Recurrent Abdominal Pain In Childhood and Adolescence Cheryl A. Little, MD clitt002@stvincent.org St. Vincent Pediatric Gastroenterology 8402 Harcourt Rd. Suite #402 Indianapolis, IN 46260 (317) 338-9450

IMPORTANT POINTS Recurrent Abdominal Pain (RAP) represents a description of symptoms, not a diagnosis The most common cause of RAP is a functional gastrointestinal disorder (FGID) There are 4 major pediatric disorders associated with recurrent abdominal pain Functional abdominal pain syndrome Functional dyspepsia Irritable Bowel Syndrome (IBS) Abdominal Migraine A FGID is a positive diagnosis Therapy of a FGID is directed at environmental modification

Introduction RAP is not a diagnosis Clinical manifestation of an organic disorder (23.6%) (Indian Pediatrics; 46: 389-399, 2009) Due to a FGID Diagnosis of a FGID meets specific criteria (Rome III criteria) Red flag symptoms concerning for an organic disorder Pain that awakens the child Significant vomiting, constipation, diarrhea, bloating, or gas Blood in the stool Unintentional weight loss or slowed growth Changes in bowel or bladder function Pain or bleeding with urination Abdominal tenderness

Epidemiology FGID occurs in 10-12% of school-aged children 21% severe enough to affect activity (J Pediatr 129:220-226, 1996) Female-to-male ratio equal up to 9 yrs of age Female-to-male ratio 1.5:1 btw 9-12 yrs of age Onset of pain <4 yrs More in-depth organic evaluation

Pathophysiology of FGIDs Different presentations Heterogeneous group of disorders Variable expressions of the same disorder Prevailing viewpoint Pain is visceral in origin Involves disordered GI motility Involves visceral hypersensitivity/hyperalgesia Genetic vulnerability Abnormalities in the enteric nervous system Dysfunction of the autonomic nervous system Altered awareness of discomfort (emotions, cognitive processes, CNS influences)

General Approach to RAP History Complete history is the MOST important component of the evaluation (Attempt to obtain directly from patient) Focus on Timing, frequency, location, quality of pain Associated GI symptoms (nausea, vomiting, diarrhea, constipation, blood in stool or emesis) Precipitating/relieving factors Systemic symptoms ( fever, wt loss, joint pain, skin rash) Family History of IBD or PUD Travel History Medication and nutritional interventions Interference with school, play, peer relations, and family dynamics

General Approach to RAP Physical Examination Complete and not only directed toward the abdomen Growth data ?Fall off in height or weight velocity Delay in pubertal development Abdominal examination General appearance, auscultation, palpation of liver and spleen, for masses and tenderness Rectal examination Perianal and digital Clubbing, rashes, arthritis Pelvic examination (if indicated by history)

Rome Criteria III Functional Abdominal Pain Syndrome At least 8 weeks of episodic or continuous abdominal pain in a school-aged child or adolescent occurring at least once/wk with one or more of the following: some loss of daily functioning additional somatic symptoms such as headache, limb pain, or difficulty sleeping The patient has insufficient criteria for other functional GI disorders that can explain the pain No evidence of an inflammatory, anatomic, metabolic or neoplastic process that is likely to explain the symptoms Gastroenterology 2006;130:1527-1537

Functional Abdominal Pain Syndrome Periumbilical location Variable in severity Pain episodes tend to cluster alternating with pain-free periods of variable length Associated GI symptoms are denied by the patient

Functional Abdominal Pain Syndrome Pain episodes begin gradually Last less than 1 hr in 50% Last less than 3 hrs in 40% Continuous pain in < 10% Child is unable to describe the pain Radiation of pain is rare Temporal relationship to meals, activity, bowel habits is unusual

Functional Abdominal Pain Syndrome Pain rarely awakens the child from sleep Parents describe the patient as “miserable” and “listless” during pain episodes During severe attacks the child may exhibit a variety of motor behaviors (“doubling over in pain”) Common associated “autonomic” symptoms Headache, pallor, nausea, dizziness, fatigue At least one is observed in 50-70% of cases

Functional Abdominal Pain Syndrome Differential Diagnosis Infectious UTI, Giardia Carbohydrate intolerance- Lactose, fructose, sorbitol, sucrase-isomaltase Inflammatory Crohn disease, ulcerative colitis, eosinophilic gastroenteritis, celiac disease, pancreatitis IBS Constipation with or without fecal impaction Psychogenic

Functional Abdominal Pain Syndrome Diagnosis There is no dependable biological marker for functional abdominal pain syndrome Most reliable diagnostic features are the symptoms Should NOT require a series of diagnostic tests to rule out organic causes of pain Reasonable to obtain CBC, ESR or CRP, UA and culture, KUB, CMP, O+P, fecal leukocytes, lactose tolerance testing/lactose elimination US and CT are low yield Excessive testing may increase parental anxiety and put the child through unnecessary stress Parental anxiety/uncertainty increases the stressful environment that provokes and reinforces the pain behavior

Functional Abdominal Pain Syndrome Treatment Begins at initial office visit Important to introduce the concept of functional pain during the initial evaluation Review the differential diagnosis to reassure parents and child that specific organic disorders have been considered and “red flags” are absent

Functional Abdominal Pain Syndrome Treatment Focus of treatment is not “cure” but management of symptoms and adaptation to illness to provide a satisfactory quality of life through support and education Accomodative or secondary engagement coping (distraction, acceptance, positive thinking, cognitive restructuring) is related to less pain Passive or disengagement coping (denial, cognitive avoidance, behavioral avoidance, wishful thinking) is associated with increased levels of pain

Functional Abdominal Pain Syndrome Treatment Directed toward environmental modification Identify, clarify, and reverse stresses that may provoke or increase the perception of pain Reverse environmental reinforcement of the pain behavior Lifestyle MUST be normalized regardless of the continued presence of pain Parents should direct less social attention toward the symptoms

Functional Abdominal Pain Syndrome Supportive counseling Target at illness behavior Can be delivered by primary care physician Listening, empathy, encouragement Do not allow ongoing pain-induced disability Patient-centered participatory arrangement Instruct parents how to respond to symptoms Encourage school officials to participate in treatment

Functional Abdominal Pain Syndrome Treatment Pharmacologic therapy directed at reasonable physical triggers of pain Constipation Altered motility Low-dose tricyclic antidepressants Act as “central analgesics” Raise the perception threshold for abdominal pain Down regulate pain receptors in the intestine Generally reserved for patients with anxiety/depression or maladaptive illness behavior

Functional Abdominal Pain Syndrome Treatment Hospitalization Reinforces pain behavior Consultation Reserved for patients with depression/anxiety, PTSD, abuse, severe disability, maladaptive illness behavior, chronic refractory pain Child Psychiatrist Child Psychologist Behavioral modification therapy

Rome Criteria III Functional Dyspepsia At least 8 weeks (which need not be consecutive) in the preceding 12 months of persistent or recurrent pain occurring at least once/week centered in the upper abdomen AND No evidence of an inflammatory, anatomic, metabolic or neoplastic process that is likely to explain the symptoms AND No evidence that dyspepsia is exclusively relieved by defecation or associated with a change in stool frequency or form Gastroenterology 2006;130:1527-1537

Clinical Presentation Functional Dyspepsia Pain localized to the epigastrium, RUQ, or LUQ Episodic vomiting Temporal relationship with meal ingestion Presence of anorexia, nausea, oral regurgitation, early satiety, post-prandial bloating, indigestion, and belching

Functional Dyspepsia No symptoms or signs that reliably distinguish functional dyspepsia from upper GI organic disorders More extensive diagnostic evaluation than functional abdominal pain syndrome Usually associated with the same signs of environmental reinforcement of pain behavior

Functional Dyspepsia Two groups Ulcer-like dyspepsia Pain most common symptom Dysmotility-like dyspepsia Often report nausea, fullness, and early satiety

Functional Dyspepsia Differential Diagnosis Acid-related disease Gastritis, duodenitis, esophagitis, peptic ulcer Infection Helicobacter pylori Allergic/Inflammatory Eosinophilic esophagitis, eosinophilic gastroenteritis, gastoduodenal Crohn disease, celiac disease Gastroparesis Chronic cholecystitis Chronic fibrosing pancreatitis

Functional Dyspepsia Diagnosis Physical exam- findings usually normal Lab evaluation- CBC,ESR or CRP,amylase, lipase, hepatic panel, H. pylori serology or stool antigen UGI +/- SBFT Abdominal US Nuclear medicine scintigraphy (HIDA scan) Upper Endoscopy- patients with dysphagia, persistent symptoms despite the use of acid-reducing medications, or to confirm H. pylori infection. ERCP

Functional Dyspepsia Treatment Positive diagnosis, education, establishment of realistic expectations of treatment Environmental and dietary modification Avoid cigarette smoking, advise smoke-free home Avoid alcohol, non-steroidal analgesics Avoid caffeinated beverages, high-fat foods, and large meals Address psychological comorbidity

Functional Dyspepsia Treatment Drug therapy 70% improvement rate by 1 year following diagnosis (JPGHAN 30: 413-418, 2000) Ulcer-like dyspepsia 4-6 week course with H2-receptor antagonist or PPI Dysmotility-like dyspepsia 4-6 week course with a prokinetic agent (metoclopramide or erythromycin) Anti-emetics or low-dose tricyclic antidepressants Serotonic agents- Buspirone (Buspar), Paroxetine (Paxil)

Rome Criteria III Irritable Bowel Syndrome At least 8 weeks in the previous 12 months of abdominal discomfort or pain occurring at least once/wk with at least 2 of the following: relief w/defecation onset associated w/change in frequency of stool onset associated w/ change in form of stool No evidence of an inflammatory, anatomic, metabolic or neoplastic process that is likely to explain the symptoms Gastroenterology 2006;130:1527-1537

Irritable Bowel Syndrome More common in adolescence Pain is typically localized to the lower abdomen Association of pain with altered bowel pattern Diarrhea (4 or more stools per day) Constipation (2 or less stools per week) Sense of incomplete evacuation Straining Urgency Passage of mucus Feeling of bloating or abdominal distention Pain is often relieved by defecation

Irritable Bowel Syndrome Differential Diagnosis Infection Giardia Chronic Clostridium difficile colitis UTI Carbohydrate intolerance Lactose, fructose, sorbitol, sucrase-isomaltase deficiency Inflammatory Crohn disease, ulcerative colitis, eosinophilic gastrenteritis, celiac disease “Microscopic” colitis

Irritable Bowel Syndrome Diagnosis Careful, sympathetic history taking Appropriate, thorough PE ( to include rectal exam) Negative routine diagnostic studies Empiric lactose elimination Full assessment of psychological and social factors as well as physical symptoms

Irritable Bowel Syndrome Diagnosis Colonoscopy is indicated in pts in whom the history or PE suggest the possibility of IBD Evidence of GI bleeding Profuse diarrhea Involuntary wt loss or growth deceleration Fe deficiency anemia Elevated ESR or CRP Extra-intestinal symptoms (fever, recurrent mouth sores, rash, joint pain)

Irritable Bowel Syndrome Management Symptomatic and supportive care Development of a positive relationship between doctor and patient/parents Validate the symptoms that they are experiencing Address the patient’s agenda by asking directly about their concerns and fears Initial Management Positive, confident diagnosis communicated with clarity and honesty Educate about the pathophysiology of FGIDs and bring focus to the multifactorial nature of IBS

Irritable Bowel Syndrome Dietary Management Constipation predominant Insoluable fiber diet ( root vegetables, skinned fruits, bran, whole-wheat products) Diarrhea predominant Eat slowly, avoid chewing gum, avoid excessive intake of alcohol, carbonated and caffeinated beverages, high-fat foods, legumes, and foods or beverages with fructose or sorbitol Soluable fiber diet (dried beans and fruits, peas, oats, barley, carrots, flesh of fruits such as apples and organges) Response rates of 70% (Lancet 2: 1115-1117, 1982)

Irritable Bowel Syndrome Drug Therapy Antispasmodics Anticholinergics Used in diarrhea predominant or variable stool IBS Dicyclomine-Bentyl Hyoscyamine-Levsin,Levbid Enteric-coated Peppermint Oil Amitiza- chloride channel activator Indicated for constipation predominant IBS in adults Antibiotics/Probiotics- to treat bacterial overgrowth Tricyclic Antidepressants Serotonic drugs- Buspar, Celexa

Summary FGIDs can occur as a well defined clinical entity (e.g. IBS) or a less defined clinical syndrome (e.g. functional abdominal pain syndrome) Essential for physicians to take a biopsychosocial approach to diagnosis and treatment Appreciate the close interaction of the gut and brain Allows the child, parent and physician to address the pain on many levels Further understanding of brain-gut axis and the role of serotonin in neural sensorimotor functions is needed

Irritable Bowel Syndrome Probiotics Replace deficiencies of “normal” colonic bacteria and reduce fermentation Randomized double-blind controlled trial Lactobacillus plantarum Reduction in the degree of flatulence Improved overall GI function at 12 months (Am J Gastroenterol 95:1231-1238, 2000)

Irritable Bowel Syndrome Tricyclic Antidepressants Effect significant on primary outcome measures and on global response and pain 89% improvement in adult pts 61% remission of symptoms (Gut 2005;54:1332-1341) Effectiveness in clinical practice limited by side effects (sleepiness) Reserved for patients with severe symptoms or symptoms resistant to common first-line approaches

Irritable Bowel Syndrome Serotonic Agents 5-HT1 agonists Buspirone (Buspar) Reduce gastric acid and colonic responses to volume distention Anxiolytic activity SSRIs Citalopram (Celexa) Reduce colonic sensation to volume distention in healthy subjects

Irritable Bowel Syndrome Psychological Treatment Stress management Psychotherapy Introduce early in the discussion of pathophysiology and management of IBS Do not leave as “last-ditch” treatment after medical therapy has proved less than optimal Therapy often combination of parent training, altering reinforcement of various behaviors and stress management Statistically significant improvement of pain with adjunctive cognitive-behavioral therapy (J Consult Clin Psychol 57: 294-300, 1989, and 62: 306-314, 1994)