- Email: [email protected]
A rare cause of painful cervical swelling: myositis ossificans progressiva in childhood. Report of a case
Joint Bone Spine 72 (2005) 335–337 http://france.elsevier.com/direct/BONSOI/
Case report
A rare cause of painful cervical swelling: myositis ossificans progressiva in childhood. Report of a case Fatine Lasry *, Abderrazak Touki, Abdelhak Abkari, Habiba Hadj Khalifa Pediatrics III, Children’s Hospital, Ibn Rochd Teaching Hospital, 172, boulevard Zerktouni, Appartement 9, 4ème étage, Casablanca, Morocco Received 6 January 2003; accepted 12 September 2003 Available online 28 July 2004
Abstract Myositis ossificans progressiva (MOP) is a rare condition of which we report a case in a 13-year-old girl with involvement of the cervical paraspinal and periscapular muscles. No ectopic ossifications were visible on plain radiographs. Computed tomography disclosed diffuse inflammation. Plain radiographs of the toes confirmed the diagnosis by visualizing characteristic bone abnormalities. Knowledge of the digital abnormalities seen in MOP is important to avoid unnecessary diagnostic investigations, most notably a surgical biopsy, which may trigger a flare of the disease. The prognosis is guarded. © 2005 Elsevier SAS. All rights reserved. Keywords: Myositis ossificans progressiva; Fibrodysplasia ossificans progressiva; Münchmeyer disease; Congenital great toe abnormalities
1. Introduction Myositis ossificans progressive (MOP), also known as fibrodysplasia ossificans progressiva (FOP) or Münchmeyer disease, is a rare inherited condition with autosomal dominant transmission and widely variable penetrance. This abnormality in mesenchymal differentiation results in the development of lamellar bone within the connective tissue and muscle. The diagnosis is readily made at an advanced stage when plain radiographs show ectopic bones and bilateral abnormalities in the hands and feet. The prognosis is bleak, with gradual loss of motion range ultimately resulting in virtually complete immobility and restrictive respiratory failure. The objective of this article is to review the frequently disconcerting presentations, characteristic radiological abnormalities present at birth, radiological changes acquired during the course of the disease, and major therapeutic challenges raised by this condition. 2. Case report This 13-year-old girl born to consanguineous parents presented with a 2-month history of swelling on the right side of * Corresponding author. Tel.: +212-22-48-17-01; fax: +212-61-45-35-35. E-mail address: [email protected] (F. Lasry). 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2003.09.013
the cervical, thoracic, and lumbar spine, which had developed by exacerbations and remissions. The mass was hard and painful. Her medical history was unremarkable, with no injuries, and her general health was good. A thoracoabdominal mass of similar appearance was found on the left side. Routine blood test results were as follows: erythrocyte sedimentation rate, 30 mm/h, hypochromic microcytic anemia with 11 g/dl of hemoglobin, and normal C-reactive protein and muscle enzyme levels. Findings were normal from a slit-lamp examination. A plain radiograph of the spine showed a gibbus (Fig. 1) and ultrasonography of the neck a triangular mass about the scapulas. Computed tomography findings were consistent with a diffuse infiltrating process involving all the muscles in the cervicooccipital area (Fig. 2), the spinal muscles, and the muscles in the right scapular fossa. A tumor was suspected initially. However, the flares separated by spontaneous remissions at different sites militated against this diagnosis. Radiographs of the feet showed abnormalities of both great toes consisting in a short triangular proximal phalanx fused with the distal phalanx (Fig. 3), strongly suggesting early-stage MOP, despite the absence of calcifications or ossifications. Lung function tests showed no evidence of a restrictive defect. Glucocorticoid therapy and gentle massaging resulted in muscle wasting followed rapidly by resumption of the initial symptoms. One year later, she had involvement of the shoulder girdle muscles impair-
336
F. Lasry et al. / Joint Bone Spine 72 (2005) 335–337
Fig. 3. Radiograph of the feet.
Fig. 1. Lateral radiograph of the chest.
Fig. 2. Computed tomography scan of the cervical and thoracic mass.
ing the activities of daily living, with ankylosis, loss of motion range, and calcification of the masses.
3. Diagnosis MOP or FOP is a rare inherited disease [1] characterized by autosomal dominant transmission and wide variability in penetrance and expressivity [2]. The cause remains unknown. Current hypotheses incriminate the bone morphogenic proteins (BMPs), most notably overproduction of BMP-4 responsible for the preossification inflammatory process via dysregulation of inflammatory cell and mediator production in the connective tissue and muscle [3]. The gene for MOP was recently identified on chromosome 4q27-31 [4]. The prevalence of MOP is not affected by gender, race, or
ethnic origin [4]. The clinical onset usually occurs within the first decade, with the development of swelling in the cervicoscapular area [5,6] that progresses by exacerbations and remissions then subsides gradually leaving a local ossification [7]. A malignant tumor or posttraumatic myositis may be difficult to rule out, particularly in patients with localized or circumscribed MOP [1,8–10]. Surgical excision is occasionally performed to establish the diagnosis [11] but can cause a severe flare of the disease. Visualization on plain radiographs of bony bridges running from the bones to the muscles attached to them is crucial to the diagnosis [6]; an ectopic skeleton may be seen in patients with advanced disease [7,12,13]. Magnetic resonance imaging can help to establish the diagnosis early in the course of the disease [14]. The diagnosis is easy in patients with ossifications and typical birth defects in the hands and feet, such as shortened digits, fused phalanges, and hypoplastic phalanges. Knowledge of these congenital abnormalities is vital as it alerts the physician to the diagnosis before the development of ossifications. The abnormalities are particularly typical at the first metatarsals and phalanges of the great toes, where they simulate hallux valgus deformity. Similar abnormalities may be visible in the phalanges of the thumb [6]. Spinal abnormalities, conductive hearing loss, and premature baldness have been reported [7]. The disease progresses by exacerbations and remissions, ultimately resulting in a stonelike appearance [6]. Death due to restrictive respiratory failure occurs before 30 years of age [4]. No satisfactory treatments are available. Glucocorticoids can be given during the flares, in dosages ranging from 0.5 to 1 mg/kg/d of prednisone. Bisphosphonates can be used but fail to prevent premature death. 4. Conclusion Although uncommon, MOP deserves to be borne in mind as the diagnosis can be strongly suggested by visualization on plain radiographs of typical congenital abnormalities in the hands and feet. Discovery of these abnormalities con-
F. Lasry et al. / Joint Bone Spine 72 (2005) 335–337
traindicates a diagnostic surgical biopsy, which can trigger an exacerbation of the disease. This genetic disease with variable expressivity progresses by exacerbations during which ossifications develop. The gradually increasing ossifications cause severe functional impairment and fatal restrictive respiratory failure. No effective treatment is available.
[6] [7]
[8]
[9]
References [10] [1]
[2]
[3]
[4] [5]
Gannon FH, Glaser D, Caron R, Thompson LD, Shore EM, Kaplan FS. Mast cell involvement in fibrodysplasia ossificans progressiva. Hum Pathol 2001;8:842–8. Fonseca JE, Branco JC, Reis J, Evangelista T, Tavaras V, Gomes AR. Fibrodysplasia ossificans progressiva: report of two cases. Clin Exp Rheumatol 2000;18:749–52. Virdi AS, Shore EM, Oreffo RO, Li M, Connor JM, Smith R. Phenotypic and molecular heterogeneity in fibrodysplasia ossificans progressiva. Calcif Tissue Int 1999;65:250–5. Mahboubi S, Glaser DL, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva. Pediatr Radiol 2001;31:307–14. Magryta CJ, Kligora CJ, Temple HT, Malik R. Clinical presentation of fibrodysplasia ossificans progressiva: pitfalls in diagnosis. J Pediatr Hematol Oncol 1999;21:539–43.
[11]
[12]
[13]
[14]
337
Maroteaux P. Myosite ossifiante. In: Les maladies osseuses de l’enfant. Paris-Médecine Sciences Flammarion; 1995. p. 467. Benjelloun A, Maani K, Ouzidane L, Ksiyer M. La myosite ossifiante progressive chez l’enfant (A propos d’un cas). Radiologie 1997;18: 36–8. Yazici M, Etensel B, Gursoy MH, Aydogu A, Erkus M. Nontraumatic myositis ossificans with an unusual location: case report. J Pediatr Surg 2002;37:1621–2. Turra CS, Gigante C, Perini L, D’Amore ES. Pseudomalignant myositis ossificans in children. Description of case and review of the literature. Chirur Organi Mov 1999;84:93–100. Gindele A, Schawamborn D, Tsironis K, Benz-Bohn G. Myositis ossificans traumatica in a young child: report of three cases and review of the literature. Pediatr Radiol 2000;30:451–9. Kocyigit H, Hizli N, Memis A, Sabah D, Memis. A severely disabling disorder: fibrodysplasia ossificans progressiva. Clin Rheumatol 2001; 4:273–5. Sy MH, Diouf A, Diallo BK, Dansokho AV, Ndiaye A, Tall A. Fibrodysplasia ossificans progressiva or Münchmeyer disease: report of two cases. Dakar Med 1999;44:126–30. Hanquinet S, Ngo L, Anooshiravani M, Garcia J, Bugman P. Magnetic resonance imaging helps in the early diagnosis of myositis ossificans in children. Pediatr Surg Int 1999;15:287–9. Nucci A, Queiroz LD, Santos AD, Camargo EE, Moura-Ribeiro MV. Fibrodysplasia ossificans progressiva: case report. Arq Neuropsiquitr 2000;58(2A):342–7.
Case report
A rare cause of painful cervical swelling: myositis ossificans progressiva in childhood. Report of a case Fatine Lasry *, Abderrazak Touki, Abdelhak Abkari, Habiba Hadj Khalifa Pediatrics III, Children’s Hospital, Ibn Rochd Teaching Hospital, 172, boulevard Zerktouni, Appartement 9, 4ème étage, Casablanca, Morocco Received 6 January 2003; accepted 12 September 2003 Available online 28 July 2004
Abstract Myositis ossificans progressiva (MOP) is a rare condition of which we report a case in a 13-year-old girl with involvement of the cervical paraspinal and periscapular muscles. No ectopic ossifications were visible on plain radiographs. Computed tomography disclosed diffuse inflammation. Plain radiographs of the toes confirmed the diagnosis by visualizing characteristic bone abnormalities. Knowledge of the digital abnormalities seen in MOP is important to avoid unnecessary diagnostic investigations, most notably a surgical biopsy, which may trigger a flare of the disease. The prognosis is guarded. © 2005 Elsevier SAS. All rights reserved. Keywords: Myositis ossificans progressiva; Fibrodysplasia ossificans progressiva; Münchmeyer disease; Congenital great toe abnormalities
1. Introduction Myositis ossificans progressive (MOP), also known as fibrodysplasia ossificans progressiva (FOP) or Münchmeyer disease, is a rare inherited condition with autosomal dominant transmission and widely variable penetrance. This abnormality in mesenchymal differentiation results in the development of lamellar bone within the connective tissue and muscle. The diagnosis is readily made at an advanced stage when plain radiographs show ectopic bones and bilateral abnormalities in the hands and feet. The prognosis is bleak, with gradual loss of motion range ultimately resulting in virtually complete immobility and restrictive respiratory failure. The objective of this article is to review the frequently disconcerting presentations, characteristic radiological abnormalities present at birth, radiological changes acquired during the course of the disease, and major therapeutic challenges raised by this condition. 2. Case report This 13-year-old girl born to consanguineous parents presented with a 2-month history of swelling on the right side of * Corresponding author. Tel.: +212-22-48-17-01; fax: +212-61-45-35-35. E-mail address: [email protected] (F. Lasry). 1297-319X/$ - see front matter © 2005 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2003.09.013
the cervical, thoracic, and lumbar spine, which had developed by exacerbations and remissions. The mass was hard and painful. Her medical history was unremarkable, with no injuries, and her general health was good. A thoracoabdominal mass of similar appearance was found on the left side. Routine blood test results were as follows: erythrocyte sedimentation rate, 30 mm/h, hypochromic microcytic anemia with 11 g/dl of hemoglobin, and normal C-reactive protein and muscle enzyme levels. Findings were normal from a slit-lamp examination. A plain radiograph of the spine showed a gibbus (Fig. 1) and ultrasonography of the neck a triangular mass about the scapulas. Computed tomography findings were consistent with a diffuse infiltrating process involving all the muscles in the cervicooccipital area (Fig. 2), the spinal muscles, and the muscles in the right scapular fossa. A tumor was suspected initially. However, the flares separated by spontaneous remissions at different sites militated against this diagnosis. Radiographs of the feet showed abnormalities of both great toes consisting in a short triangular proximal phalanx fused with the distal phalanx (Fig. 3), strongly suggesting early-stage MOP, despite the absence of calcifications or ossifications. Lung function tests showed no evidence of a restrictive defect. Glucocorticoid therapy and gentle massaging resulted in muscle wasting followed rapidly by resumption of the initial symptoms. One year later, she had involvement of the shoulder girdle muscles impair-
336
F. Lasry et al. / Joint Bone Spine 72 (2005) 335–337
Fig. 3. Radiograph of the feet.
Fig. 1. Lateral radiograph of the chest.
Fig. 2. Computed tomography scan of the cervical and thoracic mass.
ing the activities of daily living, with ankylosis, loss of motion range, and calcification of the masses.
3. Diagnosis MOP or FOP is a rare inherited disease [1] characterized by autosomal dominant transmission and wide variability in penetrance and expressivity [2]. The cause remains unknown. Current hypotheses incriminate the bone morphogenic proteins (BMPs), most notably overproduction of BMP-4 responsible for the preossification inflammatory process via dysregulation of inflammatory cell and mediator production in the connective tissue and muscle [3]. The gene for MOP was recently identified on chromosome 4q27-31 [4]. The prevalence of MOP is not affected by gender, race, or
ethnic origin [4]. The clinical onset usually occurs within the first decade, with the development of swelling in the cervicoscapular area [5,6] that progresses by exacerbations and remissions then subsides gradually leaving a local ossification [7]. A malignant tumor or posttraumatic myositis may be difficult to rule out, particularly in patients with localized or circumscribed MOP [1,8–10]. Surgical excision is occasionally performed to establish the diagnosis [11] but can cause a severe flare of the disease. Visualization on plain radiographs of bony bridges running from the bones to the muscles attached to them is crucial to the diagnosis [6]; an ectopic skeleton may be seen in patients with advanced disease [7,12,13]. Magnetic resonance imaging can help to establish the diagnosis early in the course of the disease [14]. The diagnosis is easy in patients with ossifications and typical birth defects in the hands and feet, such as shortened digits, fused phalanges, and hypoplastic phalanges. Knowledge of these congenital abnormalities is vital as it alerts the physician to the diagnosis before the development of ossifications. The abnormalities are particularly typical at the first metatarsals and phalanges of the great toes, where they simulate hallux valgus deformity. Similar abnormalities may be visible in the phalanges of the thumb [6]. Spinal abnormalities, conductive hearing loss, and premature baldness have been reported [7]. The disease progresses by exacerbations and remissions, ultimately resulting in a stonelike appearance [6]. Death due to restrictive respiratory failure occurs before 30 years of age [4]. No satisfactory treatments are available. Glucocorticoids can be given during the flares, in dosages ranging from 0.5 to 1 mg/kg/d of prednisone. Bisphosphonates can be used but fail to prevent premature death. 4. Conclusion Although uncommon, MOP deserves to be borne in mind as the diagnosis can be strongly suggested by visualization on plain radiographs of typical congenital abnormalities in the hands and feet. Discovery of these abnormalities con-
F. Lasry et al. / Joint Bone Spine 72 (2005) 335–337
traindicates a diagnostic surgical biopsy, which can trigger an exacerbation of the disease. This genetic disease with variable expressivity progresses by exacerbations during which ossifications develop. The gradually increasing ossifications cause severe functional impairment and fatal restrictive respiratory failure. No effective treatment is available.
[6] [7]
[8]
[9]
References [10] [1]
[2]
[3]
[4] [5]
Gannon FH, Glaser D, Caron R, Thompson LD, Shore EM, Kaplan FS. Mast cell involvement in fibrodysplasia ossificans progressiva. Hum Pathol 2001;8:842–8. Fonseca JE, Branco JC, Reis J, Evangelista T, Tavaras V, Gomes AR. Fibrodysplasia ossificans progressiva: report of two cases. Clin Exp Rheumatol 2000;18:749–52. Virdi AS, Shore EM, Oreffo RO, Li M, Connor JM, Smith R. Phenotypic and molecular heterogeneity in fibrodysplasia ossificans progressiva. Calcif Tissue Int 1999;65:250–5. Mahboubi S, Glaser DL, Shore EM, Kaplan FS. Fibrodysplasia ossificans progressiva. Pediatr Radiol 2001;31:307–14. Magryta CJ, Kligora CJ, Temple HT, Malik R. Clinical presentation of fibrodysplasia ossificans progressiva: pitfalls in diagnosis. J Pediatr Hematol Oncol 1999;21:539–43.
[11]
[12]
[13]
[14]
337
Maroteaux P. Myosite ossifiante. In: Les maladies osseuses de l’enfant. Paris-Médecine Sciences Flammarion; 1995. p. 467. Benjelloun A, Maani K, Ouzidane L, Ksiyer M. La myosite ossifiante progressive chez l’enfant (A propos d’un cas). Radiologie 1997;18: 36–8. Yazici M, Etensel B, Gursoy MH, Aydogu A, Erkus M. Nontraumatic myositis ossificans with an unusual location: case report. J Pediatr Surg 2002;37:1621–2. Turra CS, Gigante C, Perini L, D’Amore ES. Pseudomalignant myositis ossificans in children. Description of case and review of the literature. Chirur Organi Mov 1999;84:93–100. Gindele A, Schawamborn D, Tsironis K, Benz-Bohn G. Myositis ossificans traumatica in a young child: report of three cases and review of the literature. Pediatr Radiol 2000;30:451–9. Kocyigit H, Hizli N, Memis A, Sabah D, Memis. A severely disabling disorder: fibrodysplasia ossificans progressiva. Clin Rheumatol 2001; 4:273–5. Sy MH, Diouf A, Diallo BK, Dansokho AV, Ndiaye A, Tall A. Fibrodysplasia ossificans progressiva or Münchmeyer disease: report of two cases. Dakar Med 1999;44:126–30. Hanquinet S, Ngo L, Anooshiravani M, Garcia J, Bugman P. Magnetic resonance imaging helps in the early diagnosis of myositis ossificans in children. Pediatr Surg Int 1999;15:287–9. Nucci A, Queiroz LD, Santos AD, Camargo EE, Moura-Ribeiro MV. Fibrodysplasia ossificans progressiva: case report. Arq Neuropsiquitr 2000;58(2A):342–7.