Background and Summary: Chronic abdominal pain is a challenging complaint for both primary care providers and gastroenterologists alike, due to a broad differential diagnosis and sometimes extensive and negative workup. In the absence of red flag features that herald more acute conditions, the majority of patients with chronic abdominal pain have a benign cause or a functional disorder (e.g., irritable bowel syndrome). The costs associated with a diagnostic workup are an expensive burden to health care. A systematic approach for evaluating patients and initiating a management plan are recommended in the primary care setting. Undiagnosed abdominal pain should be investigated starting with a detailed history and physical examination. Diagnostic investigations should be limited and adapted according to the clinical features, the alarm symptoms, and the symptom severity. This review will focus on the diagnostic tools which general practitioners utilize in the evaluation of chronic abdominal pain. Key Messages: The primary role of the general practitioner is to differentiate an organic disease from a functional one, to refer to a specialist, or to provide treatment for the underlying cause of pain. The functional disorders should be considered after the organic pathology has been confidently excluded. Once a diagnosis of functional pain is established, repetitive testing is not recommended and the patient should be referred to receive psychological support (e.g., cognitive therapy) associated with available pharmacological therapeutic options.
Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” .
Chronic pain is defined as a constant or recurrent pain that lasts for 3 months or more [2, 3]. Chronic abdominal pain is mainly managed by general practitioners and it can be challenging, due to a broad differential diagnosis and extensive workup. A proportion of 24–35% of cases remain without a specific diagnosis following the primary care visit [4, 5]. It is also an expensive burden to health care because this condition is often misdiagnosed and many general practitioners are unfamiliar with how to approach the diagnosis in a cost-effective manner.
Many gastrointestinal and systemic disorders may cause abdominal pain (Table 1). The primary care physician must consider the myriad of disorders, and narrow down the differential diagnoses, and drive further diagnostic testing when appropriate. Initial workup should include a detailed history, a physical examination, and diagnostic investigations tailored to the clinical presentation. If there are any alarm symptoms, the patient should be referred to a specialist because these could suggest organic disease. However, many patients with organic conditions do not have any alarm symptoms [6, 7].
The leading causes of chronic abdominal pain are functional gastrointestinal disorders (FGIDs) or disorders of gut-brain interaction, such as functional dyspepsia (FD), irritable bowel syndrome (IBS), and centrally mediated abdominal pain syndrome (CAPS). These causes should be considered once organic pathology has been confidently excluded.
The aim of this review is to offer support to primary care physicians in a step-by-step investigation of the most common differential diagnoses, beginning with the key elements of the history and initial examination. Detailed patient history is vital for the differential diagnoses, especially as it informs a targeted physical examination, which can offer valuable clues regarding the etiology of the abdominal pain.
Abdominal pain is the most common gastrointestinal symptom and one of the leading causes for both inpatient and outpatient visits as a recent US review suggests. International cross-sectional data estimate its prevalence between 22 and 25%, with more women reporting abdominal pain than men (24 vs. 17%) [4, 8].
Most patients with abdominal pain in the US tend to seek care with their primary care physician (84%), while almost 40% see a gastroenterologist . Among the primary care visits, 10% account for acute abdominal pain, while in the case of subacute or chronic abdominal pain, the most common diagnosis (13% of visits) is IBS . A proportion of 24–35% of cases remain without a specific diagnosis following the primary care visit [4, 5].
Abdominal pain was found to be the second most common location (after back pain); around 19% of the Middle Eastern population were suffering from chronic pain . A meta-analysis of chronic pain in low- and middle-income countries estimated the prevalence of chronic abdominal pain at 17% of the general elderly population and found that chronic pain is specifically associated with the female gender, advanced age, multiple pain sites, mood and psychosomatic disorders and is predictive of increased health-care costs [12, 13].
As far as the general age distribution of patients with chronic abdominal pain is concerned, data from the UK state that almost a third of cases occur in people under 20 years old, with a steady decrease in prevalence toward the old age .
Overall, the leading causes of chronic abdominal pain are FGIDs or disorders of gut-brain interaction. According to the Rome Foundation Global Study, >40% of the global population meets the diagnosis criteria for at least one of the 22 syndromes comprised by FGIDs, and the most affected age-group is 18–39 .
The most common FGIDs responsible for chronic abdominal pain and their respective global prevalence are IBS (1–4%), FD (2–7%), functional constipation (7–11%), and unspecified bowel disorder (0–11%). A less frequent cause of FGID is CAPS (formerly known as functional abdominal pain syndrome [FAPS]). The prevalence of FAPS ranges between 0.5 and 1.7% and, similar to the general demographic distribution of FGIDs, is up to twice more frequent in women and in the 35–44 age-group [15, 16]. There is an increased geographic heterogeneity among FGID rates, but smoking was identified as a consistent risk factor for this group of diseases, which also shows an association with other chronic pain syndromes .
In addition to visceral and functional abdominal pain, an often overlooked etiology is chronic abdominal wall pain (CAWP), responsible for 2–3% of cases of chronic abdominal pain. The prevalence of CAWP can rise up to 30% in cases with no identifiable organic cause, and it is 4 times more frequent in women, peaking in incidence between ages 30–50. The most common etiology of CAWP is abdominal cutaneous nerve entrapment syndrome, accounting for 10–30% of cases of chronic abdominal pain [18, 19].
Chronic abdominal pain can arise from gastrointestinal disease and extraintestinal conditions involving the genitourinary tract, abdominal wall, thorax, and spine and often results in significant declines in function and quality of life.
According to the IASP taxonomy, chronic abdominal pain can be classified into abdominal wall pain, abdominal pain of visceral origin, abdominal pain syndromes of generalized diseases, and FGIDs (Table 1) .
Chronic abdominal pain can be roughly divided into visceral, somatosensory, and functional pain. While visceral pain typically originates from deep, internal abdominal structures, somatic pain originates from nociceptors in superficial tissues (i.e., skin) or the musculoskeletal system (i.e., bones, ligaments, and muscles) and functional pain relates primarily to visceral or central hypersensitivity .
Visceral pain is transmitted to the brain via vagal, thoracolumbar, and lumbosacral afferent nerves. Abdominal viscera receive dual innervation from the afferent and efferent system . Visceral receptors are located on the serosal surfaces, within the mesentery, and in the walls of hollow viscera. Their stimuli are primarily chemical, while visceral nociceptors are sensitive to inflammatory mediators and are activated by distension, pressure, and ischemia .
Chronic abdominal pain due to true visceral pain is diffuse and poorly localizable with marked accompanying neurovegetative symptoms: nausea, vomiting, sweating, and emotional reactions such as distress and anxiety. The pain intensity is not necessarily fully correlated with the severity of the disease (e.g., mild/no pain in colon cancer, severe pain when passing a stool in IBS), and it is not always linked to injury (functional disorders) . Chronic abdominal visceral pain may result from the following: (a) persistent inflammation (pancreatitis, cholecystitis, and inflammatory bowel disease); (b) vascular mechanisms: ischemia due to atherosclerosis or vasoconstriction (mesenteric ischemia); and (c) mechanical factors: obstruction of flow and distension of the organ (kidney stones and bile duct stones).
Chronic abdominal pain of musculoskeletal origin is sharp, localized to a small area (usually <2 cm), related to movement, and not correlated to eating and bowel function. Up to 10% of patients presenting chronic abdominal pain are diagnosed with CAWP, and it is most commonly caused by cutaneous nerve entrapment syndrome , which appears due to pressure from an intra- or extra-abdominal lesion, or a localized process such as fibrosis or edema . CAWP may also be caused by postsurgical pain, radiculopathy, diabetic neuropathy, or postherpetic neuralgia.
The leading causes of chronic abdominal pain are FGIDs or disorders of gut-brain interaction, such as FD, IBS, CAPS, and narcotic bowel syndrome. Extensive gastrointestinal evaluations often fail to show any organic cause. The pathogenesis of pain in FD and IBS is attributed to visceral hypersensitivity, through sensitization of peripheral afferent receptors or spinal dorsal horn neurons, alterations in descending modulation, or central amplification [23, 26]. However, pain in CAPS is characterized by a strong central component and is relatively correlated with motility disturbance or visceral hypersensitivity .
Clinical Presentation and Differential Diagnosis
The evaluation of chronic abdominal pain requires an understanding of the possible mechanisms liable for pain, a broad differential of common causes (Table 1), and the recognition of the typical patterns and clinical presentations.
The first step in managing a patient with chronic abdominal pain is to get a detailed history and the physical examination, even if these have a relatively low sensitivity and specificity in diagnosing the different causes of abdominal pain . The abdominal pain characteristics, such as site, radiation, onset, the evolution of time, character, exacerbating/ameliorating factors, associations, and severity (SOCRATES [mnemonics]) can offer clues to the diagnosis (Table 2). The site and radiation of abdominal pain helps narrow down the differential diagnosis because the pain syndromes typically have characteristic locations. Upper abdominal pain can arise from biliary, pancreatic, gastric, and duodenal pathology. Mid-abdominal pain can be caused by the small bowel (e.g., Crohn’s disease, celiac disease, partial small bowel obstruction, and chronic mesenteric ischemia). Lower abdominal pain arises from the colon (e.g., IBS and colitis), bladder, or reproductive organs. It is also important to establish the duration and the pattern of the pain (intermittent vs. constant) and the relationship to meals or bowel movements. Typically, the pain caused by peptic ulcer disease, chronic mesenteric ischemia, or biliary and pancreatic pathologies worsens after the meal, while in IBS pain is relieved with bowel movements. Chronic abdominal pain is defined as a constant or intermittent pain occurring for >3 months while acute abdominal pain is when the pain has been occurring for up to several days; subacute abdominal pain can span from several days up to 3 months . Intermittent pain can have many causes but constant abdominal pain results only from a few gastrointestinal etiologies, such as chronic pancreatitis, malignancy, abscess, and psychiatric causes. One should probe for coexisting symptoms such as nausea, vomiting, diarrhea, blood in stools and systemic symptoms such as fever or rash. It is also important to review the past medical history such as comorbidities and medication use, especially opiate, nonsteroidal anti-inflammatory drugs (NSAIDs) as it can also aid in gauging the cause of the abdominal pain.
The alarm symptoms or signs (termed red flags) (Table 3) such as fever, weight loss, night sweats, loss of appetite, or nocturnal awakening should never be overlooked because these could suggest organic disease. Many patients with organic disease do not have red flags .
An additional aspect to consider when taking the medical history of the patient with chronic abdominal pain is the biopsychosocial dimension of the disease. Environmental exposure and personal factors, such as genetic factors, early trauma, health care-seeking behaviors or abuse can be triggered by certain life events (infections, major loss, somatic illness, unresolved interpersonal difficulties, or substance abuse), resulting in the expression or heightening of bodily pain.
Known diagnoses of sickle cell trait or disease, familial Mediterranean fever, and porphyria should be ascertained.
A careful physical examination, including vital signs, detailed abdominal exam, and rectal examination, is the next stage, and it is important to clarify pain location and radiation patterns and to rule out significant pathology (organomegaly, masses, and acute abdomen). In the event of an acute episode of chronic abdominal pain, it is imperative to quickly rule out the possibility of a surgical abdomen.
A detailed physical examination is recommended, as it can provide useful clues of a systemic disease: lack of moist mucous membranes (dehydration); conjunctiva pallor (anemia); icteric sclera (hepatobiliary disease); dermatitis herpetiformis (celiac disease); erythema nodosum, pyoderma gangrenosum, and Sweet syndrome (inflammatory bowel disease); acanthosis nigricans (underlying malignancy); sunken eyes, prominent clavicles, and temporal wasting (significant weight loss); costovertebral angle tenderness (renal pathology); and vitamin deficiency .
A complete abdominal examination includes inspection, auscultation, percussion, palpation, and rectal examination. On inspection, the surgical scars should be noted. Identification of a bruit on auscultation may indicate chronic mesenteric ischemia. Light and deep palpation is useful to localize pain in a specific quadrant of the abdomen, to check for masses, ascites, hernias, and organomegaly and to observe the patient’s response to palpation as it can be helpful in differentiating functional from organic disease. A rectal examination can offer valuable information, such as active bleeding, mass, signs of constipation, pelvic floor dysfunction, or high anal resting tone .
The Carnett’s sign is useful to distinguish CAWP (e.g., somatic abdominal pain) from deeper visceral pain . The test has a diagnostic accuracy of more than 90% for chronic pain of the abdominal wall . The test is positive if the area of pain, which is usually quite small (≤2 cm), worsens with abdominal muscle contraction when we ask the patient to raise their head from the bed without using their arms.
Diagnostic Workup in a Primary Care Setting
We must keep in mind that not all abdominal pain is gastrointestinal in origin, and the workup of chronic abdominal pain should start with a detailed history and physical exam. Begin by determining if there are any alarm symptoms to refer to a specialist. If alarm symptoms are absent, proceed to the outpatient workup, shown in Figure 1 .
A tailored initial workup, careful consideration of clinical features, symptom severity, or alarm features, as well as prior therapeutic response, will allow the physician to limit unnecessary testing. Initial laboratory tests should include a full blood count, complete metabolic panel, serum lipase, C-reactive protein, and urinalysis. Other investigations should be based on individual patients, guided by the physician’s suspicion. Diagnostic imaging is often not needed in patients with chronic abdominal pain, but when imaging is indicated, ultrasound, computed tomography scan, or MRI (including magnetic resonance cholangiopancreatography) should be chosen depending on suspected etiologies. If the alarm features are absent, symptoms are usually sufficient to diagnose FGIDs.
Once the diagnosis of functional gastrointestinal disorder is made, it can further be categorized by the Rome IV criteria into FD (Table 4) , IBS (Table 5) , FAPS (Table 6) , and CAPS (Table 7) .
Main Aspects and Challenges of Abdominal Pain in the Elderly
The evaluation of the geriatric patients is often difficult because they wait much longer to seek medical attention and present with vague symptoms and have nonspecific findings on examination than younger patients, and also they have comorbidities and polypharmacy (e.g., β -blockers, steroids, NSAIDs, and opiates) which may alter their response to disease. The patient’s ability to provide a history is frequently compromised by normal age-related decline in hearing and vision and cognitive impairments. Vital sign abnormalities such as fever, hypotension, and tachycardia may be absent due to concomitant medications (e.g., β-blockers and NSAIDs).
The most frequent causes of chronic abdominal pain in geriatric patients are peptic ulcer disease, biliary colic (calculous or acalculous), diverticular disease, chronic mesenteric ischemia, and colon cancer. It is also important to consider extra-abdominal abnormalities that may manifest as abdominal pain: congestive heart failure, genitourinary complaints (e.g., pyelonephritis, prostatitis, neurogenic bladder, and uterine prolapse), Herpes zoster, depression, or somatization .
Elderly patients more often had specific organic disease compared to younger patients and require the use of computed tomography scanning, often with intravenous contrast. The physician should use the glomerular filtration rate instead of serum Cr because it can be falsely elevated due to decreased muscle mass and protein intake, both very common in the elderly .
Regarding the treatment, it is important to assess the risk-benefit ratios and to select dose appropriately analgesic medication according to renal and liver insufficiency, dementia and fall risk, and patient tolerance or intolerance of opiates .
Chronic abdominal pain is a challenging diagnosis that requires frequently an extensive workup to identify functional or organic conditions by avoiding excessive investigation. In general practice, a detailed history and a careful physical exam should narrow down the list of differential diagnoses and limit unnecessary testing. Laboratory, endoscopic, and imaging examinations should be recommended in a rational cost-efficient approach.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
The authors have no sources of funding to declare.
S.C.M. drafted and revised the manuscript. G.S. reviewed and revised the manuscript. Both G.S. and D.L.D. approved the final draft submitted.