Approach to Fever and Back Pain - Diagnosis

INTRODUCTION

                Back pain and fever are not uncommon complaints in either the outpatient or inpatient setting. A thorough history and physical exam will aid the clinician in diagnosing the underlying cause. Localization of the discomfort in addition to pertinent cultures and radiographic studies are invaluable for identifying possible causes.

Problem

                Back pain can occur at any level of the vertebral column; however, not all back pain is vertebral in origin. It is important to consider pain that is referred from other areas. For example, patients with acute cholecystitis will often have scapular pain. Patients with pancreatitis may have pain that shoots to the mid-back. Back pain is also not necessarily due to an infectious process, and non-infectious causes must be considered. See Table 1 for potential infectious and non-infectious causes based on their localizing areas. Identifying the location of the pain, and incorporating associated symptoms will help determine if the pain is referred or radiating, and whether or not it is due to an infectious process.

Table 1:  Differential Diagnosis of Common Problems Presenting with Fever and Back Pain

Differential Diagnosis

                Certain musculoskeletal infections can occur at any vertebral level (Table 1). These include discitis, osteomyelitis, paraspinal and epidural abscesses. A recent history of bacteremia is often suggestive of potential bone or disc infection, especially if there is a history of prolonged bacteremia or pyogenic arthritis. Negative blood cultures, however, do no rule out a musculoskeletal infection. Common pathogens in patients who were recently bacteremic include Staphylococcus aureus and Streptococcus spp. In patients with newly diagnosed musculoskeletal infections of the spine with no recent history of bacteremia or surgery, occult infection and endocarditis should be ruled out. Common pathogens often seen after orthopedic procedures also include Staphylococcus aureus and Streptococcus spp., but also include coagulase-negative Staphylococci. Not common in the United States, but deserving mention, is vertebral tuberculosis (Pott’s Disease). As an extra-pulmonary manifestation of tuberculous disease, patients with spinal erosive changes seen on pathology or radiology should be assessed for tuberculosis risk factors, and appropriate staining should be done to look for acid-fast bacilli or granuloma formation. Some non-infectious causes of musculoskeletal disease include myopathy or muscle spasm, osteoarthritis, osteoporosis, disc herniation, compression fractures, and spinal stenosis. Metastatic disease to the spine should also be considered as approximately 30-70% of patients with a primary tumor have spinal metastasis at autopsy. It is the third most common site of metastasis after lung and liver. The most common malignancy sources of spinal metastasis include lung, breast, gastrointestinal, and prostate (Table 2). Non-infectious causes of back pain like sacroileitis may have an infectious inciting event such as brucellosis or infections that are associated with reactive arthritis. Table 1 provides a differential diagnosis of common problems presenting with fever and back pain. It should also be considered that fever may be associated with the condition, but it may also be coincidental.

Table 2:  Common Causes of Musculoskeletal Back Pain

Myopathy/Muscle Spasm   Osteoarthritis   Osteoporosis   Spinal stenosis   Disc herniation   Compression fractures   Myopathy, muscle spasm   Metastatic Disease:  Breast                                  Lung                                  Gastrointestinal                                  Prostate                                  Lymphoma                                  Melanoma                                  Renal                                  Unknown                                  Other

Clinical Manifestations

                Patients will present with varying degrees of fever and varying degrees of back pain. Pain can be localized or radiating. More often than not, symptoms alone will not help differentiate whether or not the presentation is infectious or non-infectious. Clues from history that help support a diagnosis of infectious etiology include history of a) previous infection in the particular area, b) previous bacteremia, c) intravenous drug use, d) recent trauma or surgery. Accordingly, a positive culture sample, pathology suggestive of infection (such as acute inflammation or necrotizing granulomas) or abnormal laboratory values (such as leukocytosis or elevated sedimentation rates) strongly support an infectious diagnosis. Clues that support non-infectious etiologies include history of a) rheumatologic disease, b) repeated negative cultures, c) radiographic evidence unsupporting of infection, and d) pathology or laboratory values not supporting of infection.

               In addition to the clues from history that support a diagnosis of infectious etiology, certain elements should also serve as “red flags” or causes for concern. A patient with fever and pain back who has a history of intravenous drug abuse should undergo immediate imaging to evaluate for vertebral osteomyelitis or discitis associated with bacteremia and endocarditis. Similarly, a patient who was recently diagnosed with or treated for bacteremia who presents with new back pain should also be considered highly suspicious for vertebral osteomyelitis or discitis as a result of hematogenous seeding . This clinical suspicion should include hemodialysis patients and those with chronic indwelling intravenous lines. C-reactive protein and erythrocyte sedimentation rate tend to be very non-specific, however, when very elevated, should be used as a prompt for further evaluation and search for occult infection. See Table 3 for potential red flags that suggest an infectious etiology for back pain.

45 year old admitted for Group B streptococcus bacteremia. Was discharged on oral antibiotics and subsequently developed back pain. MRI and surgical specimens were consistent with vertebral osteomyelitis and diskitis.

Table 3:  Causes for Concern in Patients with Fever and Back Pain and Questions to Ask

Physical Examination

                Complete physical examination should be performed; however, special attention to be paid to the particular systems of the presenting complaints. The following examination findings may increase suspicion for certain conditions. Pain to percussion at any level of the spine can be significant for vertebral osteomyelitis or discitis. Radiating pain along the back, from the back, or to the legs, may be suggestive of disc disease, abscess, or inflammation that irritates the nerves. For patients who have had recent surgical procedures performed, especially along the back, the skin near the incisions should be inspected closely, and if there is drainage, the wounds should be explored to see if they tunnel deeper. This may indicate a deep back wound infection, abscess, or vertebral infection. Pain in the flanks is often suggestive of pyelonephritis or infections along the urologic collecting system. Abdominal exam may be helpful if there is suggestion of pancreatic or gall bladder disease with radiating back pain. Respiratory exams with crackles, evidence of consolidation, or abnormal breath sounds may help isolate pneumonia, abscess, or effusion. Patients with back pain that have difficulty with straight leg raising or bending may have other symptoms or lab values consistent with meningitis or psoas abscess. Similarly pain in the cervical spine is almost always raises concern for meningitis, aseptic or bacterial. Rashes: vesicular, crusted, or papular that have a dermatomal distribution are consistent with Varicella zoster. Table 4 provides diagnostic clues that can be identified during the physical examination.

Table 4: Potential Infectious Diagnoses for Specific Findings in a Patient with Fever and Back Pain

Laboratory Findings

               Patients presenting with fever and back pain should have diagnostic laboratory studies to help focus the differential diagnosis (Table 5). Two blood culture sets done prior to antibiotic administration should be performed for all patients. Though perhaps more directed toward the thoracic spine and urinary tract complaints, urinalysis and culture may also be helpful as often, urinary pathogens also signify blood stream infections. Erythrocyte sedimentation rate and C - reactive protein are non-specific markers, but if markedly elevated may support a diagnosis of deep-seated infection such as osteomyelitis or endocarditis. Routine complete blood count and comprehensive metabolic panel with liver enzymes should be performed. Elevation of the white blood cell count may be present but does not exclude serious disease if normal. Creatinine abnormalities may support infectious renal pathology or simply call attention the need for antibiotic dose adjustment. Liver enzyme abnormalities may suggest a biliary or hepatic source. If draining wounds are present, a sterile site culture is invaluable for identifying specific pathogens. If osteomyelitis, discitis, or paravertebral abscess are suspected, cultures and biopsies from the site are of utmost importance and will not only help direct initial therapy, but also help tailor therapy for specific pathogens.

               Acquisition of tissue in the area of question for pathology, cytology, and tissue culture can not be over emphasized. Pathology samples will often display pathognomonic appearances for specific diagnoses. Often, pathology samples will reveal microorganisms that will aid in the diagnosis, especially if they are not growing on culture. This is especially true of organisms that are sometimes difficult to isolate such as acid-fast organism, moulds and fungi. In addition, pathology helps include or exclude non-infectious conditions (such as in malignancy) that may cloud the diagnosis. As with fluid collection, tissue samples allow for a greater quantity for analysis and will improve the possibility to culturing pathogenic organisms. Tissue or biopsy can be obtained by numerous means. The preferred means is typically surgical tissue collection; however, this is not always practical or feasible. In cases where surgery is required, surgical specimens are optimal, especially if they are obtainable before administration of antibiotics. If a drainable foci or abscess is seen, CT or ultrasound-guided biopsies are safe and rapid methods to obtain tissue samples. CT-guided biopsy is also an acceptable way to obtain bone for pathology and culture in cases of suspected vertebral osteomyelitis or vertebral lesions when surgery is not immediately possible. It also allows for the acquisition of tissue quickly thereby providing tissue prior to antimicrobial administration. Interventional radiology biopsies such as CT or ultrasound-guided procedures should not be a substitute for surgical debridement; however, they should be used as an adjunct to diagnosis, and occasionally therapy.

               For patients with a tuberculosis exposure history or risk factors for tuberculosis, a tuberculin skin test should be performed. A negative skin test does not rule out tuberculosis; however, and a positive test may be falsely positive due to reader error, or placement error. A new option in tuberculosis diagnostics is the QuantiFERON-TB Gold (Cellestis, Valencia CA, USA) assay that helps detect latent tuberculosis infection and may possibly play a role in the diagnosis of active disease. This ELISA test detects interferon-gamma in fresh heparinized whole blood from sensitized persons when incubated with mixtures of synthetic peptides simulating two proteins present in Mycobacterium tuberculosis. Because it does not react to proteins commonly encountered in non-tuberculous mycobacteria, it is more specific. Though not necessarily providing a definite diagnosis, it may be helpful in the appropriate clinical setting.

Table 5:  Suggested Initial Laboratory Work-up in a Patient with Fever and Back Pain

Two sets of blood cultures Erythrocyte sedimentation rate or C-reactive protein Urinalysis and urine culture Sputum culture and sensitivity Site cultures if abscess or osteomyelitis Complete blood count with differential Complete metabolic panel Pathology or biopsy and culture of suspected infectious sites

Radiology

                All radiologic studies have some limitation because of the possible overlap of potential infectious and non-infectious etiologies in their radiologic appearance. A summary of potential initial radiographic tests is listed in Table 6. Plain radiographs of the site of concern may be helpful but are often limited at detecting acute disease. Most beneficial of all plain radiographs is probably chest radiography especially if it demonstrates pneumonia or lung abscess. Abdominal radiographs may demonstrate calcifications consistent with stones in the collecting system. Radiographs of the spine are generally limited diagnostically for patient with fever and back pain; however, patients with long-standing osteomyelitis who have bony erosion may have positive radiographic findings. Of course, findings like these often will require follow-up with further radiographic testing.

Table 6:  Suggested Initial Radiologic Work-up Based on Suspected Source

Thorax, pulmonary	Two view Chest radiography CT scan of the thorax
Abdominal	Abdominal ultrasound Renal ultrasound Plain abdominal series CT scan with contrast
Vertebral column	Plain radiograph MRI
Uncertain Source	CT scan, thorax, abdomen, pelvis Bone Scan Indium Scan

Computed tomography (CT)

                Scanning diagnostically yields more information than any other radiographic test. As it offers a more dimensional view of the body, it is helpful for diagnosing back pain etiologies at any level of the spine. CT scanning is fairly sensitive at detecting osteomyelitis and discitis. It also has reasonable ability to detect paravertebral abscesses and other soft tissue defects. For the purposes of fever and back pain, its biggest strength is probably its ability to pick up other findings that may cause referral to the back such as 1) pulmonary causes: pneumonia, pulmonary embolus, pleural effusion, empyema, 2) biliary tree defects: cholecystitis, pancreatitis, pancreatic phlegmon, liver abscess, 3) renal abnormalities: nephrolithiasis, hydronephrosis, lobar nephronia, 4) other musculoskeletal or gastrointestinal abnormalities: psoas abscess or appendicitis. CT scanning also offers the ability of guided needle biopsy, culture collection, and drainage.

Magnetic resonance imaging (MRI)

                MRI has much of the same benefits as CT scanning; however, it is probably more sensitive and specific for vertebral column abnormalities such as osteomyelitis or discitis. MRCP however, may also help with biliary tree imaging. Because of the high sensitivity and specificity and ability to differentiate between infected bone and adjacent tissue, MRI can be utilized as the sole test in evaluation of osteomyelitis. Its benefit is greatest in patients who have no acute fractures or existing metallic hardware that can leave artifact. In the setting of fever and back pain, MRI is probably the best test to use to identify potential bone lesions that may have resulted from infectious or non-infectious sources.

Nuclear scanning

                Nuclear scanning is probably more limited in the setting of fever and back pain; however, they can be helpful, especially in cases where an identifiable focus is elusive. Scans that are often employed include three phase bone scans or the Technetium-99m scan, Gallium-67 scan, and Indium-111 scan. These scans tend to be very non-specific and as such should be interpreted with caution. Sensitivity and pre-test probability varies widely depending on the circumstances. Bone scans tend to be helpful to localize specific bony abnormalities. They are very sensitive for detection of osteomyelitis, but they are not very specific; there are many false positives because of the tests ability to detect non-infectious and infectious bony abnormality. They are useful at detecting bony metastasis. Gallium scans are fairly sensitive at detecting spinal abnormalities in the setting where MRI is not possible. Like other nuclear scans, the findings are not specific, and gallium should not be used alone to diagnose osteomyelitis. Indium white blood cell scanning is helpful for localizing areas where leukocytes migrate or for detecting areas of inflammation. They are fairly sensitive, but because tissue cannot be differentiated by Indium scan, the definition is limited. Indium scan’s asset probably lies in the ability to find potential foci of infection that were previously undetectable. Results do need to be interpreted with caution, however, as specific tissues or systems can not always be deduced. Of note, nuclear scans should be selected with caution as the half-life of the isotopes may prohibit further nuclear scans for days to weeks. As with all radiographic tests, interpretation accuracy is operator dependent, and the usefulness of these tests varies widely from person to person.

Ultrasound

            Ultrasound may have some benefit for imaging of the abdominal aorta, the kidneys, and the biliary tree. Ultrasound often times offers the ability of guided biopsy or fluid aspiration as well. It is generally rapid and non-invasive, but its sensitivity is limited except in specific diagnostic situations such as diagnosing aortic aneurysms and evaluating the renal pelvis and biliary tree.