PT CASE: OSTEOMYELITIS (INSTRUCTOR VERSION) By Dan Waldman, MD Department of Family and Community Medicine GOALS FOR SESSION At the end of the session, the residents should: 1. 2. 3. 4. Know the basic presentation of osteomyelitis Know which lab tests may be helpful in suspected osteomyelitis, and their limitations Have a basic understanding of which imaging modalities to use in the evaluation of osteomyelitis Have a basic understanding of treatment options in osteomyelitis CASE PRESENTATION WITH QUESTIONS You are working in clinic, mostly seeing a mix of other providers’ patients, and acute care visits. You’ve seen 3 URI’s and a few young people with mechanical back pain, when in walks another patient with back pain. This patient is an 85 year old man with a history of only “arthritis” in his knees and back. He states that he has had the new onset of back pain in his mid to low back for the last 3 weeks. He was seen 2 weeks ago, and prescribed Tylenol with codeine and told to follow up in a few weeks. There was no specific trauma or injury, and the pain does not radiate. He has taken ibuprofen with only mild improvement. The pain is not relieved by any positional changes. His pain has been worsening for the last couple weeks. Q. What are some of the specific questions you would want to ask this patient about his back pain? A. There are many questions at this point since the history was so brief. The key here is to begin to identify possible “red flags.” Potential red flags in a back pain history are: age more than 50 years, history of cancer, fever, unexplained weight loss, pain that is worse at rest, a history of IV drug use, symptoms of an underlying infection (such as dysuria), incontinence, or pain that lasts more than 6 weeks. The patient has no fevers, chills, night sweats or pain anywhere besides his back, He denies new bowel or bladder symptoms, though he did have dysuria a few weeks ago that resolved on its own. The patient has a history of “skin cancer” for which he sees dermatology at the VA and has only needed superficial treatments, such as biopsies and freezing with liquid nitrogen. He also has a history of BPH, and chronic symptoms of urinary hesitancy. 1 Q. What are some potential causes of this patient’s back pain on your differential? A. Given the patient’s age, osteoporosis with a resulting compression fracture would be high on the differential. Mechanical back pain from an unperceived strain is also possible. The patient’s age though puts him at risk for some more serious causes of back pain, such as metastatic disease, spinal stenosis, and infection. The patient has a normal temperature, and otherwise normal vital signs. The patient’s back exam is notable for tenderness of the paraspinal muscles at about T5. Straight leg raising does not worsen the patient’s pain. Reflexes, strength and sensation testing are normal. Your prostate exam reveals a diffusely enlarged prostate without nodules. You notice a recent PSA of 6.0 ng/ml. Q. What would be a couple basic tests you could order for the beginning of the workup? A. An ESR and X-Ray would be a good place to start. The X-ray shows degenerative changes in the T1-T6 vertebra, but nothing more specific. The ESR is elevated at 104 mm/hr. You also obtain a CBC which shows a white count of 9400 with 70% neutrophils. Hemoglobin is 12.5. Q. How do you interpret these findings and the overall picture so far? A. The X-ray is helpful, but non-diagnostic in this case. Compression fractures, if present, are usually seen on plain films. Additionally, metastatic lesions from prostate cancer are usually blastic and visible on X-ray. The patient’s mildly elevated PSA may not be meaningful. The elevated ESR, however, is concerning for chronic infection, metastatic tumor, vasculitis or multiple myeloma. You arrange from admission from your clinic, to facilitate continued workup. Q. What are the next steps in the workup? A. Further imaging is probably the next step. A serum and urine protein electrophoresis should be ordered as well. Other basic tests, such as chemistry panels and LFT’s could also be helpful, as well as blood and urine cultures. In this case, the results of the electrophoresis tests are normal, and the chem.-7 and LFT results are normal. A CT is obtained and shows an abnormal soft tissue density extending from the midbody of the L3 to L4 vertebra. The radiologist gives a differential for the density that includes disc herniation, metastatic disease or infection. Q. What are some other imaging modalities that can be attempted for further evaluation? A. Bone scans can be helpful in the diagnosis of many conditions that have increased bone metabolic activity, but may not be able to differentiate between soft tissue infection, degenerative joint disease, healing fractures or stress fractures. MRI can be helpful in unclear situations, especially involving the spine, and can give help delineate the extension of anatomic abnormalities caused by the disease process. 2 An MRI is obtained, and shows destruction of the endplates of the L3 and L4 vertebral bodies, with destruction of the disc space between them. The differential remains infectious or metastatic. Q. What would be the best next step in diagnosis? A. A guided biopsy performed by interventional radiology should be performed next. A fine-needle aspiration biopsy of the L3-L4 disc space reveals blood-tinged, slightly cloudy fluid. Gram staining shows numerous white cells, but no organisms. Cytology is negative for malignant cells. Cultures obtained of the fluid are pending. Q. What should you do next? A. The combination of the MRI findings and the negative cytology suggest vertebral infection, which typically involves two adjacent vertebras and the disc space between them. Cultures can be negative, so multiple specimens should be obtained on biopsy. If the cultures from the first biopsy are negative another biopsy can be performed. If the second attempt yields no organism, the options are then empiric treatment or open surgical biopsy. Q. What are the most likely organisms to gear empiric therapy towards? A. In this case, most likely staph aureus. The specific organisms encountered vary depending on the clinical scenario and the age of the patient. S. aureus and streptococci are typical in neonates; S. aureus is found later in life; and gram-negative rods are found in the elderly. Fungal osteomyelitis is a complication of catheter-related fungemia, the use of illicit drugs contaminated by candida species and prolonged neutropenia. Pseudomonas can be isolated from injection-drug addicts, and from patients with urinary catheters in place (Lew DP W. F., 1997). Q. How long should antibiotics be given for? Traditionally, 4-6 weeks of antimicrobial therapy are used for treatment of osteomyelitis. The rationale for this duration is based on the results of animal studies and the observation that revascularization of bone after debridement takes about four weeks (Lazzarini L MD, 2004). Q. What about using oral antibiotics? A. Oral treatment of acute osteomyelitis in children has been accepted for many years, though the treatment in adults has traditionally been intravenous for most acute and chronic cases. “Sequential treatment” involves starting a patient with intravenous antibiotics for a week or two, and then switching to oral antibiotics for completion of treatment. This has been best studied in the use of quinolone antibiotics (Mader JT, 1990), though in one review the success rates may differ by organism, with cure rates of 92% being seen for enterobacter, 72% for pseudomonas and 75% for staph. aureus (Lew DP W. F., 1995). Osteomyelitis and diskitis are rare causes for back pain presenting to a primary care physician’s office. The important points with this case are recognizing that this patient had some warning signs (age, worsening over a few weeks, and presence of pain in all positions) for further workup. 3 Additionally, the lack of fever and white count is not uncommon for vertebral osteomyelitis. One study estimated that fever was present in only 52% of patients with pyogenic osteomyelitis and only 4% of patients with diskitis (Deyo, 1986). Leukocytosis is present in only about 43% of patients with spinal infection, and 6% of patients with nonspecific mechanical low back pain who do not have a spinal infection (Deyo, 1986). Thus the presence of elevated white count and fever increase the odds of spinal infection significantly, but the absence does not substantially decrease the odds. Likewise an ESR greater than 100 is also significantly associated with a serious underlying cause of back pain, which when combined with the patient’s age and symptoms, warranted an aggressive workup. OSTEOMYELITIS REVIEW Introduction Osteomyelitis is a difficult disease to diagnose. This is not helped by the lack of good quality studies that evaluate different clinical criteria for the diagnosis of osteomyelitis. Diagnostic tests must be tailored to the specific clinical scenario, as many factors can affect the accuracy of tests, including the chronicity of the infection and the amount of inflammation present. Classification There are a few different ways to classify osteomyelitis. In general, it should be categorized by 1) the chronicity of the infection, and 2) the underlying pathogenesis. Chronicity: Acute vs. chronic. There are many differences of opinion, some state that more than 10 days of symptoms means “chronic,” as signs for more than 10 days can correlate roughly with the development of necrotic bone (Lew DP, 1997). Most consider “acute” to be evolving over several days to weeks, and chronic to be evolving over weeks to months, or even years. The hallmark of chronic osteomyelitis is the presence of dead bone. “Subacute” osteomyelitis is often used for the middle ground of a few weeks of mild symptoms (see below). Pathogenesis: hematogenous spread of bacteria, contiguous spread from soft tissue infection, or local inoculation following surgery or trauma. Hematogenous spread is more common in children and elderly patients. Osteomyelitis after injury is the most prevalent type and is usually associated with open fractures or after orthopedic surgery to repair injured bones. Symptoms 4 Typical acute osteomyelitis presents with bone pain, tenderness, warmth and swelling developing over several days to a week. The pain occurs with and without movement. Many patients are febrile, and rigors are occasionally present, though patients often have no constitutional symptoms. Osteomyelitis of the hip, vertebrae and pelvis are known for presenting with very few symptoms Chronic osteomyelitis is easy to diagnose in patients with previously diagnosed and treated osteomyelitis who then have the recurrence of pain or inflammation in the same place. The difficulty arises in the unfortunately not uncommon cases of suspected osteomyelitis associated with orthopedic prosthesis, decubitus ulcers and foot ulcers from diabetes and/or vascular insufficiency. Labs Routine labs are non-specific. These include elevated ESR and elevated white counts. As an example, in patients with a foot ulcer and diabetes (in the absence of end stage renal disease), ESR greater than 100 mm/hr is highly sensitive, but non-specific for diagnosing osteomyelitis (Newman, 1991). Blood cultures are positive in 50% of cases in acute osteomyelitis. A positive blood culture and radiologic evidence of osteomyelitis obviates the need for a bone biopsy. Radiologic Evaluation 5 Plain films: inexpensive but insensitive. May help diagnose or choose further studies, or exclude other conditions. Soft tissue swelling + bone destruction + periosteal reaction is fairly specific for osteomyelitis, but bone changes take 2-3 weeks to be evident. Some situations may be complicated by bone changes from other processes. Osteomyelitis cannot be excluded if plain films are negative. Chronic osteo can be seen on plain films with bone sclerosis, periosteal new bone formation and sequestra (piece of dead bone separated from the bone in the process of necrosis). CT (with and without contrast): Can detect cortical destruction, intraosseous gas, periosteal reaction and soft tissue extension. MRI: Especially useful in imaging the vertebra and the infected foot. Also helps in providing pre-op detail for surgical debridement. In fact, MRI may be the best modality for evaluating the foot for osteomyelitis, including diabetic feet. MRI can have false positive results in fractures, bone infarcts or healed osteomyelitis. Ultrasound: Can reveal fluid collections adjacent to bone, significant elevation of the periosteum and thickening of the periosteum, but the sensitivity and specificity of this modality needs further evaluation. Bone Scan: Three phase bone scan can differentiate cellulitis from osteomyelitis. The three phase technetium bone scan is considered by many the test of choice in evaluating for acute osteomyelitis in cases of normal plain films, with a sensitivity and specificity near 95% (Schauwecker, 1996). False positive results though can be seen in any situation that causes increased bone turnover, such as after a traumatic injury, following surgery, diabetic feet, septic arthritis, inflammatory bone diseases, cancer, healed osteo and Paget’s disease (Schauwecker, 1996). Indium labeled leukocyte scan: Useful at evaluating for osteo at sites of fracture nonunion. Better than bone scans in evaluation of diabetic feet, but still relatively unspecific. This test is time consuming as it takes time to obtain the tracer and tag the patient’s cells. (the whole process can take 2-3 days from the time ordered). Dual Tracer Scans: Combine an inflammation imaging tracer (indium or gallium) with an “anatomic” tracer (a technetium labeled bone scan or marrow scan). The bone scan portion provides good sensitivity, while the indium labeled cell scan helps localize infection to bone or soft tissue (Ghiorzi, 2006). PET Scan: Recent meta-analysis shows PET scanning to be the most accurate single test to diagnose chronic osteomyelitis. Similar results were seen in the combination of bone scans and white cell scans (dual tracer scans). The quality of the studies available for the metaanalysis was generally variable (Termaat MF, 2005). Bone Biopsy Gold standard for the diagnosis of osteomyelitis. Note that open biopsy, is the gold standard, though needle biopsy is commonly used for practical reasons. Sampling error reduces the sensitivity and specificity of needle biopsy somewhat, so if the clinical suspicion is high and the needle biopsy is negative, repeating the needle biopsy, or performing an open biopsy should be done. Bone biopsy may be warranted as well in patients with decubitus ulcers and clinical suspicion of osteomyelitis, even with normal labs and imaging. Osteomyelitis associated with infected overlying wounds can present a challenge for biopsy. Correlation of the microbiology of the overlying wound and that of the causative organism of the osteomyelitis is generally poor, so biopsy of the bone should still be attempted (Khatri G, 2001), avoiding the wounded tissue. Diabetic Foot Ulcers Associated with Osteomyelitis Patients with diabetes and soft tissue infections for more than two weeks, especially if they are located over bony prominences, are at high risk for osteomyelitis. The following clinical findings were noted in a review of 35 patients with limb-threatening diabetic foot ulcers (Newman, 1991): Lesions larger than 2 cm x 2 cm had a sensitivity of 56 percent and specificity of 92 percent for osteomyelitis. Ulcers deeper than 3 mm were significantly more likely to overlie infected (osteomyelitic) bone than shallower ulcers (82 versus 33 percent). All patients with ulcers that exposed bone were associated with underlying osteomyelitis. An erythrocyte sedimentation rate greater than 70 mm/h had a sensitivity of 28 percent and specificity of 100 percent for diagnosing osteomyelitis. In another report of 76 patients with infected diabetic foot ulcers, 50 had contiguous osteomyelitis (Grayson, 1995). A probe could be passed directly to bone in 33 of these patients (66 percent), compared to four of 26 (15 percent) without osteomyelitis. As mentioned above, MRI is the best imaging choice in cases of suspected osteomyelitis in cases of diabetic foot infections. Treatment of Osteomyelitis Few studies have investigated the optimal treatment for osteomyelitis. In order to measure treatment success, patients would need to be followed for years. Also, debridement complicates the utility of antibiotics, and clinical situations and pathogens are heterogeneous. Most recommendations are therefore based on expert opinion. Obtaining a biopsy sample is essential for proper antibiotic selection. After the biopsy is obtained, empiric antibiotics should be started. In the past this meant nafcillin plus cefotaxime or ceftriaxone, but nafcillin is being replaced more and more with vancomycin with increasing MRSA prevalence. 6 Early antibiotics limit the development of bone destruction or necrosis, and must be parenterally administered for at least 4, but often 6 weeks. These can be completed as an outpatient as appropriate. If antibiotics fail, or in cases complicated by poor vascular supply or chronic infection, debridement may be necessary as well, removing the devitalized bone and soft tissue. In the absence of good oxygen delivery to a limb with chronic osteomyelitis, especially in cases where the pathogen has not been adequately identified, amputation of the limb may be required. A clear discussion regarding the pros and cons of antibiotics versus surgical debridement should be undertaken with the patient, especially when the chances for success with antibiotics alone are slim. Imaging of choice in suspected osteomyelitis, by situation (in addition to plain films): Clinical Scenario Radiologic test of choice Diabetic foot infection MRI Evaluation of acute osteomyelitis Three phase technetium bone scan in uncomplicated* cases Ferromagnetic material is Nuclear study: indium scan or dual tracer exam. Note, most present that may degrade CT or materials used in orthopedics, such as titanium, do not interfere MRI images with MRI. Evaluation of the spine for ostei MRI Chronic osteomyelitis PET scan if available, or combination of bone scan and white cell scan Diabetic ulcer where there is Consider no further imaging, proceed to biopsy either an ulcer larger than 2x2cm or bone is palpable on probing x “complicated” = complicating a fracture, postop, patients with neuropathy, vasculopathy BIBL I OGR AP H Y Carek PJ, Dickerson L, Sack J (2001). Diagnosis and Management of Osteomyelitis. Am Fam Phys, 63(12):2413-2420. Deyo, R. (1986). Early diagnostic evaluation of low back pain. J Gen Intern Med , 1:328-38. Ghiorzi, T. M. (2006). Diagnosis of Osteomyelitis in Adults. UpToDate . Grayson, M. G. (1995). Probing to bone in infected pedal ulcers. A clinical sign of underlying osteomyelitis in diabetic patients. JAMA , 273:721. Khatri G, W. D. (2001). Effect of bone biopsy in guiding antimicrobial therapy for osteomyletis complicating open wounds. AM J Med Sci , 321(6):367-71. Lazzarini L MD, M. J. (2004). Osteomyelitis in Long Bones. The Journal of Bone and Joint Surgery , 86:2305-2318 . Lew DP, W. F. (1997). Osteomyelitis. NEJM , 336: 16, 999-10073. Lew DP, W. F. (1995). Quinolones and osteomyelitis: state-of-the-art. Drugs , Suppl 2:100-101. Lurie JD, Gerber PD, Sox H (2000). A pain in the back. NEJM, 343(10):723-726. Mader JT, C. J. (1990). Oral ciprofloxacin compared with standard parenteral antibiotic therapy for chronic osteomyelitis in adults. J Bone Joint Surg Am , 72:104 -10. 7 Newman, L. W. (1991). Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitring by leukocyte scanning with indium In-111 oxyquinoline. JAMA , 266:1246. Schauwecker, D. (1996). The role of nuclear imaging in osteomyelitis. In D. Collier, Skeletal Nuclear Medicine. St Louis: Mosby. Termaat MF, R. P. (2005). The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systemic review and meta-analysis. J Bone Joint Surg Am , 87:2464-71. Post Module Evaluation Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111). 1) Topic of module:__________________________ 2) On a scale of 1-5, how effective was this module for learning this topic? _________ (1= not effective at all, 5 = extremely effective) 3) Were there any obvious errors, confusing data, or omissions? Please list/comment below: _________________________________________________________________________________________________________ _________________________________________________________________________________________________________ ______________________________________________________________________________ 4) Was the attending involved in the teaching of this module? Yes/no (please circle). 5) Please provide any further comments/feedback about this module, or the inpatient curriculum in general: 6) Please circle one: Attending 8 Resident (R2/R3) Intern Medical student