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Rheumatological presentation of developmental bone diseases
European Journal of Radiology 33 (2000) 118 – 127 www.elsevier.nl/locate/ejrad
Rheumatological presentation of developmental bone diseases Gabriel Kalifa *, Pierre a`lain Cohen, Amine Hamidou Department of Radiology, Saint Vincent de Paul Hospital, 82 a6enue Denfert Rochereau 75674 Paris cedex 14, France Received 21 July 1999; accepted 19 August 1999
Abstract Developmental bone disease may be present, with rheumatological disorders as the major symptoms, even in children. The major lesions encountered are early osteo arthritis, osteo chondromatosis and vertebral involvement with two leading types, pseudo Scheuermann’s disease or pseudo ankylosing spondylitis. This paper presents the different features and lists the rheumatological problems in bone dysplasia. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Bones, steochondra dysplasia; Spine, disease; Spine, abnormalities; Children, skeletal system
1. Introduction
2. Clinical presentation
The discovery of developmental bone disease (DBD) gives rise to several clinical concerns. A positive diagnosis to enable genetic counselling is required. This enables monitoring of potential visceral and neurological complications and allows accurate prognostic information in relation to orthopaedic problems which may be associated with the underlying dysplasia, so that these are managed appropriately [7]. Late presentation of bone dysplasia may occur in children, with rheumatological or orthopaedic complications. When this happens, it is not always clear whether the presenting symptom is attributable to the DBD itself or whether it is a secondary complication. This article is concerned with the presence of joint problems attributable to DBD, in children, in whom the diagnosis is not clinically obvious. We will not describe the classical complications of certain dysplasias observed in children and adolescents, such as scoliosis, vertebral stenoses (Fig. 1) or instability, associated with achondroplasia or mucopolysaccharidoses, e.g. but will focus on joint problems. Many of the clinical problems are a consequence of the anomalies of calcium phosphate metabolism and may be present in late teenagers or adulthood.
The clinical presentation is relatively non specific: vertebral or joint pain, malalignment, periarticular calcifications etc., However, in the presence of such symptoms, certain findings may be suggestive of an underlying DBD: 1. Very early development of osteoarthritis. 2. Morphological abnormality of one or several bones. 3. Short stature. 4. Unusual facies. 5. Family history. 6. A particular distribution of bone lesions. The main dysplasias responsible for rheumatological problems are those affecting the spine and large joints. The diseases are summarised in Table 1[11]. The main lesions of these bone dysplasias essentially involve subchondral bone, and may be associated with fragmentation of the adjacent part of the epiphyses. Multiple and often unusual articular osteochondromatosis and chondrocalcinosis are also frequently observed. When the vertebral column is involved, the lesion is much more severe than the platyspondyly or deformity specific to each disease. The disc is involved and may even disappear and vertebral fusion may occur. Disc ossification may also be detected. Histological changes are seen in cartilage, with large clumps of chondrocytes with pycnotic nuclei and a
* Corresponding author. Tel.: + 33-1-40-488187; fax: + 33-1-40488346.
0720-048X/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 7 2 0 - 0 4 8 X ( 9 9 ) 0 0 1 6 0 - 6
G. Kalifa et al. / European Journal of Radiology 33 (2000) 118–127
defect of column formation. Synovial biopsies are usually normal. Calcium pyrophosphate crystals are frequently detected in the synovial fluid.
2.1. Types of lesion [6,9] 1. Osteoarthritis (Fig. 2): Osteoarthritis occurs early in the context of DBD, sometimes at a very young age. It predominantly affects the joints most severely affected by the dysplastic process. A mechanical origin is highly probable, but these forms of osteoarthritis can also affect non weight-bearing joints, such as the shoulders and elbows. Disruption of joint dynamics, or lack of congruence due to epiphyseal deformities, is responsible for secondary
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avascular lesions. The joint spaces are generally relatively well preserved and osteophytes are usually absent. Microscopic bone cysts are frequently observed in subchondral bone. 2. Osteochondromatoses (Fig. 3): Osteochondromatoses can develop in joints affected by osteoarthritis and in non involved joints. They are frequently observed in patients with epiphyseal dysplasias. They are not associated with histological abnormalities of the synovium. 3. Vertebral involvement of DBD consists of disc changes associated with pseudospondylarthritic ossification. The appearance initially resembles that of Scheuermann’s disease, with irregularities of vertebral end plates, a flaky appearance, reduction of disc height and intraspongious herniation of disc material. Disc atrophy gradually increases during adulthood, especially in late-onset spondyloepiphyseal dysplasia, and ossification is observed in the spinal ligamentous, closely resembling the features of ankylosing spondylitis. In very advanced stages, complete bone fusion may sometimes be observed. Chondrocalcinosis may be detected radiologically or on synovial biopsy. However, regardless of the particular type of underlying lesion, these changes occur without clinical or laboratory evidence of an inflammatory process. The rheumatoid factor is negative.
2.2. Late-onset spondyloepiphyseal dysplasia [1,4] (Figs. 4 – 7)
Fig. 1. (a) A 10-year-old boy with a short stature. The plain AP film shows narrowing of the interpedicular distance from L1 to L5. The presence of ste‘nosis of the spine canal with lower limbs pain are obvious later in the life of the patient. (b) Final diagnosis: hypochondroplasia.
This disease is rarely present before the age of ten years. The child has a short stature and attains an adult height of between 1.45 and 1.50 m. There may be some limitation of hip movements, especially in adults, following the development of osteoarthritis. The initial radiological signs simply consist of an oval-shaped appearance of the vertebral bodies which deteriorates with age. In older children and adolescents, the vertebrae have a flattened appearance, especially in the thoracic spine. The middle part of the vertebral body is bulging, causing narrowing of the intervertebral space on lateral views. At a more severe stage, a block appearance may be observed with ligamentous ossification, resembling that observed in ankylosing spondylitis. Disc calcifications may also be detected. The limb epiphyses are small, the pelvis is small and fine osteoarthritic degeneration is observed fairly early. This is an X-linked disease. Apart from this late-onset spondyloepiphyseal dysplasia, many other spondyloepiphyseal dysplasias are still considered to be unclassified. Progressive pseudorheumatoid chondrodysplasia also belongs to this group of diseases (Fig. 8).
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Table 1 Main rheumatological problems and bone dysplasiaa Spine N Achondroplasia Acrodysostosis Acromesomelic dysplasia Angel-shaped phalangoepiphyseal dysplasia Brachmann-de Lange syndrome Brachyolmia Bruck syndrome Cerebro-oculofacioskeletal syndrome Chondrodysplasia punctata Chondroectodermal dysplasia Cockayne syndrome Congenital contractures, ectodermal dysplasia Diaphyseal dysplasia Diastrophic dysplasia Down syndrome Dyggve–Melchior-Clausen Dyschondrosteosis Dysplasia epiphysealis hemimelica Dyssegmental dysplasia Enchondromatosis (Ollier-disease) Exostosis (multple cartilaginous) Freeman–Sheldon syndrome Frontometaphyseal dysplasia Gaucher disease Geoderma osteodysplastica GM gangliosidosis Hajdu–Cheney syndrome Humerospinal dysostosis Hyperphosphatasia hypochondroplasia Hypophosphatasia Klippel–Feil syndrome Kniest dysplasia Larsen syndrome Lenz–Majewski dysplasia Mandibuloacral dysplasia Megaepiphyseal dyplasia Melorheostosis Mesomelic dysplasia, Langer type Mesomelic dysplasia, Nievergelt type metaphyseal chondrodysplasia scmhid type Metaphyseal chondrodysplasia Metaphyseal chondrodysplasia Jansen type Metaphyseal chondrodysplasia, McKusick type Metatropic dysplasia Mucolipidosis Mucolipidosis III Mucopolysaccharidosis Mucopolysaccharidosis IVA Multiple epiphyseal dysplasia Multiple synostosis syndrome Nail-patella syndrome Neurofibromatosis Oculodentoosseous dysplasia (hip) Opsismodysplasia Osteodysplasty, Melnick-needles Osteogenesis imperfecta,
CALC
Large joints DJD
+ + +
AAI
DJD
L
GVR D
S
GVL
C
+
+
+ +
+
+ +
+ +
+
+
+
+ + +
+
+
+
+
+ +
+ +
+
+ +
+
+ +
+
+ +
+ +
+
+ + + + + +
+
+
+ +
+
+ +
+
+ + + + + + +
+ + +
+ + +
+ + +
+
+ + +
+
+
+ + +
+
+
+ +
+ + +
+
+ + + + + + + + +
+ +
+ +
+ + + +
+ +
+ + + +
+
+ + +
+
+
+ + +
+
+
+
+ +
+ + +
+
+
+
G. Kalifa et al. / European Journal of Radiology 33 (2000) 118–127
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Table 1 (Continued) Spine N Osteogenesis imperfecta, type I Osteoglophonic dysplasia Osteopalatinodigital syndrome type I (elbow) Osteopalatinodigital syndrome type II (elbow) Pachydermoperiostosis Pallister–Killian syndrome Parastremmatic dysplasia Patterson syndrome Progeria Progressive pseudorheumatoid chondrodysplasia Pseudoachondrodysplasia Pseudodiastrophic dysplasia Pseudohypoparathyroidism Pyle dysplasia Robinow syndrome Rubinstein–Taybi syndrome Schwartx–Jampel syndrome Seckel syndrome Shprintzen–Goldberg syndrome Smith–Lemli–Opitz syndrome I Smith-McCort syndrome Spondyloenchondrodysplasia spondyloepimetaphyseal dysplasia (refer classification) Spondyloepimetaphyseal dysplasia with joint laxity Spondyloepimetaphyseal dysplasia, Irapa type Spondyloepimetaphyseal dysplasia, Iraqi type Spondyloepimetaphyseal dysplasia, Strudwick type Spondyloepiphyseal dysplasia, congenita Spondyloepiphyseal dysplasia tarda Spondyloepiphyseal dysplasia unclassified Spondylometaphyseal dysplasia, Kozlowski type Spondylometaphyseal dysplasias (refer to classification) Stickler syndrome Trichorhinophalangeal dysplasia, type I Trichorhimophalangeal dysplasia, type II Turner syndrome Werner syndrome Winchester syndrome Zellweger syndrome
Large joints
CALC
DJD
AAI
DJD
L
GVR D
S
GVL
C
+ + + + + +
+
+
+
+
+ + + +
+ +
+
+ +
+ + + +
+
+ +
+ + + + +
+ + +
+ + +
+ + +
+ +
+
+ +
+ +
+
+ + + + +
+ + + +
+
+ +
+
+
+ + + + + +
+ +
+ +
+
+
+
+ + +
+ + + +
a Spine:N, spinal canal narrowing; CALC, disc calcifications; DJD, spine degenerative disease; AAI, atlas-axis instability; Large joints:DJD, degenerative joint disease; L, joint laxity; D, joint dislocation; S, joint stiffness; C, joint space calcificatons; GVR, genu varum; GVL, genu valgum.
3. Progressive pseudo-rheumatoid chondrodysplasia [5,8,10,12] This disease, very similar to late-onset spondyloepiphyseal dysplasia, was identified by Wynne – Davies. It starts between the ages of 3 and 8 years with progressive onset of walking difficulties, fatigue, muscle weakness and joint stiffness, especially in the hands. Laboratory investigations for complement tests, including rheumatoid factor, are negative. Radiological findings, apart from platyspondyly and Scheuermann-like erosions of the vertebral plates, include narrowing of the joint spaces of the hands, widened metaphyses, and flattening of the epiphyses. In the hips, the femoral heads are enlarged, but the joint space is narrowed and
the acetabulum is irregular. Chondrocalcinosis may also be present. Histological examination reveals abnormal clumps of chondrocytes with pycnotic nuclei and defective column formation. Synovial biopsies are normal. The differential diagnosis essentially includes seronegative rheumatoid arthritis, muscular dystrophies and ankylosing spondylitis [2,4].
4. Multiple epiphyseal dysplasia Children presenting symptoms of an abnormal gait with or without joint pain, in childhood, may be first seen in an orthopaedic or rheumatology clinic. Inheri-
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Fig. 2. Deformity of the joints secondary to metaphyseal dysplasia. In these types of dysplasia, epiphyseal involvement is almost always associated. This involvement leads to joint deformity and early osteoarthritis.
tance is autosomal dominant. Two forms are described — a severe form known as Fairbank’s disease, and a milder form known as Ribbing’s disease. In the milder forms the vertebral column is often normal but in the severer forms there may be irregularity of the vertebral end plates. The epiphyses of the long bones are small and irregular. (Figs. 4 and 7) The changes are in particular seen in the hips, shoulders, knees and ankles. Early osteoarthrosis is frequent.
5. Constitution abnormalities of calcium phosphate metabolism (Figs. 9 and 10) The most frequent disorder of calcium phosphate metabolism seen in children, is that of a metabolic disease leading to rickets. These children are usually first presented to the metabolic clinics, and not primarily to the rheumatology or orthopaedic departments. Occasionally, however, children who present symptoms such as joint swelling, pain and muscle weakness, is
Fig. 3. (a) Another type of congenital bone disorder. Epiphyseal hemimelic dysplasia with joint deformity, hypertrophy of the epiphyses, presence of calcified mass. The alteration of joint congruity can explain partly the rheumatological presentation of such a patient. (b) CT scan of the same patient, the slice passing through the lower part of the knee showing the epiphyseal deformity with a bony overgrowth.
G. Kalifa et al. / European Journal of Radiology 33 (2000) 118–127
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Fig. 4. (a) Epiphyseal involvement in congenital multiple epiphyseal dysplasia. Note small femoral heads with some deformity of the acetabulum. (b) Same patient, 4 years later showing narrowing of the joint space and progressive deformity of the head which leads to early osteoarthritis.
Fig. 5. (a) Another example of epiphyseal dysplasia in a 16-year-old boy. Asymmetrical involvement with major deformity of the left hip with flattening of the femoral head, narrowing of the joint space and irregularities of the acetabulum. (b) T1W coronal view of a patient showing the deformities of the head with enlargement of the metaphyses on both sides. Early onset of osteoarthritis is frequent.
brought primarily to the Department of Rheumatology and Awareness as the causes of rickets are important. Radiologically, the diagnosis is usually obvious — the typical appearances of widened growth plates, frayed metaphyses and osteopenia being evident. The causes of rickets in childhood are seen in Table 2. It will be seen from the table that most of the causes are obvious and are easily diagnosed, when a good clinical history is taken. In clinical practice, in Western society the most frequent cause of rickets is renal disease. Nutritional and privational rickets is still occasionally seen in Negro children who live in regions with inadequate sunshine and who have a poor diet. Similar nutritional rickets may be seen in children of Indian origin who are fed a diet of chapatis made with untreated flour. Malabsorption states may cause rickets because of failure of absorption of vitamin D. Liver disease and anticonvulsants cause failure of hydroxylation of vita-
Fig. 6. Another example of epiphyseal dysplasia with displacement of both femoral heads which are flattened and subluxed.
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those of hyperparathyroidism, e.g. chalky bone, rugger jersey spine, resorption of bone in the outer ends of the clavicles and at the phalanges and dystrophic calcification. The development of brown tumours is rare in childhood. Renal tubular problems produce the more typical rickety changes — widening of the growth plate at wrists and knees and often most pronounced medially. The degree of irregularity depends on the control of the disease. With good replacement therapy, the irregularity disappears but the growth plate remains widened initially. Children with inherited disorders of the renal tubules are those most likely to be presented de novo to rheumatology or orthopaedic clinics as they exhibit the skeletal effects of their disease — namely short stature, bow legs and sometimes swollen joints and weakness.
5.2. Familial hypophosphataemic 6itamin D resistant rickets This is inherited as an X-linked autosomal dominant condition. It is present in children usually at 12–18 months of age with the symptoms of short stature and bowed legs. Radiologically the growth plates are wide, the bony trabeculae are irregular Fig. 9. Treatment results in rapid return to normality of the bony changes but corrective osteotomies may be required at skeletal maturity to correct the leg deformities. Fig. 7. Epiphyseal knee involvement in multiple epiphyseal dysplasia (Fairbank type). Irregularity of the epiphysis, with some degree of bony fragmentation and abnormal alignment are present.
min D. In biliary atresia, reduced output of bile salts, necessary for vititamin D absorption, is the cause. The cause of rickets associated with tumours is unknown. Known associates are haemangiomas, fibrous dysplasia, non osteogenic fibroma and haemangiopericytoma. Most of these conditions are obvious with typical radiological features. Excision of the tumour results in cure. The diagnosis of tumour associated rickets is difficult and is one that is made by exclusion of all other known causes and by resolution of the changes when the tumour is removed.
5.1. Renal rickets Rickets may occur secondary to renal glomerular disease. The defect here is a failure of the kidneys to hydroxylate 25 hydroxy vitamin D3 into the active form, and a failure to excrete phosphate. This leads to excess production of parathormone and hyperparathyroidism. The radiological features of such renal osteodystrophy with hyperparathyroidism supervenes are
5.3. Cystinosis (Lignac–Fanconi syndrome) [3] Due to an inborn error of metabolism there is an accumulation of cystine within many body tissues. Skeletally these manifest as severe rickets.
5.4. Renal tubular acidosis These are unlikely to be present de novo in children with joint problems, as there is hypercalcaemia, which clinically manifests as renal stones. Radiologically, there is evidence of nephrocalcinosis and renal stones in association with changes of rickets in severe cases.
5.5. Hypophosphatasia Four forms of this autosomal recessive inborn error of metabolism are described, dependent on the time of presentation. The neonatal form is usually lethal. The infantile form is present in the first few months of life. The child, being small, fails to thrive, and fractures occur. Radiographically there is a deficient mineralization of the skeleton. The childhood form, associated with knock-knee deformity and short stature, is the type most likely to be present to an orthopaedic clinic. Radiographically, the bones are osteopenic, the meta-
G. Kalifa et al. / European Journal of Radiology 33 (2000) 118–127
physes are broadened and contain cyst-like lucencies in the metaphyses. Long bone deformity, especially in the tibia, is due to softening and is common. With progression to adulthood, spinal canal stenosis with cord compression, calcification of the spinal ligaments and intervertebral discs may occur. At any age, the presence of fractures in the child may occur.
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5.6. Metaphyseal chondrodysplasia — Schmid type This is an autosomal dominant inherited skeletal dysplasia. The children are of short stature, which is relatively mild. They may have an accentuated lumbar lordosis and either a knock-knee or bow-leg deformity. The radiological changes in the long bones resemble
Fig. 8. (a) This patient, 42 years old, is the uncle of a young boy admitted to our institution for investigation of short stature. The boy has spondyloepiphyseal dysplasia tarda. The uncle was known to have a ‘rheumatological problem’. Ossification of the anterior and lateral spinal ligaments resembling ankylosing spondyarthritis is present. The intervertebral disc space is preserved. Normal sacro iliac joints are present. He is negative for HLA B27. This man, also short statured, presents classical complications of spondyloepiphyseal dysplasia tarda, known in some papers as chondrodysplastic rheumatism. (b) AP view of the lumbar spine of the same patient demonstrated normal joint space of the sacro-iliac joint.
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6. Conclusion This short article has attempted to highlight the more common DBDs which may be present primarily with a rheumatological manifestation.
Fig. 10. A 17-year-old boy with short stature and left-side limp. One can see abnormal metaphyseal lucent bands. This appearance was seen on all the metaphyses and is due to alteration of the bony architecture. This is a type of metabolic disorder which may present as limping. Studies performed on this boy confirmed the diagnosis of pseudo hypoparathyroidism, hitherto unsuspected.
Fig. 9. Vitamin D resistant rickets in a 16-year-old boy. Note the joint deformity with genu valgum. Inadequate treatment leads to relapse with recurrent deformity, if previously corrected.
rickets with widening of the growth plate, and irregular flared metaphyses which bear a superficial resemblance to rickets, except that there is no osteopenia. The biochemical profile is normal. These children do not require vitamin D supplementation as there is no deficiency, and thus, if treated, may get vitamin D poisoning. The other metaphyseal chondrodysplasias, in addition to bony changes, are features such as severe dwarfism, failure to thrive, malabsorption or other clinical features which mean that they will usually be presented to other departments.
Table 2 The causes of rickets in childhooda 1. Privational — inadequate exposure to sunlight or inadequate diet 2. Malabsorption syndromes 3. Liver diseaseboth hepatocellular disease and biliary disease 4. Drug therapyespecially anticonvulsants 5. Renal glomerular disease 6. Renal tubular disease: Hypophosphatemic vitamin D resistant rickets Renal tubular acidosis Ifosfamide therapy Cystinosis 7. Tumour rickets 8. Target cell failure: lack of end organ response to vitamin D a
Children with renal tubular problems and more rarely tumour rickets are the most likely to present to rheumatology clinics. Table adapted from [3], p. 992.
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References [1] Al Awadi SA, Farag TI, Naguib K, Ek-Khalifa MY, Cuschieri A, Hosny G, Zahran M, Al-Ansari AG. Spondyloepiphyseal tarda with progressive arthropathy. J Med Genet 1984;21(3):193– 6. [2] Bradley JD. Pseudoseptic pseudogout in progressive pseudorheumatoid arthropathy of childhood. Ann Rheum Dis 1987;46:709. [3] Carty H, Brunelle F, Shaw D, Kendall B. Imaging Children. Livingstone: Churchill, 1994:999. [4] El-Shanti HE, Omari HZ, Qubain HI. Progressive pseudorheumatoid dysplasia: report of a family and review. J Med Genet 1997;34(7):559– 63. [5] Hall CM, Elcioglu NH, Shaw DG. A distinct form of spondyloepimetaphyseal dysplasia with multiple dislocations. J Med Genet 1998;35(7):566– 72. [6] Kahn MF, Corvol MT, Jurmand SH, Couture B, Amouroux J,
.
[7] [8]
[9] [10]
[11]
[12]
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de Seze S. Le rhumatisme chondrodysplasique. Revue du Rhumatisme 1970;37(12):825– 41. Maroteaux P. Les maladies osseuses de l’enfant, 3eme edition. Flammarion ,Paris: Medicine Sciences, 1995. Rezai-Delui H, Mamoori G, Sadri-Mahvelati E, Noori NM. Progressive pseudorheumatoid chondrodysplasia: a report of nine cases in three families. Skel Radiol 1994;23(6):411– 9. Siffert RS. Patterns of deformity of the developing hip. Clin Orthop Relat Res 1981;160:14 – 29. Spranger J, Albert C, Schilling F, Bartsocas C, Stoss H. Progressive pseudorheumatoid arthritis of childhood (PPAC). Eur J Pediatr 1983;140(1):34– 40. Taybi H, Lachman RS. Radiology of Syndromes, Metabolic Disorders, and Skeletal Dysplasias, 4th ed. St Louis, MO: Mosby Year Book Inc, 1996. Wynne-Davies R, Hall C, Ansell BM. Spondyloepiphyseal dysplasia tarda with progressive arthropathy. J Bone Jt Surg (B) 1982;64(4):442– 5.
Rheumatological presentation of developmental bone diseases Gabriel Kalifa *, Pierre a`lain Cohen, Amine Hamidou Department of Radiology, Saint Vincent de Paul Hospital, 82 a6enue Denfert Rochereau 75674 Paris cedex 14, France Received 21 July 1999; accepted 19 August 1999
Abstract Developmental bone disease may be present, with rheumatological disorders as the major symptoms, even in children. The major lesions encountered are early osteo arthritis, osteo chondromatosis and vertebral involvement with two leading types, pseudo Scheuermann’s disease or pseudo ankylosing spondylitis. This paper presents the different features and lists the rheumatological problems in bone dysplasia. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Bones, steochondra dysplasia; Spine, disease; Spine, abnormalities; Children, skeletal system
1. Introduction
2. Clinical presentation
The discovery of developmental bone disease (DBD) gives rise to several clinical concerns. A positive diagnosis to enable genetic counselling is required. This enables monitoring of potential visceral and neurological complications and allows accurate prognostic information in relation to orthopaedic problems which may be associated with the underlying dysplasia, so that these are managed appropriately [7]. Late presentation of bone dysplasia may occur in children, with rheumatological or orthopaedic complications. When this happens, it is not always clear whether the presenting symptom is attributable to the DBD itself or whether it is a secondary complication. This article is concerned with the presence of joint problems attributable to DBD, in children, in whom the diagnosis is not clinically obvious. We will not describe the classical complications of certain dysplasias observed in children and adolescents, such as scoliosis, vertebral stenoses (Fig. 1) or instability, associated with achondroplasia or mucopolysaccharidoses, e.g. but will focus on joint problems. Many of the clinical problems are a consequence of the anomalies of calcium phosphate metabolism and may be present in late teenagers or adulthood.
The clinical presentation is relatively non specific: vertebral or joint pain, malalignment, periarticular calcifications etc., However, in the presence of such symptoms, certain findings may be suggestive of an underlying DBD: 1. Very early development of osteoarthritis. 2. Morphological abnormality of one or several bones. 3. Short stature. 4. Unusual facies. 5. Family history. 6. A particular distribution of bone lesions. The main dysplasias responsible for rheumatological problems are those affecting the spine and large joints. The diseases are summarised in Table 1[11]. The main lesions of these bone dysplasias essentially involve subchondral bone, and may be associated with fragmentation of the adjacent part of the epiphyses. Multiple and often unusual articular osteochondromatosis and chondrocalcinosis are also frequently observed. When the vertebral column is involved, the lesion is much more severe than the platyspondyly or deformity specific to each disease. The disc is involved and may even disappear and vertebral fusion may occur. Disc ossification may also be detected. Histological changes are seen in cartilage, with large clumps of chondrocytes with pycnotic nuclei and a
* Corresponding author. Tel.: + 33-1-40-488187; fax: + 33-1-40488346.
0720-048X/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 7 2 0 - 0 4 8 X ( 9 9 ) 0 0 1 6 0 - 6
G. Kalifa et al. / European Journal of Radiology 33 (2000) 118–127
defect of column formation. Synovial biopsies are usually normal. Calcium pyrophosphate crystals are frequently detected in the synovial fluid.
2.1. Types of lesion [6,9] 1. Osteoarthritis (Fig. 2): Osteoarthritis occurs early in the context of DBD, sometimes at a very young age. It predominantly affects the joints most severely affected by the dysplastic process. A mechanical origin is highly probable, but these forms of osteoarthritis can also affect non weight-bearing joints, such as the shoulders and elbows. Disruption of joint dynamics, or lack of congruence due to epiphyseal deformities, is responsible for secondary
119
avascular lesions. The joint spaces are generally relatively well preserved and osteophytes are usually absent. Microscopic bone cysts are frequently observed in subchondral bone. 2. Osteochondromatoses (Fig. 3): Osteochondromatoses can develop in joints affected by osteoarthritis and in non involved joints. They are frequently observed in patients with epiphyseal dysplasias. They are not associated with histological abnormalities of the synovium. 3. Vertebral involvement of DBD consists of disc changes associated with pseudospondylarthritic ossification. The appearance initially resembles that of Scheuermann’s disease, with irregularities of vertebral end plates, a flaky appearance, reduction of disc height and intraspongious herniation of disc material. Disc atrophy gradually increases during adulthood, especially in late-onset spondyloepiphyseal dysplasia, and ossification is observed in the spinal ligamentous, closely resembling the features of ankylosing spondylitis. In very advanced stages, complete bone fusion may sometimes be observed. Chondrocalcinosis may be detected radiologically or on synovial biopsy. However, regardless of the particular type of underlying lesion, these changes occur without clinical or laboratory evidence of an inflammatory process. The rheumatoid factor is negative.
2.2. Late-onset spondyloepiphyseal dysplasia [1,4] (Figs. 4 – 7)
Fig. 1. (a) A 10-year-old boy with a short stature. The plain AP film shows narrowing of the interpedicular distance from L1 to L5. The presence of ste‘nosis of the spine canal with lower limbs pain are obvious later in the life of the patient. (b) Final diagnosis: hypochondroplasia.
This disease is rarely present before the age of ten years. The child has a short stature and attains an adult height of between 1.45 and 1.50 m. There may be some limitation of hip movements, especially in adults, following the development of osteoarthritis. The initial radiological signs simply consist of an oval-shaped appearance of the vertebral bodies which deteriorates with age. In older children and adolescents, the vertebrae have a flattened appearance, especially in the thoracic spine. The middle part of the vertebral body is bulging, causing narrowing of the intervertebral space on lateral views. At a more severe stage, a block appearance may be observed with ligamentous ossification, resembling that observed in ankylosing spondylitis. Disc calcifications may also be detected. The limb epiphyses are small, the pelvis is small and fine osteoarthritic degeneration is observed fairly early. This is an X-linked disease. Apart from this late-onset spondyloepiphyseal dysplasia, many other spondyloepiphyseal dysplasias are still considered to be unclassified. Progressive pseudorheumatoid chondrodysplasia also belongs to this group of diseases (Fig. 8).
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Table 1 Main rheumatological problems and bone dysplasiaa Spine N Achondroplasia Acrodysostosis Acromesomelic dysplasia Angel-shaped phalangoepiphyseal dysplasia Brachmann-de Lange syndrome Brachyolmia Bruck syndrome Cerebro-oculofacioskeletal syndrome Chondrodysplasia punctata Chondroectodermal dysplasia Cockayne syndrome Congenital contractures, ectodermal dysplasia Diaphyseal dysplasia Diastrophic dysplasia Down syndrome Dyggve–Melchior-Clausen Dyschondrosteosis Dysplasia epiphysealis hemimelica Dyssegmental dysplasia Enchondromatosis (Ollier-disease) Exostosis (multple cartilaginous) Freeman–Sheldon syndrome Frontometaphyseal dysplasia Gaucher disease Geoderma osteodysplastica GM gangliosidosis Hajdu–Cheney syndrome Humerospinal dysostosis Hyperphosphatasia hypochondroplasia Hypophosphatasia Klippel–Feil syndrome Kniest dysplasia Larsen syndrome Lenz–Majewski dysplasia Mandibuloacral dysplasia Megaepiphyseal dyplasia Melorheostosis Mesomelic dysplasia, Langer type Mesomelic dysplasia, Nievergelt type metaphyseal chondrodysplasia scmhid type Metaphyseal chondrodysplasia Metaphyseal chondrodysplasia Jansen type Metaphyseal chondrodysplasia, McKusick type Metatropic dysplasia Mucolipidosis Mucolipidosis III Mucopolysaccharidosis Mucopolysaccharidosis IVA Multiple epiphyseal dysplasia Multiple synostosis syndrome Nail-patella syndrome Neurofibromatosis Oculodentoosseous dysplasia (hip) Opsismodysplasia Osteodysplasty, Melnick-needles Osteogenesis imperfecta,
CALC
Large joints DJD
+ + +
AAI
DJD
L
GVR D
S
GVL
C
+
+
+ +
+
+ +
+ +
+
+
+
+ + +
+
+
+
+
+ +
+ +
+
+ +
+
+ +
+
+ +
+ +
+
+ + + + + +
+
+
+ +
+
+ +
+
+ + + + + + +
+ + +
+ + +
+ + +
+
+ + +
+
+
+ + +
+
+
+ +
+ + +
+
+ + + + + + + + +
+ +
+ +
+ + + +
+ +
+ + + +
+
+ + +
+
+
+ + +
+
+
+
+ +
+ + +
+
+
+
G. Kalifa et al. / European Journal of Radiology 33 (2000) 118–127
121
Table 1 (Continued) Spine N Osteogenesis imperfecta, type I Osteoglophonic dysplasia Osteopalatinodigital syndrome type I (elbow) Osteopalatinodigital syndrome type II (elbow) Pachydermoperiostosis Pallister–Killian syndrome Parastremmatic dysplasia Patterson syndrome Progeria Progressive pseudorheumatoid chondrodysplasia Pseudoachondrodysplasia Pseudodiastrophic dysplasia Pseudohypoparathyroidism Pyle dysplasia Robinow syndrome Rubinstein–Taybi syndrome Schwartx–Jampel syndrome Seckel syndrome Shprintzen–Goldberg syndrome Smith–Lemli–Opitz syndrome I Smith-McCort syndrome Spondyloenchondrodysplasia spondyloepimetaphyseal dysplasia (refer classification) Spondyloepimetaphyseal dysplasia with joint laxity Spondyloepimetaphyseal dysplasia, Irapa type Spondyloepimetaphyseal dysplasia, Iraqi type Spondyloepimetaphyseal dysplasia, Strudwick type Spondyloepiphyseal dysplasia, congenita Spondyloepiphyseal dysplasia tarda Spondyloepiphyseal dysplasia unclassified Spondylometaphyseal dysplasia, Kozlowski type Spondylometaphyseal dysplasias (refer to classification) Stickler syndrome Trichorhinophalangeal dysplasia, type I Trichorhimophalangeal dysplasia, type II Turner syndrome Werner syndrome Winchester syndrome Zellweger syndrome
Large joints
CALC
DJD
AAI
DJD
L
GVR D
S
GVL
C
+ + + + + +
+
+
+
+
+ + + +
+ +
+
+ +
+ + + +
+
+ +
+ + + + +
+ + +
+ + +
+ + +
+ +
+
+ +
+ +
+
+ + + + +
+ + + +
+
+ +
+
+
+ + + + + +
+ +
+ +
+
+
+
+ + +
+ + + +
a Spine:N, spinal canal narrowing; CALC, disc calcifications; DJD, spine degenerative disease; AAI, atlas-axis instability; Large joints:DJD, degenerative joint disease; L, joint laxity; D, joint dislocation; S, joint stiffness; C, joint space calcificatons; GVR, genu varum; GVL, genu valgum.
3. Progressive pseudo-rheumatoid chondrodysplasia [5,8,10,12] This disease, very similar to late-onset spondyloepiphyseal dysplasia, was identified by Wynne – Davies. It starts between the ages of 3 and 8 years with progressive onset of walking difficulties, fatigue, muscle weakness and joint stiffness, especially in the hands. Laboratory investigations for complement tests, including rheumatoid factor, are negative. Radiological findings, apart from platyspondyly and Scheuermann-like erosions of the vertebral plates, include narrowing of the joint spaces of the hands, widened metaphyses, and flattening of the epiphyses. In the hips, the femoral heads are enlarged, but the joint space is narrowed and
the acetabulum is irregular. Chondrocalcinosis may also be present. Histological examination reveals abnormal clumps of chondrocytes with pycnotic nuclei and defective column formation. Synovial biopsies are normal. The differential diagnosis essentially includes seronegative rheumatoid arthritis, muscular dystrophies and ankylosing spondylitis [2,4].
4. Multiple epiphyseal dysplasia Children presenting symptoms of an abnormal gait with or without joint pain, in childhood, may be first seen in an orthopaedic or rheumatology clinic. Inheri-
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Fig. 2. Deformity of the joints secondary to metaphyseal dysplasia. In these types of dysplasia, epiphyseal involvement is almost always associated. This involvement leads to joint deformity and early osteoarthritis.
tance is autosomal dominant. Two forms are described — a severe form known as Fairbank’s disease, and a milder form known as Ribbing’s disease. In the milder forms the vertebral column is often normal but in the severer forms there may be irregularity of the vertebral end plates. The epiphyses of the long bones are small and irregular. (Figs. 4 and 7) The changes are in particular seen in the hips, shoulders, knees and ankles. Early osteoarthrosis is frequent.
5. Constitution abnormalities of calcium phosphate metabolism (Figs. 9 and 10) The most frequent disorder of calcium phosphate metabolism seen in children, is that of a metabolic disease leading to rickets. These children are usually first presented to the metabolic clinics, and not primarily to the rheumatology or orthopaedic departments. Occasionally, however, children who present symptoms such as joint swelling, pain and muscle weakness, is
Fig. 3. (a) Another type of congenital bone disorder. Epiphyseal hemimelic dysplasia with joint deformity, hypertrophy of the epiphyses, presence of calcified mass. The alteration of joint congruity can explain partly the rheumatological presentation of such a patient. (b) CT scan of the same patient, the slice passing through the lower part of the knee showing the epiphyseal deformity with a bony overgrowth.
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Fig. 4. (a) Epiphyseal involvement in congenital multiple epiphyseal dysplasia. Note small femoral heads with some deformity of the acetabulum. (b) Same patient, 4 years later showing narrowing of the joint space and progressive deformity of the head which leads to early osteoarthritis.
Fig. 5. (a) Another example of epiphyseal dysplasia in a 16-year-old boy. Asymmetrical involvement with major deformity of the left hip with flattening of the femoral head, narrowing of the joint space and irregularities of the acetabulum. (b) T1W coronal view of a patient showing the deformities of the head with enlargement of the metaphyses on both sides. Early onset of osteoarthritis is frequent.
brought primarily to the Department of Rheumatology and Awareness as the causes of rickets are important. Radiologically, the diagnosis is usually obvious — the typical appearances of widened growth plates, frayed metaphyses and osteopenia being evident. The causes of rickets in childhood are seen in Table 2. It will be seen from the table that most of the causes are obvious and are easily diagnosed, when a good clinical history is taken. In clinical practice, in Western society the most frequent cause of rickets is renal disease. Nutritional and privational rickets is still occasionally seen in Negro children who live in regions with inadequate sunshine and who have a poor diet. Similar nutritional rickets may be seen in children of Indian origin who are fed a diet of chapatis made with untreated flour. Malabsorption states may cause rickets because of failure of absorption of vitamin D. Liver disease and anticonvulsants cause failure of hydroxylation of vita-
Fig. 6. Another example of epiphyseal dysplasia with displacement of both femoral heads which are flattened and subluxed.
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those of hyperparathyroidism, e.g. chalky bone, rugger jersey spine, resorption of bone in the outer ends of the clavicles and at the phalanges and dystrophic calcification. The development of brown tumours is rare in childhood. Renal tubular problems produce the more typical rickety changes — widening of the growth plate at wrists and knees and often most pronounced medially. The degree of irregularity depends on the control of the disease. With good replacement therapy, the irregularity disappears but the growth plate remains widened initially. Children with inherited disorders of the renal tubules are those most likely to be presented de novo to rheumatology or orthopaedic clinics as they exhibit the skeletal effects of their disease — namely short stature, bow legs and sometimes swollen joints and weakness.
5.2. Familial hypophosphataemic 6itamin D resistant rickets This is inherited as an X-linked autosomal dominant condition. It is present in children usually at 12–18 months of age with the symptoms of short stature and bowed legs. Radiologically the growth plates are wide, the bony trabeculae are irregular Fig. 9. Treatment results in rapid return to normality of the bony changes but corrective osteotomies may be required at skeletal maturity to correct the leg deformities. Fig. 7. Epiphyseal knee involvement in multiple epiphyseal dysplasia (Fairbank type). Irregularity of the epiphysis, with some degree of bony fragmentation and abnormal alignment are present.
min D. In biliary atresia, reduced output of bile salts, necessary for vititamin D absorption, is the cause. The cause of rickets associated with tumours is unknown. Known associates are haemangiomas, fibrous dysplasia, non osteogenic fibroma and haemangiopericytoma. Most of these conditions are obvious with typical radiological features. Excision of the tumour results in cure. The diagnosis of tumour associated rickets is difficult and is one that is made by exclusion of all other known causes and by resolution of the changes when the tumour is removed.
5.1. Renal rickets Rickets may occur secondary to renal glomerular disease. The defect here is a failure of the kidneys to hydroxylate 25 hydroxy vitamin D3 into the active form, and a failure to excrete phosphate. This leads to excess production of parathormone and hyperparathyroidism. The radiological features of such renal osteodystrophy with hyperparathyroidism supervenes are
5.3. Cystinosis (Lignac–Fanconi syndrome) [3] Due to an inborn error of metabolism there is an accumulation of cystine within many body tissues. Skeletally these manifest as severe rickets.
5.4. Renal tubular acidosis These are unlikely to be present de novo in children with joint problems, as there is hypercalcaemia, which clinically manifests as renal stones. Radiologically, there is evidence of nephrocalcinosis and renal stones in association with changes of rickets in severe cases.
5.5. Hypophosphatasia Four forms of this autosomal recessive inborn error of metabolism are described, dependent on the time of presentation. The neonatal form is usually lethal. The infantile form is present in the first few months of life. The child, being small, fails to thrive, and fractures occur. Radiographically there is a deficient mineralization of the skeleton. The childhood form, associated with knock-knee deformity and short stature, is the type most likely to be present to an orthopaedic clinic. Radiographically, the bones are osteopenic, the meta-
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physes are broadened and contain cyst-like lucencies in the metaphyses. Long bone deformity, especially in the tibia, is due to softening and is common. With progression to adulthood, spinal canal stenosis with cord compression, calcification of the spinal ligaments and intervertebral discs may occur. At any age, the presence of fractures in the child may occur.
125
5.6. Metaphyseal chondrodysplasia — Schmid type This is an autosomal dominant inherited skeletal dysplasia. The children are of short stature, which is relatively mild. They may have an accentuated lumbar lordosis and either a knock-knee or bow-leg deformity. The radiological changes in the long bones resemble
Fig. 8. (a) This patient, 42 years old, is the uncle of a young boy admitted to our institution for investigation of short stature. The boy has spondyloepiphyseal dysplasia tarda. The uncle was known to have a ‘rheumatological problem’. Ossification of the anterior and lateral spinal ligaments resembling ankylosing spondyarthritis is present. The intervertebral disc space is preserved. Normal sacro iliac joints are present. He is negative for HLA B27. This man, also short statured, presents classical complications of spondyloepiphyseal dysplasia tarda, known in some papers as chondrodysplastic rheumatism. (b) AP view of the lumbar spine of the same patient demonstrated normal joint space of the sacro-iliac joint.
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6. Conclusion This short article has attempted to highlight the more common DBDs which may be present primarily with a rheumatological manifestation.
Fig. 10. A 17-year-old boy with short stature and left-side limp. One can see abnormal metaphyseal lucent bands. This appearance was seen on all the metaphyses and is due to alteration of the bony architecture. This is a type of metabolic disorder which may present as limping. Studies performed on this boy confirmed the diagnosis of pseudo hypoparathyroidism, hitherto unsuspected.
Fig. 9. Vitamin D resistant rickets in a 16-year-old boy. Note the joint deformity with genu valgum. Inadequate treatment leads to relapse with recurrent deformity, if previously corrected.
rickets with widening of the growth plate, and irregular flared metaphyses which bear a superficial resemblance to rickets, except that there is no osteopenia. The biochemical profile is normal. These children do not require vitamin D supplementation as there is no deficiency, and thus, if treated, may get vitamin D poisoning. The other metaphyseal chondrodysplasias, in addition to bony changes, are features such as severe dwarfism, failure to thrive, malabsorption or other clinical features which mean that they will usually be presented to other departments.
Table 2 The causes of rickets in childhooda 1. Privational — inadequate exposure to sunlight or inadequate diet 2. Malabsorption syndromes 3. Liver diseaseboth hepatocellular disease and biliary disease 4. Drug therapyespecially anticonvulsants 5. Renal glomerular disease 6. Renal tubular disease: Hypophosphatemic vitamin D resistant rickets Renal tubular acidosis Ifosfamide therapy Cystinosis 7. Tumour rickets 8. Target cell failure: lack of end organ response to vitamin D a
Children with renal tubular problems and more rarely tumour rickets are the most likely to present to rheumatology clinics. Table adapted from [3], p. 992.
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