Etiology

Classification by location

The following etiologic classification may be practical and helpful for the evaluation of patients with chronic abdominal pain, although pain may arise from a vast number of causes in any system (only the more common causes are covered in further detail):

I. Pain originating from the abdominal viscera (visceral abdominal pain)

  1. Gastrointestinal (GI) tract: hollow organs

    • Esophagus: esophagitis (e.g., GERD); drug-induced (e.g., bisphosphonate, erythromycin); motility disorders (e.g., atypical achalasia); esophageal cancer

    • Stomach: chronic gastritis (e.g., Helicobacter pylori); drug/alcohol-induced; peptic ulcer disease; gastric cancer

    • Small bowel: inflammation (e.g., Crohn disease); drug-induced (e.g., aspirin, nonsteroidal anti-inflammatory drug [NSAID]); subacute obstruction (e.g., volvulus, intussusception)

    • Large bowel: inflammation (e.g., ulcerative colitis, Crohn colitis, infectious gastroenteritis); subacute obstruction (e.g., volvulus, tumor); colorectal cancer

  2. GI tract: solid organs

    • Liver: hepatocellular carcinoma, metastasis, abscesses

    • Pancreas: chronic pancreatitis, pancreatic cysts/pseudocysts

    • Gallbladder: cholecystitis, cholelithiasis

  3. Urogenital tract

    • Kidneys/ureter/bladder: nephrolithiasis, pyelonephritis, perinephric abscess

    • Female gynecologic diseases within the abdomen: endometriosis

  4. Abdominal vasculature

    • Chronic mesenteric ischemia/intestinal ischemia/abdominal angina

    • Superior mesenteric syndrome

II. Pain referred from an extra-abdominal source (referred abdominal pain)

  1. Pelvis

    • Chronic pelvic pain (CPP) (e.g., interstitial cystitis, endometriosis, adhesions, urethral syndrome, changes or dysfunction of the pelvic muscles)[19]​​

    • Female genitalia and reproductive organs (e.g., pelvic inflammatory disease [PID], endometriosis, ovarian cystic diseases, gynecologic malignancies)

    • Male genitalia and reproductive organs (e.g., prostatitis, prostate cancer, epididymitis, intermittent/recurrent torsion of testicle)[20]​​

  2. Chest/thorax

    • Lungs (e.g., malignancy)

    • Pleura and chest wall

  3. Musculoskeletal

    • Abdominal wall (e.g., abdominal cutaneous nerve entrapment syndrome, abdominal wall hernia)[21]​​

    • Spine (e.g., radiculitis)

  4. Neurogenic causes

    • Herpes zoster

III. Systemic/metabolic causes

  • Celiac disease

  • Lactose intolerance/lactase deficiency

  • Drugs: narcotics, non-dihydropyridine calcium-channel blockers, vitamins, mineral supplements (e.g., iron, calcium, magnesium, and aluminum)

  • Porphyria: acute intermittent

  • Heavy metal poisoning: lead/arsenic poisoning

  • Familial Mediterranean fever

  • Paroxysmal nocturnal hemoglobinuria

IV. Neurogastroenterology

  • Irritable bowel syndrome

  • Functional dyspepsia

  • Centrally mediated abdominal pain syndrome (formerly functional abdominal pain syndrome)

  • Narcotic bowel syndrome

  • Abdominal migraine.

Classification by pathophysiology

In addition to categorization by organ or system involvement, the underlying pathophysiology should also be considered.

1. Mechanical obstruction

  • Intestinal, urinary, or biliary tract obstruction usually presents acutely. Partial or intermittent obstruction may take longer to recognize and lead to chronic or recurrent abdominal symptoms.

2. Rupture of hollow viscera

  • Usually associated with an acute presentation. However, small perforations with spontaneous sealing and resulting in the formation of local abscesses may lead to chronic abdominal pain.

3. Chronic inflammation

  • Can lead to symptoms of chronic abdominal pain.

  • Intestinal inflammation can involve different segments of the GI tract and be secondary to various etiologies. Common examples are esophageal inflammation due to gastroesophageal reflux, gastric inflammation due to Helicobacter pylori, and small and/or large bowel inflammation due to ulcerative colitis or Crohn disease.

  • Inflammatory processes involving other GI organs (e.g., pancreas, liver, gallbladder) and non-GI organs (e.g., urinary bladder and kidneys) should also be considered.

4. Ischemia

  • Reduction in intestinal blood flow (intestinal/mesenteric ischemia) may be acute in onset with serious and, sometimes, catastrophic consequences, or it may be chronic, leading to chronic or recurrent GI symptoms. Most patients with chronic mesenteric ischemia are asymptomatic due to good collateral circulation between the 3 mesenteric arteries. Symptoms arise when there is a significant occlusion of 2 of the 3 main mesenteric arteries.[22]

  • Chronic mesenteric ischemia (sometimes also called intestinal angina) should be suspected mainly in older adult patients with underlying atherosclerotic vascular disease and/or a heavy smoking history who present with dull, crampy, upper/epigastric abdominal pain that usually appears within 1 hour after meals and subsides spontaneously over 2 to 3 hours. Other symptoms include nausea and vomiting, weight loss, and food aversion.

  • Microvascular occlusive disease in patients with sickle cell disease, small-vessel vasculitis, low-flow state, or veno-occlusive disease.

  • Calcification of mesenteric vessels on radiography is suggestive, but further testing with computed tomography or magnetic resonance imaging angiography is usually needed to confirm the diagnosis.[23]

5. Drugs/medications

  • Various drugs cause inflammation, injury, or even ulceration of the intestinal mucosa.

  • Examples include esophageal inflammation due to erythromycin or bisphosphonates, and gastric or small intestine inflammation due to chronic use of aspirin or NSAIDs.

  • Certain drugs can cause abdominal symptoms, including pain, without overt inflammatory manifestations. Non-dihydropyridine calcium-channel blockers, such as diltiazem and verapamil, slow gut motility and lead to chronic constipation and pain. Common vitamin and mineral supplements, such as iron and calcium, can exacerbate constipation and abdominal pain, while magnesium and aluminum, in high doses, can cause loose stools, occasionally with crampy pain.

  • Chronic narcotic use, in addition to contributing to chronic constipation, can contribute to visceral hyperalgesia or an oversensitive bowel. Prolonged use of narcotics, especially short-acting agents, causes a "soar and crash" effect where temporary pain relief leads to a more sensitive intestinal tract and thus greater pain and escalating narcotic use. Chronic abdominal pain that occurs in the setting of chronic narcotic use, with or without escalating doses, and providing no relief of the pain, is known as narcotic bowel syndrome (opioid-induced gastrointestinal hyperalgesia).[24] Symptoms of narcotic bowel syndrome may improve upon withdrawal of the opioid.[25]

6. Centrally mediated disorders of gastrointestinal pain

  • Centrally mediated abdominal pain syndrome (CAPS) is a functional GI disorder. It refers to conditions resulting from central nervous system sensitization with disinhibition of pain signals, rather than increased peripheral afferent excitability. Unlike irritable bowel syndrome and functional dyspepsia, pain associated with CAPS is reported to be constant and unrelated to peripheral events such as food intake or defecation.[25]

  • Narcotic bowel syndrome (opioid-induced GI hyperalgesia) symptoms may improve upon withdrawal of the opioid.[25]

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