足踝类风湿关节炎与骨髓水肿

ARTHRITIS&RHEUMATISMVol.62,No.8,August2010,pp2353–2358DOI10.1002/art.27547©2010,American College of RheumatologyLigament and Bone Pathologic Abnormalities More Frequent in Neuropathic Joint Disease in Comparison With DegenerativeArthritis of the Foot and AnkleImplications for Understanding Rapidly Progressive Joint DegenerationJill Halstead,1Diane Bergin,2Anne-Maree Keenan,1Julie Madden,3and Dennis McGonagle1Objective.The variable disease progression of osteoarthritis(OA)and the basis for rapid joint deteri-oration in some subgroups of patients are poorly under-stood.To explore an anatomic basis for rapidly progres-sive OA,this observational study compared the magnetic resonance imaging(MRI)patterns of disease between patients with neuropathic joint disease(NJD) and patients with degenerative arthritis of the ankle and foot.Methods.MR images of the foot and ankle of patients with early NJD(n؍7)and patients with OA (n؍15)were assessed.The anonomized MR images were dichotomously scored by a musculoskeletal radiol-ogist for the presence of the following abnormalities per bone(of a total of14bones):cartilage defects,bone cysts,bone marrow edema,fractures,joint debris,joint effusions,tendinopathy,tendinitis,and ligament tears.Results.Although the degree of cartilage damage and joint cyst formation was comparable between the groups,the degree of ligament tears,or change in MRI signal intensity in the ligaments,was significantly greater in patients with NJD compared with patients with OA(median of3tears versus0,of14total bones; P<0.01).Moreover,in patients with early NJD com-pared with patients with OA,there was a significantly greater degree of diffuse bone marrow edema(median of 6.5tarsal bones versus2adjacent bones,of14total bones;P<0.01),a greater number of bone fractures (median4versus0;P<0.01),and more frequent bone debris(median4.5versus0;P؍0.013).Conclusion.This analysis of NJD in the foot and ankle shows the predominance of bone and ligament abnormalities in NJD compared with the pattern of involvement in OA.These findings highlight the impor-tance of structures other than articular cartilage in OA of the ankle and foot,and suggest that rapid joint degeneration in NJD may be more ligamentogenic or osteogenic in nature.Osteoarthritis(OA)is a major cause of morbidity and suffering,particularly in the older population.In advanced cases,OA may lead to severe functional impairment and disability.The progression of OA is heterogeneous,and its course may be rapidly progres-sive at one extreme and remain relatively stable at the other.The basis for this variable prognosis is poorly understood,but scintigraphic(1)and magnetic reso-nance imaging(MRI)studies have shown that synovitis and bone marrow edema(attributed to inflammatory infiltrates,extracellular fluid,and fibrosis)can be asso-ciated with disease progression(2).There are only limited imaging data on the anatomic factors that may be predictive of progressive degenerative joint disease at the time that the radiographic findings are still normal.Presented in part at the British Society of Rheumatology Annual Conference,Glasgow,UK,April28–May1,2009.Mrs.Halstead’s work was supported by Arthritis Research UK.Dr.Keenan’s work was supported by the National Institute of Health Research.Prof.McGonagle’s work was supported by Arthritis Research UK,the National Institute of Health Research,and The Wellcome Trust.1Jill Halstead,MSc,Anne-Maree Keenan,PhD,Dennis McGonagle,PhD,FRCPI:University of Leeds,Leeds,UK;2Diane Bergin,MD,FRCR:Galway University Hospital,Galway,Ireland;3Julie Madden,MSc:Calderdale and Huddersfield National Health Service Trust,Halifax,UK.Address correspondence and reprint requests to Dennis McGonagle,PhD,FRCPI,Section of Musculoskeletal Disease,Leeds Institute of Molecular Medicine,University of Leeds,Leeds LS29JT, UK.E-mail:D.G.McGonagle@.Submitted for publication November27,2009;accepted in revised form April27,2010.2353Neuropathic joint disease(NJD)represents a particularly severe form of rapidly progressive OA.NJD commonly affects the foot and ankle in patients with diabetes mellitus(3)and is associated with substantial morbidity(4).In comparison,OA of the foot and ankle, often linked to a preceding injury,can be unpredictable and slowly progressive,and rarely leads to the deformity typical of NJD(5).Radiographic changes of end-stage NJD are characterized by bone debris,joint destruction, and new bone formation(4,6).Conventional radiogra-phy is insensitive to early NJD(7),whereas simultaneous MRI sequences can show widespread bone marrow edema in the ankle and midfoot(8,9).The distinction between the rapidly progressive joint destruction in NJD and the changes that occur in OA of nonneuropathic origin is poorly understood. Knowledge of the preradiographic features of NJD,as compared with those of OA of the ankle and foot,is critical for a better understanding of different progres-sion rates and timely intervention.The aim of the present study was to compare NJD with nonneuropathic OA of the ankle and foot to ascertain the anatomic and pathologic patterns indicative of rapidly progressive OA at this site.PATIENTS AND METHODSParticipants.The present study was conducted as a preliminary investigation,considering that it is difficult to recruit large numbers of patients with clinically recognizable NJD at the preradiographic stage.Participants were recruited retrospectively from the rheumatology and podiatry depart-ments at Calderdale and Huddersfield Hospital Trust in the UK,prior to which ethics and hospital approvals were ob-tained.The OA group consisted of15participants(ages27–71 years,12of whom were male)with symptoms and signs compatible with OA of the ankle and foot;none of these patients had neuropathy.The NJD group comprised7partic-ipants with NJD of the foot(total of8feet in7patients,ages 30–69years,5male),6of whom had diabetes mellitus(median disease duration12years,range9–35years;median duration of sensory neuropathy7years,range1–20years)and1of whom had a history of alcoholism(pedal neuropathy for4 years).The clinical diagnosis of OA was made by an experi-enced rheumatologist(DMcG)based on evidence of minor degenerative changes observed on plain film radiographs,joint pain,decreased range of motion,and the absence of an alternative diagnosis.All OA participants had an MRI exam-ination that confirmed the clinical diagnosis.This group of OA patients continued to have intermittent foot and ankle pain related to activity,which also sometimes occurred at rest, without evidence of sustained joint swelling.None of the OA patients had an elevated acute-phase response.The group of participants with early NJD was selected on the basis of a clinical presentation of ankle and foot arthritis,joint warmth and swelling in the presence of neurop-athy,and the absence of alternative diagnoses such as gout or infection.At the time of diagnosis,MRI confirmed the clinical impression of NJD,after radiographic imaging had been nondiagnostic(Kellgren/Lawrence score of radiographic sever-ityϽ2[10]).The final diagnosis of NJD or OA was corroborated by retrospective evaluation of the case notes to exclude an alternative diagnosis.In response to emerging data on the efficacy of bisphosphonates in the treatment of NJD,4of7of the participants in the NJD group were promptly treated with intravenous pamidronate at diagnosis.There are data from randomized controlled trials showing that this treatment may improve established disease and could,therefore,alter the natural history of rapidly progressive radiographic joint de-struction as has been previously noted in patients with NJD (8).Analyses by MRI.MRI of the ankle and foot was performed using a Philips Gyro scan(1.5-Tesla ACS-NT scanner;Philips Medical Systems).The image protocol in-cluded T1-and T2-weighted sequences and fat-suppressed fluid-sensitive sequences in the sagittal,coronal,and axial planes of the ankle to midfoot and midfoot to forefoot. Imaging parameters were as follows:section thickness of3 mm,intersection gap of0.6–0.8mm,time to recovery(TR) 280–560msec and time to echo(TE)12–20msec for T1-weighted images,TR2,500–6,120msec and TE80–100msec for T2-weighted images,spectral presaturation inversion-recovery comprising TR of500msec,TE of12–14msec,and inversion time of160msec for T1-weighted sequencing and TR of2,500–5,789msec,TE of90–100msec,and inversion time of 160msec for T2-weighted sequencing,field of view16–18cm, and512ϫ512–pixel matrix.All images were scored by a musculoskeletal radiolo-gist(DB)using eFilm Lite software(Merge Technologies). The radiologist was blinded to all clinical and imaging details. Abnormal imaging features(confirmed in2planes)were dichotomously scored per bone as present or absent,from the ankle to the metatarsals(total of14bones).Using operative definitions,mainly adapted from Ahmadi et al(11),the following features were scored per bone,per participant: fractures,joint debris,cartilage defects,bone marrow edema, cyst formation,and joint effusion.Tendon and ligament ab-normalities were predefined for this study.Tendon tears were defined as an irregular or linear abnormality of the tendon margin on T1-weighted sequences,while fluid-sensitive hyper-intensity of the tendon was used to define tendinopathy. Tenosynovitis was defined according to the presence of tendon hyperintensity on fluid-sensitive sequences,coupled with focal tendon enlargement.Ligament tears were recorded as present if the ligament fibers were partially replaced with fluid signal (partial tears)or there was complete discontinuity of ligament (complete tears).After assessing the MR image from each participant,the radiologist(DB)decided on a global diagnosis of OA or NJD.Statistical analysis.This was an exploratory study with relatively small study groups,and therefore inferential statis-tical data were conservative.In order to assess the consistency of the scorer,MRI scans of5participants were scored twice by an observer(DB).Intra-and interobserver agreement was2354HALSTEAD ET ALassessed using kappa statistics and by calculating Bland/ Altman plots(12)with SPSS software(version15;SPSS). Analyses of descriptive data were undertaken,and the pres-ence of abnormal features on MRI was described in terms of total frequency per group.Statistically significant differences in the median score of MRI features between groups was calculated with the Wilcoxon-Mann-Whitney U test.Due to the small numbers of patients and unequal distribution be-tween the groups,the significance level was set as P values less than or equal to0.01.RESULTSThe clinical presentation of the patients differed between the NJD group and OA group,in that a history of trauma and pain upon weight bearing was more typical in the OA group(60%and100%of OA patients, respectively).In the NJD group,the disease was less symptomatic(only71%reported having mild-to-moderate pain),and patients with NJD less frequently reported a history of trauma(29%)than did patients with OA.The median symptom duration was3months in the NJD group and27months in the OA group.The consistency data for agreement on MRI scoring showed a total diagnostic agreement of100%for either NJD or OA,indicating high diagnostic discrimi-nation.For imaging features,the overall kappa score for agreement per abnormality was0.603.Bland/Altman plots showed that the difference was within the95% confidence interval,and most plots showed no patterned variation,indicating good consistency.Descriptive data on the MRI scores for specific abnormalities in both groups are presented in Table1. The most common soft tissue abnormality was partial and complete ligament tears.These occurred frequently in patients with NJD(median of3tears),as compared with no ligament tears in the foot joints of OA patients (Pϭ0.005).In patients with NJD,ligament and capsular disruption were observed,along with joint subluxation, in the hindfoot(Figure1).Joint diastases and subluxa-tion occurred in conjunction with abnormalities of the major supporting ligaments of the midfoot,including the Lisfranc ligament and dorsal intercuneiform ligaments. Ligament abnormalities were frequently seen in associ-ation with joint debris and diffuse bone marrow edema. Indeed,there was often coexistence of these features,so it was difficult to determine which may have occurred first in these patients.A higher score for diffuse bone marrow edema was noted in the NJD group(median of6.5tarsal bones) as compared with the OA group(median of2adjacent bones).The presence of extensive diffuse bone marrow edema in a large number of bones was a consistent feature in all acute cases of NJD,but not in OA(PϽ0.01)(Figures1and2).Linear bone disruption consis-tent with the presence of fractures was characterized by patterns of diffuse bone marrow edema(Figure1); nearly the entire group of patients with NJD presented withՆ2affected bones,compared with only a single fracture in1OA patient(PϽ0.01).The frequency of fractures was closely matched with the presence of joint debris,although joint debris was present to a lesser extent in the OA group(Pϭ0.013versus NJD).Some patterns of signal abnormalities were com-mon in both groups,particularly in the joints and immediate subchondral regions.These abnormalitiesTable1.Abnormalities detected by magnetic resonance imaging(MRI)in patients with neuropathic joint disease(NJD)and patients with osteoarthritis(OA)*Median(interquartile range)score†MRI featureNJD(nϭ7)OA(nϭ15)Between-groupdifference Mann-Whitney U PAbnormal bones10.0(5.8)5(4.0) 5.023.00.016Focal bone marrow edema 3.0(1.8)4(3.0) 1.047.00.428Diffuse bone marrow edema 6.5(5.5)2(5.0) 4.518.50.005*Joint effusion7.0(6.5)3(3.0) 4.029.50.047Fractures 4.0(8.0)0(0) 3.511.50.001*Joint debris 4.5(6.5)0(0) 4.522.50.013Subchondral cysts 2.5(5.8)2(2.0)0.556.00.825Osteochondral defects 2.0(4.0)0(0) 2.038.00.169Cartilage damage11.0(5.0)5(2.0) 6.040.00.213Ligament tears 3.0(6.3)0(0) 3.018.00.005*Tendinitis or tendinopathy0.5(1.8)0(0)0.533.00.087*Significant difference(PՅ0.01).†Values are the median from a total of14bones,and values in parentheses represent the spread of the25th–75th percentiles.LIGAMENT AND BONE ABNORMALITIES IN NEUROPATHIC JOINT DISEASE2355included focal bone marrow edema occurring with cysts,osteochondral defects,cartilage defects,and joint effu-sion.Although OA has been considered a disease pri-marily of cartilage,there were no significant differences with respect to cartilage damage between the NJD and OA groups.A change in MRI signal intensity in the tendon,typical of tendinitis,was present in 3feet in the NJD group and in 1in the OA group.DISCUSSIONThis is the first study to systematically assess MRI features of NJD in comparison with OA of the ankle and foot.This NJD cohort generally had early disease,as indicated by the lack of,or only mild,radiographic joint changes and maintained joint alignment.The occurrence of diffuse signal changes in the bone and occult fractures has been described previously in cases of early NJD (13),but joint debris or ligament damage have not beenpreviously noted.The present findings confirm that extensive bone edema and fracture formation are fea-tures of NJD during the early stages of the disease,near the time of clinical presentation,and this helps explain the presence of bone debris in the synovium,a long-described early histologic feature of NJD (14).Articular cartilage damage was evident in both groups,but there were no systematic differences identified using this scoring system.Importantly,the results of this study link the outcome of degenerative arthritis of the foot and ankle to ligament-and bone-based,rather than articular cartilage–based,pathologic abnormalities.Moreover,our findings support the recent classification of OA with NJD determined according to the anatomic sites of origin,which could possibly represent either an osteo-genic or ligamentogenic type of disease (15).Joint subluxation and ligament damage,usuallyassociated with joint diastasis and dissolution,are often associated with the later stages of NJD as well as with OA accompanied by joint deformity (7,11).LigamentFigure 2.A and B,Long axial plane fluid–sensitive sequence from magnetic resonance imaging (MRI)of the foot of a patient with neuropathic joint disease (NJD),showing extensive marrow edema (arrowheads)of the cuneiforms and complex joint effusions (arrows).C,Sagittal fluid–sensitive sequence from MRI of the ankle of a patient with NJD,showing diffuse bone marrow edema of the midfoot.There is diastasis between the talar head and lateral cuneiform (arrowhead),with complex effusion and a partial tear of the spring ligament.D,Sagittal fluid–sensitive sequence from MRI of the ankle of a patient with osteoarthritis (OA),showing reciprocal subchondral marrow edema (arrowheads)with posterior osteophyte formation (arrow)in the subtalar joint,consistent with MRI evidence of subtalarOA.Figure 1.A and B,Sagittal fluid–sensitive sequence from magnetic resonance imaging (MRI)of the ankle of a patient with neuropathic joint disease (NJD),showing marrow edema of the talus and navicular bone,collapse of the head of the talus,with disruption of the dorsal talonavicular capsule (arrowheads in A and B),and an anterior tibiotalar joint effusion.In addition,a fracture of the plantar aspect of the calcaneus (arrow in B),with adjacent edema,is evident.C,Sagittal fluid–sensitive sequence from MRI of the ankle of a patient with NJD,showing bone edema of the distal tibia,talus,and calcaneus as well as flattening of the talar dome and subluxation of the tibiotalar joint (black arrowhead),consistent with disruption of the medial and lateral ankle ligaments as well as the joint capsule.In addition,a transverse incomplete fracture of the anterior distal tibia (arrow)is evident.D,Sagittal fluid–sensitive sequence from MRI of the foot of a patient with osteoarthritis (OA),showing focal subchondral marrow edema in the head of the first metatarsal and in the medial cuneiform (arrows),consistent with MRI evidence of early OA.2356HALSTEAD ET ALdamage in OA has traditionally been associated with secondary traumatic OA,such as that following anterior cruciate ligament rupture.Recent MRI and in vitro studies,however,suggest that ligaments and insertions can play a role in the degenerative joint process at other sites(16,17).In this study,we observed that ligament damage along with bone marrow edema and fractures were common in patients with early NJD.However,it remains to be determined whether bone or ligament changes are primary.Given the prominent role of the ligaments in proprioception,it is possible that the dis-ease may be more likely to start at these sites.In general,the natural history of OA is difficult to study,given the slow evolution of the disease.An exception to this is the rapidly progressive OA that typifies NJD.In this study,diffuse bone edema and fractures associated with ligament tears were frequent in early NJD.These findings support the theory of a neurotraumatic origin for this type of neurogenic OA,in which it has been proposed that the loss of sensation and proprioception is associated with rapidly progressive joint damage,leading to OA development.The diffuse bone involvement that we noted in early NJD further supports early use of bisphosphonate therapy to decel-erate the joint remodeling.This suggests that the use of MRI as a means of selecting patients with bone edema in OA may help define the optimal role for bisphospho-nates in more common variants of the disease.Our findings indicated a greater involvement of the whole joints in NJD,as compared with that in the nonneuro-pathic OA group,reflecting that the pathologic mecha-nisms of NJD affect the foot joints as a unit.This was a pragmatic,retrospective study that focused on an early presentation of a rare joint disease in comparison with a more common joint problem.The main limitations of this study were sample size,un-matched sizes of the OA and NJD groups,and unequal timing of the MRI scan between the NJD group and the OA group,all of which may have influenced the presen-tation of features on MRI.The interesting finding of ligament damage and bone debris in early NJD requires further investigation in a larger cohort.Thus,our findngs show that,in contrast to non-neuropathic OA of the ankle and foot,NJD can be associated with diffuse bone edema and ligament abnor-malities.The degree of ligament abnormality in the present study,including loss of proprioception associ-ated with neuropathy,may lead to rapidly progressive bone damage with subsequent joint failure.Taken to-gether,our findings have implications for both the diagnosis and therapeutic management of NJD and for understanding the variable prognosis and rate of pro-gression of ankle and foot joint disease.ACKNOWLEDGMENTSWe would like to acknowledge Dr.Elizabeth Hensor for her statistical advice,and Mr.Jason Rastrick for assistance with processing of the MR images.AUTHOR CONTRIBUTIONSAll authors were involved in drafting the article or revising it critically for important intellectual content,and all authors approved the final version to be published.Mrs.Halstead had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Study conception and design.Halstead,Bergin,Keenan,Madden, McGonagle.Acquisition of data.Halstead,Bergin,Madden,McGonagle. 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