Wk3 Osteomyelitis of the Lower Extremity PDF

Emerg Radiol (2018) 25:175–188 https://doi.org/10.1007/s10140-017-1564-9 REVIEW ARTICLE Osteomyelitis of the lower extremity: pathophysiology, imaging, and classification, with an emphasis on diabetic foot infection Jacob C. Mandell 1 & Bharti Khurana 2 & Jeremy T. Smith 3 & Gregory J. Czuczma...

Emerg Radiol (2018) 25:175–188 https://doi.org/10.1007/s10140-017-1564-9 REVIEW ARTICLE Osteomyelitis of the lower extremity: pathophysiology, imaging, and classification, with an emphasis on diabetic foot infection Jacob C. Mandell 1 & Bharti Khurana 2 & Jeremy T. Smith 3 & Gregory J. Czuczman 1 & Varand Ghazikhanian 1 & Stacy E. Smith 1 Received: 9 September 2017 / Accepted: 11 October 2017 / Published online: 20 October 2017 # American Society of Emergency Radiology 2017 Abstract Osteomyelitis is inflammation of the bone caused subjacent to an ulcer or sinus tract. In contrast, neuropathic by an infectious organism, and is a difficult clinical problem. arthropathy tends to involve multiple bones of the midfoot. The pathophysiology, imaging, and classification of osteomy- Subchondral cystic change, thin rim enhancement of a joint elitis are challenging, varying with the age of the patient (child effusion, and the presence of intra-articular bodies are more versus adult), the chronicity of the infection (acute versus indicative of a neuropathic joint without infection. Biopsy can chronic), and the route of spread (hematogenous versus con- play an important role in diagnosis and treatment of tiguous focus), as well as the immune and vascular status of osteomyelitis. the patient and affected region. The two most common clas- sification schemes are those of Lew and Waldvogel, and Keywords Osteomyelitis. Lower extremity. Foot and ankle. Cierny and Mader. Brodie’s abscess is seen in subacute oste- Neuropathic arthropathy. Diabetic foot infection omyelitis, while sequestrum, involucrum, and cloaca are inter- related entities of chronic osteomyelitis. Imaging workup of suspected osteomyelitis should begin with radiographs, al- though MRI is the most accurate imaging test. Three patterns Introduction of T1 signal change have been described in the setting of suspected osteomyelitis including confluent intramedullary, Osteomyelitis, defined as inflammation of the bone caused by hazy reticular, and subcortical. The confluent intramedullary an infectious organism, is a difficult clinical problem to diag- pattern is most associated with osteomyelitis, while hazy re- nose, treat, and classify, often requiring a multidisciplinary ticular is rarely associated with hematogenous osteomyelitis, approach. Patients commonly present to the emergency and subcortical is not associated with osteomyelitis. It can be department with either signs or symptoms related to underly- challenging to differentiate neuropathic arthropathy from os- ing osteomyelitis, or with clinical concern for possible osteo- teomyelitis. Osteomyelitis tends to involve a single bone myelitis. It is therefore important for the emergency radiolo- gist to have a thorough understanding of the imaging and pathophysiology of this challenging problem. Osteomyelitis * Jacob C. Mandell has afflicted humanity since the earliest recorded history, with [email protected] the oldest recorded account in the Edwin Smith papyrus dat- ing from the seventeenth century BC, although signs of chron- 1 ic osteomyelitis have also been identified in hominid fossils Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Brigham and Women’s Hospital, Harvard Medical from far earlier. In modern times, the incidence of osteo- School, Boston, MA 02115, USA myelitis has nearly tripled among older adults in the past 2 Division of Emergency Radiology, Department of Radiology, 30 years, driven predominantly by an increase in diabetes- Brigham and Women’s Hospital, Harvard Medical School, related pedal osteomyelitis. Post-traumatic osteomyelitis, Boston, MA, USA most commonly due to open fractures, has also increased in 3 Department of Orthopedic Surgery, Brigham and Women’s Hospital, prevalence in the past century, thought to be due to improved Harvard Medical School, Boston, MA, USA survival following traumatic injury. 176 Emerg Radiol (2018) 25:175–188 The pathophysiology, imaging, and classification of osteo- The terminology of various entities seen in non-acute oste- myelitis is challenging, varying with the age of the patient omyelitis can be confusing. There are four named lesions that (child versus adult), the chronicity of the infection (acute ver- deserve clarification, which include Brodie’s abscess, seques- sus chronic), and the route of spread (hematogenous versus trum, involucrum, and cloaca. Brodie’s abscess is a localized contiguous focus), as well as the immune and vascular status manifestation of subacute osteomyelitis, while sequestrum, of the patient and affected region. To further complicate mat- involucrum, and cloaca are inter-related entities of chronic ters, common clinical scenarios such as diabetic pedal osteo- osteomyelitis. myelitis have unique anatomic, imaging, and treatment con- Brodie’s abscess, first described by Sir Benjamin Brodie in siderations. In this review, we will describe the pathophysiol- 1832, represents an intra-osseous abscess (Fig. 3). It is con- ogy and imaging of osteomyelitis of the lower extremity in sidered a form of subacute osteomyelitis, although Brodie’s adults, present an overview of the classification of osteomye- abscess has been reported to develop within a variable time litis, and provide a focused discussion on diabetic pedal period ranging from 1 week to 1 year after the first acute osteomyelitis. symptoms. The signs and symptoms of acute osteomye- litis, such as fever and recent onset pain, are typically absent. The Roberts classification of Brodie’s abscesses, which is be- yond the scope of this article, defines six types depending on Pathophysiology of osteomyelitis the anatomic location, with the most classic case a metaphyseal lucent lesion with sclerotic borders. On Osteomyelitis can be acute, subacute, or chronic in duration MRI, the classic appearance of a Brodie’s abscess is a fluid (Fig. 1), although the differentiation between these designa- signal intensity lesion, sometimes with a peripheral tions is variably described. In general, acute osteomyelitis is Bpenumbra^ sign. The Bpenumbra^ sign represents a thin defined as either less than 10-day or 2-week duration, rim of vascularized granulation tissue and is reflected as hy- while subacute osteomyelitis describes the phase of disease perintense signal on T1-weighted images at the periphery of lasting less than 3-month duration but lacking acute symp- the intra-osseous abscess. The Bpenumbra^ sign is report- toms. However, this distinction between acute and subacute ed to have a specificity of 96% for the presence of infection phases is arbitrary , and the chronicity of osteomyelitis can (although a sensitivity of only 27%) and has been advocated also be divided into acute and non-acute (encompassing both as being a reliable sign to differentiate between subacute os- subacute and chronic) phases. The hallmark of chronic osteo- teomyelitis (Bpenumbra^ sign present) and neoplasm. myelitis is the development of bone necrosis, which is usually A sequestrum is a segment of devascularized bone that surrounded by sclerotic, hypovascular bone, thickened perios- becomes separated (Bsequestered^) from host bone due to teum, and compromised surrounding soft tissues. surrounding necrosis, thereby providing a safe harbor for bac- Bone may become infected through contiguous spread, teria that is inaccessible to antibiotics. A sequestrum is a such as extension of an adjacent soft-tissue infection or direct lesion of chronic osteomyelitis. The definitive treatment of a inoculation from trauma, or by hematogenous dissemination. sequestrum is surgical resection. A sequestrum is best imaged Non-spinal hematogenous osteomyelitis is predominantly a with CT (Fig. 4), where it will appear as a mineralized seg- disease of childhood due to its predilection to involve the ment of bone with circumferential surrounding lucency. highly vascularized metaphyseal region of growing bone. However, the imaging appearance of an apparent sequestrum Although pediatric osteomyelitis is not the focus of this re- is not pathognomonic for chronic osteomyelitis. Several pri- view, it is helpful to understand the role of osseous blood mary bone tumors may produce a mineralized matrix that can supply in the etiology of hematogenous osteomyelitis. simulate a sequestrum, most notably osteoid tumors such as Specifically, the metaphysis is the primary site of infection osteoid osteoma or osteoblastoma. In contrast to a seques- in older children and adults due to sluggish flow in terminal trum, which typically features an irregular margin, the calcifi- capillaries at the junction between the physis and the cation at the center of an osteoid osteoma nidus (Fig. 5) is metaphysis. This is in contrast to the pattern of infection smooth and round. typically seen in young children under 18 months of age, Involucrum describes reactive bone sclerosis that surrounds where direct vascular communication between the epiphyseal the sequestrum , and which functions to isolate the se- and metaphyseal vessels contributes to early extension of in- questrum from the bloodstream similar to a walled-off abscess fection into the epiphysis and resultant greater incidence of. septic arthritis in this young age group. In adults, hema- Finally, a cloaca is an opening or rupture of the involucrum togenous osteomyelitis predominantly involves the spine, that allows granulation tissue to be discharged , and which with the vertebral body endplate the most common nidus of can give rise to a subperiosteal abscess. Eventually, a infection. Non-spinal hematogenous osteomyelitis (Fig. 2) in sinus tract may result if the cloaca communicates with the skin adults is rare. surface through the soft tissues. Longstanding sinus tracts Emerg Radiol (2018) 25:175–188 177 Fig. 1 Illustration demonstrates the findings in acute, subacute, and typically seen in young adults. Chronic osteomyelitis features chronic osteomyelitis. The initial infection in acute hematogenous characteristic bony lesions including sequestrum (devitalized, necrotic osteomyelitis is usually metaphyseal. In subacute osteomyelitis, a bone surrounded by osteomyelitis) and involucrum (reactive new bone Brodie’s abscess may develop, which is an intra-osseous abscess that is through which sinus tracts may form) from chronic osteomyelitis may lead to malignant transforma- osteopenia and periosteal new bone formation. It typically tion, with squamous cell carcinoma the most frequent malig- takes 2–3 weeks for a cortical erosion to develop , and bony nancy [1, 17]. destruction may be evident in the late stage of disease. In contiguous focus osteomyelitis, the radiologist should carefully search for an ulcer tract, which can be seen on radio- Imaging of osteomyelitis graphs as a lucent soft tissue defect at the skin surface, often with foci of gas extending to the underlying bone. Imaging workup of suspected osteomyelitis should begin with Radiographic findings of contiguous focus osteomyelitis in- radiographs [15, 18], which are often negative but can provide clude ill-defined cortical erosion contiguous with the ulcer a helpful anatomic overview and allow one to evaluate for tract and focal osteopenia , corresponding to trabecular possible alternative diagnoses such as fracture. The radio- lysis. Bony destruction and soft tissue or intra-osseous gas graphic findings of osteomyelitis may differ depending on can be present in advanced cases. the route of spread, although the imaging findings mirror the CT is able to image a large anatomic region rapidly and is pathophysiology in both hematogenous and contiguous focus therefore commonly used in the assessment of infection in the osteomyelitis. The earliest radiographic changes of hematog- emergency department. While CT is less sensitive than enous osteomyelitis occur in the soft tissues, with soft tissue MR and nuclear medicine studies for detecting early swelling evident within 2–3 days of symptom onset [19, 20]. intramedullary changes of osteomyelitis, CT is an excellent Bony changes of hematogenous osteomyelitis are not typical- modality to evaluate for soft-tissue infection in the emergency ly seen until 10–12 days and begin in the medullary department, due to its ability to reliably detect soft tissue ab- cavity and extend outward. In general, at least 30% of the bone scess and soft tissue gas. CT can also detect small foreign matrix must be destroyed for changes to be evident on con- bodies that may serve as a nidus of infection. Similar to ventional radiography. Early bone changes include focal radiography, the CT findings of osteomyelitis depend on the A B C Fig. 2 A 31-year-old male with a history of intravenous drug abuse and and sagittal proton-density-weighted image with fat suppression (c) show biopsy-proven acute hematogenous osteomyelitis. Frontal radiograph of heterogeneous bone marrow edema-like signal in the central femoral the knee (a) demonstrates a lytic lesion of the distal femoral metaphysis metaphysis, which appears confluent on the T1-weighted sequence (arrows) with a wide zone of transition. Coronal T1-weighted image (b) (arrows) 178 Emerg Radiol (2018) 25:175–188 A B C Fig. 3 A 34-year-old female with Brodie’s abscess. Frontal knee abscess of the proximal tibial metaphysis, consistent with a Brodie’s radiograph (a) demonstrates a lucent lesion in the proximal tibial abscess. There is disruption of the anterior cortex and the periosteum, metaphysis with a sclerotic margin (yellow arrows). Sagittal proton- and formation of a sinus tract (red arrows) into the pretibial soft tissues. density weighted MR (b) and T1-weighted post-contrast MR (c), both Edema-like signal tracks superiorly into the inferior margin of Hoffa’s fat with fat suppression, demonstrate a peripherally enhancing intra-osseous pad (blue arrow), raising concern for developing septic arthritis route of spread but generally include soft tissue swelling, peri- therefore rarely a helpful test in isolation. In contrast, a osteal reaction, decreased attenuation of the medullary space, radiolabeled leuokocyte scan is both sensitive and specific, and cortical erosions. Additionally, CT is the best modal- and is considered the radionuclide test of choice for evaluation ity to assess characteristic bony changes of chronic osteomy- of osteomyelitis, with an accuracy of approximately 90% elitis including sequestrum, involucrum, and cloaca [15, 24]. when combined with sulfur colloid imaging. A recent Ultrasound can visualize superficial fluid collections, joint systematic review of imaging tests to evaluate for diabetic foot effusions, or subperiosteal abscesses in pediatric patients ; infection found that a radiolabeled leukocyte scan with 99mTc- however, ultrasound is not a first-line modality for assessment hexamethylpropyleneamineoxime (HMPAO) had a sensitivity of suspected osteomyelitis. of 91% and specificity of 92%, in contrast to MR with a Radionuclide imaging can play a role in problem solving sensitivity of 93% and specificity of 75% for this specific extremity infection. Notably, radionuclide imaging may be clinical scenario. However, MRI remains the preferred helpful in the setting of suspected osteomyelitis with extensive modality for comprehensive assessment of suspected extrem- hardware present , and also in differentiating osteomyeli- ity infection in most cases. tis from neuropathic arthropathy. A three-phase bone MRI is the most accurate imaging test for assessment of scan is sensitive, although not specific in differentiating oste- suspected osteomyelitis, with a meta-analysis showing a sen- omyelitis from a neuropathic foot due to the increased osteo- sitivity of 90% and specificity of 79%. Intravenous con- blastic activity seen in both infection and arthropathy, and is trast is preferred for assessment of suspected osteomyelitis, A B C Fig. 4 A 27-year-old male with chronic osteomyelitis, sequestrum, and femur demonstrates a central lucent lesion, completely surrounding a involucrum. Lateral radiograph of the femur (a) demonstrates extensive sclerotic and irregular segment of bone. The central sclerotic segment cortical thickening, and an intramedullary lucency with central sclerosis (yellow arrows) represents a sequestrum. There is surrounding reactive (yellow arrow). Axial (b) and sagittal (c) noncontrast CT through the bone formation (red arrows), also known as involucrum Emerg Radiol (2018) 25:175–188 179 Fig. 5 A 55-year-old male with A B osteoid osteoma of the talus. Axial (a) and sagittal (b) non- contrast CT images of the ankle demonstrate a lucent lesion of the anterior aspect of the talar neck with a round calcified central nidus (yellow arrows). In contrast to a sequestrum, which features a central calcification with irregular margins and irregular shape, the central mineralization of an osteoid osteoma has smooth margins and round shape but is not necessary for its diagnosis. Specifically, soft-tissue Not all signal alterations evident on T1-weighted images abscesses may not be apparent without the presence of con- correspond to osteomyelitis, however. Three discrete patterns trast to delineate the typical peripheral enhancement pattern. of decreased (iso- or hypointense relative to muscle) signal on Additionally, the presence of non-enhancing necrotic bone T1-weighted imaging performed for suspected pedal osteomy- with preserved T1 signal intensity may be masked in the ab- elitis were initially described by Collins et al. , including sence of intravenous contrast. Intravenous contrast can help to confluent intramedullary, subcortical, and hazy reticular guide surgical management, as the preferred treatment of ne- (Fig. 6). Collins reported that all confirmed cases of osteomy- crotic tissues is surgical resection , and contrast assists in elitis demonstrated the confluent intramedullary pattern (Fig. 7) identification and demarcation of areas of necrotic, non- of decreased signal intensity on T1-weighted images, although enhancing bone or soft tissue. this pattern was not specific. The hazy reticular (Fig. 8) and The imaging assessment of suspected osteomyelitis should subcortical (Fig. 9) patterns did not represent osteomyelitis in begin with a fluid sensitive sequence (T2-weighted/PD- any case. A follow-up study of pedal osteomyelitis by Johnson weighted with fat suppression or STIR), which is the most et al. confirmed that the confluent intramedullary pattern of sensitive sequence type to evaluate for osteomyelitis. If the decreased signal on T1-weighted images corresponded to a fluid sensitive sequence is normal, osteomyelitis is exceeding- sensitivity of 95% and specificity of 91% for detection of oste- ly unlikely to be present. However, bone marrow edema-like omyelitis; however, this pattern was also present in 9% of cases signal is a non-specific finding and its presence only alerts one proven not to represent osteomyelitis. Johnson also confirmed to the possible presence of osteomyelitis. If bone marrow ede- that none of the cases of subcortical or hazy reticular pattern of ma is present, the T1-weighted sequence is critical to further decreased signal on T1-weighted images represented osteomy- characterize the signal abnormality and increase specificity. elitis. Howe et al. applied these patterns of T1-weighted Although rare false negatives have been reported (as will be imaging seen in pedal osteomyelitis by Collins and Johnson to subsequently discussed), it is generally considered necessary both contiguous focus and hematogenous non-pedal osteomy- to demonstrate decreased signal intensity on T1-weighted im- elitis and found that non-pedal osteomyelitis largely followed ages to diagnose osteomyelitis. the T1-weighted imaging features of pedal osteomyelitis, dem- When bone marrow edema is evident on T2-weighted im- onstrating confluent intramedullary decreased signal intensity. ages but the T1-weighted images are normal, radiologists may However, Howe also described five cases of osteomyelitis with describe this phenomenon as osteitis, rather than osteomyeli- Batypical^ imaging findings, where confluent intramedullary tis, implying that infection is thought to be not present. This decreased signal intensity was absent; four of which were he- terminology may lead to confusion, as osteitis means matological in etiology. Binflammation of the bone^ and has been used to imply in- Although decreased signal intensity on T1-weighted im- flammation of the cortex only. In contrast, osteomyelitis ages is almost always present in osteomyelitis, there have been means Binflammation of the medullary cavity of bone.^ rare reports of pathologically or culture-proven osteomyelitis Neither term strictly describes the presence or absence of in- corresponding to regions of normal T1 signal [33, 35], possi- fection, although osteomyelitis is universally understood to bly reflecting necrotic bone with fatty marrow signal. mean infection of the bone. To avoid this potential confusion, Additionally, if bone marrow edema is evident on T2- the authors suggest using terminology such as Bbone marrow weighted sequences subjacent to an ulcer, then normal T1- edema-like signal, thought to be most likely reactive^ or sim- weighted images should be interpreted with caution. Duryea ply Breactive osteitis^ when describing bone marrow edema et al. recently demonstrated that 61% of patients with with normal T1-weighted images. suspected pedal osteomyelitis and isolated T2 signal 180 Emerg Radiol (2018) 25:175–188 Fig. 6 Illustration demonstrates three described patterns of T1 signal osteomyelitis, but it has rarely been reported to represent hematogenous alteration. The confluent medullary pattern is highly associated with osteomyelitis. Subcortical T1 signal changes are not associated with osteomyelitis. The hazy reticular pattern of decreased signal intensity osteomyelitis on T1-weighted images is not associated with contiguous focus abnormality deep to an ulcer with corresponding normal T1- In 1985, Cierny and Mader developed a classification of weighted imaging ultimately developed osteomyelitis, and osteomyelitis that combined four anatomic types with three therefore these patients should be carefully followed clinically host physiologic classes (Table 1). The Cierny-Mader even if treated empirically. classification can be helpful to guide treatment options, al- though this classification scheme is most useful in large or long bones with large marrow spaces and is less helpful in the digits or small bones, such as the foot. Anatomic type Classification of osteomyelitis 1 represents infection of the medullary space, with the primary lesion endosteal in location, typically due to early hematoge- In 1970, Lew and Waldvogel described three fundamental nous spread. Type 2 represents early contiguous focus osteo- types of osteomyelitis as hematogenous, contiguous focus, myelitis involving either the periosteum or the cortex. Type 3 and contiguous focus with vascular insufficiency [37–39]. is a full thickness cortical disruption, most commonly follow- Additionally, any of these categories may be acute or chronic. ing trauma but possibly resulting from extension of medullary These basic concepts are still in wide use today; however, no osteomyelitis. Type 4 is circumferential or Bthrough-and- guidance is provided as to the severity of each type of infec- through^ involvement of the bone and surrounding soft tissue. tion or treatment implications. Of these four primary anatomic types of osteomyelitis, type 4 Fig. 7 A 61-year-old woman with osteomyelitis of the fibular stump after below-the-knee amputation, demonstrating typical confluent intramedullary pattern of decreased signal intensity on T1-weighted images. Coronal STIR (a) and coronal T1- weighted (b) images demonstrates extensive bone marrow edema within the residual fibular stump, corresponding to diffusely decreased signal intensity on T1-weighted images extending through the intramedullary space (arrows), consistent with a confluent intramedullary pattern A B Emerg Radiol (2018) 25:175–188 181 A B Fig. 8 A 58-year-old man with an ulcer (yellow arrow) subjacent to the between the intact cortex and the regions of signal change. Given the great toe MTP, demonstrating the hazy reticular pattern of T1 signal presence of the ulcer directly subjacent to the area of signal change, a change, which is not associated with osteomyelitis. There is mild bone CT-guided biopsy was performed, which was negative for osteomyelitis. marrow edema of the head of the first metatarsal evident on the sagittal Although the hazy reticular pattern is not associated with contiguous STIR image (a). The corresponding T1-weighted image (b) demonstrates focus osteomyelitis, this pattern has rarely been associated with hazy reticular decreased signal (red arrow), with intervening fat present hematogenous osteomyelitis is the most severe and difficult to treat, with aggressive de- Differential diagnosis of non-pedal osteomyelitis bridement necessary to lower the treatment failure rate, but with surgery inevitably causing unstable bone and soft tissue The differential diagnosis of greatest clinical concern when defects. The host physiology is divided into three classes, evaluating a case of non-pedal osteomyelitis is malignancy. including normal immunity (A-host), local or systemically In particular, the imaging appearance of Ewing sarcoma compromised immunity (B-host), and hosts in whom treat- (Fig. 11) often overlaps with osteomyelitis, especially in the ment is worse than disease (C-host). younger patient population. Ewing sarcoma is the second For simplification, the authors suggest thinking of an- most common primary bone neoplasm in children and young atomic types 1 and 2 as early disease (type 1 is early adults, typically occurring in the long bones of the lower ex- hematogenous and type 2 is early contiguous focus). tremities and pelvis in patients between 1 and 30 years of age Types 3 and 4 are simply more advanced disease, which. The clinical presentation of Ewing sarcoma may mimic may be from progression of contiguous focus or hematog- osteomyelitis, commonly presenting with pain, swelling, and enous osteomyelitis. Since types 1 and 2 are not progres- fever from tumor necrosis. Additionally, it is often difficult to sive, it may be more intuitive to emphasize the descriptive differentiate osteomyelitis from Ewing sarcoma on radio- name of each anatomic type rather than the number graphs and MRI. One study showed that the most reliable (Fig. 10). MR imaging feature to differentiate between these two entities A B Fig. 9 A 61-year-old woman with mild signal changes of the plantar sagittal T1-weighted image (b) demonstrates corresponding decreased calcaneus demonstrating the subcortical pattern of decreased signal on signal intensity confined to the subcortical region (red arrows). A T1-weighted images, which is not associated with osteomyelitis. Sagittal biopsy was not performed in this case; however, the patient recovered STIR MR (a) demonstrates edema of the plantar fat pad and mild bone fully with conservative management only marrow edema of the calcaneus more posteriorly (yellow arrow). The 182 Emerg Radiol (2018) 25:175–188 Table 1 The Cierny-Mader combined anatomic and physiologic clas- recent study of 63 patients (32 with osteomyelitis and 31 with sification of osteomyelitis Ewing sarcoma) found no single distinguishing feature, Anatomic type although permeative cortical involvement and soft-tissue mass Type 1 Medullary osteomyelitis (early hematogenous) were more likely in subjects with Ewing sarcoma, while a Type 2 Superficial osteomyelitis (early contiguous focus) serpiginous tract was more likely in osteomyelitis. Type 3 Localized osteomyelitis Additionally, as previously mentioned, the Bpenumbra^ sign Type 4 Diffuse osteomyelitis of a Brodie’s abscess, representing vascular, T1-hyperintense granulation tissue, is highly specific for infectious etiology, Physiologic class although to our knowledge, there is a single case report where A-host Normal physiologic response to infection a diffuse large B cell lymphoma mimicked Brodie’s abscess B-host Immunity compromised locally or systematically with an apparent penumbra sign. C-host Treatment worse than disease Diabetic pedal osteomyelitis is the presence of a sharp and well-defined margin of the bone lesion on T1-weighted and STIR sequences, seen in all pa- Over one million cases of diabetic foot complications present- tients with Ewing sarcoma but in no patients with osteomye- ed to United States emergency departments from 2006 to litis in a study of 28 patients. However, a larger and more 2010, with serious adverse outcomes in 22.1% including mor- tality (2%), sepsis (9.6%), and amputation (10.5%). Foot ulcers are a common complication of diabetes, seen in 5.8% of diabetic patients over a 3-year period of observation, and greatly contribute to health care spending with the average cost per patient reaching nearly $28,000 in 1999. Fifteen percent of diabetic patients with ulcers also develop osteomyelitis ; however, the imaging assessment of suspected osteomyelitis in diabetic patients is made more dif- ficult by the often-concomitant presence of neuropathic ar- thropathy and other bony changes in the feet including infarct, avascular necrosis, osteochondritis, and occult fracture. The etiology of diabetic foot infection is complex, with sen- sory, autonomic, and motor neuropathy thought to be the pri- mary factors, and vascular insufficiency and relative immuno- deficiency the secondary factors. The sensory neuropathy predisposes to mechanical trauma without awareness. The au- tonomic neuropathy decreases sweat production, leading to a buildup of abnormal dry callus that is prone to cracking and ulcer formation, thereby allowing entry of microorganisms into the soft tissues. The motor neuropathy affecting the intrinsic muscles of the foot leads to gait disturbances, including ham- mer toes and claw toes, which result in maldistribution of weight-bearing and elevated focal skin pressure. Additionally, diabetic patients often develop an Achilles contracture, which leads to increased plantar forefoot pressures that contribute to forefoot callus and ulceration [49, 50]. Finally, when micro- organism entry occurs, the secondary factors of vascular insuf- ficiency and relative immunodeficiency of diabetes hinder proper healing. Successful healing requires an increase in local Fig. 10 The Cierny-Mader classification of osteomyelitis. Medullary perfusion, which the ischemic lower extremity cannot ade- osteomyelitis (type 1) and superficial osteomyelitis (type 2) can be quately supply since its microcirculation is already maximally thought of as early hematogenous and early contiguous focus, or near-maximally vasodilated to provide rest perfusion. respectively. Note that types 1 and 2 are not sequential. Localized osteomyelitis (type 3) is from progression of contiguous focus or By the Lew and Waldvogel classification, nearly all hematogenous osteomyelitis, and diffuse osteomyelitis (type 4) is diabetic patients with pedal osteomyelitis have chronic Bthrough-and-through^ disease of the bone and surrounding soft tissues contiguous focus infections , typically associated with Emerg Radiol (2018) 25:175–188 183 A B C Fig. 11 A 21-year-old male with Ewing sarcoma. Radiograph (a) (red arrow) between the lesion and normal marrow at the greater demonstrates a subtle lucency (yellow arrows) of the left proximal trochanter, a feature that is suggestive of tumor rather than infection. femoral diaphysis with associated endosteal scalloping laterally and Sagittal PD-weighted image with fat suppression (c) shows diffuse bone cortical thickening medially. This appearance can mimic osteomyelitis. marrow edema of the proximal femur with an associated soft-tissue mass Coronal T1-weighted STIR image of both hips (b) demonstrates diffusely (blue arrows), an additional feature that is seen in Ewing sarcoma rather decreased signal intensity of the proximal femur. Note the sharp transition than infection vasculopathy. By the Cierny and Mader classifica- the fifth and first metatarsophalangeal joints and manifesting tions, the majority of diabetic pedal osteomyelitis would on MR as synovial enhancement and adjacent cellulitis. be classified as superficial (type 2) in a physiologically Primary and secondary signs have been described in the compromised host with local and systemic compromise MR imaging of pedal osteomyelitis. As previously discussed, (B-host), while more severe or chronic infections may a confluent intramedullary pattern of decreased signal intensi- progress to localized (type 3) or diffuse (type 4) osteomy- ty on T1-weighted images is the most accurate primary imag- elitis. The Cierny-Mader classification is not espe- ing finding of osteomyelitis in the foot or elsewhere in the cially useful in the evaluation of pedal osteomyelitis, skeleton. Secondary signs of osteomyelitis can greatly in- and to our knowledge, this classification system is not crease the confidence of diagnosis, especially if there are al- used in the radiology literature of pedal osteomyelitis. terations in bone marrow signal due to concomitant non- The fifth metatarsal, first metatarsal (Fig. 12), calcaneus infectious processes, and include the presence of cutaneous (Fig. 13), and great toe distal phalanx are the four most fre- ulcer, sinus tract, and cortical disruption. Early infection quently involved anatomic sites of pedal osteomyelitis. may begin with periostitis , manifesting on imaging as Septic arthritis is commonly seen, reportedly in 33% of all feet fluid signal overlying the cortex. Cortical lesions are common, imaged for suspected osteomyelitis, most frequently involving reflecting the contiguous focus etiology of spread. A B Fig. 12 A 61-year-old male with osteomyelitis of the great toe involving a confluent intramedullary pattern of decreased signal intensity on the T1- the distal aspect of the first metatarsal and the entire proximal phalanx. weighted image (b). There is also septic arthritis of the great toe MTP Sagittal STIR MR (a) demonstrates extensive bone marrow edema-like with destruction of the joint signal throughout the metatarsal and proximal phalanx, corresponding to 184 Emerg Radiol (2018) 25:175–188 Fig. 13 A 45-year-old male with calcaneal osteomyelitis. Sagittal A B STIR MR (a) of the foot demonstrates extensive bone marrow edema throughout the posterior aspect of the calcaneus, contiguous with a posterior heel ulcer (arrows). The T1-weighted sagittal MR (b) demonstrates corresponding confluent intramedullary pattern of decreased signal intensity. Distinguishing between neuropathic arthropathy arthropathy, it was not until 1959 that diabetes was recognized and osteomyelitis as an important cause of neuropathic arthropathy of the foot. A common and challenging task for the radiologist is to dif- Several imaging features have been described to help dif- ferentiate between osteomyelitis and neuropathic arthropathy, ferentiate between neuropathic arthropathy and osteomyelitis otherwise known as Charcot arthropathy. The eminent neurol- [57, 58], as summarized in Table 2. However, it can often be ogist Jean-Martin Charcot first described arthropathy of atax- very difficult to distinguish between these two entities, espe- ic patients in 1868 as being caused by neurosyphilis. cially if a patient has an underlying neuropathic foot with a Interestingly, although diabetes is now by far the most com- clinical question of superimposed infection. In general, oste- mon cause of peripheral neuropathy leading to neuropathic omyelitis tends to involve a single weight-bearing bone sub- jacent to an ulcer, with the calcaneus, fifth metatarsal, first metatarsal, and first distal phalanx the most common sites Table 2 Imaging findings to aid in the differentiation between (Fig. 14). In contrast, neuropathic arthropathy (Fig. 15) tends osteomyelitis and neuropathic arthropathy to involve multiple bones of the midfoot. However, the Imaging finding Osteomyelitis Non- altered gait of neuropathic arthropathy can cause typically infected non-weight-bearing bones, such as the cuboid, to become Charcot weight-bearing and predispose to subjacent callus and ulcera- arthropathy tion with subsequent development of osteomyelitis and septic Direct imaging findings suggestive of osteomyelitis arthritis of the midfoot [58, 59]. Bone marrow edema-like Confluent, medullary Common Less signal is almost invariably present in both osteomyelitis and decreased signal intensity common non-infected neuropathic arthropathy and is not helpful to on T1-weighted imaging differentiate between the two entities. Metatarsal, phalangeal, or Very common Rare calcaneal location The only imaging feature of conventional MRI that has BGhost sign^ Suggests infected Not been shown to be exclusive to osteomyelitis is a sinus tract (disappearance of cortices neuropathic arthropathy reported extending from the ulcer to the infected bone. on T1-weighted imaging) to date Interestingly, the presence of an ulcer alone is seen equally Indirect imaging findings suggestive of osteomyelitis commonly in patients with neuropathic joints with and with- Single bone involved Common Rare out superimposed infection. Therefore, the presence of an ul- Cortical disruption Common Rare cer does not help to differentiate between neuropathic arthrop- Replacement of soft-tissue Common Less athy and osteomyelitis, unless a sinus tract to bone is present. fat common However, the absence of an ulcer is a helpful ancillary finding Sinus tract Exclusive Never to exclude osteomyelitis, as pedal osteomyelitis is consider- Imaging findings suggesting absence of infection ably less likely to be present in the absence of ulceration. Midfoot location Uncommon, unless Common Imaging features seen more commonly in infection include weight-bearing bone due to midfoot collapse replacement of soft-tissue fat, soft-tissue fluid collection, and Normal marrow signal on Very rare (may represent Uncommon extensive marrow abnormality. Subchondral cystic change, T1-weighted images focal necrosis) thin rim enhancement of a joint effusion, and the presence of Cystic change Very rare Common intra-articular bodies are more indicative of a neuropathic joint Thin rim enhancement of Uncommon Common without infection. The Bghost sign^ (Fig. 16) may also be joints Intra-articular bodies Uncommon Common helpful to differentiate non-infected neuropathic arthropathy from superimposed infection. The Bghost sign^ is said to Emerg Radiol (2018) 25:175–188 185 Fig. 14 Illustration demonstrates the typical location of neuropathic arthropathy (blue), which predominantly involves the midfoot, and osteomyelitis (red), which occurs most commonly in the calcaneus, the fifth and first metatarsals, and the first distal phalanx be indicative of superinfection and is present when the cortical traditional management of diabetic foot infection is surgical margins Bdisappear^ on T1-weighted images and Breappear^ resection of the infected bone and soft tissues, there is an on T2-weighted or contrast-enhanced T1-weighted images. emerging trend to perform non-surgical management with The absence of the Bghost sign^ is said to be due to true prolonged, targeted antibiotic therapy. Bone biopsy is destruction of the bones by advanced neuropathic arthropathy; considered especially helpful in patients treated conservative- however, this sign has not been clinically validated. ly, as the patients who received targeted therapy based on Recently, diffusion-weighted imaging has been suggested biopsy culture results have greater therapeutic success com- as allowing accurate differentiation between neuropathic ar- pared to those patients who did not receive bone biopsy. thropathy and osteomyelitis. Additional advanced MRI Image guidance of percutaneous bone biopsy has the ad- techniques include dynamic contrast-enhanced MR, MR an- vantage of precisely localizing even small target areas, to doc- giography, and MR neurography , although these tech- ument that the targeted area was actually biopsied and to tri- niques are not in widespread clinical use. angulate the needle path to the target area from the skin entry site. The specimen should be obtained by going through intact skin, and pre-procedure imaging should be carefully reviewed Role of image-guided biopsy in diabetic foot infection to ensure that a deep fluid collection or phlegmon is not tra- versed by the needle. The highest diagnostic yield is obtained Evaluation of a bone specimen is considered the gold standard by performing the biopsy before antibiotic therapy is initiated, to diagnose osteomyelitis and to determine the responsible or by imposing an antibiotic vacation for 14 days if the organism and its antibiotic susceptibility [63, 64]. Wound patient is able, although a shorter antibiotic-free period may swabs are not considered a reliable method to identify the also be acceptable. Complications such as bleeding, in- causative organism, as wound culture results are only concor- troduction of bacteria into bone, or fracture are rare. The dant with bone cultures in a minority of cases. While the bone specimen should be sent for both histology and culture, Fig. 15 A 60-year-old female with neuropathic arthropathy, A B without superimposed infection. Sagittal STIR (a) and T1- weighted image (b) demonstrate diffuse bone marrow edema involving multiple bones of the midfoot including the navicular and the cuneiforms. There is no plantar ulcer and the subcutaneous fat is preserved 186 Emerg Radiol (2018) 25:175–188 A B C Fig. 16 BGhost^ sign of osteomyelitis superimposed upon neuropathic midfoot. The margins of the bones appear to disappear on the T1- arthropathy. Lateral radiograph of the foot (a) demonstrates extensive weighted image (blue arrows), suggestive of the Bghost^ sign, which destruction and debris formation of the midfoot with marked has been reported to be indicative of osteomyelitis. There is also plantarflexion of the talus and fragmentation of the cuboid (yellow tenosynovitis of the peroneus longus tendon (red arrows), which may arrows), consistent with neuropathic joint. Sagittal STIR (b) and T1- be infectious weighted (c) MR images demonstrate severe extensive edema of the which maximizes the chance of an accurate diagnosis of oste- contiguous focus of infection, and non-spinal hematoge- omyelitis as well as specifically identifying the pathogenic nous osteomyelitis in adults is rare. Radiographs are often organism(s). negative in the early stage of osteomyelitis, with bony Treatment of lower extremity osteomyelitis varies depend- changes evident after 10–12 days including focal ing upon the extent of infection and patient-specific factors osteopenia, periosteal reaction, and cortical erosion, de- such as co-morbidities and vascular status. While antibiotic pendent on the route of spread. MRI is the best non- therapy alone can be successful, often patients with pedal invasive imaging modality to evaluate for osteomyelitis, osteomyelitis present with chronic osteomyelitis adjacent to and the confluent intramedullary pattern of decreased sig- an ulcer. In these patients, an operative debridement of the nal intensity on T1-weighted images is the single most ulcer and infected bone may be required, followed by reliable sign to diagnose osteomyelitis. In children and culture-specific antibiotic therapy. Pressure-offloading opera- young adults, a primary differential consideration of oste- tive techniques are also critical to prevent ulcer persistence or omyelitis is Ewing sarcoma. In the adult diabetic patient, recurrence. Common offloading techniques include claw differentiation between neuropathic arthropathy and oste- toe or hammertoe correction and Achilles tendon lengthening omyelitis can be challenging, although there are helpful procedures. If removal of all devitalized bone will render the M R i m a g i n g fe a t ur e s t o ai d i n t h e di st i n c t i o n. extremity unstable or dysfunctional, amputation may be the Additionally, a radiolabeled leukocyte scan is a sensitive most appropriate course. Many different amputation levels and specific test and may be helpful to differentiate pedal exist, including digit, trans-metatarsal, Chopart joint, and be- osteomyelitis from neuropathic arthropathy. Biopsy is the low knee—with the decision dependent upon the specific clin- gold standard to diagnose osteomyelitis and determine the ical scenario. optimal antibiotic therapy, which can lead to greater ther- apeutic success. Conclusion Osteomyelitis is a common clinical problem with increas- Compliance with ethical standards ing incidence, driven primarily by the increased preva- lence of diabetes-related foot infection. 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