Isolated inflammatory coxitis associated with protrusio acetabuli: a new form of juvenile idiopathic arthritis?
N. Adib,
K. L. Owers2,
J. D. Witt2,
C. M. Owens1,
P. Woo and
K. J. Murray3
Departments of Rheumatology and 1 Radiology, Great Ormond Street Hospital and 2 Department of Orthopaedics, Middlesex Hospital, London, UK. 3 Present address: Rheumatology Department, Princess Margaret Hospital for Children, Perth, Australia.
Correspondence to: K. J. Murray Rheumatology Department, School of Paediatrics and Child Health, University of Western Australia and Princess Margaret Hospital for Children, GPO Box D184, Perth, WA, Australia 6001. E-mail: kevin.murray{at}health.wa.gov.au
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Abstract
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Background. Isolated hip disease in the context of chronic childhood inflammatory arthritis is uncommon. This paper reports 14 children who presented to the rheumatology and orthopaedic departments of our hospitals with severe hip symptoms, and who continued to have primarily hip disease throughout their clinical course. Our aim was to characterize and present the relevant demographic, clinical, investigational, treatment and outcome data from the above cohort.
Methods. All paediatric cases with the diagnosis of protrusio acetabuli, Otto pelvis or idiopathic chondrolysis who were seen in the past 15 yr at Great Ormond Hospital and Middlesex Hospital in London were identified and their case notes were searched retrospectively for relevant information.
Results. In 11 cases, the disease progressed to involve no joints other than the contralateral hip. None were considered to have a specific subtype of juvenile idiopathic arthritis (JIA) and all tested were negative for HLA-B27. Elevation of serum inflammatory markers was variable. Protrusio acetabuli was the predominant radiological feature. There were definite inflammatory changes on the gadolinium-enhanced magnetic resonance imaging study in all patients who had this procedure performed (seven cases). Microbiological investigations were all consistently negative. Severe hip disease resulted in considerable ongoing symptoms and disability. Six cases were treated with disease-modifying anti-rheumatic drugs. Total hip replacement has been required in four patients to date, with major functional improvement.
Conclusions. These cases represent severe and disabling primary hip disease with considerable clinical and investigational inflammatory features. Such a mode of presentation has not been described previously in the context of childhood chronic inflammatory arthritides, and may represent a separate oligoarthritis subtype of JIA.
KEY WORDS: Inflammatory hip disease, Coxitis, Protrusio acetabuli, Idiopathic chondrolysis, Juvenile arthritis
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Introduction
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Inflammatory or non-mechanical hip disorders are not uncommon in the paediatric population. Examples include infection-related aetiologies such as irritable hip (a form of reactive arthritis) and septic arthritis, and juvenile idiopathic arthritis (JIA). In the majority of cases, there is spontaneous or therapy-induced resolution of symptoms and signs. In some cases chronic arthritis of the hip ensues, with symptoms typically persisting or progressing in spite of symptomatic and first-line anti-inflammatory treatment. For instance, in some subtypes of JIA, such as the systemic arthritis form (SOJIA), rheumatoid factor-positive polyarthritis and enthesitis-related arthritis (ERA), hip disease usually occurs in the context of more widespread arthritis or other associated clinical features. With the exception of HLA-B27-positive ERA, it is considered to be highly unusual for hip disease to be the presenting feature of JIA or to be its predominant manifestation over time. The cases we describe, although similar to the arthritides mentioned above in their significant morbidity, reduced function and direct impact on the quality of life, differ considerably in their clinical characteristics and pattern of presentation.
A number of reports have described cases or cohorts similar to our group. Shore et al. [1] reported eight children with idiopathic protrusio acetabuli and attempted to separate them according to disease progression into a subgroup with aggressive and rapidly progressive disease requiring hip replacement after 15 yr, and another, larger, subgroup with less destructive disease course. Although some observations regarding premorbid history (trauma), hypermobility and family history were made, no firm aetiological explanation was offered. Hughes et al. [2], from the same centre, reported nine cases with unknown aetiology, four said to have idiopathic protrusio acetabuli (IPA) and five with idiopathic chondrolysis (IC). In both of these case series and other available literature, there is preponderance of female gender and African ancestry. Traditionally, these cases were considered to be non-inflammatory arthritis, the above terms (IPA and IC) being used to label patients with this or similar patterns of presentation. These terms are essentially descriptive and ambiguous in the sense that they do not impart information regarding the likely pathophysiology of the disease. Although this mode of presentation is considered highly unusual in the traditional context of chronic inflammatory arthritides of childhood, we would argue that one cannot exclude chronic inflammation as an aetiological factor, given the paucity of histological studies performed in the past and, where performed, their similarity to that seen in JIA. Furthermore, there is considerable clinical similarity with JIA, progressive destructive arthropathy, and ongoing hip disease is the common finding. The advent of investigations such as MRI (particularly with gadolinium enhancement) permits demonstration of synovial hypertrophy and enhancement consistent with chronic inflammation in many of these cases, further supporting the contention that they represent a true chronic inflammatory arthritis. The main aim of this paper is to describe a cohort of paediatric and adolescent patients with isolated hip disease and protrusio acetabuli (PA), and to highlight the role of a chronic inflammatory process in its aetiology and outcome.
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Materials and methods
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Case definition
All cases with a radiographic diagnosis of IPA were identified from a prospectively collected local paediatric rheumatology diagnostic index. Further cases were identified from the hospitals information systems using the keywords protrusio acetabuli, Otto pelvis and chondrolysis. All cases identified from the Hospital Orthopaedic Surgical Database with similar clinical features and who had received total hip replacement were also reviewed and included as appropriate. Finally, similar searches were performed to identify cases with severe hip symptoms as their sole or predominant and/or presenting complaint. A total of 18 possible cases were identified and their hospital records were examined in detail. Cases were included if they had definite radiological evidence of PA and/or a history of presentation with isolated unilateral or bilateral hip disease. Cases were excluded if they had fulfilled criteria for other specific forms of JIA, or other diagnoses associated with PA. Four such cases were excluded because other specific diagnoses were eventually made. This included two with JIA (one with ERA and one with systemic arthritis), one mucopolysaccharidosis type III, and one with SchwartzJample syndrome. The remaining 14 cases were seen in the above hospitals between 1989 and 2002; for these cases demographic information, clinical history, examination findings, investigation results, management details, and outcome data were recorded in detail. All subjects included in this study were required to provide consent, and approval was obtained from the hospital's ethics committee.
Radiological investigations
These included plain anteroposterior radiographs of the pelvis and magnetic resonance imaging (MRI) of the hips. Eight of 14 cases had their films reported by a specialist paediatric radiologist (CMO). The remainder were reported by single consultant radiologist at a university teaching hospital. PA was said to be present when modified Armbuster criteria were satisfied, the acetabular line crossing ilio-ischiatic line medially by at least 1 mm in boys and 3 mm in girls [3].
Two cases with a short history of disease that did not have definitive radiological evidence of PA require further explanation. An 8-yr-old male had severe isolated inflammatory hip disease, in terms of symptoms, clinical examination, inflammatory markers and destructive radiological findings suggestive of early PA, with definitive synovial enhancement on MRI. A 9-yr-old girl also had significant major clinical findings of isolated hip disease. The initial hip radiographs did not show PA, although there was major synovial enhancement on the MRI. It was felt that the early presentation and identification (and subsequent treatment) in these cases probably prevented development of severe structural damage and the radiological progression of PA.
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Results
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Demographic information regarding the study group is presented in Table 1. There is marked gender bias, with 13 females and one male. The age values did not have a normal distribution, requiring cautious interpretation of the mean and standard deviation (S.D.) and, more appropriately, the sample interquartile range is provided (IQR). Data reflect this disorder having its primary presentation in the later years of childhood, with age range at onset ranging from 8.7 to 15.5 yr and at review from 9.4 to 23.7 yr. The cohort was predominantly non-Caucasian/white, in contrast to the normal referral populations of these units, which is predominantly Caucasian. The race/ethnic origins included seven of African/Afro-Caribbean origin in particular. A family history of spondyloarthropathies, psoriasis/psoriatic arthritis or inflammatory bowel disease was not reported by any patient.
Table 2 details the major clinical characteristics of this cohort. All patients had pain in the lower limb as their main complaint, and the majority had loss of motion of the affected joint with abnormal gait. In addition to hip pain, there were thigh and knee/leg pains present in four patients, which may have been related to hip disease alone. None had other apparent clinical joint involvement at presentation. Interestingly, none of the patients displayed any associated constitutional symptoms, such as fever, weight loss, generalized pain, rash or lymphadenopathy. Nor was prolonged gelling or early morning stiffness a major complaint, but pain on weight-bearing and stiffness in general was a major complaint in all patients. The contralateral hip was found to be involved at the time in 11 patients, based on the clinical examination and radiological findings, but in none of these cases had involvement of the other hip been noted (by either patient or referring practitioner) prior to referral. A brief episode of mild arthritis was found in joints other than the contralateral hip (knee twice and an ankle) in three separate cases over the passage of time, but in all cases it was mild, non-deforming, non-destructive and rapidly remissive with treatment. Uveitis/iridocyclitis was not found in any of the cases.
Plain radiographic and MRI findings are listed in Table 3. Thirteen patients had reported abnormalities on plain radiographs, with major PA and joint space loss occurring in 11 and seven cases, respectively (Figs 1 and 2). Less common anatomical changes, such as coxa magna and heterotopic ossification (each in two cases), were also seen. MRI was performed in 12 patients, and significant abnormalities were seen in all cases (Table 3, Figs 3 and 4). Synovial enhancement was present in all cases where gadolinium was used. However, probable synovitis was felt to be present (synovial hypertrophy) in only two of five studies when gadolinium was not used. This difference in the prevalence of synovial enhancement with and without gadolinium was statistically significant using Fisher's exact test (P = 0.045). A similar relationship existed between the above groups with regard to the presence or absence of joint effusion. Seven of eight in the gadolinium group, compared with one of five in the no gadolinium group, had positive findings (P = 0.01).

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FIG. 1. Plain anterior-posterior hip radiograph (from the same case as illustrated in Fig. 3) with PA noted in both hips, worse on the left (black arrow) associated with abnormal pelvic tilt and externally rotated left femur.
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FIG. 2. Eight-yr-old girl with coxa magna acetabular changes, and narrowing of the joint space of the right hip (black arrow), and early similar changes in the left hip.
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FIG. 3. (a) MRI scan of hips, pre-gadolinium T1-weighted images in a 10-yr-old female who presented with a painful stiff left hip. The image shows flattening of the femoral head and loss of femoral cartilage. (b) T1-weighted hip MRI in the same case with significant enhancement of the left hip synovium (black arrows) after gadolinium injection.
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FIG. 4. (a) T1-weighted MRI of the hips pre-gadolinium injection in 13-yr-old female who presented with loss of motion and pain in the left hip due to apparent idiopathic PA. Image shows loss of joint space and cartilage on left femoral head (black arrow). (b) MRI of hips of same child shown in panel (a), with significant enhancement of synovium after gadolinium. The changes are more pronounced in the left hip, with evidence of synovial proliferation and vascularity (white arrow) generally and probable invasion of the fovea in the femoral head by pannus (black arrow).
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Laboratory measures, including blood inflammatory indices and immunological, haematological, microbiological and histological findings, were studied. The highest measured values for the inflammatory index measured during the patient's initial attendances (first 3 months, prior to DMARD therapy), deemed to be related to the underlying arthropathy, are presented. Five of 14 patients tested had erythrocyte sedimentation rate (ESR) values greater than 20 mm/h (overall mean 30 mm/h, IQR 56), whilst six of 12 had C-reactive protein (CRP) values greater than 15 mg/l (overall mean 15 mg/l, IQR 13). Serological investigations revealed that six out of 14 had a positive ANA (1:80 to 1:320), with mixed homogeneous and speckled patterns seen; none (0/13) was positive for rheumatoid factor, and all of those tested (6/6) were negative for HLA-B27. The sickle cell screen was negative in all (5/5) cases tested. Tuberculosis investigations showed one positive Mantoux of seven available results, which subsequently proved not to be relevant to the hip disease. None of the joint tissues or aspirates was culture-positive for acid-fast bacilli. Four of six reported joint histologies had significant abnormalities. Two were consistent with chronic inflammation, whilst another two were reported as having non-specific abnormalities (one with dense fibrous changes in synovium and the other with oedema and swelling in synovium but no inflammatory cell infiltrate). The biopsy specimen did not contain any synovium in two further cases, reflecting, we believe, occasional difficulties in performing this investigation and possibly the sampling bias inherent in the patchy nature of inflammatory infiltrate in chronic arthritis cases. In three of the four cases in which total hip replacement was carried out, histology was unfortunately not performed.
In terms of treatment, 11 patients received non-steroidal anti-inflammatory drugs (NSAIDs) for substantial time periods with only minimal to moderate symptomatic relief noted. DMARDs were used in six patients. Overall, only minimal impact on the functional and radiological characteristics of the major presenting hip involved was seen. We believe this may reflect permanent damage having occurred prior to treatment. Similarly, intra-articular steroids were used in two cases, with substantial but transient benefits. Eight patients received extended physiotherapy input but with only modest improvement. Of the 11 patients who received a combination of medical (drug) treatment and physiotherapy, only five were considered to have had any major functional benefit in the main affected hip joint. However, one of the patients who underwent total hip replacement and has been continued on methotrexate has had both radiological and major clinical improvement in her affected contralateral hip. However, the apparent prevention of progression of disease in the contralateral involved hips in the six patients who were treated with DMARDs is notable.
Surgical procedures were performed in five, with four undergoing total hip replacement. This was considered a major success in each case, with no complications and major sustained improvement in function and deformity noted. Soft-tissue release was performed on one subject with modest and transient effect.
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Discussion
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Most previous reports regarding PA have been from adult-onset cohorts. Our paediatric cohort reflects a greater diversity of clinical settings where this radiological phenomenon may be found. The potential differential diagnosis of PA (including primary and secondary forms) at presentation is summarized in Table 4.
Hip pain as the dominant presenting and ongoing dominant complaint has previously been reported in another retrospective cohort of patients from this unit (known as the Juvenile Rheumatology Clinic when it was at Northwick Park Hospital, London) [2]. Four of 26 of these patients were termed idiopathic protrusio acetabuli and five idiopathic chondrolysis.
The older age of onset of our reported cohort with an oligoarthritis pattern contrasts with the peak of onset of age of 23 yr for the common or classical oligoarthritis JIA subtype. Such late childhood or adolescent onset is documented in other similar studies also [2], as well as PA in more defined forms of JIA, where, when it occurs, disease onset is usually later than 8 yr [35].
The preponderance of female gender in our cohort is similar to that reported in many other case series [1, 2, 69]. In the ERA subtype of JIA (juvenile spondyloarthropathy), when PA occurs it is reported to occur predominantly in females, in contrast to ERA cohorts as a whole, in which males predominate [10]. Though the female gender is over-represented in JIA in general, in known subtypes in which hip disease is common (SOJIA and ERA) the gender balance is usually equal or male-dominant.
Our report emphasizes a preponderance of cases of negroid and South Asian ethnicity, also seen in the previous report from this unit, where three-quarters of the female cases with idiopathic chondrolysis were of African or Afro-Caribbean race [2]. In a black South African population with isolated severe hip disease, 17 of 92 had documented PA [11].
Though early reports of PA suggested slow progression [9, 12] in our cohort and those described by others [1, 2, 68], a subgroup with apparent accelerated destruction and deformity is seen. Such pathology might be considered typical of undiagnosed infective processes but all investigations in our study and other studies have failed to find an infective aetiology.
In contrast to our series, classical oligoarticular JIA most commonly involves the knee and ankle, with the hips almost always spared [13, 14]. In contrast, the hip may be the site of presentation in juvenile ankylosing spondylitis (and other forms of ERA) [15]. None of our patients in this cohort were considered to have had this form of arthritis, with a negative family history for B27-associated disease, psoriasis and psoriatic arthritis; where tested, all were HLA-B27 negative.
Pathological results, where reported, in most series identify changes which could be consistent with chronic inflammation [1, 2, 16, 17]. In 17 reported cases with so-called idiopathic chondrolysis, changes in synovial thickening and oedema and non-specific inflammatory changes were seen [8]. These findings are consistent with those of our cohort and strongly suggest an inflammatory component in this condition.
Mechanisms involved in the pathogenesis and evolution of the actual acetabular protrusion have not yet been delineated. Bone pathology in the medial acetabular wall, and subsequent lack of support for the femoral head, has been proposed [18], as have steroid-induced osteoporosis and acetabular medial wall fractures in adult patients with rheumatoid arthritis [19]. In our cohort and other cohorts [3, 10], steroid treatment was not found to be a significant factor in development of PA. Presentation in the later part of childhood has also been described in the development of coxa magna in patients with juvenile chronic arthritis [20].
In an early report [1] of idiopathic PA, six of eight cases (all girls) had underlying generalized joint hypermobility. Six cases ultimately required total hip replacement, all within 25 yr of presentation. Abnormal acetabular deepening or PA was reported in 26 of 52 patients with Marfan's syndrome [21]. Clinical hypermobility was present in all of the cases with PA or idiopathic chondrolysis reported by Hughes et al. [2], and there is a preponderance of reports regarding the presence of PA in children with other conditions (osteogenesis imperfecta [22], Stickler syndrome [23]) in which hypermobility is a feature, suggesting a genetic contribution. Significant familial clusters of hypermobility associated with PA have been described [24, 25], suggesting an apparent autosomal dominant mode of transmission. None of our patients were documented as having significant hypermobility. Neoplastic and haematological conditions (such as sickle cell disease) are associated with a secondary form of PA and should be excluded where appropriate [26, 27].
The issue with the so-called idiopathic cases has been with our inability to postulate aetiological factors until recently. The use of MRI, particularly with gadolinium, shows earlier and more significant changes than plain radiography in our study, a finding consistent with the existing recent literature [28], and helps elucidate the inflammatory component.
Our observations and review of the literature suggest strongly that a considerable number of cases of IPA are likely to be associated with the presence of chronic inflammation, very similar to that of JIA at the hip joint. Histological studies and laboratory studies support the contention that this is an inflammatory autoimmune disorder. The characteristic isolated hip involvement, typical ethnicity, predominant female gender and late age of onset point to this being a unique oligoarthritis pattern of JIA. To help classify patients with this disorder we suggest the following criteria: (1) isolated uni- or bilateral hip disease; (2) radiological evidence of PA; (3) female gender; (4) African or South Asian ancestry; (5) MRI evidence of inflammatory synovial disease. Cases would be excluded if found to be HLA-B27-positive, to fulfil criteria for other forms of JIA (other than oligoarthritis), or to have a family history of HLA-B27-associated disease or psoriasis or psoriatic arthritis. Cases would be included if they fulfilled criterion 1, plus at least two of the criteria 25.
Further we propose that for patients who present with primary hip disease in childhood or adolescence, especially with early signs of PA, an inflammatory origin for this disorder should be sought. MRI (with gadolinium enhancement) should be considered in all cases to identify the presence of inflammatory synovitis in apparent IPA; it may also be considered in isolated destructive or deforming hip disease if the joint is not deemed to be unstable or to be undergoing avascular necrosis.
This approach should allow early commencement of disease-modifying or immunosuppressive therapy, including intra-articular long-acting corticosteroid injections, and perhaps prevent the progression of PA in one or both hips, which might otherwise lead to major morbidity and the need for THR.
The authors have declared no conflicts of interest.
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Submitted 15 April 2004;
revised version accepted 14 September 2004.