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Prognosis and Prognostic Factors of Legg-Calve-Perthes Disease

Cheng, Jack Chun-yiu MD, FRCS Ed(Orth); Lam, Tsz Ping FHKAM(Ortho Surg); Ng, Bobby Kin-wah FHKAM(Ortho Surg)

Journal of Pediatric Orthopaedics: September 2011 - Volume 31 - Issue - p S147–S151
doi: 10.1097/BPO.0b013e318223b470
Introduction
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This is an overall review of the published literature in the past 100 years on the prognosis and prognostic factors of Legg-Calve-Perthes disease (LCPD). There were considerable limitations and inadequacies of the reported series. LCPD is not a common disease, and thus most reports were based on relatively small series collected retrospectively over a long period of time without clearly defined case selection, assessment, treatment, follow-up period, and outcome measures. Few studies, if any, would satisfy the strict definition of prognosis, which should only mean those prognostic factors derived from observation of the natural history of the disease—that is the uninterrupted progressive development of a disease that runs its course from onset-inception to resolution without any intervention or treatment. This review attempted to summarize from the mixed series of studies the generally described demographic, clinical, and radiologic prognostic factors of LCPD. The most important radiologic prognostic signs include the extent of femoral capital epiphysis involvement, the degree of metaphyseal changes, and lateral subluxation of femoral head and depend significantly on the time of assessment after the onset of the disease. More detailed discussions on prognostication based on the structured classification systems that have evolved in the past few decades would be described.

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

The authors declare no conflict of interest.

Reprint: Jack Chun-yiu Cheng, MD, Department of Orthopaedics and Traumatology, Prince of Wales Hospital, 5/F., Clinical Science Building, Shatin, NT, Hong Kong SAR, China. e-mail: jackcheng@cuhk.edu.hk.

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INTRODUCTION AND LITERATURE REVIEW

Prognosis is defined as a prediction of the probable course and outcome of a disease, the likelihood of recovery from a disease. In the definition, prognosis should only mean those prognostic factors derived from observation of the natural history of the disease that is the uninterrupted progressive development of a disease that runs its course from onset-inception to resolution without treatment or manipulated in any way. However, from an extensive review of over 100 publications and monographs on the prognosis and prognostic factors in Legg-Calve-Perthes disease (LCPD) over the past century (some of which were selectively included in the reference), there were hardly any publications that could meet the strict definition. This could partly be explained by the relatively uncommon occurrence of LCPD. Most of the reports were small retrospective historical review series consisting of mixed age groups and presentations collected over a long period of time that ranged from case reports to medium-size series.1–3 There were no clear uniform case inclusion criteria, grouping, pretreatment, and outcome assessment system. The follow-up period was highly variable and ranged from few years to skeletal maturity and in the longest up to 64 years.4 Except for a few reports, each of <100 patients,3,5–7 most of the series had mixed mode of treatment without standardized protocols. The literature was heavily based on publications in English with serious lack of information on ethnic differences and major epidemiological comparative studies.

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GENERAL PROGNOSIS AND PROGNOSTIC FACTORS IN LCPD

The overall observations revealed that in general 60% to 80% of LCPDs could be expected to have excellent and good results on follow-up to the age of 40 years.8–10 The age of presentation is widely reported as an important prognostic factor. LCPD presented before the age of 5 to 7 years were found to have a significantly better outcome than those presented after 8 to 9 years.3,4,11–15 The late presenting LCPD in adolescence generally has poorer results.1,16 Those presented in the very early age of <6 years did not necessarily result in good outcome, particularly in around 20% to 25% of the cases with Catterall III and IV.17–19 The age at the time of healing of the disease was suggested to be a more important prognostic factor than the age of presentation.9,20

LCPD occurs more commonly in boys with a mean ratio of around 4 to 1 (boy vs. girls). The prognosis was found to be worse in girls.9,21–23 Girls with age over 8 years at onset were significantly worse.3 Others had reported that with the same Herring Catterall grading, the prognosis could be similar to the boys.24 Some clinical features at different stages were found to be associated with poorer prognosis. These included heavy child; progressive loss of hip movement; adduction contracture at the affected hip9; longer duration from onset to completion of healing phase9,20; and poorer Iowa hip score4 and Mayo hip score.25 Bilateral disease was found in 4% to 16% of LCPDs1,24 and was believed to be atypical disease associated with other systemic problems and variable prognosis.18,24,26

The time at follow-up assessment seemed to be one of the most important factors affecting the prognosis. Longer-term follow-up regularly revealed that clinical findings were usually less severe than the corresponding radiologic appearances.4,5,13,16,27–29 The clinical symptoms and signs up to the age of 40 years were generally good, which then became increasingly symptomatic by the age of 50 to 60 years. Radiologic deterioration tends to develop earlier and progressively after the age of 40 years, and by 65 years, 86% had symptoms of osteoarthritis of the affected hip.28,30

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RADIOLOGIC PROGNOSTIC SIGN

It is important to realize that radiologic sign is a dynamic process and would vary significantly with the stage of the disease at the time of presentation, diagnosis, and follow-up assessment. In general, the most important reported prognostic signs of LCPD can be grouped under 3 categories: the extent of femoral capital epiphysis involvement, associated metaphyseal changes, and degree of lateral subluxation of the femoral head (containment). Under the category of the extent of radiologic femoral capital epiphysis involvement, many parameters have been described: presence of subchondral fracture line2,9,31,32; increased epiphyseal density33,34; increased size of epiphyseal nucleus32; extent of involvement,15 shape and contour, epiphysis inclination angle, femoral neck length, and flattening with decreased head-height9; abnormal ratio and quotient of the epiphysis and joint surface28 lateral third of femoral head involvement35; lateral pillar sign36; coxa magna37; femoral head deformity index38; and others. Metaphyseal changes of prognostic significance was described by Catterall's “Head at risk sign.”9 Others have also reported the significance of premature arrest of the growth plate.9,39–45 The degree of lateral subluxation of the femoral head was found to be highly correlated with poorer outcome. Parameters that were described included the head-socket distance31; acetabulum-head quotient46; center edge (CE) angle47; combination of measurements48; changes in acetabulum side, such as bicompartmentalization; and femoral head extrusion of >20%.1,12

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PROGNOSTIC DATA RELATED TO SPECIFIC RADIOLOGIC STAGING, CLASSIFICATION, AND GROUPINGS

Many prognostic indices have been proposed over the past century, including for example the epiphyseal index,49 epiphyseal quotient,50 acetabulum head quotient,46 sphericity of the femoral head,51 shape of surface of epiphysis,52 joint surface quotient and radius quotient,53 and acetabular roof angle.54

More systematic radiologic staging, classification, or grouping has evolved over the years aiming at better standardized criteria that are more user friendly and reproducible. Major landmark ones included the Waldenstrom classification (1923),31 Mose circles (1977),30 Catterall grouping and “head at risk sign” (1971),9 Stulberg staging (1981),29 and the Herring grouping (1992).36 It is important to understand that each of these systems has its own limitations and none could be perfect. Below is a brief review of the more commonly reported systems subgrouped into earlier and late radiologic prognostic classifications.

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Earlier Radiologic Classification of Prognostic Significance

Catterall Grouping (1971)

Patients with LCPD were grouped into 4 radiologic subgroups I to IV at diagnosis according to the site and extent of involvement of the femoral capital epiphysis. Final grading of results were listed as good, fair, and poor according to clinical decrease in range of motion of hip and radiologically the presence of >one-fifth uncovered femoral head, degree of flattening, and acetabular changes with widening of medial joint space.9

Poorer Prognosis was found to be associated with presentation after the age of 5 years, girls, groups III and IV (91%), and presence of 2 or more head at risk sign. For those classified as groups I and II, 90% of them achieved good results. It was also found that once healing was started, no further deterioration was expected. Despite the initial enthusiasm, studies had reported many limitations including: difficult and inaccurate initial assessment until reabsorption of avascular bone has commenced which tend to occur relatively late; grouping appear to change if the classification is applied too early and approximately 30% needs subsequent upgrading on follow-up55; relatively poor level of interobserver agreement56–59; and much less prognostic value after the age of 9 years.12

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Danielsson (1982)

Classification was based on 4 radiographic parameters at first year of disease that is metaphyseal width of femur (M); position of femoral head in relation to acetabulum (L); acetabular breadth (B); and acetabular height (H). The computed prognosis was expressed as:

P=7+t−320M−480L+460B+1130H

(P=prognosis index, t=interval in months after diagnosis). The prognostic index was, however, not subjected to further validation studies.48

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Salter Thompson Classification (1984)

On the basis of a large number of radiographs of patients with LCPD collected over a 25-year period from 4 major children hospitals, Salter and Thompson2 proposed a simpler 3 group classification system from radiographs taken within 4 months of the clinical onset of the disease: groups A and B with radiograph of the hip showing subchondral fracture line involving less than and more than half of the femoral epiphysis, respectively.

The prognosis was found to be uniformly good and satisfactory in group A and in those with younger age of presentation and was poorer in group B and in those with loss of containment and range of motion of the affected hip. The classification, although simple, has not been widely used due to the observed limitation that appropriate radiographs may not be taken early enough in the course of the disease to see the subchondral fracture and that only a small percentage (15% to 30%) of patients' radiograph showed subchondral fracture.60–62

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Herring Lateral Pillar Sign (1992)

Herring Lateral Pillar Sign is a relatively simple classification and remained one of the most commonly used system with reported better interobserver (>80%), intraobserver agreement, and prognostic value.60,63,64 Patients with LCPD were grouped into groups A, B, and C according to the status of the lateral pillar height.36

The prognosis was found to be uniformly poor in group C, irrespective of age and treatment and was uniformly good in groups A, B, B/C before the age of 8 years irrespective of treatment. For those aged >8 years, groups B and B/C yielded better result with surgery. For the very young patients with ages <6 years, an overall of 80% had good results.18,65 The reported limitations of this classification included: only anteroposterior view of the hips was taken; difficult to classify in very young patients; it took an average of 7 months of symptoms before reliable classification could be made; and an average of 30% of cases needed subsequent upgrading and of these only 4% belongs to group A on final grading.66,67 It was also difficult to classify in bilateral cases.

Herring et al3 later put forward an improved revised expanded grading system with groups A, B, B/C border and C which was later reported to be more reliable classification. All lateral pillar group A and two-thirds of group B hips had good result. Almost half of the B/C border hips had an intermediate result, but only 1 in 4 had a good result and only 1 in 8 group C hips had a good result.65

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Late Radiologic Classifications of Prognostic Significance

Mose Classification (1964, 1977, 1980)

Mose classification was used quite extensively over the years since it was first described. The radiologic measurement of the sphericity of femoral head using anteroposterior and lateral concentric circles of the healed femoral head after the age of 16 years was found to correlate significantly and can predict the long-term outcome of osteoarthritic changes of the affected hip. Those classified as spherical, spherical but crescent shaped, nonspherical were associated with good, fair, and poor outcomes, respectively.28,30

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Stulberg Staging (1981)

Stulberg classification focused on the status of the femoral head and its relationship with the acetabulum at the completion of remodeling and skeletal maturity. Spherical congruency was present in those with class I and II hips, aspherical congruency was present in those with class III and IV hips, and aspherical incongruency was present in those with class V hips.29 The classification and type of congruency were found to correlate well with clinical findings, Mose circles, Catterall grouping, and long-term outcome of osteoarthritis of the hip.4,12,68 The relatively low interobserver and intraobserver reliabilities were found to be improved by Herring's expanded classification system to over 90%.60,63,69,70

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Joseph Classification (2003)

On the basis of the analysis of 610 patients and multiple serial radiographs on various stages of changes of the femoral head, Joseph et al1 proposed a more sophisticated classification of stages Ia, Ib, IIa, IIb, IIIa, IIIb, and IV. He also found that each stage in general spanned over several months. Stage I ab to II ab took an average of 3.5 to 4 months with stage IIIa spanning across twice and stage IIIb 3 times the duration.

Significantly worse prognosis was found in patients presented after the age of 6 to 7 years and with epiphyseal extrusion of >20% which tend to occurs abruptly during stage IIb. The review has, however, included large number of patients already treated with femoral osteotomies.1

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Kamegaya (2005)

Kamegaya et al14 studied 145 hips with nonoperative treatment followed for 16 to 27.5 years and proposed a composite prognostic formula based on the age at onset and 2 other radiologic factors: Y=−0.697+0.418 (age score)+0.860 (head involvement score)+0.248 (subluxation score). However, no further validation studies of this prognostic formula could be found.

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Other Radiologic Imaging Studies

Attempts to use modern imaging technique in studying the prognostic prediction of outcome evolved over the past 2 decades with the advancement of medical diagnostic technology. Some of these reports are represented below.

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Serial Bone Scintigraphy71

Pinhole magnification technetium-99m diphosphonate serial bone scintigraphy of the hip was performed at 3 to 4 months intervals till definitive pattern was recognized. Good prognosis was found to correlate with the described pathway A, and poorer prognosis was found to correlate with pathways B and C.71 The limitations of serial bone scan entailed radiation exposure, cost, and quality of the image.

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Magnetic Resonance Imaging (MRI)72

De Sanctis and Rondinella72 proposed a classification based on a number of MRI indices at fragmentation stage: the extension of necrosis (EXT), lateral extrusion (LAT), physeal involvement (PHY), metaphyseal changes (MET). Group A with <50% epiphyseal involvement had good prognosis in contrast to the poorer results in group B with >50% involvement. The limitation of MRI classification centered on the cost, lack of larger scale validation study, and long-term follow-up data.

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Comparative Study of Different Radiologic Classifications Versus Outcome

A number of comparative studies of different radiologic classifications versus outcome have been reported.60,61,69,73 Systematic review in general found unsatisfactory reliability and reproducibility in most of the series.70

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OVERALL SUMMARY

Our knowledge about LCPD is still incomplete and fragmented, and sizable data on the true natural history and prognosis are lacking. Many fundamental questions remained inadequately answered. Is LCPD a single disease or a common pathway resulting from different etiopathogenetic mechanisms? The current treatment modalities are only treating the morphologic, functional sequel, and complications and not the cause. In moving ahead, it is critically important to have more multidisciplinary and multicenter collaboration in both basic and translational research, to pool enough clinical cases for studies; to define better the clinical, radiologic and other parameters with standardized clinical database, assessment, classification, staging, and protocol of treatment. Also it is important to cross validate and replicate studies groups across different ethnic groups and to conduct better planned evidence based multicenter, prospective, randomized and longitudinal long term studies.

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Keywords:

prognosis; prognostic factor; Legg-Calve-Perthes disease

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