While the differential diagnosis of chronic abdominal pain is broad, a fairly simple approach can be utilized to help determine the etiology of the pain. The first decision point, as depicted in Figure 7–1, concerns the location of the pain. If the patient defines the location, the differential diagnosis becomes more focused, and the etiology is often discernable from organs in the vicinity of the pain. In general, location alone does not allow for clear differentiation of infectious from noninfectious causes. If the patient cannot define the location, either because the pain is diffuse or the patient is too young or is nonverbal, the clinician must rely on other symptoms to identify the problem. This approach is detailed more fully below.
Pain emanating from the right upper quadrant usually originates from the liver and/or biliary tree. Occasionally, right upper quadrant pain is caused by diseases of the stomach, duodenum, or colon (Figure 7–1). Phrenic pain may also present as right upper quadrant pain.
Pain originating from the liver itself is because of stretching of the liver capsule, as that is the only part of the liver innervated with pain fibers. Thus, liver pain occurs when the liver becomes swollen, such as after trauma or during episodes of severe inflammation and edema. This is not likely to cause chronic abdominal pain, but chronic hepatitis may have periods of more severe inflammation, during which the liver may become edematous, causing the capsule to stretch. A more detailed discussion of hepatitis is found elsewhere in this textbook. Perihepatitis, or inflammation of the capsule itself, will lead to right upper quadrant pain. This is occasionally a component of pelvic inflammatory disease (see Chapter 43).
Cholelithiasis refers to the presence of symptomatic gallstones and may present as intermittent severe right upper quadrant pain, or as milder pain following meals. Most children with cholelithiasis have underlying hemolytic disorders such as sickle cell disease, or have a prolonged history of total parenteral nutrition; however, increasing rates of obesity in children have also led to a greater incidence of cholelithiasis.2 Obstruction of the biliary tree leads to choledocholithiasis, while obstruction of the gallbladder leads to cholecystitis. While these are important causes of acute right upper quadrant pain, cholecystitis in particular may be chronic. Chronic cholecystitis is frequently associated with poor gallbladder emptying (gallbladder dyskinesia) rather than obstruction; therefore, jaundice does not typically occur in these patients. Cholangitis refers to inflammation or infection of the intrahepatic biliary tree and rarely causes pain, although it is a risk factor for gallstone formation. Choledochal cysts are congenital malformations of the bile ducts, and typically cause pain when obstructed; as bile flow is generally poor through the cyst, infection and stone formation occur commonly.
Intestinal causes of right upper quadrant pain, such as colitis and bowel ischemia, are discussed more fully below, as they are more frequently causes of lower quadrant pain. Pneumonia and phrenic abscesses lead to right upper quadrant pain because of irritation to the diaphragm, which can be interpreted as right upper quadrant pain.
Pain in this region typically derives from the distal esophagus, stomach, duodenum, or pancreas. Occasionally, functional pain may be epigastric in origin, but other more easily treated entities should be evaluated.
Esophagitis has a multitude of causes. Typically, pain occurs while eating. Esophagitis may be infectious in nature, most commonly in immunocompromised patients where Candida spp., herpes simplex virus, and cytomegalovirus are relatively common causes. Retrosternal burning dysphagia and chronic nausea or vomiting should alert the clinician to the possibility of esophageal infection. Gastroesophageal reflux disease may lead to inflammation of the esophagus, but increasingly esophagitis is caused by food or environmental allergies that trigger eosinophilic esophagitis. Pain is not a typical presentation of eosinophilic esophagitis, but given the increasing prevalence of this condition it should be a consideration, particularly in patients with poor response to empiric acid blockade.3 Gastroesophageal reflux without esophagitis may also lead to epigastric pain, typically associated with heartburn and dyspepsia.
Gastric causes of epigastric pain include gastritis and the related peptic ulcer disease. Gastritis is simply defined as inflammation of the stomach; the most common cause is Helicobacter pylori. Less common infectious causes of gastritis include cytomegalovirus, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, and fungi. Chronic nonsteroidal anti-inflammatory drug (NSAID) overuse is also an important cause. Peptic ulcer disease refers to ulcers exacerbated by acid, and in the stomach can be caused by medications such as nonsteroidal anti-inflammatory drugs or glucocorticoids—either exogenous in the form of medication or endogenous from extreme physiologic stress such as burns or trauma. Ulcers from H. pylori are more typically found in the duodenum, although gastric ulcers from H. pylori do occur. Epigastric pain may also arise from gastroparesis, or delayed gastric emptying. This may be present after either a viral or parasitic gastroenteritis. H. pylori may also be associated with this condition.
In addition to peptic ulcers in the duodenum from H. pylori, epigastric pain may be caused by chronic illnesses that affect the small bowel, such as celiac disease and Crohn disease. Celiac disease is a chronic intolerance to gluten, a protein found in wheat, rye, and barley; this condition is now recognized as a strikingly common condition, affecting ∼1:100 individuals in the United States.4 Celiac disease can be associated with other features such as diarrhea, constipation, weight loss, or poor growth, but may in fact present with pain as the only feature. Crohn disease is an inflammatory bowel disease that can affect any part of the gastrointestinal tract, and like celiac disease, is frequently, but not always, associated with other features such as diarrhea, vomiting, weight loss, or poor growth. Lactose intolerance is fairly common in select patient populations (persons of Asian, African, and Native American descent5) and is often associated with bloating and diarrhea after ingestion of dairy products. Small bowel bacterial overgrowth occurs when there is stasis in the intestinal lumen, such as upstream of strictures, or in individuals with poor intestinal motility; bacteria proliferate in these static regions and lead to symptoms such as pain, nausea, and bloating.
Acute pancreatitis in children most frequently has an infectious cause, although drugs and trauma are also important causes. Infectious causes of acute pancreatitis include multiple viruses (e.g., enteroviruses, adenovirus, cytomegalovirus, Epstein–Barr virus, mumps, measles), bacteria (e.g., Salmonella spp., Campylobacter spp., Mycoplasma pneumoniae, M.tuberculosis), and parasites (especially ascariasis).6 Chronic or recurrent pancreatitis most often is idiopathic and may be triggered by an initial infectious agent, but may also be caused by anatomic anomalies, metabolic disorders, or heritable genetic disorders.7
Isolated left upper quadrant pain is extraordinarily rare as a complaint. Generally, the etiologies of left upper quadrant are similar to midepigastric pain, as gastric pain may be felt in the left upper quadrant. Phrenic pain may be secondary to pneumonia or a subphrenic abscess. Splenic pain is more frequently associated with hematological conditions such as sickle cell disease or with viral infections such as Epstein–Barr virus. Chronic constipation may occasionally present as left upper quadrant pain, as may colitis.
Right lower quadrant pain should be, similar to right upper quadrant pain, a concerning location of pain. Within the right lower quadrant lie the terminal ileum, cecum, appendix, ascending colon, and, in females, the right ovary and adnexa. Certainly in the acute setting, the possibility of appendicitis necessitates prompt attention. Chronic causes of right lower quadrant pain are listed in Figure 7–1. Chronic appendicitis with or without abscess formation leads to pain and discomfort, and may be accompanied by fevers. Crohn disease may also lead to abscess or fistula formation, and Crohn disease without abscess may present as right lower quadrant pain, as the terminal ileum and ascending colon are the most frequently affected sites in Crohn disease.8 Mesenteric adenitis, in which multiple lymph nodes within the abdomen are chronically enlarged, may present as right lower quadrant pain. Infectious causes of mesenteric adenitis include viruses (e.g., coxsackie viruses, adenovirus, rubeola, human immunodeficiency virus, Epstein–Barr virus), bacteria (most commonly Yersinia sp., occasionally nontyphoid Salmonella, M. tuberculosis, and various Staphylococcus and Streptococcus spp.), and parasites (commonly Giardialamblia). In female patients, tubo-ovarian abscesses, ectopic pregnancy, and pelvic inflammatory disease may present as right lower quadrant pain. It is possible for constipation or colitis to present as right lower quadrant pain, although this is probably the least likely location for these entities.
The hypogastrum, or suprapubic area, covers the bladder, rectum, and the uterus in females. Chronic pain in this region generally derives from inflammation in these structures, with the exception of chronic constipation, which in the absence of other symptoms is the most likely cause. Irritable bowel syndrome may present as chronic hypogastric or infraumbilical pain, and this condition is frequently associated with diarrhea or constipation. Chronic cystitis with or without pyelonephritis may lead to hypogastric pain. Colitis or proctitis may be caused by ulcerative colitis or by an infectious cause. Pelvic inflammatory disease may also lead to hypogastric pain.
The left lower quadrant contains the descending and sigmoid colon, as well as the right ovary and adnexa in females. Thus, the causes of chronic left lower quadrant include constipation, colitis (infectious or ulcerative), and pelvic inflammatory disease or tubo-ovarian abscess. Diverticulitis, an important cause of left lower quadrant pain in adults, is rare in children.
In general, patients with periumbilical or diffuse chronic abdominal pain are less likely to have an organic etiology to their pain. However, when chronic pain is associated with other gastrointestinal symptoms, such as vomiting, diarrhea, or constipation, there is much more likely to be an organic etiology. Thus, it is helpful to subdivide causes of chronic periumbilical pain based on associated symptoms.
Chronic diffuse abdominal pain associated with vomiting may arise from the upper gastrointestinal tract, from intestinal obstruction, or from nongastrointestinal problems. There is considerable overlap between the conditions causing diffuse or periumbilical pain and conditions that can present with localized pain discussed above. Malrotation and associated intermittent volvulus can present with chronic or intermittent abdominal pain and vomiting. The incidence of malrotation in the general pediatric population is estimated at 1/5009 suggesting that this diagnosis should always be considered in this setting. Chronic intestinal pseudo-obstruction is a debilitating condition in which symptoms are indistinguishable from a true obstruction, but there is no physical obstruction. The etiology of this condition is unclear, and it may result in eventual intestinal failure.10 A milder version may be seen transiently after gastroenteritis, which is often associated with carbohydrate malabsorption. Parasitic infections, particularly Giardia and Blastocystis hominis, may lead to chronic abdominal pain with gastroesophageal reflux-like symptoms, and occasional vomiting.
Occasionally, chronic or insidious conditions not within the abdomen lead to abdominal pain, and these conditions may also be associated with vomiting. Increased intracranial pressure, often from a mass, may lead to abdominal pain and vomiting, particularly early in the morning after the patient has been lying down. Various metabolic disorders, in particular fatty acid oxidation disorders and organic acidemias, may present with vomiting and pain, but typically pain is not an important component. If the abdominal pain and vomiting are paroxysmal, the patient may have cyclic vomiting syndrome, a condition associated with a family history of migraine headaches and with potential development of migraines in the patient.11 Chronic sinusitis may present as abdominal pain and intermittent vomiting because of the persistent postnasal drip. Diabetes may also present as abdominal pain and vomiting, secondary to the ileus that develops from acidosis and severe illness. Patients with eating disorders may also present with chronic abdominal pain, vomiting, and weight loss; these patients almost always have poor body image and have intentional weight loss, in contrast to patients with celiac disease or inflammatory bowel disease.
Diffuse abdominal pain is a common complaint of patients with constipation. The vast majority of patients with chronic constipation have functional constipation. There are several potential organic causes of chronic constipation, including Hirschsprung disease, lead toxicity, celiac disease, spina bifida (including occulta) and other spinal cord lesions, hypothyroidism, hypercalcemia and cystic fibrosis. Parasitic infections, particularly pinworm infection, may lead to constipation, but typically not without anal pruritis. Irritable bowel syndrome, a variant of functional abdominal pain, may present with diffuse abdominal pain and episodes of constipation.
Many of the conditions that cause diarrhea also present with localized pain and thus have been mentioned above. In some cases, the diarrhea is bloody, and that changes the differential diagnosis (Figure 7–1). Patients with nonbloody diarrhea and abdominal pain typically have conditions affecting the small intestine, such as celiac disease, lactose intolerance, or infections such as Giardia or Cryptosporidium. Crohn disease of the small intestine also may result in nonbloody diarrhea. Crohn disease may be associated with a history of oral ulcers or perianal disease, or with extraintestinal complaints such as fevers, arthralgias or arthritis, and rashes. As stated above, weight loss is also a common feature.
Less commonly, patients may develop a “flat villous lesion,” a condition in which intestinal villi have been destroyed following severe gastroenteritis, occasionally requiring parenteral nutrition until the villi have regrown. The lack of intestinal absorption is a common feature of all of these conditions, which results in increased intraluminal water and thus diarrhea. Irritable bowel syndrome may also present as diffuse abdominal pain with intermittent nonbloody diarrhea, although the etiology of this diarrhea is unclear.
As stated above, the presence of bloody diarrhea suggests colitis, whether from an infectious cause or from inflammatory bowel disease, either ulcerative colitis or Crohn disease. Salmonella,Shigella,E. coli 0157:H7, and other pathogens most frequently cause acute infectious colitis, as discussed elsewhere. These agents occasionally result in chronic colitis as well, but Clostridium difficile infection is more likely to become chronic. While these conditions may produce diffuse abdominal pain, patients with distal colitis or proctitis often will complain of tenesmus, which localizes to the rectum.
No Additional Gastrointestinal Symptoms
Diffuse abdominal pain that is not accompanied by other symptoms is the most common presentation for chronic abdominal pain. While this can certainly be a manifestation of virtually every condition listed above, it most likely represents functional abdominal pain. Functional abdominal pain is defined as debilitating pain for which there is no clear organic etiology. Because organic causes of chronic abdominal pain may present with no other symptoms, though, a thorough evaluation of the patient is usually required prior to diagnosing functional pain.