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Home , Involucrum, Nonunion, Osteomyelitis

The Indium White Cell Scan in the Evaluation of

Case Presentation and Discussion: John L. Esterhai, Jr. and Douglas Silfen Guest Editor: Abass Alavi

From the case recordsat the Hospital ofthe UniversityofPennsylvania, Philadelphia,Pennsylvania

purulent necrotic soft tissue as well as necrotic callous. J NucIMed 1990;31:2029—2033 These were debrided extensively. Over the next two weeks, he had low grade despite continuing i.v. and continued drain age of seropurulent material. At one time of further 17-yr-old boy was referred to the nuclear mcd , an throughout most of the icine department for evaluation of a left femoral infec femoral shaft was seen. Both the involucrum and the tion in February 1986. inner femoral shaft were debrided without evidence of bleeding, suggestive of extensive . It was felt CASE HISTORY that most of the shaft had undergone septic . Gross motion could be elicited at the fracture site, which The patient was in excellent health until August 1985 was surrounded by necrotic and an outer shell of when he was hit by a truck while crossing the street. He involucrum. Extensive debridement was performed. sustained a segmental of the left The wound was irrigated copiously. Percutaneous and was brought to another institution for emergency care (Fig. 1). The patient was stabilized and subse drains were placed and the wounds were closed. One week postop, he continued to have seropurulent quently repaired by open reduction/ drainage from his wounds as well as low grade fevers in using two metal plates. He tolerated the surgery well spite of continued i.v. antibiotics. The decision was and was discharged shortly thereafter. made to transfer the patient to our institution for further The fracture appeared to heal well and he progressed treatment. to walking without much difficulty. Four months later Upon admission, radiographs were obtained and in he noted swelling of his left thigh and knee. Shortly terpreted as extensive chronic and subacute osteomye thereafter, he developed seropurulent drainage from his litis of the shaft of the left femur with bone destruction left leg wound proximal to his knee. Wound cultures and extensive involucrum formation (Fig. 3). were obtained and the patient was started on oral The patient was brought to the OR three times in the Bactrim empirically, with no improvement. Wound cultures revealed , first week of his admission. The first operation was performed 2 days after admission. Wound cultures were his (WBC) count was 11.1 with a left obtained intraoperatively and the patient then was shift, and an X-ray of the left femur demonstrated an started on i.v. Amikacin and Mezlocillin. During this exuberant callous formation extending from the proxi operation, the distal aspect of the femoral shaft as well mal femoral diaphysis to the supracondylar area with as the entire lateral bony sequestrum were debrided lytic lesions of the distal femur suggestive of osteomye sharply with extreme care taken to preserve the knee litis (Fig. 2). . Two days later, the patient was brought back to He was readmitted to the same hospital with the the OR where the dissection was extended proximally diagnosis of osteomyelitis and placed on i.v. and distally. More exudate and necrotic tissue were therapy with and cefazolin (the cultured encountered and removed. Three days later, additional Pseudomonas was shown to be sensitive to these). Ap soft tissue and bone were debrided. At the conclusion proximately one week later, he had surgery to remove of this third operation, no further necrotic tissue could hardware and debride the lesion. be found and all remaining bone appeared viable. The At surgery, abundant callous was seen and both dissection had run from the subcondylar bone at the fractures appeared well healed, but there was much knee to within three finger breadths of the lesser tro Recalved Jul. 13, 1990; revision accepted Aug. 6, 1990. chanter. For reprints contact: John L Esterhal,Jr., Orthopedic Section, Dept. of Surgeryand DMSIOnof NuclearMedicine,Hospitalof the Universityof The wound was irrigated and packed open with Pennsylvani@Philadelphia,PA 19104. betadine-soaked gauze sponges. Sterile dressings were

Indium-Labeled WBC Scintigraphy in Evaluating Osteomyelitis •Esterhai and Silfen 2029 FIGURE3. Lateral(A)and oblique(B)views of the left distal femur taken after pa tient@stransfer to HUP. The patient was 7 days postop after extensive debridement of the femur (performed at FIGURE1. Radiographwastakenim outside hospital) and drains mediatelyafter the patient's accidentin the were still in place.The X-rays emergencyroom.Thefilmdemonstratesa demonstratethat muchofthe compoundfractureof the leftfemurinvolv involucrum has been re ingthe midshaftand subcondylarregion. moved during surgery with sparing of most of the distal femoral shaft. However, applied and the patient was brought to the recovery there are lytic lesions on much of the distal femoral room in satisfactory condition. Figure 4 demonstrates cortex, suggesting bone de the appearance after surgery. struction consistent with The next day hyperbaric therapy was started chronicosteomyelitis. and was continued for the next 4 wk. Over the following 2 wk, the patient did well with no and he tolerated ambulate with full weight bearing on his left leg without bedside physical therapy. Examination ofthe wound at protection. Examination at that time revealed the soft this time demonstrated some improvement but the tissues to be well healed and nontender and he had full wound was not healing as well as was expected in a range of motion of his knee joint with no tenderness healthy young patient. Thus, an indium-WBC scan was and no evidence of effusion or synovitis. An X-ray at ordered to determine if there was any further evidence that time revealed remodeling of the femur (Fig. 6). of in the leg (Fig. 5). The scan revealed exten The patient denied any fever or other symptoms of sive soft-tissue activity in the lateral thigh related to the infection and was participating in weight-lifting activi surgical wound, but there was also an area of significant ties at school. activity in the distal femur at the level ofthe epiphyseal plate, suggesting persistent infection at that site. The DISCUSSION patient was brought back to the OR on March 4, 1986 where further dissection medially revealed a hole in the Chronic osteomyelitis secondary to open fractures or femur from the patient's original blade plate internal open reduction and internal fixation of closed fractures fixation device just superior to the knee. continues to be a therapeutic challenge for the or Some granulation tissue in this area was debrided thopedic surgeon. thoroughly. The wound was packed open with saline The overall incidence of in orthopedics soaked gauze sponges and sterile dressings were applied. varies depending upon the nature ofthe and the The patient tolerated the surgery well and did well surgical intervention undertaken. Several classification postoperatively. One week later his wound was closed systems have been developed to standardize data ac by plastic surgery with vastus lateralis flap. Following quisition, data analysis, and estimates offinal outcome. surgery, the patient was afebrile and his wound healed The Gustilo classification system is used for opening well with no complications. Two weeks later he was fractures (1). An open fracture with a clean wound less discharged. than 1 cm long is considered a Gustilo Type I injury. He returned 3 wk later for from the An open fracture with a laceration more than 1 cm iliac crest to increase the strength of the femur. In May long without extensive soft-tissue damage, flaps, or 1986, he was discharged with partial weight bearing on the left leg. One month later the patient returned to school. By November 1986, the patient was able to

FiGURE 4. X-rays in the FIGURE2. X-raywasob AP (A)andlateral(B)projec tamed 4 mo after the accident tions obtained after the third and demonstrates metal debridement.Sharp resec plates at the femoral midshaft tion of the distal femoraldi (A)and distalfemur(B) with physisduringsurgeryhasleft surrounding exuberant cat little of the previous distal bus formation.In the distal femoral cortex which had femur, there is an extensive gone onto septic necrosis. involucrumwith ly@clesions The involucrumwas viable intheboneshaftsuggesting and leftmainlyintactas were sequestrum development the distalfemoralmetaphysis and infection. and proximalfemoralshaft.

2030 The Journal of Nuclear Medicine•Vol.31 •No. 12 •December 1990 @ ANT A @LNT•:@

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R , I R FIGURE5 lndium-WBCscan obtained 2 wk after surgery. (A) and proximal , (B)femoral midshaft, and (C) distal femurs and knees in the anteriorprojection.Activityis noted in the lateralleftthigh involvingsuperficialstructures, and related to post surgical changes and wound healing. However, there is also a focus of activity in the left femoral /epiphysis just superiorto the knee,consistentwith infection.

avulsions is classified as a Gustilo Type II. An open These include inadequate debridement with remaining fracture with massive soft-tissue damage, compromised sequestra. vascular supply, and severe wound contamination and The diagnostic evaluation for infection includes as marked instability is termed a Type III. Even with the sessment of many parameters including risk factors best ofcare, the incidence ofinfection increases to more such as initial open fracture, multiple operative proce than 25% with more extensive soft-tissue and bone dures, past history of osteomyelitis, or persistent sinus. . Unfortunately, neither the peripheral WBC count nor Once osteomyelitis has developed, medical manage the erythrocyte sedimentation rate is reliable in the ment requires administration ofappropriate antibiotics work-up of patients suspected of having chronic osteo in bacteriocidal doses. In many circumstances, consul . Plain roentgenographs and CAT scans have tation with infectious disease specialists is necessary for been used to help determine the presence and extent of an optimal result. infection, but interpretation ofthese studies is extremely The surgical management of chronic bone infection difficult in the presence of trauma, past surgery, and involves: drainage of purulent , removal of ongoing . foreign material, necrotic bone and dense scar, and The ideal nuclear medicine technique for diagnosis obliteration of dead space. The available data shows ofbone infection should have a high degree of sensitiv that there is no blood/bone barrier indicating that an ity and specificity, be readily available, provide quick tibiotics readily penetrate viable bone (2). However, results and deliver an acceptable radiation dose to the there is no evidence that administered antibiotics are patient. able to penetrate poorly vascularized necrotic bone or Bone scans with technetium-99m-labeled phosphates areas encapsulated by dense fibrous scar. Thus, there primarily reflect a reparative process due to a variety of are reasons for failure following surgical intervention. disorders. Despite its excellent sensitivity for identifying bone lesions, it lacks specificity for infection. Likewise, gallium-67-citrate uptake at sites of inflammation after FIGURE 6. Antero-posterior (A)and lateral(B)projections intravenous injection is not specific for infection. The of leftfemurX-raysobtained accumulation of the radiopharmaceutical is thought to 9 mo after finaldebridement occur because of vascular permeability, uptake by mi and 6 mo after bone grafting to the distal femur from the croorganisms, and in vivo labeling of serum proteins, iliaccrest. There is remodel leukocytic lysosomes or endoplasmicreticulum present ing of the femur with in in the inflammatory exudate. Although there are some creased density throughout reports ofimproved accuracy with sequential bone scan most of the bone and no evi gallium studies, more recent work indicates an accuracy dence of new lytic lesionsor other abnormalitiesto sug in the range of5O%-60% (3). gest recurrent osteomyelitis. The use of intravenously injected indium-i 1l-chlo The patient was able to am ride (‘‘‘In-chloride)to detect infection has been re bulatewithfullweightand had full range of motion of ported by Sayle (4). It has been postulated that follow the knee joint.There was no ing administration, ‘I‘Inbinds in vivo to transferrmn dinical evidenceof infection. and albumin. The authors were unable to explain the

Indium-LabeledWBC Scintigraphy in Evaluating Osteomyelitis •Esterhai and Silfen 2031 mechanisms of enhanced ‘‘‘In-chlorideaccumulation and without significant segmental loss), “B― over and above that noted with gallium-67-citrate. (tibial defect more than 3 cm in length with intact The possibility of using labeled leukocytes to detect fibula), and “C―(tibial defect more than 3 cm long with abscesses was hampered for years by the lack of a fractured fibula) (14). suitable gamma-emitting preparation. In the mid The classification system used at this institution is a 1970s, McAfee et al. demonstrated that leukocytes modification of that developed by Cierny and Mader. could be successfully labeled with ‘‘‘Inand still remain In the Cierny-Mader classification the extent of bone physiologically active (5). Recent work published in the involvement is described as: 1-medullary; Il-superficial; orthopedic literature from the Mayo Clinic (6) and Ill-localized; N-diffuse. The physiologic class of the Walter Reed Army Hospital (7) have documented the host is described as either. A, uncompromised; BL, soft effectiveness of using ‘‘‘In-labeledleukocytes to evalu tissues compromised locally; BS, patient systemically ate painful total joint arthroplasty prostheses for possi compromised; and BL,BS, patient with local and sys ble infection. temic compromise. Examples of local compromise Twenty patients were studied prospectively at our would include venostasis, chronic lymphedema, major institution with indium-labeled leukocyte imaging to vessel compromise, radiation fibrosis, or extensive scar evaluate its effectiveness in differentiating noninfected, ring. Examples of systemic host compromise would delayed, or nonunion from osteomyelitis complicating include malnutrition, immune deficiency, chronic hy these entities. All patients underwent an open surgical poxia, malignancy, extremes of age, renal or liver fail procedure within 24 hr ofthe indium scan. Bone spec ure, and . imens from the nommmune site were obtained for The patient presented in this CPC is typical of pa microbiologic and histologic analysis to confirm the tients with chronic infection who are referred for defin presence or absence of osteomyelitis. In these 20 pa itive management. His intimal injury was severe and tients, the overall accuracy for indium-labeled leukocyte progressed to chronic infection in spite of appropriate scintigraphy was 100%. medical and surgical care. During three aggressive de Why is the presence and exact localization of infec bridement surgeries at this institution, the entire femo tion so important to the orthopedic surgeon? Preoper ml shaft sequestration was removed without compro ative planning involves gathering as much information misc ofthe structural integrity ofthe involucrum. Com as possible to guarantee a good outcome from the pare the appearance of the femur in Figure 3 with that surgical procedure. Many patients with chronic osteo in Figure 4. However, the wound did not heal as cx myelitis have undergone multiple surgeries over an pected in a healthy young patient. The indium-WBC extended period of time. Their anatomy is distorted. scan documented a significant amount of residual ac Adequate knowledge about the nature ofthe underlying tivity in the distal femur at the level of the epiphyseal processes allows the surgeon to intelligently inform his plate suggesting persistent infection at that site. Subse patient about the impending surgery. quent debridement concentrating specifically at that Clearly, all patients with osteomyelitis are not iden level revealed persistent granulation tissue in the tract tical. Several classification systems have been suggested of the patient's original blade plate. Knowledge of this to allow for optimal comparison of published results. remaining focus allowed the specific area to be success Waldvogel described three categories of osteomyelitis: fully debrided culminating in eradicatiOn of the osteo hematogenous; contiguous focus; and osteomyelitis as myelitis. sociated with major vessel disease (9). Kelley's classifi The records of 33 patients operated on at this insti cation emphasized the etiology of the infection and the tution for infection revealed that 14 had region involved: chronic hematogenous osteomyeitis; sustained initial open fractures. The interval from in osteomyelitis with fracture nonunion; post-traumatic jury to referral was 26 mo. Each patient had had prior or postoperative osteomyeitis; vertebral osteomyeitis; surgery. The average number of previous surgeries was involvement of small of the foot, skull, face, and 5.5 (range 1-47). The interval from the last surgery to hand (10). Gere's classification addressed the physiol the evaluation at HUP averaged 10 mo (range 1-28 ogy of the wound: simple sinus; chronic superficial mo). Indium-i 11-labeled WBC scintigraphy performed ; multiple sinuses; multiple -lined sinuses (11). on these patients was accurate in detecting infection In 1984, Weiland proposed a three-part classification: and in localizing the site. Schauwecker has reported Type I, characterized by open exposed bone with soft imaging results of 9 patients with hematogenous or tissue but no bone infection; Type II, characterized by contiguous spread osteomyelitis, 19 patients after bone circumferential cortical and endosteal infection; and surgery or , 8 with prosthetic loosening, 7 Type III, cortical and endosteal infection with associ post-fracture, 7 with neuropathic , and 4 with ated segmental bone loss (12). Gordon related the prog (15). The ‘‘‘In-labeledWBC scintigraphy was nosis in his classification to the severity of the under 100% sensitive in osteomyeitis and 60% sensitive lying bone damage, describing Types “A―(tibial defect in chronic osteomyelitis. Only 33 of his 57 patients had

2032 The Journal of Nuclear Medicine•Vol.31 •No. 12 •December 1990 surgical . He attributed the 60% sensitivity in REFERENCES chronic osteomyelitis to the differential content of the chronic inflammatory cell population, with relatively 1. Gustilo RB, Merkow RL, Templeman D. Current concepts fewer granulocytes. review:the management of open fractures.J BoneJoint Surg Merkel reported on the pathologic and microbiologic 1990;72A:299—304. 2. FitzgeraldRH. Experimentalosteomyelitis:descriptionof a findings of 30 patients evaluated with ‘‘In-WBC and canine model and the role of depot administration of antibi sequential conventional bone and gallium scintigraphy. otics in the prevention and treatment of .J Bone Joint For indium-WBC scintigraphy, the overall sensitivity Surg 1983;65A:371—380. was 83% with a specificity of86% and accuracy of 83%. 3. Esterhai JL, Alavi A, Mandell GA, Brown J. Sequential The authors felt that not only was indium-WBC scan technetium-99m/gallium-67 scintigraphic evaluation of sub clinical osteomyelitis complicating fracture nonunion. J Orth ning more accurate than gallium but that it was also Res 1985;3:219—225. easier to interpret (3). 4. Sayle BA, Fawcett HD, Wilkey DJ, Ciemy G, Mader JT. False-negative indium-WBC studies secondary to Indium-i 11-chloride imaging in chronic osteomyelitis. JNucl poor labeling of the leukocytes have been reported. Med 1985;26:225—229. Strict quality control is ofparamount importance if the 5. McAfee JG, Thakur ML. Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. J NucI Med 1976; study is to have optimal accuracy. Although some au 17:480—487. thors have reported difficulty in documenting chronic 6. MerkelKD, BrownML, DewanjeeMK, FitzgeraldRH. Corn osteomyelitis, indium-WBC imaging has proven quite parison of indium-labeled leukocyte imaging with sequential accurate in defining even subtle infections in the series technetium-gallium scanning in the diagnosis of low-grade described above from our institution (8). musculoskeletalsepsis.J BoneJoint Surg 1985;67:465—476. 7. Wukich DK. Diagnosis of infection by preoperative scintig Indium-labeled leukocyte imaging, though perfectly raphy with indium-labeled white blood cells. J Bone Joint acceptable, fails to fulfill one of the criteria for scinti Surg1987;69:1353—1360. graphic approach to detect occult bone infection. Al 8. Esterhai JL, Goll SR, McCarthy KE, et al. Indium-l 11- though there are no contraindications and no compli leukocyte scintigraphic detection of subclinical osteornyelitis cations are associated with the labeled leukocytes, the complicating delayed and nonunion long bone fractures. A prospectivestudy. J Orth Res 1987;5:1—6. radiation dose is not insignificant. The labeling of the 9. Waldvogel FA, Medoff G, Swartz MN. Osteornyelitis: a re autologous leukocytes with indium requires time-con viewof clinical features, therapeutic considerations, and un suming red blood cell sedimentation, differential cen usual aspects. N Engl J Med 1970; 282:198—206;260—266; trifugation, separation of leukocytes from platelet-rich 316—322. plasma, and washing to remove plasma-borne indium 10. Kelly PJ. Infected nonunion of the femur and . Orthop ClinNorthAm 1984;13:481—490. transferrin if optimal labeling efficiency is to be ob I 1. Ger R. Muscle transposition for the treatment of osteomye tamed. This process is quite labor-intensive and requires litis.InstructionalCourseLecture#204. 49th Annual Meeting special skills. Twenty-four hours is typically required ofAAOS, New Orleans, Louisiana, 1982. between injection of the labeled cells and imaging. 12. Weiland AJ, Moore JR, Daniel RK. The efficacy offree tissue Indium-labeled leukocyte imaging does not always pre transfer in the treatment of osteomyelitis.J Bone Joint Surg 1984;66A:l8l—193. cisely define the proximal and distal bone extent of the 13. Gordon L, Chiu E. Treatment of infected and infection. Research involving magnetic resonance im segmental defects ofthe tibia with staged rnicrovascular mus aging and indium-labeled IgG scans may offer alterna dc transplantation and bone grafting. JBoneJoint Surg 1988; tive approaches to defining the presence and extent of 70A:377—386. infection. 14. Cierny G, Mader JT. Adult chronic osteomyelitis. Orthopaed ics 1984; 7:1557. At present, indium-labeled WBC scintigraphy is the 15. Schauwecker DS, Park HM, Mock BH, et at. Evaluation of imaging study of choice for long bone infection com complicating osteornyelitiswith Tc-99m-MDP, In-l 1l-gran plicating trauma. ulocytes,Ga-67-citrate.J Nuci Med 1984;25:849—854.

Indium-Labeled WBC Scintigraphy in Evaluating Osteomyelitis •Esterhai and Silfen 2033