Rudolph's Pediatrics, 22nd Ed.

CHAPTER 384. Chronic Abdominal Pain

Adrian Miranda

Chronic abdominal pain is characterized by intermittent or persistent pain that occurs over a period greater than 2 months. Chronic or recurrent abdominal pain (RAP) is reported to occur in 10% to 15% of children between the ages of 4 and 16 years and accounts for 2% to 4% of all pediatric office visits.1 RAP is not a diagnosis but is a descriptive term that applies to intermittent, severe, episodic pain. It is frightening to both families and care providers who are concerned that it is a harbinger of serious disease such as an infectious, inflammatory, metabolic, anatomical, or neoplastic disorder. However, in most cases, the pain is functional, without demonstrable evidence of a pathological condition.

PATHOPHYSIOLOGY

An evolving understanding of the mechanisms of functional pain disorders suggests that a transient noxious event or inflammatory event results in a persistent sensitization of neural pain pathways, altering the conscious awareness of gastrointestinal sensory input, also described as visceral hyperalgesia. An example of this hyperalgesia is found in a subset of patients with functional abdominal pain who experience exaggerated pain compared to normal subjects during equal pressures of balloon distension in the rectosigmoid. The lower sensory pain threshold observed in patients with functional abdominal pain (FAP) may be due to increased responsiveness of intraluminal mechanoreceptors, primary sensory afferent neurons, second-order neurons in the spinal cord, or abnormal processing of sensory information in the brain. Some patients with FAP may also experience headaches, dizziness, motion sickness, pallor, temperature intolerance, and nausea, suggesting a generalized dysfunction of the autonomic nervous system. The central corticotropin-releasing factor system has also been implicated in mediating the effects of early life stress and possibly contributing to the development of abnormal reactivity of the hypothalamic-pituitary-adrenal axis to stress later in life.2

Psychological comorbidities may also increase the likelihood of a child having visceral hyperalgesia. Up to 80% of children with functional abdominal pain have some form of anxiety, and approximately 40% will meet the criteria for a depressive disorder.6 Genetic vulnerability for functional disorders is suggested by a high frequency of functional disorders among family members. Sex, intelligence, and personality traits do not distinguish patients with functional pain from those with organic pain. The generalization that patients with functional abdominal pain are perfectionists, overachievers, or constant worriers is without foundation.

CLINICAL FEATURES AND DIFFERENTIAL DIAGNOSIS

Pain behaviors include grimacing, verbalizing, sighing, visibly guarding abdominal muscles, and rubbing the painful area. Children with chronic pain often undergo lifestyle alterations that include decreased school attendance, participation in age-appropriate activities, and alteration in eating behavior or sleep pattern. The diagnostic evaluation begins with a history to distinguish chronic from acute pain, to identify alarm signs that indicate underlying pathology and trigger specific investigations, and then subcategorizing the clinical presentation of functional pain disorders. Chronic abdominal pain is described as intermittent or persistent pain for greater than 2 months. Alarm signals that raise suspicion of an underlying organic disorder are listed in Table 384-1.

In the absence of alarm signals, a functional gastrointestinal disorder should be considered. These disorders have been classified by the Rome III International Working Team Committee as functional abdominal pain of childhood (FAP), irritable bowel syndrome (IBS), functional dyspepsia (FD), and abdominal migraine (eTable 384.1 ).2 These diagnostic definitions require that the episodic or chronic pain occur over a period longer than 2 months; however, in clinical practice, patients do not often present in a typical fashion, and a presumptive diagnosis is often made when symptoms persist for more than 2 weeks. Management of these patients should not await fulfillment of these strict criteria. Furthermore, many patients do not fit clearly into any of the groups. Despite these limitations, the Rome classifications provide a framework to allow a working diagnosis of a functional pain syndrome based on history, physical examination, and a focused laboratory evaluation.

DIAGNOSTIC EVALUATION

A stepwise approach to diagnosis and treatment of functional pain is outlined in Table 384-2. In patients without alarm signals, a working diagnosis of functional abdominal pain should be introduced to the family at the initial evaluation. If any additional laboratory or radiographic evaluation seems warranted on the basis of alarm signals, it is useful to explain to the family that tests are being performed to rule out any serious disorders but that a functional disorder likely explains the clinical presentation. If these same tests are performed with an apparent expectation that disease is present, even normal results often will not allay the family’s anxiety about more serious disease. Functional pain should be presented as a positive diagnosis, and further focused diagnostic testing and treatment strategies described in this chapter can be initiated.

The diagnostic possibilities and the approach to evaluation of chronic abdominal pain vary depending on the presence of associated symptoms. Establishing a working diagnosis of functional pain and initiating conservative therapy does not preclude a later focused diagnostic workup when indicated by emerging alarm signals. Thus, the care provider should not feel obligated to perform multiple tests to rule out an organic etiology for the pain. In fact, such an approach can lead to increased anxiety and frustration that a cause of the pain is not being found, and families often become invested in finding a cause because they believe that if the physician undertook such an extensive evaluation, the symptoms must suggest a serious disorder. Recurrent testing leads to increasing anxiety about the symptoms, and the focus on symptoms can contribute to progressive disability.

Table 384-1. Alarm Signals (Red Flags) That Suggest an Organic Etiology for Abdominal Pain

Persistent pain

Pain is localized away from umbilicus

Pain that awakens from sleep

Pain related to menstrual cycle

Back pain

Dysphagia

Perirectal disease

Nocturnal diarrhea or fecal soiling

Unexplained weight loss or growth deceleration

Extraintestinal signs and symptoms such as fever, rash, arthralgias, jaundice, uveitis, aphthous ulcers, dysuria

Gastrointestinal bleeding, anemia, hemoccult-positive stools

Positive family history of inflammatory bowel disease or autoimmune disorders

Age younger than 4 years Elevated erythrocyte sedimentation rate or C-reactive protein

Hypoalbuminemia, abnormal liver or kidney function tests, elevated amylase or lipase

Psychological stressors may provoke all forms of functional pain by altering the conscious threshold of gastrointestinal sensory input in the central nervous system. A history of death or separation of a significant family member, physical illness or chronic handicap in parents or sibling, school problems, altered peer relationships, family financial problems, or a recent geographic move are all likely to precipitate symptoms in susceptible individuals.

Table 384-2. General Approach to Diagnosis and Treatment of Functional Pain

Establish a symptom-based diagnosis

Perform limited workup in the absence of red flags

Initiate discussion of functional pain at first visit

Explore potential underlying psychosocial factors

Identify possible dietary triggers

Reassure and educate the patient and family

Identify the main symptom leading to distress (ie, diarrhea vs pain)

Initiate therapy (pharmacological, psychological, or expectant)

Reevaluate in 3–6 weeks

Isolated Recurrent Abdominal Pain

Isolated recurrent abdominal pain most often presents a pattern of episodic, acute, intense midline abdominal pain lasting a few hours to several days with intervening symptom-free intervals lasting days to months. Commonly associated symptoms include headache, pallor, dizziness, and fatigue, at least one of which is observed in 50% to 70% of cases. Although many children complain of pain at the time of office visits, their behavior, affect, and activity are seldom consistent with the degree of expressed discomfort. Poorly localized pressure tenderness is frequently elicited during abdominal palpation. Between episodes, the abdominal examination is normal. Table 384-3 lists the major differential diagnoses of recurrent, periumbilical abdominal pain in children.

Occult constipation should be suspected if a left lower quadrant or suprapubic fullness or mass effect is appreciated on abdominal examination. Constipation should also be suspected if the rectal examination reveals evidence of firm stool in the rectal vault or soft stool in a dilated rectal vault with evidence of perianal soiling. Often, a history of constipation is unknown to the parent. Gross inspection of the perianal area may reveal fistulas or tags suggestive of Crohn disease. It is important to recognize that Crohn disease can present with isolated abdominal pain and often with a history suggestive of constipation. Recurrent fevers, aphthous ulcers, or rash in patients with abdominal pain should prompt an investigation for inflammatory bowel disease. During the evaluation, it is also important to determine whether pain is arising from the abdominal wall or has an intra-abdominal origin. The Carnett test is useful in this situation. The site of maximum tenderness is found through palpation. The patient is then asked to cross his or her arms and assume a partial sitting position (crunch), which results in tension of the abdominal wall. If there is greater tenderness on repeat palpation in this position, abdominal wall disorders such as cutaneous nerve entrapment syndromes, abdominal wall hernia, myofascial pain syndromes, rectus sheath hematoma, or costochondritis should be suspected. Discitis may present as a combination of back and abdominal pain. The condition is usually associated with intermittent fever, elevated peripheral white blood cell count, and elevated erythrocyte sedimentation rate. Pain with palpation over a rib may suggest a diagnosis of costochondritis or painful rib syndrome, which is often misinterpreted as representing abdominal pain.

Appendiceal colic and chronic appendicitis are controversial entities that cause chronic abdominal pain associated with recurrent acute episodes of well-localized abdominal pain and tenderness, most commonly in the right lower quadrant, demonstrated on several examinations (see Chapter 413). Dull, midline, or generalized lower abdominal pain at the onset of a menstrual period suggests dysmenorrhea. The pain may coincide with the start of bleeding or precede the bleeding by several hours. Gynecologic disorders associated with secondary dysmenorrhea include endometriosis, partially obstructed genital duplications, ectopic pregnancy, and adhesions following pelvic inflammatory disease. Cystic teratoma has been described in prepubertal patients presenting with right or left lower quadrant pain. The vast majority of such patients have a palpable abdominal mass. Benign ovarian cysts in adolescent girls do not cause recurrent abdominal pain. Recurrent fever associated with generalized abdominal pain and peritoneal signs suggest the possibility of familial Mediterranean fever. Acute intermittent porphyria is a rare disorder characterized by the temporal association of paroxysmal abdominal pain and a wide variety of central nervous system symptoms, including headache, dizziness, weakness, syncope, confusion, memory loss, hallucinations, seizures, and transient blindness. Acute intermittent porphyria is often precipitated by low intake of carbohydrate or by specific drugs such as barbiturates or sulfonamides.

Table 384-3. Some Causes of Chronic or Recurrent Abdominal Pain in Children

No laboratory tests or radiographic evaluation is routinely required to manage children with a typical presentation of isolated recurrent abdominal pain, although screening laboratory studies are usually performed. These include a complete blood count with differential, urinalysis and urine culture, and erythrocyte sedimentation rate. Some experts routinely perform a chemistry profile and serum amylase as well as celiac disease screening tests. Low serum albumin along with a high sedimentation rate and iron deficiency anemia is highly suggestive of inflammatory bowel disease. Parasitic infections, particularly Giardia lamblia, Blastocystis hominis, and Dientamoeba fragilis, may cause chronic pain in the absence of altered bowel pattern, so stool ova and parasite evaluation may be useful. In adolescent females, pregnancy testing and culture for sexually transmitted diseases may be necessary. Breath hydrogen testing for carbohydrate malabsorption (lactose, sucrose, fructose) is of low yield, as are food allergy tests. Upper gastrointestinal radiography may aid in diagnosis of gastrointestinal structural disorders such as a malrotation, internal hernia and intussusception, or inflammatory disorders such as Crohn disease. Other rare conditions, such as lymphoma, angioneurotic edema, mesenteric vein thrombosis with ischemia, and pseudoobstruction, may also be identified. Abdominal ultrasound and abdominal CAT scan have low diagnostic yields but may be useful to identify appendiceal abnormalities, especially when pain is recurrently localized to the right lower abdomen, suggestive of chronic appendicitis, Crohn disease, cholelithiasis, and ureteropelvic abnormalities. Colonoscopy and ileoscopy is necessary to confirm Crohn disease.

Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is characterized by an abnormal frequency and/or consistency of stools (diarrhea or constipation), straining, urgency, relief of pain with defecation, a feeling of incomplete evacuation, passage of mucus, or a feeling of bloating or abdominal distention. Table 384-3 lists the differential diagnosis of abdominal pain associated with symptoms of altered bowel pattern. Abnormal stool frequency may be defined as more than 3 bowel movements per day or fewer than 3 bowel movements per week. Abnormal stool form includes loose/watery stool, lumpy/hard stool, or passage of mucus with stool. Patients with IBS often report alternating between diarrhea and constipation. Irritable bowel is usually associated with the same autonomic-type symptoms and signs observed in isolated functional abdominal pain. In patients with diarrhea, the laboratory evaluation should include screening laboratory studies described previously; measurement of C-reactive protein, celiac disease screening studies, and stool samples for ova and parasites and for Clostridium difficile toxin. Lactose intolerance or malabsorption of other carbohydrates such as sorbitol should be considered a potential primary etiology of chronic abdominal pain in the presence of diarrhea. A trial of a lactose-free diet or performance of a lactose breath hydrogen test is prudent in children with pain associated with loose bowels, bloating, and increased flatulence. In patients with persistent diarrhea or constipation, the evaluation should include a thorough evaluation of possible causes of these symptoms, as outlined in Chapters 385 and 386.

Abdominal Pain Associated with Dyspepsia

Abdominal pain associated with symptoms of dyspepsia is characterized by pain or discomfort localized in the upper abdomen, pain related to eating, nausea, bloating, early satiety, and occasional heartburn and oral regurgitation. Table 384-3 lists the differential diagnosis of abdominal pain associated with symptoms of dyspepsia. Concurrent anorexia, vomiting, weight loss, or evidence of gastrointestinal bleeding (hematemesis, melena, occult bleeding) suggest an upper gastrointestinal inflammatory, infectious, or structural disorder. Evaluation of these alarm signals may require screening laboratory studies, radiographic testing, and possibly upper endoscopy with biopsy to diagnose disorders such as malrotation, esophagitis, gastritis, peptic ulcer disease, ureteropelvic junction obstruction, and cholelithiasis. Other disorders, such as gastroparesis, chronic cholecystitis, and biliary dyskinesia, are uncommonly associated with this symptom presentation in children, so gastric emptying tests, hepatobiliary scans to assess gallbladder emptying, and endoscopic retrograde pancreatography are rarely indicated. In a patient without alarm signals, a short-term (8 to 12 weeks) empiric trial of medical therapy with a proton-pump inhibitor should be considered. Upper endoscopy should be considered in untreated patients with symptoms beyond 2 months, patients who fail to respond to short-term antisecretory therapy, and patients in whom symptoms recur after the end of treatment.

Abdominal Migraine

Abdominal migraine is a variant of functional abdominal pain and might comprise a continuum of other disorders, such as migraine headaches and cyclic vomiting. It is characterized by paroxysmal, intense pain that is usually periumbilical. Associated symptoms include anorexia, nausea, vomiting, headache, photophobia, and pallor. Abdominal migraine affects approximately 1% to 4% of children and is more common in girls than in boys (3:2). All other causes of episodic severe abdominal pain, including intermittent bowel obstruction, obstructive uropathy, relapsing pancreatitis, biliary tract disease, angioedema, porphyria, and intracranial space-occupying lesions should be considered. Treatment approaches are similar to those used for cyclical vomiting and for other forms of migraine (see Chapters 382 and 565).

TREATMENT

Management of functional pain is facilitated by early diagnosis, parental education, reassurance, and the clear delineation of goals of therapy. These are to alleviate the chronic symptoms and/or to return the patient to normal functioning and improved quality of life in spite of pain. Most families accept that emotional stressors or anxiety can cause headaches or gastrointestinal symptoms. They also recognize that different children have different levels of pain tolerance. Reinforcement of these concepts, along with an explanation of visceral hypersensitivity (see Pathophysiology section above), provides the family with a better understanding of the cause of the pain and increases the likelihood of their engaging in behavioral treatment strategies. Providing a positive diagnostic label reinforces the concept that further diagnostic testing to find a cause of symptoms is not necessary.

Treatment of the pediatric patient with chronic abdominal pain requires patience and a substantial time commitment. In certain cases, simply identifying a major stressor can help the pediatrician set manageable goals. A dearth of pediatric literature evaluating treatment options contributes to uncertainty regarding the approach to management, which further exacerbates the discomfort of practitioners managing these patients. A positive clinical diagnosis, reassurance, explanation of the pathophysiology, environmental modifications, dietary modifications, and selective pharmacologic and/or behavioral therapy constitute the mainstay of treatment.

Behavioral Management

The first goal is to identify, clarify, and possibly reverse physical and psychological stress factors that may have an important role in onset, severity, exacerbations, or maintenance of pain. Equally important is to reverse environmental reinforcers of the pain behavior.

The morbidity associated with functional abdominal pain is rarely physical but results from interference in normal school attendance and performance; peer relationships; and participation in organizations, sports, and personal and family activities. Only 1 of 10 children with functional abdominal pain attends school regularly, and absenteeism is greater than 1 day in 10 in 28% of patients. A common misconception is that pain is the direct cause of the morbidity. In fact, focus on symptom relief by parents, school, and physicians reinforces the pain behavior. Increased attention and rest periods during pain episodes along with tactile stimulation and medication to alleviate pain symptoms further reinforces the behaviors. Parents and the school must be engaged to support the child rather than the pain. Regular school attendance is essential regardless of the continued presence of pain. In many cases, it is helpful for the physician to communicate directly with school officials to explain the nature of the problem. School officials must be encouraged to be responsive to the pain behavior but not to let it disrupt attendance, class activity, or performance expectations.

Within the family, less social attention should be directed toward the symptoms. It has been recently shown that complaints of pain in children with functional pain can be significantly decreased if parents use distraction techniques during episodes of pain, whereas symptoms nearly double under conditions of parent attention.7 Consultation with a child psychologist may be indicated when there is concern about a maladaptive family, a need to teach or reinforce coping mechanisms, or if attempts at environmental modification do not result in a return to a normalized life style.

Referral for psychological treatment can be proposed as part of a multicomponent treatment package to help the patient more successfully manage the pain symptoms. Cognitive behavior therapy (CBT) and hypnosis are shown to be effective in reducing physiologic arousal in patients with functional bowel disorders and may alleviate symptoms in some patients.

Trigger Identification

Triggers that exacerbate bowel symptoms must also be identified, with an attempt to modify them. Postprandial symptoms in functional dyspepsia may be improved by eating low-fat meals or by ingesting more frequent but smaller meals throughout the day. A high-fiber diet is recommended for both diarrhea-predominant and constipation-predominant irritable bowel, but care must be taken because excessive fiber in the diet may result in increased gas and distension and actually provoke pain. Similarly, avoidance of excessive intake of milk products (lactose), caffeine, carbonated beverages (fructose), dietary starches (corn, potatoes, wheat, oats), or sorbitol-containing products (vehicle for oral medication, sugar substitute in gum and candy, ingredient in toothpaste, and a plasticizer in gelatin capsules) is reasonable if they provoke symptoms. Excessive gas in patients with irritable bowel syndrome can be managed by advising the patient to eat slowly, to avoid chewing gum, and to avoid excessive intake of carbonated beverages, legumes, foods of the cabbage family, and foods or beverages sweetened with aspartame.

Pharmacologic Therapy

Symptom-based pharmacological therapy can be useful in selected cases but must be used judiciously as an adjuvant to a multifaceted approach. There are currently no evidence-based data on the effects of pharmacologic therapy in pediatric patients with functional dyspepsia. However, specific treatments may be of benefit in the right clinical setting. As described above, short term, empiric treatment with proton pump inhibitors is acceptable as an initial trial in patients with functional dyspepsia. There are very few evidence-based data on the effects of pharmacologic therapy in pediatric patients with irritable bowel syndrome. Enteric-coated peppermint oil capsules have been shown to improve abdominal pain scores in children with irritable bowel syndrome (IBS)–like symptoms.8 However, there was no significant improvement in associated symptoms such as gas, stool pattern, or stool consistency. In IBS patients in which the predominant symptom is diarrhea, synthetic opioids such as loperamide and diphenoxylate may be effective. Loperamide is preferred over diphenoxylate because it does not cross the blood-brain barrier. For patients with IBS in which the predominant symptom is constipation, nonstimulating laxatives such as mineral oil, milk of magnesia, lactulose, or polyethylene glycol may be effective adjuncts. Fiber supplements such as psyllium, methylcellu-lose, or polycarbophil are effective in treating both constipation and diarrhea, but their value in relief of IBS–associated abdominal pain is controversial.

Novel drugs for treatment of irritable bowel syndrome in adults include 5-hydroxytryptamine (5-HT3 and 5-HT4)-receptor agonists and antagonists aimed at reducing visceral hypersensitivity and altering bowel habits. Alosetron led to symptom improvement among adult women with diarrhea-predominant irritable bowel syndrome, but because of complications of ischemic colitis, it is available only in a restricted manner. Tegaserod was shown to improve symptoms in adolescents with constipation-predominant irritable bowel syndrome. In a recent retrospective study in children, tegaserod improved global assessment scores for constipation, abdominal pain, and bloating without serious side effects.9,10 Marketing of tegaserod was suspended in the United States in 2007 following reports of cardiovascular ischemic events in adult patients.

Antispasmodic/anticholinergic agents are commonly used in clinical practice to treat functional bowel disorders, although efficacy is controversial. Anticholinergic agents block the muscarinic effect of acetylcholine and can theoretically slow intestinal motility, reduce spasm, and improve diarrhea. There are no good pediatric trials evaluating effectiveness in children with chronic abdominal pain or irritable bowel syndrome. Hyoscyamine and dicyclomine are used occasionally in children but are useful only for predictable episodes of pain. Long-term use in children may be associated with significant side effects such as dry mouth, urinary retention, blurred vision, tachycardia, drowsiness, and constipation.

Although there is a lack of formal randomized, placebo-controlled trials, there has been a recent surge in the use of antidepressant and psychotropic agents to treat both diarrhea-predominant irritable bowel syndrome and functional dyspepsia in adults.11 There are as yet no data on treatment of pediatric patients.

PROGNOSIS

There are no prospective studies of the outcome of any of the various presentations of functional abdominal pain in childhood. Following the diagnosis of functional abdominal pain, an occult organic disorder is very rarely identified. The pain resolves completely in 30% to 50% of patients within 2 weeks of diagnosis, which suggests a benefit of simple reassurance that the pain is not due to a serious underlying disorder. However, 30% to 50% of children with functional abdominal pain in childhood experience pain as adults, although in 70% of such individuals, the pain does not limit normal activity. Thirty percent of patients with functional abdominal pain develop other chronic complaints as adults, including headaches, backaches, and menstrual irregularities.12 Based on a small number of patients, Apley and Hale have described several factors that adversely influence prognosis for a lasting resolution of pain symptoms during childhood, including male sex, age of onset at less than 6 years, a strong history of a “painful family,” and more than 6 months elapsed time from onset of pain symptoms to establishment of a functional diagnosis.13