Keywords

Case Study

A 50-year-old woman presents with a 2-year history of right upper quadrant pain. She describes it as constant and burning with no radiation. Exacerbating factors include sitting or lying on the right side, and she reports no alleviating factors. She denies any other gastrointestinal or systemic symptoms. She has a past medical history of hypertension and hyperlipidemia. She underwent cholecystectomy 3 years ago for biliary colic symptoms. Physical exam is notable for a scar in the right upper quadrant at the site of prior cholecystectomy. Palpation of the right upper quadrant elicits a focal area of tenderness that worsens when the patient is asked to raise both legs off the examination table. Prior laboratory tests, including complete blood count, electrolyte panel, liver biochemistries, and inflammatory markers, were all unremarkable. A right upper quadrant ultrasound and computed tomography abdomen performed within the last year were both normal without any abnormalities detected. She is becoming increasingly concerned and worried about her pain given its duration and the lack of a formal diagnosis. What is the most likely etiology of this patient’s abdominal pain, and how would you manage this patient?

Objectives

  • Categorize the broad differential diagnoses for chronic abdominal pain.

  • Define a stepwise approach to the work-up of a patient with chronic abdominal pain.

  • Review treatment options for unspecified chronic abdominal pain.

Epidemiology

Chronic abdominal pain is commonly encountered throughout medicine, especially in primary care and gastroenterology clinics. In fact, abdominal pain impacts close to 22% of the adult population, affecting slightly more women than men [1]. While there is no formal criterion regarding duration of symptoms that defines chronic abdominal pain, most experts agree that symptoms are generally present for at least 6 months [2, 3]. Chronic abdominal pain can affect patients of all age groups, ethnicities, and backgrounds, although women and those from lower socioeconomic groups are at higher risk. The symptoms can vary from one individual to another and range in intensity from mild with no associated morbidity to severe with major limitations in daily activities.

The disease course and prognosis are variable and depend on the underlying etiology. Functional disorders associated with abdominal pain, including functional dyspepsia and irritable bowel syndrome (IBS), are present in approximately one-fourth of the general population [4]. In patients with symptoms secondary to functional gastrointestinal disorders, approximately 40% had no further symptoms, 20% had the same symptoms, and 40% had different symptoms at 1-year follow-up [5]. A frequently overlooked cause of chronic idiopathic abdominal pain is abdominal wall pain, which accounts for up to 10% of such cases [6]. Chronic abdominal pain can present a diagnostic challenge for clinicians given the broad differential it encompasses and frustration for patients who often have a negative diagnostic work-up and high healthcare costs. Also, there can be an unawareness of exam maneuvers to make specific diagnoses, such as abdominal wall pain. Chronic pain accounts for increased healthcare utilization, with a total financial cost of approximately $600 billion annually, with a significant portion due to abdominal pain [7].

Etiology

Chronic abdominal pain has a wide array of underlying etiologies, including both organic and functional disorders. Organic disorders occur secondary to structural or physiologic causes, while functional disorders have no clear explanation.

The organic etiologies associated with chronic abdominal pain can be captured using a location-based approach, depending on whether the pain occurs predominantly in the right upper quadrant (RUQ), epigastric region, left upper quadrant (LUQ), or lower abdominal region (Fig. 11.1). The organs present in each of these regions help to narrow the differential diagnoses. Right upper quadrant pain is most commonly associated with liver, gallbladder, or biliary tree pathology. Epigastric and LUQ pain can occur secondary to disorders of the esophagus, stomach, duodenum, pancreas, or spleen. In particular, it is important to exclude cardiopulmonary causes of epigastric or LUQ pain, as these can potentially be life-threatening. For example, angina pectoris can have an atypical presentation in women, the elderly, and those with diabetes. Lower abdominal pain may occur secondary to disorders of the small or large intestine, appendix, or genitourinary system. In women, the ovaries and uterus may be responsible for lower abdominal pain, while scrotal or inguinal pathology can cause similar pain in men.

Figure 11.1
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A location-and character-based approach to etiologies of chronic abdominal pain. (Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved)

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Certain organic etiologies cannot be easily captured using a quadrant-based approach but, rather, can be considered using a character-based approach (focal vs. diffuse) (Fig. 11.1). Focal abdominal pain may occur secondary to musculoskeletal issues, nerve entrapment, or irritation of the parietal peritoneum. Diffuse abdominal pain has a broad differential and can occur secondary to inflammatory, ischemic, metabolic, neoplastic, or malabsorptive etiologies. In cases where the history, physical exam, and diagnostic testing reveal no obvious structural cause of abdominal pain, functional bowel disorders should be considered. The three most common functional disorders associated with abdominal pain include functional dyspepsia, IBS (constipation-predominant, diarrhea-predominant, and mixed-pattern subtypes), and functional abdominal pain syndrome [4]. New developments in our understanding of visceral and central pain led the Rome IV committee to change the term functional abdominal pain syndrome to centrally mediated abdominal pain syndrome (CAP), reflecting the importance of glial and nerve cells [3]. Other common functional bowel disorders include functional constipation, functional diarrhea, functional abdominal bloating, narcotic bowel syndrome, and opioid-induced constipation [8].

Pathophysiology

The pathophysiology of disorders that result in chronic abdominal pain is extensive and wide-ranging. Inflammation can occur throughout the gastrointestinal tract and can present with chronic abdominal pain. Examples of inflammatory conditions include esophagitis due to gastroesophageal reflux disease (GERD), gastritis due to nonsteroidal anti-inflammatory drug (NSAID) use or Helicobacter pylori infection, eosinophilic gastroenteritis, chronic pancreatitis due to alcohol abuse, and enteritis or colitis due to inflammatory bowel disease (IBD). The gut microbiome plays a fundamental role in metabolism and immunity, and alterations in gut flora may play a part in various gastrointestinal disorders, including inflammatory conditions, malignancy, and functional bowel disorders [9,10,11,12]. Additionally, small intestinal bacterial overgrowth can occur when the normal enteric flora is disrupted, often due to reduced gastric acid production, altered small bowel anatomy, or small intestinal dysmotility [13]. Ischemia occurs when the blood flow to an organ becomes reduced, and patients with mesenteric ischemia are classically elderly with cardiovascular disease, or may occur in those with underlying thromboembolic or hypercoagulable conditions. Chronic mesenteric ischemia presents with postprandial pain, sitophobia, and weight loss and occurs when atherosclerosis is present in at least two of the three mesenteric vessels (celiac artery, superior mesenteric artery, and inferior mesenteric artery) [14]. Mechanical obstruction of the alimentary system, biliary tree, and urinary tract classically presents with acute abdominal pain; however, partial or intermittent obstruction can result in chronic or recurrent symptoms. Similarly, while perforation of gastrointestinal organs such as the stomach, small bowel, or colon typically presents with peritonitis and acute abdominal pain, smaller perforations may heal spontaneously and present with late complications, such as abscesses and fistulae. Medications can result in inflammation and injury (e.g., NSAIDs, bisphosphonates, doxycycline), altered bowel motility with constipation (e.g., opioids, antihistamines, calcium, iron supplements) or diarrhea (e.g., metformin, selective serotonin reuptake inhibitors, proton pump inhibitors, magnesium), and visceral hyperalgesia (opioids). Functional gastrointestinal disorders can be explained using a biopsychosocial model, which includes genetic predisposition, psychological factors, gastrointestinal dysfunction, and central sensitization due to alterations in the brain-gut axis [4].

Symptoms

Chronic abdominal pain is often a nonspecific complaint that can involve discomfort anywhere from the lower chest to the pelvis. The quality, description, location, and radiation of the pain depend on the organ system(s) involved. While patients with chronic abdominal pain may present with isolated abdominal pain, they may also have other concomitant symptoms (Table 11.1). In patients with multiple symptoms, it is important to elucidate the most distressing symptom through a careful history, review of systems, and physical exam. Identifying the primary symptom can provide useful clues to the underlying diagnosis.

Table 11.1 Symptoms to assess in patients presenting with chronic abdominal pain
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Cardiopulmonary causes (e.g., ischemia, pericarditis, pulmonary embolus) must be strongly considered and ruled out if chest pain and shortness of breath are present, especially if these are exertional or inspirational in nature. Alarm features suggestive of a serious underlying issue include fevers, unintentional weight loss, anemia, dysphagia, persistent vomiting, sudden change in bowel habits, hematemesis, melena, hematochezia, or a family history of gastrointestinal cancer. In particular, unintentional weight loss, especially greater than 10% of ideal body weight, should raise the suspicion for malignancy, particularly in elderly patients.

In many patients, abdominal pain can be associated with constipation or diarrhea. The Bristol stool form scale can help provide useful information regarding stool form and consistency [15]. Other patients may complain of bloating or a sensation of increased abdominal pressure with or without visible distention [16]. Heartburn, regurgitation, nausea, and chronic cough may be suggestive of GERD. Melena or black, tarry stool is indicative of an upper gastrointestinal bleed and may be a clue to peptic ulcer disease in the patient presenting with epigastric pain, while hematochezia is more typical of lower gastrointestinal bleeding and may occur in those with abdominal pain due to ischemia or inflammation. Hepatomegaly, jaundice, scleral icterus, clay-colored stools, and tea-colored urine are suggestive of hepatobiliary or pancreatic pathology. Genitourinary disorders should be suspected in patients with dysuria, increased urinary frequency, hematuria, nocturia, or pain in the suprapubic, testicular, or flank regions. Patients with coexisting depression and anxiety are more likely to have a functional disorder compared to the normal population.

Diagnostic Evaluation

The diagnostic evaluation of a patient with chronic abdominal pain begins with a thorough history and comprehensive physical exam (Table 11.2). The history should focus on eliciting the pain description, quality, location, radiation, and intensity, along with exacerbating and alleviating factors. An exhaustive review of systems should be performed to identify concomitant symptoms (Table 11.1) as these may provide clues to the underlying diagnosis. The past medical, family, and social history can be useful in identifying risk factors for certain disorders. Given the chronicity of the pain, the clinician should review prior laboratory and imaging studies along with previous procedures in order to understand the work-up to date and to avoid repeating tests when possible. The physical exam should include a complete abdominal and rectal exam. While auscultating for bowel sounds, gentle pressure may be applied to the stethoscope; classically, abdominal tenderness lessens in patients with functional bowel disorders when they become distracted, while the pain may worsen in those with structural bowel disorders. Carnett’s sign (Fig. 11.2), a clinical test that can help identify abdominal wall pain, should be routinely performed in patients presenting with chronic abdominal pain that is focal in nature [17]. The remainder of the physical exam should be guided by the patient’s history.

Table 11.2 Important history and physical exam elements to obtain in a patient presenting with chronic abdominal pain
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Figure 11.2
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Carnett’s sign can help identify abdominal wall pain. Step 1: The clinician identifies and palpates the point of maximal abdominal tenderness (resting supine position). Step 2: The patient raises both legs off the examination table (tense position) while the clinician palpates the abdomen. Alternatively, the patient can raise their head and shoulders off the bed, tensing the abdominal wall. Positive Carnett’s sign: Palpation of abdominal muscles in the tense position elicits the same or more tenderness as the rest position → musculoskeletal source (abdominal wall pain). (Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved)

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The next step in the evaluation of chronic abdominal pain consists of obtaining standard laboratory tests, as indicated (Fig. 11.2). For most patients, this may include some or all of the following: complete blood count, electrolyte panel, calcium, creatinine, liver biochemistries, lipase, C-reactive protein, and thyroid-stimulating hormone. IgA-tissue transglutaminase antibody should be considered in those with bloating, diarrhea, weight loss, or other manifestations of celiac disease. In women who are sexually active and of childbearing age, pregnancy should be ruled out. Patients younger than 60 years of age with dyspepsia and without alarm symptoms should be evaluated for H. pylori infection with a stool antigen or breath test [18]. In patients with microcytic anemia, iron studies including iron, total iron binding capacity, and ferritin should be obtained. If IBD is suspected, fecal calprotectin may be helpful; the prevalence of IBD is less than 1% when the C-reactive protein and fecal calprotectin are low [4]. Patients with abdominal pain associated with nausea, hypotension, skin hyperpigmentation, hyponatremia, or hyperkalemia should have a morning cortisol level checked to rule out adrenal insufficiency. Additional laboratory testing should be guided by the history and physical exam.

If the testing above reveals an underlying etiology for the patient’s symptoms, disease specific medical management should be initiated. However, if no underlying etiology is identified, patients should be stratified into low-risk and high-risk categories based on age and alarm features. Patients less than 60 years of age and without alarm features may be considered low-risk and should be offered empiric pharmacotherapy and/or psycho-behavioral therapy based on their principal symptom. Many low-risk patients may have a functional etiology of their chronic abdominal pain. Patients aged 60 years and older or with alarm features are more likely to have organic disease and may require additional evaluation. For both low-risk and high-risk patients, close follow-up is necessary to verify the diagnosis and assess treatment response.

Ultrasound is the imaging modality of choice for RUQ pain to exclude gallstone-related disorders or biliary obstruction; Doppler evaluation can be added to assess the portal, hepatic, and mesenteric veins, as indicated [19]. A computed tomography of the abdomen (with or without pelvis) is the imaging modality of choice for evaluation of mid, diffuse, or lower abdominal pain when the diagnosis is unclear from the history, physical exam, and laboratory results. Oral contrast is used for bowel visualization, while IV contrast is used for visualization of vascular structures and solid organs [20]. In a pregnant patient, ultrasound and magnetic resonance imaging are the modalities of choice to minimize ionizing radiation exposure. An esophagogastroduodenoscopy should be performed when a patient presents with epigastric pain, heartburn, nausea/vomiting, dysphagia, or features of upper GI bleeding, to allow for visualization of the esophagus, stomach, and duodenum. A colonoscopy may provide useful diagnostic information in the evaluation of chronic abdominal pain in the presence of lower GI bleeding, iron-deficiency anemia, chronic diarrhea, or new-onset constipation and should be offered to all patients who are due for colorectal cancer screening or surveillance [21].

Treatment

An effective patient-physician interaction is essential in the management of patients with chronic abdominal pain. Given the chronicity of symptoms, many patients are frustrated and unsatisfied with their health and healthcare providers. Therefore, it is essential to build a strong rapport with these patients in order to gain their trust and develop a therapeutic relationship. This not only improves compliance with recommended tests and treatments but also improves outcomes and patient satisfaction. Clinicians should approach patients with empathy and listen to their symptoms carefully. Even when a prior evaluation has been unrevealing or other providers have dismissed patient symptoms as functional or patients believe their abdominal pain is “all in their head,” clinicians should be systematic in their approach to avoid anchoring bias [22]. Instead, a diagnostic algorithm, as outlined in Fig. 11.3, should be followed.

Figure 11.3
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Diagnostic algorithm to evaluate patients with chronic abdominal pain

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The treatment of chronic abdominal pain also depends on whether an underlying etiology is found. When a specific cause is identified, it should be treated using standard medical management. For example, if a patient is found to have celiac disease, a gluten-free diet should be instituted. Similarly, if a patient is found to have H. pylori infection, she should be treated with appropriate therapy, and testing should be performed to confirm eradication [18]. Those with classic biliary colic or gallstone-related complications usually benefit from cholecystectomy. A trigger point injection may offer effective pain control for patients with abdominal wall pain [23].

If no underlying etiology can be identified, patients can be treated empirically with pharmacotherapy and/or psycho-behavioral counseling based on their principal symptom. Patients may benefit from dietary and medication modifications if these factors are felt to be causally related to the pain. Over-the-counter medications tailed to patient symptoms can be initiated (Table 11.3). Prescription medications, such as tricyclic antidepressants or other neuromodulating agents, may be required and can be used in conjunction with behavioral and/or psychological therapies, if necessary [4]. In general, serotonin-norepinephrine reuptake inhibitors are more effective than selective serotonin reuptake inhibitors for the treatment of chronic visceral pain [24]. Cognitive behavioral therapy (CBT) helps patients identify maladaptive thoughts and behaviors and is the most effective psychological therapy for functional abdominal pain [4]. Continued and escalating doses of opioids can lead to worsening abdominal pain and should be avoided. In refractory cases, a multidisciplinary pain management program that combines physical therapy, occupational therapy, and CBT can prove useful [4].

Table 11.3 Treatment of unspecified chronic abdominal pain
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Case Study: Follow-Up

This patient’s chronic abdominal pain was secondary to abdominal wall pain. As with our patient, other patients with abdominal wall pain may not have any abnormalities on laboratory or imaging studies. This diagnosis is primarily based on the physical exam, specifically Carnett’s sign. With this examination technique, the clinician first palpates the area of maximal abdominal tenderness with the patient lying supine and relaxing the abdominal wall. The patient is then asked to lift both legs off the examination table or raise their upper torso in an “abdominal crunch,” with both maneuvers designed to tense the abdominal wall muscles. Carnett’s sign is considered positive when there is increased tenderness to palpation with tensing of the abdominal wall muscles and is strongly suggestive of abdominal wall pain. In contrast, those with visceral abdominal pain have amelioration of their abdominal tenderness as the tensed musculature protects the abdominal viscera. The positive and negative likelihood ratios for Carnett’s sign in the diagnosis of abdominal wall pain are 2.62 and 0.23, respectively [25]. This patient underwent a right upper quadrant trigger point injection with 2 ml of 1% lidocaine and 0.5 ml of betamethasone at the site of maximal tenderness, with dramatic improvement in her pain. At a follow-up visit 6 months later, she remained free of pain.

Clinical Pearls

  • The diagnostic evaluation of a patient with chronic abdominal pain requires a thorough history, comprehensive physical exam, and individualized laboratory testing.

  • If the diagnostic evaluation does not reveal an underlying etiology, patients should be stratified into low-risk and high-risk categories based on age and alarm symptoms.

  • Carnett’s sign is a physical exam maneuver that can identify abdominal wall pain and should be routinely performed in the evaluation of patients with focal chronic abdominal pain.

  • Low-risk patients (age <60 years and without alarm symptoms) may be treated empirically with pharmacotherapy and/or psycho-behavioral therapy based on their principal underlying symptom, whereas high-risk patients (age ≥60 years or with alarm features) may require additional evaluation prior to treatment.