the ages of 4 and 16 years • Persists for more than 3 months • Affects normal activity • Has been equated in the literature as a diagnosis Recurrent Abdominal Pain (RAP) RAP is not a diagnosis RAP should be considered a synonym for chronic abdominal pain The key concept when thinking about chronic abdominal pain is pain that affects normal lifestyle • • • • • School attendance Ability to focus in school Participation in extracurricular activities Feeding behavior Sleep pattern Differential diagnosis of Chronic Abdominal Pain Organic pain • • • • Anatomical disorders Infectious Non-infectious inflammatory bowel disease Biochemical abnormalities Psychosomatic pain • Primary factors that influence the perception of pain are cognitive and emotional Functional abdominal pain • Dysfunction of the autonomic nervous system in the gastrointestinal tract Traditional Concept of Functional Bowel disease A negative diagnosis No specific structural, infectious, inflammatory, biochemical, or psychosomatic cause can be determined Frequency of Diagnosis Organic Psychogenic Psychogenic Functional Organic Functional Key Concepts in Approach to Chronic Abdominal Pain Functional abdominal pain should not be a diagnosis of exclusion Primary care physicians should be able to make a primary diagnosis of functional abdominal pain A large battery of biochemical and x-ray tests should not be necessary in the majority of patients who present with recurrent abdominal pain Algorithm for Evaluation of Chronic Abdominal Pain Value of the Pain History in Differentiating Organic from Functional Abdominal Pain The characteristics of the pain itself do not allow the physician to discriminate between organic, functional, or psychosomatic disorders Frequency of pain Character of pain Location of pain Pain awakening patient at night Associated GI symptoms including anorexia, nausea, vomiting, increased gas, or altered bowel • Associated extra-intestinal symptoms including fatigue, headache, arthralgia • Affects of pain on lifestyle • • • • • Algorithm for Evaluation of Recurrent Abdominal Pain The Presence of Alarm Signals Should Trigger Work-Up of Organic Disorder Involuntary weight loss Growth retardation Significant vomiting Significant diarrhea GI blood loss Consistent RUQ or RLQ abdominal pain Associated fever, arthritis, rash, amenorrhea Symptoms of psychiatric disorder Family history of inflammatory bowel disease Abnormal physical exam Abnormal Physical Findings Localized tenderness in RUQ or RLQ Localized fullness or mass Hepatomegaly Splenomegaly Spine or CVA tenderness Perianal fissure or fistula Visible soiling Guaiac positive stool Algorithm for Evaluation of Recurrent Abdominal Pain Algorithm for Evaluation of Recurrent Abdominal Pain Sub-categories of Functional Abdominal Pain Based on Distinctive Clinical Features Isolated abdominal pain (Functional abdominal pain) Dyspepsia (Functional dyspepsia) • Usually epigastric pain, associated with eating, nausea, episodic vomiting, early satiety, bloating, occasional heartburn, or oral regurgitation Irritable bowel syndrome • Pain associated with change in frequency or consistency of bowel movements, pain relieved by defecation, or a sense of incomplete evacuation after bowel movement Abdominal migraine • Cyclical pain associated with nausea, vomiting, pallor, headache, or photophobia as well as a family history of migraine Personal Experience at Rainbow Babies & Children’s Hospital Isolated Pain Dyspepsia # Patients % of Total Mean age % Male % Functional 59 19% 8.9 yrs 39% 85% 128 40% 11.1 yrs 46% 77% Irritable Bowel 132 41% 9.1yrs 42% 66% Diagnostic Testing May Be Considered: To reassure the parent, patient, or physician To support the absence of organic disease if it is believed that the pain significantly diminishes the quality of life of the patient Major Organic Etiologies of Isolated Chronic Abdominal Pain • • • • • • • • • • Unrecognized constipation Gastroesophageal reflux disease (young children) Parasitic infection Crohn’s disease Musculoskeletal disorders Partial small bowel obstruction (malrotation, postsurgical adhesions, lymphoma Infection (tuberculosis, yersinea) Endometriosis Occult urinary tract infection Acute intermittent porphyria Reasonable Diagnostic Evaluation of Isolated Chronic Abdominal Pain in the Absence of Alarm Signals Stool guaiac CBC with differential ESR Urinalysis Stool O & P Major Organic Etiologies of Abdominal Pain Associated with Symptoms of Dyspepsia Helicobacter pylori gastritis Peptic ulcer Gastroesophageal reflux disease Choledocholithiasis Relapsing pancreatitis Crohn’s disease Parasitic infection Malrotation Reasonable Diagnostic Evaluation of Dyspepsia in the Absence of Alarm Signals Stool guaiac CBC with differential ESR H. pylori serology or stool antigen Comprehensive metabolic panel Vomiting is a Key Variable which Expands the Differential Diagnosis Malrotation/ other anatomical GI disorders Crohn’s disease Gallstones Hydronephrosis Pancreatic cyst Reasonable Diagnostic Evaluation of Dyspepsia Where There is Concern About the Frequency of Vomiting Stool guaiac CBC with differential ESR H. pylori serology or stool antigen Comprehensive metabolic panel Amylase/lipase UGI-SBFT Abdominal Ultrasound Major Organic Etiologies of Abdominal Pain Associated with Altered Bowel Pattern Chronic fecal retention Parasitic infection Chronic C. difficile enteritis Lactose intolerance Inflammatory bowel disease Celiac disease Reasonable Diagnostic Evaluation of Abdominal Pain with Altered Bowel Pattern in the Absence of Alarm Signals Stool guaiac CBC with differential ESR Stool for O & P C. difficile toxin Celiac panel Lactose breath test Algorithm for Evaluation of Recurrent Abdominal Pain Pathophysiology of Functional Abdominal Pain Exact etiology and pathogenesis are unknown Genetic vulnerability Most children “outgrow” symptoms, suggesting a developmental component Current speculation on pathogenesis: dysfunction of the autonomic nervous system in the gastrointestinal tract • Disordered gastrointestinal motility • Visceral hypersensitivity • Central excitability Autonomic Dysfunction in Children with Functional Abdominal Pain Disordered motility • Increased intensity of intestinal muscle contraction • Increased or decreased intestinal transit Visceral hypersensitivity • Increased visceral perception → felt as pain • Potential mechanisms: – Reduced threshold of gut wall afferent sensory receptors – Stress factors that reduce set point at which visceral afferent fibers are stimulated Autonomic Dysfunction in Children with Functional Abdominal Pain Central excitability • • Increased central perception felt as pain Potential mechanisms: – Amplification of sensory traffic as it travels from gut to brain – Altered conscious threshold in the central nervous system triggered by convergent somatic inputs Rectal and Gastric Hyperalgesia in Children with RAP (DiLorenzo et al. Gastroenterology, 1998) Visceral pain perception was measured in the stomach and rectum using an electronic barostat in 15 pts with RAP and 10 age-matched controls RAP Control p-value Rectal pain threshold (mmHg) 28.4 Stomach pain threshold (ml) 187 37 287 <0.05 <0.07 Conclusion: Children with RAP have generalized visceral hyperalgesia Consequences of Reduced Threshold of Gut Wall Sensory Afferent Receptors Painful sensations may be provoked by physiologic stimuli • • • • • • Postprandial gastric or intestinal distention Gastric emptying Intestinal contractions or migrating motor complex Gastroesophageal reflux GI gas Minor noxious irritants such as spicy foods Physical stress factors that may reduce set point at which visceral afferent fibers are stimulated Recent physical illness Lactose intolerance Other food intolerance (e.g. fructose, sorbitol) Aerophagia Mucosal inflammation (H. pylori gastritis) Celiac disease Side effects of drug therapy (e.g.. antibiotics) Simple constipation Psychological stress factors that may alter conscious threshold in the central nervous system Death of significant family member Separation of significant family member Physical illness or chronic handicap in parents or sibling School problems Altered peer relationships Family financial problems Recent geographical move Goals of Treatment of Functional Abdominal Pain The focus of treatment is not “cure” or rapid recovery, but rather management of symptoms and adaptation to illness Outcome variables • • • • • School attendance and performance Participation in extracurricular activities Normal sleep pattern Normal weight gain and growth Pain frequency and severity Treatment of Functional Abdominal Pain Make a positive, confident diagnosis Explain pathophysiology, natural history, and goals of therapy Dietary modification Drug therapy • No proof that any drug regimen is effective for all patients with functional pain Psychological support Explanation of the Mechanism of Functional Abdominal Pain Legitimize symptoms: The pain is real Equate pain to “headache” Differentiate voluntary from involuntary (autonomic) processes Explain the role of the autonomic nervous system • “You don’t have to tell your heart to beat” • “You don’t have to tell the blood to circulate through the body” • “You don’t have to tell your intestines to work” Explain the concept of autonomic dysfunction Explanation of the Mechanism of Functional Abdominal Pain Normal sensitivity threshold – rarely feel muscle contractions Sensitivity threshold of patients is reduced – patient perceives muscle activity as pain Stress factors lower the sensitivity threshold increasing the frequency and intensity of pain Explanation of Goal of Therapy of Functional Abdominal Pain Identify and reduce stress factors Use diet, medication, and cognitive behavioral therapy to raise the visceral and central sensitivity threshold Pharmacological modulation of gastrointestinal motor abnormalities Antispasmodics aimed at reducing the force of smooth muscle contractions • hyoscyamine, dicyclomine, glycopyrrolate, peppermint oil, calcium channel blockers • work best for postprandial abdominal pain • high side effect profile at higher doses that are effective in pain relief Fiber supplements • increase propulsive activity, reduce segmenting myoelectric activity, enhance water-holding properties and bulk of stool Pharmacological modulation of factors that may exaggerate visceral perception Gastric acid • Antisecretory agents (H2RA’s or PPI’s) Intestinal gas • Antigas preparations (simethicone, activated charcoal, lactase, Beano) • Lactase enzymes for patients wih lactose intolerance Low-dose tricyclic antidepressants to treat functional abdominal pain Control abdominal pain symptoms whether or not a psychiatric illness is identified Doses that reduce pain are below usual psychiatric dosages Mechanism of action unknown • do not seem to affect visceral afferent sensation thresholds • May effect central processing of visceral afferent traffic Low-dose tricyclic antidepressants to treat functional abdominal pain Negligible potential for dependency TCAs are more sedating and this property may help some patients with sleep disorders High side-effect profile including constipation, sedation, restlessness, weight gain, impaired cognitive function As with cisapride, may prolong QTc interval 5-HT4 receptor agonist Tegaserod (Zelnorm) Received FDA approval for women with severe constipation-predominant IBS Binds to 5-HT4 receptors, stimulating GI peristalsis and decreasing visceral sensitivity Not released for children in the U.S. 5-HT3 receptor antagonist Alosetron HCl (Lotronex) Received FDA approval for Rx of IBS in women with abdominal pain & diarrhea Inhibits activation of type 3 serotonin (5-HT3 ) receptors on GI tract neurons decreasing intestinal secretion, motility, and afferent pain signals 41% of patients taking alosteron reported relief of abdominal pain compared to 29% taking placebo Not released for children in the U.S. Psychological and Behavioral Treatment of Functional Bowel Disease Relaxation techniques Coping strategies • Cognitive behavioral therapy • Hypnotherapy • Psychotherapy Finding appropriately trained mental health providers is difficult Factors That Affect Prognosis of Functional Abdominal Pain Factor Family Gender Age of Onset Period before Treatment Apley J, Hale B Prognosis Better Normal Female >6 years < 6 months Brit Med J 3:7, 1973 Prognosis Worse “Painful” Male <6 years > 6 months