Differential Diagnosis of Flank Pain

Emerg Med 36(12):18-28, 2004

The authors discuss presenting characteristics in abdominal aortic aneurysm, renal infarction, urolithiasis, pyelonephritis, renal abscess, renal vein thrombosis, herpes zoster, neuromuscular conditions, and other problems that may cause flank pain.

By Kriti Bhatia, MD, and David F. M. Brown, MD, FACEP

Flank pain is a common and potentially complex patient complaint that may be caused by renal and extrarenal etiologies resulting in similar clinical presentations. Although they cause discomfort, many of the common causes of flank pain, such as nephrolithiasis, are relatively benign. In these cases, conservative management that provides patients with adequate pain control is often appropriate. However, there are a number of more serious processes that require immediate diagnosis, management, and treatment. These diseases and conditions, if not recognized in a timely fashion, may lead to morbidity or mortality. For this reason, the clinician evaluating flank pain must have a thorough understanding of the range of etiologies and must be able to recognize risk factors that suggest a diagnosis requiring prompt attention.
 

INITIAL PATIENT ASSESSMENT

Initial assessment of the patient with flank pain requires a detailed medical history, a focused physical examination, and appropriate diagnostic tests. The clinician must consider urinary tract disorders, vascular disease, gastrointestinal processes, obstetric or gynecologic conditions, pulmonary illnesses, musculoskeletal problems, dermatologic entities, and neurologic pathology in the differential diagnosis.

Certain factors influence the differential diagnosis. The patient's age is an example. A 75-year-old woman with flank pain would be more likely to have a vascular etiology than a gynecologic one. Hypertension is another risk factor for vascular causes of flank pain because it increases the likelihood of symptomatic aortic aneurysm.

A thorough review of systems may offer insight into the underlying cause. Hematuria suggests a urinary tract stone or infection. Numbness or tingling radiating down the leg raises concern for a neurologic process. Constipation or diarrhea should lead to consideration of gastrointestinal entities. A missed menstrual period in a woman of reproductive age raises the suspicion of an ectopic pregnancy.

The patient should be asked to describe the quality, location, duration, and radiation of the pain. Pain caused by a renal calculus is typically described as colicky, and the patient is usually unable to find a comfortable position. However, the pain may also be constant. Unruptured abdominal aortic aneurysms may cause a vague, dull pain; however, the pain has also been described as constant, throbbing, colicky, or sharp. Pain from an aortic dissection is typically described as most severe at onset and sharp in quality. Pyelonephritis generally causes pain that is achy, while herpes zoster often causes moderately severe burning pain.

Flank tenderness is most likely to be elicited with an underlying renal, musculoskeletal, or dermatologic process. Aortic pathology rarely causes flank tenderness. Gastrointestinal conditions, such as cholecystitis, often cause right upper quadrant tenderness. Similarly, gynecologic processes such as large, ruptured, or torsed ovarian cysts are more likely to produce lower abdominal tenderness than flank tenderness. Other physical diagnostic tools such as a neurologic examination and a rectal examination may help elucidate the cause of the patient's flank pain. For example, a positive straight leg test is indicative of sciatica.

Flank pain duration at the time of presentation is also an important factor in formulating a differential diagnosis for a patient. Some disease processes typically present in the acute phase, whereas others are more chronic. For example, sudden-onset sharp pain that began shortly before presentation is consistent with aortic dissection. Pain that increases with movement and has been present for several days is more suspicious for musculoskeletal causes.

We will now review various causes of flank pain that may need to be considered in the differential diagnosis.

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ABDOMINAL AORTIC ANEURYSM

Abdominal aortic aneurysms (AAAs) are caused by focal dilation of the aortic wall with a resultant increase in the aorta's diameter of at least 50%. Classically, the cause of AAAs has been attributed to a weakening of the arterial wall by atherosclerotic disease. However, recent evidence implicates other cofactors including age-related changes, inflammation, proteolysis, and a genetic predisposition. The condition is present in approximately 4% of individuals over age 70, and it accounts for 15,000 deaths per year in the United States. However, because patients are usually asymptomatic, the true prevalence is likely higher.

Risk factors for AAA include male gender, age over 65, family history of AAA, cigarette smoking, atherosclerosis, hypertension, and chronic obstructive pulmonary disease. The condition is more common in white males than in black males. This finding is thought to be multifactorial: better access to health care for white males, genetic predisposition, and environmental exposures probably all play a role. Interestingly, other diseases resulting from atherosclerosis do not follow this same racial pattern.

As an aneurysm enlarges, the risk of rupture increases. Aneurysms smaller than 4 cm in diameter have a five-year rupture risk of 2%, whereas aneurysms larger than 5 cm have a rupture risk of more than 25%. Larger aneurysms expand more rapidly than smaller ones. Though unruptured aneurysms are most often asymptomatic, patients may complain of vague abdominal or flank pain. Survival after elective repair of an AAA is much better than survival after emergent surgery for rupture. Therefore, AAA should always be considered in patients at risk for this condition.

The presentation of AAA is variable and sometimes vague. Patients may complain of hip pain, urinary urgency, tenesmus, nausea, and vomiting. Rarely, AAA presents as chronic contained ruptures with blood loss limited by thrombus. Pain is caused by the inflammatory response and may continue for a significant length of time.

Palpation of a pulsatile mass on abdominal examination is indicative of AAA. Recent studies show that physical examination by physicians is very accurate in the detection or exclusion of clinically significant AAA. However, this finding did not take into account the patient's body habitus.

Calcification of the abdominal aortic wall is often seen incidentally on plain radiographs of the abdomen. These are most easily visualized on lateral views. The visualization of both opposing walls of the aorta is useful to distinguish the presence of AAA from a tortuous, calcified aorta with a normal diameter. Thus, unless the opposing walls are both calcified, this diagnosis cannot be made definitively using plain films. Even when the above criteria are met, a confirmatory imaging test is generally indicated.

Ultrasound is convenient, does not expose the patient to radiation, is relatively inexpensive, and is readily available for many physicians. The abdominal aorta tapers distally. Any increase in its diameter is pathologic (see image, below). The larger the aneurysm, the greater the sensitivity of ultrasound in detecting it. If the abdominal aorta can be seen in its entirety, ultrasound does provide a reliable, low-cost screening test in the appropriate setting, such as a stable patient with the incidental discovery of a pulsatile mass on an abdominal exam in his primary care physician's office. Detection of AAA by ultrasound is limited by large body habitus, interposed bowel gas, and operator skill.

Transverse abdominal sonogram showing a 7-cm AAA.

Computed tomography (CT) has emerged as the diagnostic imaging modality of choice for AAA, with an accuracy approaching 100%. This test allows for aneurysm identification and delineates relevant anatomy, facilitating an appropriate treatment plan. It is also helpful in identifying leakage and other processes that may cause flank pain. An IV contrast-enhanced study is necessary to obtain details; however, a non-contrast study will accurately confirm AAA (see image, below).

Non-contrast abdominal CT scan showing ruptured 8-cm AAA (short arrow) with right retroperitoneal bleeding (long arrows).

Once an AAA has been identified, appropriate management is determined by the aneurysm size and extent and the patient's symptoms. Prompt repair of AAA is indicated in the following situations: documented or suspected rupture; a rapidly expanding aneurysm, regardless of size; an aneurysm with concomitant embolic or thrombotic disease; and atypical aneurysms, such as dissecting, mycotic, or thrombotic disease. Patients with symptomatic disease who do not meet the above criteria must be admitted for close observation, with a very low threshold for immediate repair.

Endovascular repair, such as stent-graft placement, is emerging as an alternative to conventional open surgical repair for infrarenal aneurysms. The factors that determine suitability for endovascular repair are the diameter and length of the proximal neck of the aneurysm, the tortuosity of the aorta, and the anatomy of the iliac arteries. If the angle between the aneurysmal neck and the aorta is too great, the graft may be displaced from its position with resultant leakage. Tortuosity of the iliac arteries can prevent proper advancement of the stent or opposition of the stent against the arterial wall. In the proper patient, however, this technique can be extremely successful.

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RENAL INFARCTION

The most common disorder involving the renal arteries is atherosclerotic narrowing. Resultant renal infarctions can be caused by embolism from mural thrombi or atheroembolism, fat or tumor emboli, trauma, and dissecting lesions, among other etiologies. Patients may present with colicky or constant pain; in either case, the pain is severe. Hypoperfusion is classically asymptomatic but results in sustained hypertension. Complete occlusions typically cause aching pain that is commonly associated with fever, nausea, and vomiting. Flank tenderness may be present. Gross or microscopic hematuria is present in less than one-third of cases.

Laboratory evaluation may be significant for elevated plasma lactose dehydrogenase without an increase in hepatic transaminase. However, this finding is not always present. Diagnosis is by renal arteriography or spiral CT with intravenous (IV) contrast (see image, below).

Contrast-enhanced abdominal CT scan showing a wedge-shaped hypodense left renal infarction (white arrow).

Occlusion of the renal artery for more than two hours usually results in infarction. The normal kidney typically loses viability after 90 to 180 minutes of ischemia. Thrombolytic therapy alone is usually effective in restoring renal function if the occlusion is incomplete or thrombolysis is performed within the stipulated timeframe. In patients without a contraindication, intra-arterial injection of urokinase or streptokinase may be considered. Surgery is necessary for patients with traumatic renal artery thrombosis.
 

UROLITHIASIS

The most common cause of persistent flank pain of sudden onset is urolithiasis. Up to 12% of the adult population suffers from urolithiasis at some point during their lives. A family history of kidney stones doubles the risk. Caucasians are twice as likely as African Americans to develop stones. The male-to-female ratio is 2:1.

Although kidney stones occur in people of all ages, peak incidence is in the third to fifth decades of life. There is a higher incidence in people living in the southeastern United States. People who lead relatively sedentary lifestyles are more prone to stones. Numerous disease processes such as Crohn's disease, sarcoidosis, milk-alkali syndrome, peptic ulcer disease, hyperparathyroidism, and renal tubular acidosis type I increase the likelihood of stone development. Various drugs, such as diuretics and the protease inhibitor indinavir sulfate, also predispose to urolithiasis.

About 75% of renal stones contain calcium oxalate alone or in combination with calcium phosphate. Hyperexcretion of calcium secondary to increased intake is a major contributor to the formation of such stones. Approximately 15% of renal calculi are magnesium-ammonium-phosphate (struvite) stones. They occur almost exclusively in patients with urinary tract infections caused by urea-splitting organisms such as Proteus, Klebsiella, Pseudomonas, and Staphylococcus.

Patients classically present with sudden-onset flank pain, often radiating to the ipsilateral abdomen and groin. Men may complain of testicular pain and women of labial discomfort. The pain is caused by distension of the renal pelvis and upper ureter as well as by peristalsis of the ureter. Patients are usually writhing in pain, unable to find a comfortable position. Nausea and vomiting are common.

An accompanying fever is strongly suggestive of a superimposed infection. In this situation, a urologist should be called immediately and IV antibiotics administered expediently. Laboratory tests to evaluate renal function should be ordered and an imaging study to evaluate the size and location of the stone should be obtained. Flank tenderness can be elicited; however, abdominal and genital examinations are generally normal. One-third of patients have gross hematuria, but up to 15% of patients with urolithiasis have neither gross nor microscopic hematuria.

Approximately 90% of renal stones are radiopaque and therefore are potentially visible on plain films of the abdomen or the kidney, ureter, and bladder (KUB). However, small stones may not be visualized and overlying bowel gas, stool, soft tissue, or bone may prevent detection of stones as well. Non-urologic calcifications such as phleboliths, vascular calcifications, mesenteric lymph nodes, undigested pill fragments, or gallstones may also appear on a KUB radiograph and may be confused with uroliths. Although the KUB is readily available and cheap, its low sensitivity and specificity mandate the need for more definitive imaging. The best role for the KUB is as a tracking measure to detect stone migration in already-established cases; thus, it does not usually have a significant role in the acute setting.

Ultrasound is fast, easy, and safe but of limited value in the initial work-up of a patient with suspected renal colic. Stones smaller than 5 mm are usually not detected using this modality. Ureteral stones are difficult to identify, regardless of size, except occasionally at the ureteropelvic junction. Renal ultrasound is most useful in detecting unilateral hydronephrosis (see image, below), an important secondary sign of ureterolithiasis, and large stones within the renal pelvis or kidney. Ultrasound is the study of choice for pregnant patients because the fetus is not exposed to radiation. Pregnancy is associated with a physiologic hydronephrosis; therefore, ultrasound findings may be inconclusive or falsely positive for obstructive pathology.

Right renal ultrasound showing marked hydronephrosis.

Other potential causes of false positive results include normal variations, an extrarenal pelvis, a full bladder, and renal cysts. Additionally, a rapid bolus of IV fluid, which is usually given to patients suspected of having renal colic, may yield a false positive reading.

For many decades, IV pyelography was used to detect urolithiasis. In addition to providing excellent anatomic detail, this test assesses renal excretory function. The main drawbacks are the need for IV contrast and the length of time it takes to complete the study.

Non-contrast-enhanced spiral CT scan has emerged as the study of choice for diagnosing urolithiasis (see image, below). It allows for identification of calculi anywhere in the urinary system as well as resultant hydronephrosis. It also provides information about other anatomic structures, which is especially beneficial if the cause of flank pain does not turn out to be urolithiasis. Spiral CT is rapid and easy to obtain in most institutions. The main disadvantages are its expense and its inability to provide assessment of renal function.

Unenhanced spiral CT scan showing a small stone in the right ureter (white arrow).

Appropriate pain control is the mainstay of treatment for patients with urolithiasis. Narcotics, usually morphine or meperidine, are given in repeated doses. The recommended morphine dose is a 0.1 mg/kg bolus that should be titrated to effect. Although they control pain, narcotics do not target the cause of that pain. Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID) available for injection, inhibits the prostaglandin synthesis pathways that cause not only peristalsis of the ureter but also sensitization of nociceptors to stimuli such as bradykinin. It decreases pain by minimizing ureterospasm and renal capsular pressure.

Ketorolac tromethamine should be administered with caution to elderly and diabetic patients in order to prevent a decline in renal function. For elderly patients, a decreased dose of 15 mg is recommended. It is also relatively contraindicated in patients with a history of gastrointestinal bleeding or cardiovascular disease. Antiemetics should be administered as necessary, as well as IV fluids if the patient is dehydrated. If urinalysis reveals concomitant infection, early administration of antibiotics and a urology consultation are indicated.

It is impossible to conclusively predict which stones will pass spontaneously and which will continue to be problematic for the patient and require intervention. Factors that play a role include the shape, orientation, and location of the stone as well as the patient's anatomy. Generally, smaller stones are more likely to pass. Stones that are 2 mm or less in size have a 90% chance of spontaneous passage, while those that are 3 to 7 mm in size have only a 50% chance. Stones larger than 8 mm always require procedural intervention. Other patients who require prompt consultation with a urologist are those with intractable pain or vomiting, renal failure, underlying kidney disease, only one kidney, renal transplant, or severe obstruction.

Urosepsis in a patient with an obstructing stone is a true emergency. These patients must be admitted and treated with IV antibiotics and fluids and early drainage of the involved kidney by a urologist. Patients whose pain and nausea are controlled with oral medications and whose stones are likely to pass are candidates for discharge with instructions to strain their urine, return for evaluation for symptoms such as decreased urine output, increasing pain, fevers, chills, and vomiting, and an early follow-up appointment.

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PYELONEPHRITIS

Pyelonephritis, a common cause of flank pain, occurs when bacteria ascend from the lower urinary tract into the renal parenchyma. The discomfort associated with pyelonephritis is classically achy, dull, and constant. Patients commonly complain of body aches, fever, chills, malaise, nausea, vomiting, and headaches. Suprapubic pain with dysuria and urinary frequency and urgency also occur. Patients often appear ill. On physical examination, suprapubic and flank tenderness is frequently elicited.

Before age 40, pyelonephritis affects females more often than males. After age 40, the ratio evens out. Risk factors include urinary tract instrumentation, anatomical abnormalities (such as strictures), neurologic conditions resulting in urinary stasis (such as neurogenic bladder), immunosuppressed status, diabetes mellitus, pregnancy, and infection with a multi-drug-resistant organism.

Pyuria and, often, hematuria are present. Laboratory tests are not mandatory, although many physicians order a complete blood count to determine the white blood cell count and a chemistry panel to assess renal function. Several studies demonstrate that positive blood cultures correlate with urine culture results. Positive blood cultures do not correlate with more severe disease, however, and thus they should not be routinely ordered. A helical CT scan may be obtained if the diagnosis is unclear, there is suspicion of obstruction, or there is concern about renal abscess or emphysema.

Severe pain, decreased urine output, elevated renal function, or risk factors such as immunosuppresion should increase suspicion for pyelonephritis. The most frequent causative organisms are Escherichia coli, Klebsiella and Proteus species, Enterococcus, and Staphylococcus saprophyticus.

The mainstay of treatment is antibiotic therapy. Parenteral antibiotics are indicated for very young or very old patients, concomitant urinary obstruction, pregnancy, immunosuppression, failure of oral antibiotic therapy, toxic-appearing patients, and suspected antibiotic-resistant organisms based on previous culture data. Intravenous fluids, analgesics, and antiemetics should be administered as needed. Patients who are toxic-appearing, have unstable vital signs, are unable to complete oral therapy, are pregnant, have obstructive disease or anatomic abnormalities, are immunosuppressed, have an abscess, or are very young or very old should be admitted to the hospital.
 

RENAL ABSCESS

Renal abscesses may cause intense flank pain. Corticomedullary abscesses are typically caused by an ascending urinary infection. There is often an associated anatomic or functional abnormality such as vesicoureteral reflux. The most common pathogen for this condition is E. coli.

Cortical renal abscesses usually result from hematogenous spread of a distant primary infection. The most common causative organism is Staphylococcus aureus. Patients present with flank pain, fever and chills, and occasionally a palpable flank mass. Examination may be notable for crackles or decreased breath sounds over the ipsilateral hemithorax as a result of diaphragmatic irritation. In fact, chest X-rays may reveal a pleural effusion or elevated diaphragm. Treatment includes IV antibiotics, analgesics, and abscess drainage.
 

RENAL VEIN THROMBOSIS

Renal vein thrombosis (RVT), a very rare condition, may occur in both infants and adults. It is very difficult to determine the incidence of this condition because patients are often asymptomatic. About 75% of pediatric cases occur in the first month of life. In children, this process usually occurs after an episode of extreme dehydration. A history of a dehydrating illness, along with signs of dehydration, hematuria, and elevated renal function tests, should raise suspicion for this condition in children.

Adults may develop RVT as a result of trauma, steroid use, invading renal tumors, and renal tubular diseases. Oral contraceptive use is a risk factor, and patients with the nephritic syndrome are at increased risk. Many adults with RVT are asymptomatic. Those with acute onset present with flank pain, fever, hematuria, oliguria, and sometimes frank renal failure. Renal insufficiency and proteinuria are the usual signs of gradual-onset RVT.

Imaging options include renal venography, CT scan, and magnetic resonance imaging (MRI). Ultrasound is not sensitive enough to routinely aid in the diagnosis, although the addition of Doppler imaging improves the yield. A KUB may show an increased renal shadow; however, it offers no additional information.

The goals of treatment are to prevent propagation of the clot, which may result in pulmonary embolism and recurrent clot. Once the condition is diagnosed, anticoagulants should be started. Thrombolytic therapy may be considered in patients with bilateral RVT, acute renal failure, a massive clot with high risk of acute embolic events, pulmonary emboli, propagation of the clot despite heparin therapy, or severe flank pain. Most patients with RVT do not have permanent renal damage.
 

HERPES ZOSTER

Herpes zoster causes a burning or stabbing pain, usually in a band-like, dermatomal distribution around the flank to the abdomen. The pain often begins prior to eruption of vesicles and can last for weeks after resolution of the rash. Fever and lymphadenopathy may be present. The condition occurs more commonly in adults than children. Antiviral therapy is indicated, especially if it can be initiated in the first 48 hours after the onset of symptoms. Options include acyclovir 800 mg five times a day and valcyclovir 1000 mg three times a day. In addition, pain medications should be prescribed.

Older patients usually have a more severe course and are more prone to develop postherpetic neuralgia. Patients with postherpetic neuralgia have an increased incidence of depression; their complaints are often mistaken for drug-seeking behavior and their constant pain frequently causes social isolation.
 

RADICULAR AND MUSCULAR PAIN

About 98% of disk herniations involve the disk at either L4-L5 or L5-S1. Dull back pain usually precedes radicular symptoms, which result from nerve root compression. Herniated disks can be clinically diagnosed by identifying the involved nerve root and detecting corresponding neurologic symptoms. An MRI is the imaging modality of choice for patients with neurologic dysfunction or severe symptoms. The goal of treatment is to achieve adequate anesthesia. Patients with motor symptoms should be referred to a spine surgeon for possible intervention.

Muscular strain can cause dull, aching discomfort in the thoracolumbar region that may radiate to the buttocks or thigh. Patients often give a history of heavy lifting or strenuous exercise a few days prior to the onset of the pain. Changes in position may exacerbate the pain. Typically, the pain is worse in the morning because the involved muscles stiffen overnight. Light palpation in the flank area may elicit pain. Treatment measures include NSAIDs, narcotic analgesics, muscle relaxants, localized heat application, and an appropriate exercise regimen.
 

MISCELLANEOUS CAUSES

The list of potential causes of flank pain is extensive and is not limited to the conditions we have covered here. A thorough history and careful physical examination should lead the evaluating physician to formulate a differential diagnosis that is appropriate for the individual patient. Nausea, vomiting, a change in bowel patterns, or the correlation of pain to meals may raise suspicion for gastrointestinal processes such as biliary colic, diverticulitis, small bowel obstruction, or even simple constipation. If cough, dyspnea, or other respiratory symptoms are present, then diaphragmatic irritation from pneumonia, pleurisy, or even pulmonary embolism should be considered. The differential diagnosis for menstruating women presenting with flank pain must include ectopic pregnancy, ovarian cyst or torsion, endometriosis, pelvic inflammatory disease, and tubo-ovarian abscess. In older women, ovarian cancer may cause flank pain and should be considered in the appropriate setting.

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