Camurati-Engelmann disease

Introduction Camurati-Engelmann disease (CED), or progressive diaphyseal dysplasia, is a rare sclerosing dysplasia of which 250 cases have been described in the English literature. The disease affects one in a million people and is autosomal dominant with variable penetrance. It was initially described by Cockayne in 1920; Camurati was the first to suggest its hereditary nature in 1922. A single case of muscular wasting and marked bone involvement was reported by Engelmann in 1929. As the name suggests, there is progressive hyperostosis and predominant involvement of the diaphyses. The onset of the disease is usually during childhood; patients usually present by puberty and usually before age 30, with limb pain, muscular weakness, waddling gait and easy fatigue. Other symptoms and signs may include delayed growth, reduced muscle mass, anorexia and enlargement of the arms and legs. Systemic manifestations of hepatosplenomegaly, bone marrow dysfunction (anaemia and leucopaenia) and delayed sexual development occasionally occur. In a few patients, abnormal values of bone resorption and formation have been described. Radiologically, the hallmark of the disorder is bilateral, symmetrical cortical thickening of the diaphyses of the long bones on both the periosteal and endosteal sides of the diaphyses. In decreasing order of frequency, the tibia, femur, fibula, humerus, ulna and radius are affected. CED results from disturbance of intramembranous ossification (Fig.1) affecting the long bones, calvaria, mandible and facial Camurati-Engelmann disease


Introduction
7][8] A single case of muscular wasting and marked bone involvement was reported by Engelmann in 1929. 6,9As the name suggests, there is progressive hyperostosis and predominant involvement of the diaphyses. 6,10he onset of the disease is usually during childhood; patients usually present by puberty and usually before age 30, with limb pain, muscular weakness, waddling gait and easy fatigue.Other symptoms and signs may include delayed growth, reduced muscle mass, anorexia and enlargement of the arms and legs. 6,11,13 In a few patients, abnormal values of bone resorption and formation have been described. 10adiologically, the hallmark of the disorder is bilateral, symmetrical cortical thickening of the diaphyses of the long bones 14,15 on both the periosteal and endosteal sides of the diaphyses.In decreasing order of frequency, the tibia, femur, fibula, humerus, ulna and radius are affected.CED results from disturbance of intramembranous ossification (Fig. 1) affecting the long bones, calvaria, mandible and facial bones. 11,16There are a few reported cases of involvement of the skull base (a site of endochondral ossification), but these occur in advanced stages. 3,11,17,18
Radiographically, endosteal and periosteal thickening of the diaphyses of long bones (Figs.2a -f) is seen in CED. 3,11,17,18The result is narrowing of the medullary cavity (Figs 3a, b). 4 The metaphyses can become affected, but typically the epiphyses are spared (Figs 4a, b). 4,6Sclerosis of the skull base (Figs 5a, b) can be present, leading to hearing impairment owing to progressive stenosis of the external auditory canal (EAC), and foraminal stenosis causing cranial nerve dysfunction. 6,11,19ncreased osteoblastic activity detected scintigraphically with 99Tc-HMDP (hyfroxymethylene diphosphonate) is seen bilaterally symmetrical in the upper and lower limb long bones, longitudinally  along the bone cortices. 6,15Before sclerosis is seen radiologically, increased tracer uptake can be seen and is thus valuable in the early diagnosis. 6

Diagnosis
1][22][23][24][25][26][27] The TGFB1 gene is located on the chromosomal region 19q13.1.4All investigated mutations increase the activity of TGFB1. 6Under physiological conditions, TGFB1 has been shown to suppress bone formation and the mutation stimulates bone formation6 thus disrupting bone turnover, causing increased bone formation.TGFB1 also inhibits myogenesis, causing muscle wasting as well as lipogensis. 6ED is classified as a sclerosing bone dysplasia with diaphyseal involvement (Table I).The differential diagnosis is endosteal hyperostosis -van Buchem sclerosteosis, Kenny-Caffey disease or Worth type.Owing to inheritance, one can rule out van Buchem sclerosteosis (autosomal recessive (AR)), and Worth type is a more benign form and has associated mandible enlargement. 4,13 combination of clinical, radiological, scintigraphic and molecular data are mandatory for a definitive diagnosis.

Treatment
Immunosuppressive agents such as anti-inflammatories and glucocorticosteroids have the negative side-effect of decreasing bone density; and this is used in CED as treatment.The role of the agents is to increase the apoptosis rate of osteoblasts and osteocytes and at the same time to suppress osteoblast proliferation, differentiation and bone matrix synthesis. 6Further effects are to enhance proliferation and differentiation of osteoclast precursors 6 and also to decrease intestinal calcium absorption. 6Glucocorticosteroids as well as counteracting bone formation exert a direct effect on TGFB expression.Prednisolone has been described as an effective treatment in a number of cases. 6ong-term treatment is not advisable owing to its unfavourable sideeffects such as impaired growth and spinal osteoporosis.A good starting dose is 1mg/kg/day, but should be lowered in long-term treatment.
An alternative to medication is surgery.Reaming of the medullary cavity may be done to decrease the narrowing of the canal, or an osteotomy can be performed. 6,28Further decompression in optic nerve compression has also been done.Gene therapy is a possibility in the future.

Conclusion
Camurati-Engelmann disease (CED), or progressive diaphyseal dysplasia, is a rare sclerosing dysplasia whose onset is usually during childhood.Patients usually present by puberty or before age 30.Radiologically, the hallmark of the disorder is bilateral, symmetrical cortical thickening of the diaphyses of the long bones occuring on both the periosteal and endosteal sides of the diaphyses.
The differential diagnosis is of CED is endosteal hyperostosisvan Buchem, sclerosteosis, Kenny-Caffey disease and Worth type.Inheritance can rule out van Buchem and sclerosteosis (AR), whereas Worth type is a more benign form and has associated mandible enlargement.A combination of clinical, radiological, scintigraphic and molecular data may be necessary for a definitive diagnosis.

Y O U R S A T I S F A C T I O N I S G U A R A N T E E D
3 easy order options: 1. PHONE EDWARD OR BYRON -021 6817000 2. FAX the completed SAMF order form to 0866006218 3. EMAIL: edwardm@hmpg.co.zaOR byronm@hmpg.co.za Fig. 1.Both clavicles demonstrate marked bony cortical thickening with sparing of the distal ends.The humeral epiphyses are spared.

Figs
Figs 3a and b.The marked cortical thickening results in narrowing of the medullary cavity.

Figs
Figs 5a and b.The skull radiographs demonstrate sclerosis of the skull base and temporal bone, particularly of the external auditory canal.a b

ISBN
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