Legg-Calve-Perthes' disease: an opportunity to prevent blindness?

Legg-Calve-Perthes' disease (LCP) is defined as avascular necrosis of the femoral head in a child and may present to a variety of disciplines from general practice to orthopaedics, paediatrics, rheumatology and more. The Stickler syndromes are a group of disorders of type II, IX and XI collagen associated with hip dysplasia, retinal detachment, deafness and cleft palate. The pathogenesis of LCP disease remains an enigma but there have been a small number of cases reporting variants in the gene encoding the α1 chain of type II collagen (COL2A1). Variants in COL2A1 are known to cause type 1 Stickler syndrome (MIM 108300, 609508), which is a connective tissue disorder with a very high risk of childhood blindness, and it is also associated with dysplastic development of the femoral head. It is unclear whether COL2A1 variants make a definitive contribution to both disorders, or whether the two are indistinguishable using current clinical diagnostic techniques. In this paper, we compare the two conditions and present a case series of 19 patients with genetically confirmed type 1 Stickler syndrome presenting with a historic diagnosis of LCP. In contrast to isolated LCP, children with type 1 Stickler syndrome have a very high risk of blindness from giant retinal tear detachment, but this is now largely preventable if a timely diagnosis is made. This paper highlights the potential for avoidable blindness in children presenting to clinicians with features suggestive of LCP disease but with underlying Stickler syndrome and proposes a simple scoring system to assist clinicians.

Prothrombin Time and Coagulation Factor IX as Hemostatic Risk Markers for Legg- Calvé-Perthes Disease.

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a pediatric disorder that occurs due to the avascular necrosis of the femoral head and affects the range of motion of the hip in various degrees. Its etiology is still unknown, although it has been associated with coagulation abnormalities, however, the lack of reproducibility in the results in various studies has created a controversy as to whether hemostasis disorders are related to LCPD. On the other hand, there is little information on laboratory studies that could facilitate the diagnosis and treatment of LCPD. METHODS: Blood and plasma samples were tested from 25 patients with LCPD and 50 healthy controls, matched by sex and age. Cellular markers were evaluated through complete blood count, as well as coagulation times, coagulation factors activity, antithrombotic proteins, and homocysteine concentration. RESULTS: After assessing activity value frequencies in each group, the results showed more significant activity in some of the biological risk markers of thrombophilia, presenting a substantial difference in prothrombin time↘, FV↗, FVIII↗, FIX↗, and Hcy↗. These values imply that there may be hypercoagulable states in patients, which can cause thrombotic events. CONCLUSIONS: Diminished prothrombin time and increase in FV activity, FVIII, FIX, and Hcy concentration support the hypothesis that microthrombi formation in small-caliber vessels could be causing avascularity and femoral necrosis, which are traits of LCPD. In addition, based on our results, we believe that the laboratory studies carried out are very useful in the diagnosis and treatment of LCPD.

Predictive ability of inflammatory markers and laboratory parameters in Legg-Calvé-Perthes disease: A single-center retrospective comparative study.

ABSTRACT: Legg-Calvé-Perthes disease (LCPD) presents with chronic nature of inflammation, characterized by prolonged synovitis. So far, no single blood marker has been identified to guide clinicians in estimating the severity and prognosis. Blood neutrophil to lymphocyte ratio (NLR) or systemic immune inflammation index (SII) is a simple indicator of subclinical inflammation. This study aims to examine the predictive ability of NLR, SII, and common laboratory parameters for estimating the severity of LCPD. The pre-operative laboratory findings at the time of osteotomy and implant removal in patients with unilateral LCPD who had been treated with the Salter innominate osteotomy and followed up until skeletal maturity as well as those of age-matched control patients with idiopathic noninflammatory conditions were analyzed. The datasets of 26 or 38 LCPD patients at the time of osteotomy or implant removal, respectively, and those of 20 control patients were available for analysis. At the time of osteotomy, compared to the control group, a significantly higher mean NLR or SII and a significantly lower mean alkaline phosphatase value were observed in the LCPD group. The alkaline phosphatase levels of patients with the modified lateral pillar (LP) group-A hips were significantly lower than those with the non-LP-A hips, whereas no significant differences were observed in any of the parameters between patients with favorable LP-A or -B hips and those with unfavorable LP-B|C border or -C hips. In agreement with the conventional opinion, it may be difficult to predict a meaningful prognosis of LCPD with the use of inflammatory markers or common laboratory parameters obtained in the initial stage of the disease.

Can large doses of glucocorticoids lead to Perthes? a case report and review of the literature.

BACKGROUND: Perthes disease (Legg-Calvé-Perthes, LCP) is a self-limited and non-systemic disease occurring in the femoral heads of children, which is mainly manifested as an ischemic necrosis of the femoral head epiphysis, leading to subchondral ossification injury of the femoral head. CASE PRESENTATION: Here we report a case of 11-year-old child with long-term use of high-dose glucocorticoids. With MRI examination finding the epiphyseal necrosis of right humeral head, femur and tibia, and X-ray examination finding bilateral femoral head necrosis, the child was diagnosed as Perthes disease based on his clinical and imaging data. CONCLUSIONS: Long-term and high-dose glucocorticoids may be one of the causes of Perthes disease.

METHODS OF TREATMENT OF LEGG-СALVÉ-PERTHES DISEASE (REVIEW).

This Literature Review presents various treatments, including operative and conservative therapies, of Legg - Calvé - Perthes Disease. The problem is relevant because of the prevalence of the disease. The authors presented a review of literature, which managed to classify the main methods of treatment by the principles of action, practical application, and presented the interpretation of the effectiveness of modern research from the point of view of evidence-based medicine.

Hip Injuries in the Adolescent Athlete.

This article provides concise and up-to-date information on the most common hip pathologies that affect adolescent athletes. We cover the evaluation and treatment of avulsion injuries, stress fractures, slipped capital femoral epiphysis (SCFE), femoroacetabular impingement, developmental dysplasia of the hip, Legg-Calve-Perthes disease, and coxa saltans focusing on minimizing advanced imaging and using conservative therapy when applicable. Although this is not an all-encompassing list of disorders, it is key to understand these hip pathologies because these injuries occur commonly and can also have detrimental complications if not diagnosed and addressed early, especially SCFE and femoral neck stress fractures.

Demographics and Clinical Presentation of Early-Stage Legg-Calvé-Perthes Disease: A Prospective, Multicenter, International Study.

BACKGROUND: Children with Legg-Calvé-Perthes disease (LCPD) are classically described as small, thin, high-energy children presenting with a painless limp. Epidemiologic studies have historically been retrospective and regional in nature. The purpose of this study was to determine the demographic and clinical features of children presenting in the early stages of LCPD in an international, multicenter cohort. METHODS: Children (6 to 10 years) in the early stages of LCPD (modified Waldenström stage I to IIa) were enrolled in a prospective, multicenter study. Demographic and clinical data at presentation were analyzed. Body mass index percentiles were determined using country-specific growth charts for children in the United States and India, two countries with largest enrollment. Statistical analyses included t-tests and chi-square. RESULTS: A total of 209 children (86% males; mean age 7.9 ± 1.2 years) from 25 centers (six countries) were included. Eight-four percent of children presented with pain with or without a limp. Average pain score at presentation was 3 ± 2 (range 0 to 9), and 63% of children (n = 105) used pain medications. Of these children 65% required medication more than once per week. Thirty percent of children missed school due to pain in the past month, and of those, 74% missed at least 1 day per week. Twenty-nine percent of children from the United States and 20% of children from India were overweight or obese. Nineteen percent reported household smoking. DISCUSSION: This prospective study provides a new international multicenter representation of early LCPD. The frequency of pain and missed school highlights the substantial morbidity and potential social cost and burden for children and families. The prevalence of being overweight/obese in our LCPD cohort was comparable to rates within the pediatric cohort as a whole, and fewer children have a history of smoke exposure than in previous reports. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Displasia epifisaria de Meyer. Presentación de un caso / Meyer epiphyseal dysplasia. Case presentation

RESUMEN Se presentó el caso de una niña con el diagnóstico de displasia de Meyer. Consiste en una alteración en el desarrollo de la cadera en el niño dado por irregularidad y retraso en la osificación del núcleo de la epífisis femoral, aunque muchos ortopedistas la consideran como una variante fisiológica normal. Radiológicamente se manifiesta como un patrón granular múltiple de osificación y clínicamente si bien puede ser sintomática en algunos casos, lo más frecuente es que sea asintomática. Se enfatizó en la importancia de considerar a la displasia de Meyer como posibilidad diagnóstica ante alteraciones en la osificación de la epífisis femoral. Se señaló a la displasia congénita de la cadera y la enfermedad de Perthes como principales entidades a tener en cuenta al hacer el diagnóstico diferencial. Se analizó la evolución clínico-radiológica de la paciente a partir de los datos recogidos en la historia clínica. Se concluyó enfatizando que la displasia de Meyer debe tenerse presente como posibilidad diagnóstica ante casos similares, realizar una cuidadosa valoración de cada paciente y tener en cuenta a la displasia congénita de la cadera y la enfermedad de Perthes como diagnóstico diferencial atendiendo a la edad del paciente (AU).

ABSTRACT The authors present the case of a female child diagnosed with Meyers dysplasia. It is an alteration of the hip development in children, given the ossification irregularity and retardation of the femoral epiphysis nucleus, although several orthopedists consider it a normal physiological variant. Radiologically, it shows like a multiple granular pattern of ossification, and clinically it could be symptomatic in several cases, but more frequently it is asymptomatic. It was emphasized the importance of considering Meyer dysplasia as a diagnostic possibility in the presence of alterations in the femoral epiphysis ossification. The authors indicated hip congenital dysplasia and Perthes disease as main entities to take into account when making the differential diagnosis. They also analyzed clinic-radiological evolution of the patient on the basis of the data collected in the clinical record. They concluded emphasizing that Meyer dysplasia must be taken into consideration as a diagnostic possibility in similar cases, each patient should be carefully assessed and that hip congenital dysplasia and Perthes disease have to be considered as differential diagnosis given the age of the patient (AU).

Influence of passive smoking on the onset of Legg-Calvè-Perthes disease: a systematic review and meta-analysis.

The relationship between passive smoking and the onset of Legg-Calvè-Perthes disease is still controversial. Therefore, we conducted the study to systematically evaluate and analyze the relationship. A comprehensive search was conducted. Meta-analysis was performed with RevMan 5.3 software, with the odds ratio as the effect size. Eight English articles with a total of 1379 Legg-Calvè-Perthes disease patients were eventually included. Passive smoking type of family members smoking in indoor (odds ratio = 2.53), paternal smoking (odds ratio = 2.76), maternal smoking (odds ratio = 2.02), maternal smoking during pregnancy (odds ratio = 1.68), using stove indoor (odds ratio = 2.56) are statistically significant (P < 0.05). For the family members smoking indoor, region may be a confounding factor (European group I = 92%, odds ratio = 2.51; USA group I = 5%, odds ratio = 3.26; and Asian group I = 0%, odds ratio = 2.25). In addition, the type of maternal smoking (odds ratio = 0.80, for 1-10 per day; odds ratio = 2.73, for 10-20 per day; odds ratio = 2.78, for >20 per day) and the type of maternal smoking during pregnancy (odds ratio = 1.36, for 1-9 per day; odds ratio = 2.02, for ≥10 per day) may show a dose-effect relationship. Passive smoking is a risk factor for the onset of Legg-Calvè-Perthes disease, but the specific types of passive smoking (haze, etc.), dose, dose-effect relationship, regional confounding, pathological mechanisms, etc. also require clinicians and researchers to continue exploring.

Namaqualand hip dysplasia in South Africa: The molecular determinant elucidated.

BACKGROUND: Namaqualand hip dysplasia (NHD) is a mild form of spondyloepiphyseal dysplasia in which progressive arthropathy of the hip joint is a major manifestation. The disorder was documented in a multigenerational South African (SA) family with antecedents from Namaqualand, a region in the north-west of the country. Linkage analysis revealed a locus that includes the collagen type II gene, COL2A1. OBJECTIVES: To identify the pathogenic COL2A1 variant causing NHD in an SA family. METHODS: One affected male with a clear diagnosis of NHD was selected for whole-exome sequencing (WES) on the Ion Torrent Proton platform. A probe-based assay and direct cycle sequencing were used to confirm that the prioritised variant segregated with the phenotype in the NHD family and was not present in unrelated controls from the same population. RESULTS: WES identified one heterozygous variant, c.2014G>T; p.(Gly672Cys), in the coding sequence of the COL2A1 gene. The variant segregated with NHD in 23 affected family members and was previously reported in a Caucasian male with Perthes disease-like presentation. CONCLUSIONS: It is now possible to provide a molecular diagnosis of NHD before hip problems present. The large, clinically well-characterised NHD family is a valuable resource that could provide more insight into the mechanisms responsible for the variable expression observed in individuals with this variant.

Arthrodiastasis in the management of Perthes disease: a systematic review.

This systematic review explores the relevant literature to assess the efficacy of the use of arthrodiastasis in the management of Perthes disease. Until this moment, arthrodiastasis is not well established for its use in Perthes disease as opposed to other containment procedures. Furthermore, there are no clear indications for its use in this disease. Twelve articles were matched to the inclusion criteria and all articles were reviewed and radiological and clinical data were collected and compiled. As regards the hip flexion range of motion, the average preoperative flexion range of motion was 55.32°, while the postoperative was 90°. The average preoperative hip abduction range of motion was 12.28° and postoperative was 35.28°. Mean preoperative hip internal rotation range of motion was 8.69° and postoperatively was 24.93°. Mean preoperative external rotation range of motion was 21.73°, while the postoperative range was 33.71°. Final Stulberg classification was ascertained showing most patients ending with stages two and three. Complications were also assessed with most of which being superficial pin tract infections. The use of arthrodiastasis is a valid treatment option for Perthes disease; however, more articles need to be produced showing comparative data of arthrodiastasis versus other containment procedures. Level of evidence - level 1: systematic review.

Pediatric Hip and Pelvis.

The most common pediatric orthopedic conditions of the hip and pelvis involve abnormal architecture of the joint leading to pain and dysfunction. Developmental dysplasia of the hip and femoroacetabular impingement are 2 common and distinct forms of structural pathology in the pediatric hip. The authors also discuss 2 of the more common, and often questioned, pediatric hip disorders-slipped capital femoral epiphysis and Legg-Calvé-Perthes disease. Future investigations are aimed at identifying risk factors to provide pediatric orthopedists tools to risk stratify their patients and understand when conservative approaches such as close observation versus surgical interventions are more appropriate.

[The limping child: a red flag for every physician]. / Het mankend kind: een rode vlag voor iedere medicus.

A limping gait pattern in a child is a red flag for every physician until proven otherwise. Among the most common causes are coxitis fugax, infection (septic arthritis, osteomyelitis), Perthes disease, and slipped capital femoral epiphysis, depending on the age of the patient. A high index of suspicion is required because clinical findings are often subtle, and the diagnosis may be present even if initial radiographs are negative. A missed or delayed diagnosis may have devastating consequences. Therefore, this paper describes the main characteristics of different causes of a limping child, based on four typical cases. Tools are provided to recognize each diagnosis. Early referral to a paediatric orthopaedic surgeon is recommended.

[Perthes disease-news in diagnostics and treatment]. / Morbus Perthes ­ Neuigkeiten in der Diagnostik und Behandlung.

DIAGNOSTICS: Perthes disease remains a challenge for paediatric orthopedic surgeons. X­ray imaging is still the method of choice for diagnostics and follow-up examination. A more detailed differentiation of Waldenström's classification, especially in early and late fragmentation stages, might be relevant to optimize timing of containment surgery. So-called "advanced MRI" imaging might help to detect patients at risk earlier than conventional x­ray imaging, which could lead to earlier surgical intervention. TREATMENT: Currently there is no treatment modality available which would improve the bone changes in Perthes disease. Non-operative treatment like improving hip range of motion as well as unloading is still the basic standard of care, with analgesic and/or anti-inflammatory medication, according to symptoms or findings. In the case of loss of containment, especially in children older than 6 years, surgery is indicated. Currently, there is a trend favoring acetabular reorientation techniques-especially the triple osteotomy, since the biomechanical relations would not be additionally impaired as in case of femoral varus osteotomy.

Hip arthroscopy for Legg-Calvè-Perthes disease in paediatric population.

OBJECTIVE: The aim of this study was to represent the findings and long-term clinical results of the children who underwent hip arthroscopy because of Legg-Calve-Perthes Disease (LCPD). METHODS: This study included the retrospective findings of ten patients (mean age: 12.7 ± 2.75; range 7-16 years) who underwent arthroscopic hip debridement between 2010 and 2016 for LCPD disease. All of the patients underwent arthroscopic excision of the unstable osteochondral fragment following unsuccessful conservative treatment. In the statistical analysis, age, side, follow-up, Stulberg and Waldenström classification, preoperative and postoperative modified Harris Hip Score (mHHS) were evaluated. RESULTS: The mean follow-up period was 55.4 ± 13.05 months (range: 40-72 months). There was no statistically significant association between good postoperative results and age, side, and the stage of the disease (p > 0.05). However, there was a significant difference between preoperative and postoperative mHHS (p = 0.005). CONCLUSION: This study demonstrates an increase in the functional results and life quality of the patients who underwent hip arthroscopy due to LCPD. It is thought that hip arthroscopy, a minimally invasive procedure, may have an important role in the algorithm of LCPD treatment, especially in patients with severe pain and mechanical symptoms. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Intra- and inter-observer reliability of Laredo classification system in Legg-Calvé-Perthes Disease.

The purpose of the current study was to investigate intra- and inter-observer reliability of arthrographic Laredo classification system in Perthes disease. Forty-seven patients were included in this cross-sectional descriptive study. Patients' age, gender, physical findings and hip arthrographs were collected from hospital medical records. Two different sets of power point slides were prepared in which the order of cases was randomized and blinded. Observers were divided into three groups according to their surgical experience (9 residents, 10 seniors, 10 pediatric orthopedists), and they assessed two times 1 month's intervals. Statistical analysis was performed by using the SPSS v21. Inter- and intra-observer reliabilities were calculated using intra-class correlation coefficient, weighted kappa and percentage agreement. Percentage agreement of Laredo classification was about 50% for all groups (residents, seniors and pediatric orthopedists); intra-observer reliabilities were excellent, excellent and fair, respectively. Inter-observer reliability of Laredo classification for each set was found to be excellent for all groups. Length of experience did not correlated significantly with the level of intra-observer agreement. As a conclusion, our results showed that Laredo's arthrographic classification system's intra-observer reliability is at least at a fair level and inter-observer reliability is at an excellent level. We believe that this classification system is valuable for an orthopedic surgeon who deals with the treatment of Perthes disease.

Determining Hinge Abduction in Legg-Calvé-Perthes Disease: Can We Reliably Make the Diagnosis?

BACKGROUND: Although hinge abduction is recognized as an important finding in children with Legg-Calvé-Perthes disease, variable diagnostic criteria exist. The purpose of this study was (1) to test the interobserver and intraobserver agreement of the current definition of hinge abduction and (2) to develop consensus regarding key diagnostic features that could be used to improve our diagnostic criteria. METHODS: Four orthopaedic surgeons with subspecialty pediatric hip interest independently assessed 30 randomly ordered cases of Legg-Calvé-Perthes disease. Each case included 2 fluoroscopic images of hip arthrograms (anteroposterior and abduction views). Surgeons graded the cases in a binary manner (hinge/no-hinge) on 2 separate occasions separated by a 4-week interval. Following reliability testing and comprehensive review of the literature, consensus-building sessions were conducted to identify key diagnostic features. Surgeons then regraded a new series of cases. Interobserver and intraobserver agreement between first/second and third/fourth readings were assessed using the Fleiss κ. RESULTS: Interobserver κ for hinge abduction between the first and second surveys was 0.52 (with 0.41 to 0.60 considered moderate agreement), compared with 0.56 for the third and fourth surveys. First and second reading intraobserver agreement ranged from 0.59 to 0.83 compared with 0.75 to 1.00 for third and fourth reading. Consensus sessions identified several key diagnostic factors including: adequate visualization of the labral contour and ability of the lateral epiphysis to slip below the chondrolabral complex in abduction. Medial dye pooling, often due to asphericity of the femoral head, was not found to be a useful diagnostic criterion. CONCLUSIONS: Despite a combined experience of over 70 years among the reviewers, we found just slightly better than 50:50 agreement in what constitutes hinge abduction. Consensus discussions did improve our agreement but these modest changes emphasize how difficult it is to develop reliable diagnostic criteria for hinge abduction. As a result, we caution against using hinge abduction as an inclusion criteria or outcome measure for research purposes, as the diagnostic agreement can be inconsistent. LEVEL OF EVIDENCE: Level III-diagnostic study.