Chronic abdominal pain in children and adolescents: Approach to the evaluation

INTRODUCTION — Chronic abdominal pain is common in children and adolescents. The evaluation of the child or adolescent with chronic abdominal pain requires an understanding of the pathogenesis of abdominal pain, the most common causes of abdominal pain in children and adolescents, and the typical patterns of presentation.

The evaluation of the child or adolescent with chronic abdominal pain will be discussed here. Our approach is generally consistent with that in the American Academy of Pediatrics and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition clinical report [1].

The management of functional abdominal pain in children and adolescents, causes of acute abdominal pain, and evaluation of children with acute abdominal pain are discussed separately:

●(See "Functional abdominal pain in children and adolescents: Management in primary care".)

●(See "Causes of acute abdominal pain in children and adolescents".)

●(See "Emergency evaluation of the child with acute abdominal pain".)

TERMINOLOGY

●Chronic abdominal pain – In this topic, we will use the term "chronic abdominal pain" to describe intermittent or constant abdominal pain (of functional or organic etiology) that has been present for at least two months. The two-month timeline is consistent with the Rome IV criteria for functional abdominal pain disorders [2]. In clinical practice, the distinction between acute and chronic abdominal pain can overlap [3].

●Recurrent abdominal pain – The term "recurrent abdominal pain" should not be used as a diagnosis; it is encompassed in the term "chronic abdominal pain." Classically, recurrent abdominal pain was defined by four criteria [4]:

•≥3 episodes of abdominal pain

•Pain sufficiently severe to affect activities

•Episodes occur over a period of ≥3 months

•No known organic cause

We no longer use "recurrent abdominal pain of childhood" as a diagnosis because it is a heterogenous symptom complex with both organic and functional etiologies [5-9].

●Functional disorders – Functional disorders are conditions in which the patient has variable combinations of symptoms without any readily identifiable or strong suspicion of a distinctly organic condition. Functional disorders are now referred to as "disorders of gut-brain interaction" to emphasize the interplay between the enteric and central nervous systems and that gastrointestinal and psychosocial factors contribute to symptoms [10]. Moreover, the term "functional" is not intuitive for patients and parents. These disorders may be associated with visceral hyperalgesia (reduced threshold for pain), abnormal pain referral after rectal distension, or impaired gastric relaxation response to meals [11-16]. (See 'Pathogenesis' below.)

These disorders are categorized into four subtypes (table 1) (see 'Functional disorders' below) [2]:

•Functional dyspepsia

•Irritable bowel syndrome (IBS)

•Abdominal migraine

•Functional abdominal pain not otherwise specified

Functional constipation is grouped separately as a functional defecation disorder but is a consideration when evaluating symptoms of chronic abdominal pain.

EPIDEMIOLOGY — Complaints of chronic abdominal pain occur in 10 to 19 percent of children [17-19]. The prevalence is highest in children age four to six years and early adolescents [17,19]. In a community-based population study, as many as 17 percent of middle and high school students reported weekly episodes of abdominal pain [20]. Among the pupils who reported abdominal pain, approximately 21 percent had discomfort that was sufficiently severe to affect activity. In a 2015 meta-analysis of 58 studies including 196,472 children from around the world, the pooled prevalence of functional abdominal pain disorders was 13.5 percent (95% 11.8-15.3) [21].

PATHOGENESIS — Pain receptors in the abdomen respond to mechanical and chemical stimuli. Stretch is the principal mechanical stimulus involved in visceral pain and is induced by distension, contraction, traction, compression, and torsion [22]. Mucosal receptors respond primarily to chemical stimuli (eg, substance P, bradykinin, serotonin, histamine, prostaglandins), which are released in response to inflammation or ischemia [23,24]. Different types of stimuli may act together to influence the perception of pain. As an example, the gastric mucosa typically is insensitive to pressure or chemical stimuli; however, these stimuli may cause pain if the gastric mucosa is inflamed [25].

The threshold for perceiving pain from visceral stimuli varies among individuals. Pain perception is complex and involves visceral sensitivity and psychological processing [26]. The central nervous system's interpretation of visceral pain as serious or not serious influences the perception of pain (figure 1) [13,27]. Chronic pain may be triggered by an initial insult (eg, a gastrointestinal infection). In many children with functional abdominal pain, brain-gut communication is altered by a distortion of visceral sensation [28]. Normal processes (eg, peristalsis) may be perceived as painful. Visceral hypersensitivity occurs through peripheral sensitization at the point of inflammation, central sensitization, and recruitment of noninvolved adjacent neurons [29]; these mechanisms may predispose to chronic pain even after the initial stimulus (eg, infection) has resolved. (See "Pathophysiology of irritable bowel syndrome", section on 'Visceral hypersensitivity'.)

Sometimes, pain originating in the viscera is perceived to originate at a distant site (ie, referred pain). Referred pain usually is located in the cutaneous dermatomes sharing the same spinal cord level as the visceral inputs (figure 2). As an example, nociceptive stimuli from the gallbladder enter the spinal cord at T5 to T10. Thus, pain from an inflamed gallbladder may be perceived in the scapula. Precise localization of the pain to the right upper quadrant in patients with acute cholecystitis usually occurs once the overlying parietal peritoneum (which is somatically innervated) becomes inflamed.

ETIOLOGY — The two broad categories of causes of chronic abdominal pain in children and adolescents are organic disorders (table 2) and functional abdominal pain disorders (table 1) [5]. Most children with chronic abdominal pain have functional abdominal pain disorders [7,30,31]. However, organic and functional abdominal pain are not mutually exclusive. Functional and organic conditions can coexist and interact [32-35]. In addition, psychological comorbidities are common in both organic and especially functional disorders in children and adolescents [36,37].

Organic disorders — Organic disorders are conditions that are associated with physiologic, structural, or biochemical abnormalities (table 2). Organic disorders are more likely in children with "alarm" findings (table 3).

Functional disorders

●Clinical features – In most cases, functional abdominal pain is ill defined and poorly localized or periumbilical [38]. Episodes of pain usually last for less than one hour, resolve spontaneously, and may be accompanied by autonomic features (eg, pallor, nausea, dizziness, headache, fatigue) [32,39,40]. Episodes seem more common after awakening and in the evening, and they may be triggered or exacerbated during times of stress (eg, school transitions, caregiver divorce, emotional trauma). The child is well and functions normally between episodes but may have symptoms of anxiety or depression (separation anxiety, social phobias, specific phobias, generalized anxiety [41,42]). Alarm symptoms (table 3) are lacking [1,43]. The family history often is positive for gastrointestinal complaints (eg, irritable bowel syndrome [IBS], reflux, constipation) [20,44].

●Prevalence – In a large population-based survey, the overall prevalence of functional abdominal pain disorders (according to Rome IV criteria) was 8.2 percent [45]. The prevalences of specific functional abdominal pain disorders were as follows:

•Functional dyspepsia – 3 percent

•Functional abdominal pain not otherwise specified – 2.4 percent

•IBS – 2.3 percent

•Abdominal migraine – 0.5 percent

The prevalence of functional constipation was 10.7 percent [45]. The Rome classification does not categorize functional constipation as a functional abdominal pain disorder; however, it can be associated with abdominal pain in children. (See "Functional constipation in infants, children, and adolescents: Clinical features and diagnosis".)

●Specific disorders – Several functional abdominal pain disorders of childhood/adolescence have recognizable patterns of symptoms (table 1) [2].

•Functional dyspepsia – Dyspepsia is pain or discomfort that is centered in the epigastric region. Discomfort may be characterized by fullness, early satiety, bloating, nausea, retching, or vomiting [2]. The pain or discomfort may be exacerbated by eating. Children with dyspepsia and alarm findings should be evaluated for an organic disorder (eg, acid peptic disease).

The Rome IV classification of functional gastrointestinal disorders in children includes two subtypes of functional dyspepsia [2]:

-Postprandial distress syndrome is characterized by postprandial fullness or early satiety that prevents finishing a regular meal; supportive features include upper abdominal bloating, nausea, and excessive belching.

-Epigastric pain syndrome is characterized by bothersome epigastric pain or burning not relieved by defecation; supportive features include a burning quality of pain and induction or relief by a meal, although it can occur during fasting.

The pathophysiology of functional dyspepsia is not clear. Abnormalities in gastric electrical rhythm, delayed gastric emptying, reduced gastric accommodation (expansion) response to feeding, and antroduodenal dysmotility have been demonstrated in some children and adolescents [46-50]. Abnormal motor function, visceral sensitivity, and psychosocial factors have been studied as possible contributing factors in adults. (See "Functional dyspepsia in adults", section on 'Epidemiology and pathophysiology'.)

•Functional abdominal pain not otherwise specified – The Rome IV criteria use the term "functional abdominal pain not otherwise specified" to describe chronic abdominal pain (≥2 months' duration) in children without alarm findings who do not meet criteria for other functional abdominal pain disorders (table 1). However, they recognize that the term "functional abdominal pain" will be used for clinical purposes.

This category most closely resembles, but is not a substitute for, the classically defined recurrent abdominal pain of childhood [51]. "Nonorganic abdominal pain" and "psychogenic abdominal pain" are sometimes used interchangeably with "functional abdominal pain" [43]. However, we prefer "functional abdominal pain."

•Irritable bowel syndrome (IBS) – IBS is characterized by chronic abdominal pain and altered bowel habits (diarrhea or constipation) in the absence of any alarm findings. Children with chronic abdominal pain, altered bowel habits, and alarm findings should be evaluated for organic conditions. (See 'Patients with alarm findings' below.)

IBS occurs less frequently before late adolescence and may be preceded by a long history of constipation or an episode of gastroenteritis (sentinel illness) [20,32,52-54]. Compared with healthy volunteers and children with childhood functional abdominal pain syndrome (a Rome III diagnosis, which Rome IV calls "functional abdominal pain not otherwise specified"), children with IBS have a lowered rectal pain threshold and disturbed rectal contractile response to meals [55,56]. Compared with control subjects and children with functional dyspepsia, children with IBS have abnormal pain referral after rectal distension (ie, they report pain at a location other than the S3 dermatome) [14]. In addition, adolescents who have IBS-type symptoms have higher anxiety and depression scores than do those without such symptoms [20]. (See "Pathophysiology of irritable bowel syndrome".)

•Abdominal migraine – Abdominal migraine is characterized by recurrent episodes of abdominal pain for at least six months, typically midline or poorly localized, dull, and moderate to severe in intensity. Abdominal pain is associated with at least two additional features including anorexia, nausea, vomiting, headache, photophobia, and pallor [2]. Family history of migraine headache is common. (See "Types of migraine and related syndromes in children", section on 'Abdominal migraine'.)

Children who have recurrent episodes of abdominal pain and alarm findings should be evaluated for an organic cause. (See 'Patients with alarm findings' below.)

INITIAL EVALUATION — The evaluation consists of a focused history and physical examination, followed by focused laboratory testing for selected patients (algorithm 1).

Objectives

●Identify alarm findings – The initial evaluation of the child or adolescent with chronic abdominal pain includes history, physical examination, and stool testing for occult blood to determine whether the child has any "alarm findings" (table 3), which help to distinguish organic from functional abdominal pain and direct the need for additional evaluation [1,43,44]. In an observational study, weight loss, hematochezia, and anemia were more common in children with Crohn disease than with functional gastrointestinal disorders, with a cumulative sensitivity of 94 percent [44]. The specifics of the additional evaluation depend on the diagnostic considerations. (See 'Patients with alarm findings' below.)

●Identify contributing factors – Information other than alarm findings obtained in the initial evaluation helps to distinguish among organic etiologies and provides insight into biopsychosocial factors that may trigger or reinforce pain (independent of etiology) and are helpful when formulating a management plan [11,57-61]. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Management of triggers'.)

●Form a therapeutic alliance – Comprehensive initial history and examination helps to reassure the patient and family that the clinician is taking their complaints seriously. At the time of presentation, the caregivers and child may be frustrated and anxious; they may have tried over-the-counter or dietary interventions without improvement and may be increasingly concerned that the child has a serious disorder [3]. The caregivers should be asked what they think is causing the pain (or what they are worried is causing the pain) so that their concerns can be directly addressed. It is important to establish a therapeutic alliance early in the course of evaluation and treatment. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Therapeutic relationship'.)

It may be helpful to introduce the concept and high likelihood of functional gastrointestinal disorders as a possible cause at the initial evaluation, even if the pain has not been present long enough to qualify as "chronic" [3,62]. It also may be helpful to educate the patient/family about the biopsychosocial model of pain and possible role of stress (figure 1). Providing examples of how stress can directly cause abdominal pain or other symptoms (ie, churning of the stomach or headache before a test) may help them understand this relationship.

The patient and family should be assured that the clinician will search for identifiable causes, initiate a treatment plan, and continue to follow the patient on a regular basis [63]. Periodic follow-up validates the clinician's continued support and interest in the child/adolescent and family. Testing should be kept to a minimum and tailored to alleviate the patient's and parents' concerns. Unnecessary testing may lead to incidental findings, which may contribute to increased morbidity, further inappropriate testing, and inappropriate treatments [64]. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Follow-up'.)

History — The history may provide clues to the etiology of chronic abdominal pain. It must assess possible organic causes for the pain, as well as biologic and psychosocial factors that may be contributing to it [11,57-60].

●Alarm findings – It is important to ask specifically about alarm findings (table 3). In a systematic review, alarm findings were helpful in distinguishing organic from functional pain [43]. (See 'Etiology' above.)

Alarm findings from the history include:

•Involuntary weight loss or unexplained fever

•Difficulty swallowing or painful swallowing

•Vomiting that is bilious, protracted, projectile, or otherwise worrisome

•Diarrhea that is severe and chronic (≥3 loose or watery stools per day for ≥2 weeks), nocturnal, or bloody

•Urinary symptoms

•Back pain

•Family history of inflammatory bowel disease (IBD), celiac disease, or peptic ulcer disease

•Skin changes (eg, rash, eczema, hives)

●Other history – Other aspects of the history may help to distinguish among organic causes or provide insight into exacerbating factors and how the pain affects the child/family. Details of the history (triggers, onset, timing, location, quality and impact of the pain, and associated symptoms) and their implications are outlined in the table (table 4) [43].

A pain diary can help clarify the details of the pain history and possible areas of intervention. The patient, with assistance from family members, if necessary, should be instructed to record the following information at the end of each day for one week:

•Time of day the pain occurred. Pain that occurs consistently after awakening on school days suggests that the stress of attending school is the likely cause of the pain, rather than an organic disease. Nighttime awakening with pain is often seen in children with peptic disease.

•Pain location and severity using a scale of zero (no pain) to five (worst pain) or the FACES scale (figure 3) and including whether the pain prevented activities.

•Possible triggering factors (eg, foods, activities, stressors, thoughts, feelings, geographic locations [eg, in school, at home]).

•Pain duration.

•Remedies/interventions that were tried and whether they were successful.

For adolescent females, the menstrual history should be obtained, including age of menarche, date of last two menstrual periods, and frequency of menstrual periods, as well as any perceived relationship between menstrual periods and the pain. The child's bowel habits (stool frequency and form) should also be evaluated. If constipation is present, it should be treated, but it is important to recognize that the constipation may not be the cause of the abdominal pain.

●Psychosocial history – The psychosocial history is an important part of the evaluation of children and adolescents with chronic abdominal pain. Psychosocial factors do not help to distinguish organic from functional abdominal pain but may contribute to the perception or maintenance of abdominal pain, regardless of the etiology [11,57-60]. In some children, abdominal pain may be reinforced by caregiver attention or being allowed to stay home from school. Abdominal pain also may be a physiologic response to traumatic events (eg, physical or sexual abuse) [65-67]. This interaction between stress and pain may be mediated by abnormalities in the autonomic nervous system [68]. (See 'Pathogenesis' above.)

The HEEADSSS acronym (table 5) is a psychosocial screening tool that is commonly used for adolescents. The adolescent should be interviewed alone; questions regarding the adolescent's sexual history, psychological fears and inappropriately high levels of anxiety (prior to onset of pain and during pain), or caregiver issues should be asked without the caregiver present.

Physical examination — The physical examination of the child or adolescent with complaints of chronic abdominal pain focuses on the abdominal, pelvic, rectal, and genitourinary regions to identify alarm findings (table 3), which require additional evaluation. (See 'Patients with alarm findings' below.)

●Alarm findings – Alarm findings from the examination include:

•Weight loss, poor weight gain, or deceleration in linear growth.

•Oral ulcers or perianal abnormalities (eg, skin tags, fissures, fistulae).

•Localized or lateralized abdominal pain, suprapubic tenderness, costovertebral angle tenderness, or rebound tenderness.

•Delayed puberty.

•Hepatosplenomegaly.

●Other relevant findings – Important aspects of the examination include [1,60]:

•The general appearance and level of comfort or discomfort (as an indication of severity).

•Growth parameters, including weight (percentile or percent ideal body weight), height, and growth velocity. Significant growth delay (an alarm finding) is suggested by height increase of <5 cm (2 inches) per year in a prepubertal child and/or substantial decrease in height percentile (eg, crossing two major percentile lines). (See "Measurement of growth in children".)

•Blood pressure; hypertension may indicate organic disease. (See "Epidemiology, risk factors, and etiology of hypertension in children and adolescents", section on 'Secondary hypertension'.)

•Oropharyngeal examination:

-Aphthous ulcers (picture 1) may indicate Crohn disease. (See "Clinical manifestations and complications of inflammatory bowel disease in children and adolescents", section on 'Oral and perianal disease'.)

-Loss of tooth enamel may indicate recurrent vomiting.

•Abdominal examination:

-The position assumed by the patient when in pain.

-Palpation, performed gently and while the patient is distracted, to assess enlarged organs or masses (eg, stool in the left lower quadrant).

-Guarding typically is absent with deeper sources of pain (eg, pancreatitis, renal colic); however, determining if abdominal tenderness is deep (implicating disease of visceral organs) or superficial may be difficult.

-Carnett sign to differentiate visceral from abdominal wall pain – With the child in the supine position, ask them to cross their arms and sit halfway forward (to elicit abdominal muscle contraction). The Carnett sign consists of focal tenderness that increases or remains the same during abdominal wall contraction, which suggests pain originating in the abdominal wall (eg, hernia, hematoma, abdominal wall musculature, anterior cutaneous nerve entrapment syndrome) [69,70]. (See "Anterior cutaneous nerve entrapment syndrome", section on 'Diagnostic approach'.)

•Hyperextension of the hip – Pain that is reproduced with hyperextension at the hip (psoas sign) is suggestive of inflammation of the psoas muscle. (See "Psoas abscess", section on 'Symptoms and signs'.)

•Sexual maturity rating – Delayed puberty may be a clue to organic disease (eg, IBD); absence of menarche despite sexual maturity may be a clue to hematocolpos. (See "Normal puberty", section on 'Sexual maturity rating (Tanner stages)'.)

•Perianal and digital rectal examination with stool testing for occult blood – Perianal fistulas, deep fissures, or large skin tags (picture 2) may indicate Crohn disease. Impacted stool, rectal dilation, and superficial fissures may suggest constipation.

•External genital inspection – This should be conducted alongside the perianal examination. A pelvic examination (speculum and bimanual examination) may be difficult to perform in a prepubertal or peripubertal female or an adolescent who is not sexually active; however, the digital rectal examination can assess the posterior pelvic cavity for pain or a mass (which may suggest gynecologic pathology) in addition to gastrointestinal pathology. (See "Gynecologic examination of the newborn and child", section on 'History and physical examination'.)

If gynecologic problems are suspected (eg, hematocolpos, subclinical pelvic inflammatory disease, ovarian mass), a pelvic ultrasound or a referral to a pediatric gynecologist or adolescent medicine specialist can be helpful. (See "Congenital anomalies of the hymen and vagina" and "Pelvic inflammatory disease: Clinical manifestations and diagnosis" and "Ovarian cysts in infants, children, and adolescents".)

Laboratory evaluation — The laboratory evaluation of children with chronic abdominal pain may include [1]:

●Celiac serology – For most children, the best test for celiac disease is immunoglobulin (Ig) A tissue transglutaminase antibodies. Total IgA should also be measured (if not previously tested) to exclude IgA deficiency. Testing must be done while on a gluten-containing diet. (See "Diagnosis of celiac disease in children", section on 'Pretesting diet'.)

●Stool test for occult blood (if available) – Gross or occult gastrointestinal bleeding suggests organic disease. Note that point-of-care (office) testing for occult blood is discouraged (and may not be permitted in some institutions) due to quality-control issues. (See "Approach to upper gastrointestinal bleeding in children" and "Lower gastrointestinal bleeding in children: Causes and diagnostic approach".)

For children without alarm findings, further testing or imaging has low yield and is generally unnecessary (see 'Other tests' below). By contrast, for children with alarm findings (table 3), or clinical features that suggest a particular diagnosis (table 2), other laboratory tests may be required to evaluate for that disorder. (See 'Patients with alarm findings' below.)

PATIENTS WITHOUT ALARM FINDINGS

Diagnosis of functional abdominal pain — The diagnosis of functional abdominal pain can be made without additional diagnostic testing in children and adolescents with chronic abdominal pain who meet the following criteria [1,2,11]:

●No alarm findings (table 3)

●Normal physical examination

●Stool sample negative for occult blood, if available and approved for office use

Functional abdominal pain in children and adolescents can be classified according to recognizable patterns of symptoms (table 1) [2]. Diagnosis of the specific functional pain subtype can usually be made by fulfilling diagnostic criteria rather than laboratory exclusion of organic conditions. Although the diagnosis of a functional abdominal pain disorder can be made on the basis of symptoms alone, it is also reasonable to screen such patients for celiac disease. In a prospective cohort of 992 children referred for chronic abdominal pain, 270 met criteria for irritable bowel syndrome (IBS) [71]. Among these, 12 (4.4 percent) had positive serology for celiac disease (compared with <1.5 percent in the general pediatric population). If the celiac serology is positive, further evaluation is required to establish the diagnosis and determine its contribution to the abdominal symptoms. (See 'Functional disorders' above and "Diagnosis of celiac disease in children".)

Other tests — Limited additional testing may be appropriate for some children, such as those with equivocal symptoms or if the family desires additional information before accepting a diagnosis of functional abdominal pain [1,2]. The limited additional testing may include a complete blood count, celiac disease screening (if not already done), inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]), stool calprotectin or lactoferrin, and urinalysis.

For these children without alarm findings, gastrointestinal imaging (abdominal/pelvic ultrasonography) or other studies (endoscopy or esophageal pH monitoring or noninvasive tests for Helicobacter pylori) have low yield and are generally unnecessary [1], as shown in a systematic review [43]. Similarly, in a retrospective review of abdominal/pelvic ultrasonography in 598 children with recurrent abdominal pain (defined as ≥3 episodes during the three months before presentation) and typical features (eg, midline pain and absence of all of the following: suspicious findings on abdominal palpation, urinary symptoms, significant weight loss, jaundice, and gastrointestinal bleeding), abnormalities were detected in only five (<1 percent) [72]. In contrast, in the 46 children who had atypical features, five had ultrasonographic abnormalities (11 percent). Abnormalities included extrahepatic bile ducts (choledochal cysts), ovarian teratoma, and fecal mass.

Family communication — If any additional testing is performed, it may be helpful to set the expectations for normal results (if appropriate) [58]. Extensive evaluation to exclude organic disease should be avoided; the yield is low, costs are high, appropriate management may be delayed, and caregiver concerns about an undiagnosed organic disease may be reinforced [8,39,73,74]. (See 'Laboratory evaluation' above and "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Patient education'.)

When conveying the diagnosis of functional abdominal pain, it may be helpful to emphasize that functional abdominal pain is a valid diagnosis that causes the child physiologic pain. It is diagnosed by symptom pattern rather than specific laboratory or radiographic tests. It is helpful to review the diagnostic criteria and highlight the child's overall health (ie, normal growth and development, well-being between episodes, absence of symptoms or signs suggestive of organic disease). Education regarding the proposed mechanisms for functional disorders (eg, visceral hyperalgesia, reduced pain threshold, impaired gastric relaxation response to meals [12-16,75,76]) validates the patient's pain and establishes the basis for therapeutic interventions [1]. Understanding may be facilitated by using headache as an example of pain that does not necessarily result from organic disease [75]. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'General management strategies'.)

PATIENTS WITH ALARM FINDINGS — Patients with alarm findings (table 3) require additional evaluation for organic disorders. The components and urgency of the evaluation depend on the diagnostic possibilities suggested by the initial evaluation (table 2).

Additional laboratory evaluation — We suggest the following initial tests for most children and adolescents with chronic abdominal pain and alarm findings (table 6) [39,75]:

●Complete blood count with differential.

●Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP).

●Metabolic panel (ie, electrolytes, glucose, blood urea nitrogen, creatinine, calcium, total protein, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase).

●Lipase.

●Urinalysis with urine culture as indicated.

●Serologic tests for celiac disease (eg, IgA tissue transglutaminase antibodies with total IgA) if not already done during the initial evaluation. (See "Diagnosis of celiac disease in children", section on 'Pretesting diet'.)

●Stool for calprotectin or lactoferrin. Calprotectin and lactoferrin are both noninvasive biomarkers of inflammation in the gastrointestinal tract, and elevation in either one of these two tests is sensitive and specific in discriminating inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) [77,78]. If choosing one, calprotectin appears slightly better [79]. (See 'Laboratory evaluation' above.)

Additional laboratory testing or evaluation may be warranted if specific organic conditions are suspected (table 2). As examples:

●Inflammatory bowel disease (IBD) – Suggested by occult or gross blood in stools, diarrhea, and/or growth faltering. In addition to the laboratory tests above, measure fecal calprotectin or lactoferrin. Fecal calprotectin and lactoferrin are generally elevated in inflammatory intestinal diseases, including IBD. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children".)

●Food allergy – An IgE-mediated reaction is suggested by onset of abdominal pain, nausea, or vomiting within minutes to two hours after ingestion of offending food and onset of diarrhea within two to six hours after ingestion of offending food. A non-IgE-mediated reaction can present with chronic vomiting and diarrhea, poor weight gain, and blood or mucus in stools. Testing for food allergy is discussed separately. (See "Diagnostic evaluation of IgE-mediated food allergy".)

●Chronic constipation – For most children with chronic constipation, the evaluation focuses on the history and physical examination. Laboratory testing is helpful for selected patients with signs or symptoms of a specific organic cause of constipation (eg, celiac disease, lead toxicity, hypothyroidism). (See "Constipation in infants and children: Evaluation".)

●Enteric parasitic or protozoal infection – Suggested by diarrhea, eosinophilia, and/or relevant exposures. The evaluation includes stools for ova/parasites and Giardia antigen (giardiasis can cause abdominal pain without diarrhea). In a series of 220 children with chronic abdominal pain, protozoal infections accounted for the pain in 6 to 11 percent [80]. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis", section on 'Acute giardiasis'.)

●Enteric bacterial infections – Stool testing for Clostridioides difficile and stool cultures (eg, for Salmonella, Shigella, Yersinia, Campylobacter, and Escherichia coli) [3,39]. (See "Diagnostic approach to diarrhea in children in resource-abundant settings", section on 'Chronic diarrhea (duration >1 month)' and "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Testing for C. difficile'.)

●H. pylori – For children with clinical suspicion of H. pylori infection (eg, upper abdominal or epigastric pain with alarm signs such as weight loss or vomiting, nighttime wakening with pain, occult blood in stool, iron deficiency anemia), endoscopic evaluation is generally indicated and provides the information needed for a definitive diagnosis and targeted treatment. Noninvasive tests (stool antigen or urea breath test) provide supportive evidence for H. pylori infection but are not recommended for the initial diagnosis and management [81]. (See "Helicobacter pylori: Diagnosis and management in the pediatric patient", section on 'Evaluation'.)

●Pancreatitis – Pancreatitis is suggested by epigastric pain that radiates to the back, sometimes with growth failure or signs of exocrine pancreatic insufficiency. A family history of pancreatitis suggests shared genetic risk factors. Initial evaluation includes serum amylase and lipase; abnormal results support a diagnosis of chronic pancreatitis, but normal results to not exclude it. (See "Clinical manifestations and diagnosis of chronic and acute recurrent pancreatitis in children".)

●Eating disorders – For children with early satiety and poor weight gain, the possibility of an eating disorder should be considered. Possibilities include ARFID (characterized by low appetitive drive and/or food aversions that is not driven by body image concerns) and anorexia nervosa [82]. ARFID is highly prevalent among children with functional dyspepsia, and children with dyspeptic symptoms should be screened for ARFID. (See "Eating disorders: Overview of epidemiology, clinical features, and diagnosis", section on 'Avoidant/restrictive food intake disorder' and "Eating disorders: Overview of epidemiology, clinical features, and diagnosis", section on 'Anorexia nervosa'.)

●Pregnancy – Urine test for human chorionic gonadotropin. (See "Pregnancy in adolescents", section on 'Diagnosis of pregnancy'.)

Imaging — The radiologic evaluation of the child and adolescent with chronic abdominal pain and alarm findings depends on the diagnostic possibilities that are being considered [3,43]:

●Abdominal ultrasonography may be indicated to evaluate for gallstones, extrahepatic bile ducts (choledochal cyst), pancreatic pseudocyst, hydronephrosis (eg, due to ureteropelvic junction obstruction), or retroperitoneal mass.

●Pelvic ultrasonography may be indicated to evaluate ovarian masses or pregnancy. (See "Ovarian cysts in infants, children, and adolescents" and "Overview of ultrasound examination in obstetrics and gynecology".)

●An upper gastrointestinal series may be warranted to evaluate bowel obstruction (eg, late presentation of malrotation, surgical adhesions) in patients with significant vomiting (eg, bilious, protracted). Small bowel follow-through may be added if IBD (particularly Crohn disease) is suspected, but magnetic resonance enterography is increasingly used. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Imaging'.)

●Magnetic resonance enterography may be warranted if IBD is suspected. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Diagnostic evaluation'.)

●Computed tomography (CT) of the abdomen with contrast may be warranted to evaluate retroperitoneal or intraabdominal abscess (eg, associated with IBD). CT usually is reserved for urgent evaluation (eg, abscess, mass), given concerns about radiation exposure. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Imaging'.)

Indications for referral

●Referral to a gastroenterologist may be warranted for children and adolescents with chronic abdominal pain, alarm findings (table 3), and any of the following [32,75]:

•Suspicion of a serious organic condition such as IBD (eg, involuntary weight loss, growth deceleration, delayed puberty, oral ulcers, perianal abnormalities, anemia, elevated ESR or CRP, elevated fecal calprotectin) or celiac disease (positive IgA tissue transglutaminase antibodies). (See "Clinical presentation and diagnosis of inflammatory bowel disease in children", section on 'Clinical manifestations'.)

•Persistent alarm symptoms without a clear diagnosis after evaluation by a primary care provider.

•Suspicion of acid-peptic disease with persistent pain despite a trial (at least four weeks) of treatment with histamine 2 blockers or proton pump inhibitors.

•Desire to confirm lactose intolerance (eg, before long-term continuation of a lactose-free diet).

•Need for upper or lower endoscopy (eg, suspicion of H. pylori infection or IBD, persistent vomiting, gastrointestinal bleeding, chronic diarrhea).

•Constipation that has not responded to primary care interventions. (See "Chronic functional constipation and fecal incontinence in infants, children, and adolescents: Treatment".)

●Referral to a pediatric surgeon may be warranted for children with conditions that require surgery (eg, gallstones) or diagnostic laparoscopy (eg, persistent right lower quadrant pain and tenderness of unclear etiology affecting quality of life) [75].

●Referral to an adolescent medicine specialist or mental health specialist may be warranted to conduct a detailed biopsychosocial evaluation for potential triggers or symptoms of anxiety or depression or to evaluate a suspected eating disorder.

●Referral to an adolescent medicine specialist or gynecologist may be warranted for adolescents with gynecologic causes of chronic abdominal pain (eg, endometriosis, dysmenorrhea) [32,75]. Abnormal menses also may be a symptom of an eating disorder.

Additional referral indications depend on the condition identified or suspected (eg, posterior urethral valves, angioedema).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic abdominal pain in children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: Chronic abdominal pain in children and adolescents (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Terminology and epidemiology – We define chronic abdominal pain as intermittent or constant abdominal pain (of either functional or organic etiology) that has been present for at least two months. Chronic abdominal pain is common, occurring in 10 to 18 percent of children and adolescents. (See 'Terminology' above and 'Epidemiology' above.)

●Etiology – The two major categories of causes for chronic abdominal pain in children and adolescents are functional disorders (table 1) (also known as disorders of gut-brain interaction) and organic disorders (table 2). Functional disorders are far more prevalent. (See 'Etiology' above.)

●Initial evaluation – The initial evaluation of the child or adolescent with chronic abdominal pain generally includes history (table 4), physical examination (focusing on growth and development and the abdominal, rectal, pelvic, and genitourinary regions), serologic testing for celiac disease (IgA tissue transglutaminase antibodies, along with total IgA), and stool testing for occult blood and calprotectin or lactoferrin to determine whether the child has any "alarm findings" (table 3). Alarm findings help to distinguish the subgroup of children with a higher risk of organic disease from the majority of children with functional abdominal pain. Alarm findings also direct the need for additional evaluation. (See 'Initial evaluation' above.)

At the time of the initial evaluation, it may be helpful to educate the patient/family about the biopsychosocial model of pain (figure 1) and to introduce the concept and high likelihood of functional gastrointestinal disorders as a possible cause. (See 'Initial evaluation' above.)

●Additional evaluation

•Patients without alarm findings – Patients without alarm findings usually do not require evaluation beyond history and physical examination (algorithm 1). In children without alarm findings, abnormal studies rarely change management but may cause anxiety or lead to unnecessary additional evaluation. (See 'Patients without alarm findings' above.)

-Diagnosis of functional abdominal pain – The diagnosis of functional abdominal pain can be made in children and adolescents with chronic abdominal pain and no alarm findings, normal physical examination, and negative basic laboratory evaluation (typically consisting of serologic screening for celiac disease and a stool sample negative for occult blood and/or stool calprotectin or lactoferrin). Functional abdominal pain in children and adolescents can be specifically classified according to recognizable patterns of symptoms (table 1). (See 'Diagnosis of functional abdominal pain' above.)

Education regarding the proposed mechanisms of functional abdominal pain (eg, visceral hyperalgesia, reduced pain threshold, impaired gastric relaxation response to meals) validates the patient's pain and establishes the basis for therapeutic interventions. (See "Functional abdominal pain in children and adolescents: Management in primary care".)

•Patients with alarm findings – Patients with alarm findings require additional evaluation for organic disorders (algorithm 1). The components and urgency of the evaluation depend on the diagnostic possibilities suggested by the initial evaluation (table 3). (See 'Patients with alarm findings' above.)

For most patients with alarm findings, we suggest (table 6) (see 'Additional laboratory evaluation' above):

-Celiac serology (if not already performed)

-Complete blood count with differential

-Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)

-Metabolic panel (ie, electrolytes, glucose, blood urea nitrogen, creatinine, calcium, total protein, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase)

-Lipase

-Stool for occult blood (if not already performed) and calprotectin or lactoferrin

Additional laboratory tests, imaging, or referral may be warranted if specific organic conditions are suspected. (See 'Patients with alarm findings' above and 'Additional laboratory evaluation' above and 'Imaging' above and 'Indications for referral' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Mariam R Chacko, MD, who contributed to earlier versions of this topic review.