Camurati–Engelmann disease—a case report and literature review

A. V. Ramanan, M. J. Hall, E. M. Baildam and Z. Mughal1

Department of Paediatric Rheumatology, Royal Manchester Children's Hospital and 1 Department of Paediatrics, Saint Mary's Hospital, Manchester, UK

Correspondence to: A. V. Ramanan, Department of Paediatric Rheumatology, Southmead Hospital, Westbury-on-Trym, Bristol BS9 3SB, UK. E-mail: avramanan{at}hotmail.com

SIR, Camurati–Engelmann disease is a rare autosomal dominant condition characterized by progressive diaphyseal dysplasia. We report a child presenting with non-specific limb pains and a waddling gait in whom the clinical and radiological appearances led to a diagnosis of Camurati-Engelmann disease.

A 4-yr-old boy presented with a history of pains in both lower limbs for ‘several years’, worsening over the preceding 3 months. The pain was localized to his calf and thigh muscles. The pain was initially only during the day but with time there was pain at night as well. He had become less active and was noted to walk very cautiously. There was a history of weight loss of 1 kg over the previous 4 months. There was no history of joint swelling. He had been previously well with no relevant past medical history. The child was the older of two boys born to consanguineous parents of Pakistani origin. He was developmentally appropriate and fully immunized.

Clinical examination revealed the child to be pale, lethargic and to have a waddling gait. There was evidence of proximal muscle weakness in his lower limbs and brisk lower limb reflexes. The remainder of the musculoskeletal, neurological and systemic examinations were normal and there was no evidence of arthritis.

Initial investigations revealed a haemoglobin level of 8.1 g/dl [normal range (N) 11.5–14.5 g/dl], white cell count 15.5x109/l [N (4.5–13.5)x109/l], platelets 658x109/l [N (150–400)x109/l], mean corpuscular volume 61.0 fl (N 77–91 fl) and zinc protoporphyrin 168 µmol/mol haem (N 30–80 µmol/mol haem). Erythrocyte sedimentation rate was 79 mm/h (N 1–7 mm/h) and C-reactive protein was 53 mg/l (N <6 mg/l). Renal and liver function tests, bone biochemistry and muscle enzyme levels were within the normal ranges. His immunoglobulin and complement levels were raised: IgG 19.4 g/l (N 6.7–11 g/l), IgA 4.08 g/l (N 0.6–1.2 g/l), IgM 2.01 g/l (N 0.3–0.7 g/l), C3 1.93 g/l (N 0.83–1.46 g/l), C4 0.55 g/l (N 0.2–0.52 g/l). Autoantibodies, viral serology and Mantoux testing were negative. Urinalysis was normal.

To exclude malignancy a bone marrow aspirate was performed revealing normal marrow. Muscle biopsy excluded active inflammation. The abdominal ultrasound was normal. A skeletal survey demonstrated widespread patchy sclerosis throughout the skeleton, predominately affecting the diaphyses of the long bones and the skull. There was some widening and cortical thickening in the left distal femoral diaphysis and marked periarticular osteopenia in the left distal femur and proximal tibia (Figs 1 and 2). Bone scintigraphy revealed symmetrical increased uptake in the ribs and the metaphyses of the distal femora, proximal tibia, forearms and proximal humeri.




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FIG. 1. Plain radiograph (AP and lateral) of the leg reveals abnormal endosteal thickening in the diaphysis of the tibia along with minimal periosteal reaction more marked in the lower tibia along the posterior aspect.

 


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FIG. 2. Lateral X-ray of the skull shows osteosclerosis of the skull base especially prominent in the perisellar area and the petromastoid region.

 
The clinical findings and characteristic radiological appearances led to the diagnosis of Camurati–Engelmann disease. Genetic screening for the known mutations was negative (courtesy of Dr W. Van Hul, Belgium).

The child was managed conservatively with non-steroidal anti-inflammatory drugs (NSAIDs) and his symptoms improved over the next few months. Follow-up over the last year has not shown any deterioration in symptoms, although he continues to experience leg pains which are alleviated by ibuprofen. There is no evidence of muscle weakness currently. He has normal growth velocity and his inflammatory markers are currently normal.

Camurati–Engelmann disease (CED) (also known as progressive diaphyseal dysplasia) is a rare genetic disorder characterized by progressive expansion and sclerosis predominately affecting the diaphyses of the long bones and associated with cranial sclerosis. CED typically presents in childhood with generalized muscle weakness, lower limb pains and a waddling gait [1, 2]. Other manifestations such as anaemia, hepatosplenomegaly and cranial nerve compression due to involvement of the base of the skull are less common [3]. The gene responsible for CED has been identified on chromosome 19q13 [4]. This encodes the latency-associated peptide of transforming growth factor-B1 (TGF-ß1), an important mediator of bone remodelling [4]. Biochemical parameters of bone and mineral metabolism are usually normal but the erythrocyte sedimentation rate may be elevated [2, 3, 5–7]. The classical radiological changes include both endosteal and subperiosteal cortical thickening affecting the diaphyses, which may extend to the metaphyses but consistently spare the epiphyses [1, 2]. Typically the long bones, especially the femora and tibiae, are affected but skull, mandible and vertebral involvement is recognized [1, 2]. It is thought, based on cases in the literature, that the clinical and radiological features of CED progress with age [1].

Corticosteroids have been reported to provide effective symptomatic improvement and reduction of the erythrocyte sedimentation rate [3, 5, 6, 8, 9]. There are conflicting reports as to whether they produce radiological improvements [5, 6]. The use of pamidronate in Camurati–Engelmann disease has been reported with both improvement and exacerbation in clinical symptoms [9, 10].

The child in our report presented with the typical clinical features of leg pains and a waddling gait. The plain radiographs, in conjunction with the normal biochemical parameters and the clinical presentation, led to the diagnosis. The child was managed symptomatically with NSAIDs with good clinical improvement such that corticosteroids were not required. We believe that this case highlights the need to consider skeletal dysplasias in the differential diagnosis of non-specific limb pains in addition to arthropathy, neuromuscular disorders, malignancy and non-organic causes.

The authors have declared no conflicts of interest.

References

  1. Vanhoenacker FM, Janssens K, Van Hul W, Gershoni-Baruch R, Brik R, De Schepper AM. Camurati-Engelmann disease. Review of radioclinical features. Acta Radiol 2003;44:430–4.[CrossRef][ISI][Medline]
  2. Naveh Y, Kaftori JK, Alon U, Ben-David J, Berant M. Progressive diaphyseal dysplasia: genetics and clinical and radiologic manifestations. Pediatrics 1984;74:399–405.[Abstract]
  3. Crisp AJ, Brenton DP. Engelmann's disease of bone—a systemic disorder? Ann Rheum Dis 1982;41:183–8.[Abstract]
  4. Janssens K, Gershoni-Baruch R, Guanabens N et al. Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease. Nat Genet 2000;26:273–5.[CrossRef][ISI][Medline]
  5. Bas F, Darendeliler F, Petorak I et al. Deflazacort treatment in progressive diaphyseal dysplasia (Camurati-Engelmann disease). J Paediatr Child Health 1999;35:401–5.[CrossRef][ISI][Medline]
  6. Heymans O, Gebhart M, Alexiou J, Sokolow Y. Camurati-Engelmann disease. Effects of corticosteroids. Acta Clin Belg 1998;53:189–92.[ISI][Medline]
  7. Kormas N, Diamond T, Shnier R. Camurati-Engelmann disease: two case reports describing metadiaphyseal dysplasia associated with cerebellar ataxia. J Bone Miner Res 1998;13:1203–7.[ISI][Medline]
  8. Allen DT, Saunders AM, Northway WH, Williams GF, Schafer IA. Corticosteroids in the treatment of Engelmann's disease: progressive diaphyseal dysplasia. Pediatrics 1970;46:523–31.[Abstract]
  9. Inaoka T, Shuke N, Sato J et al. Scintigraphic evaluation of pamidronate and corticosteroid therapy in a patient with progressive diaphyseal dysplasia (Camurati-Engelmann disease). Clin Nucl Med 2001;26:680–2.[CrossRef][ISI][Medline]
  10. Cherie-Ligniere G, Santalena G, Parafioriti A. Pamidronate in the treatment of progressive diaphyseal dysplasia (Camurati-Engelmann disease). Clin Exp Rheumatol 1999;17:264.[ISI][Medline]
Accepted 10 March 2005





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