Diagnostic points and possible origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a radiographic study of 77 mandibular osteomyelitis cases

Y. Suei, A. Taguchi and K. Tanimoto1

Department of Oral and Maxillofacial Radiology, Hiroshima University Dental Hospital and 1Department of Oral and Maxillofacial Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

Correspondence to: Y. Suei, Department of Oral and Maxillofacial Radiology, Hiroshima University Dental Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan. E-mail: suei{at}hiroshima-u.ac.jp


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
Objectives. To find diagnostic points and to identify the origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome.

Methods. Fifty-two patients with mandibular suppurative osteomyelitis and 25 patients with mandibular osteomyelitis in SAPHO syndrome were included in the study. Radiographic patterns of the lesion, types of periosteal reaction and the presence of external bone resorption and bone enlargement were investigated in each case and compared between the two entities.

Results. Suppurative osteomyelitis demonstrated an osteolytic pattern and a lamellated type of periosteal reaction, whereas SAPHO syndrome revealed a mixed-pattern, solid-type periosteal reaction, external bone resorption and bone enlargement.

Conclusions. Radiographic examination is suggested to be convenient and a useful diagnostic method of differentiating osteomyelitis in SAPHO syndrome from suppurative osteomyelitis. The periosteum is suspected to be the original site of osteomyelitic lesions in SAPHO syndrome.

KEY WORDS: Radiology, Bone diseases, Hyperostosis, Bone resorption.


    Introduction
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
Except for special and unusual types, osteomyelitis can be conveniently divided into two groups: osteomyelitis caused by bacterial infection and osteomyelitis of unknown aetiology [1]. Because many appellations have been proposed, we select the terms ‘suppurative osteomyelitis’ and ‘synovitis, acne, pustulosis, hyperostosis and osteitis syndrome’ (SAPHO syndrome) to represent the entities in each group. SAPHO syndrome is a clinical entity combining osteomyelitis, arthritis and skin disease (palmoplantar pustulosis, pustular psoriasis or severe acne) [2]. As shown in Table 1, combinations of these manifestations lead to a diagnosis. However, a single bone may be symptomatic and skin disease does not always occur simultaneously with bone/joint lesions [35]. In cases with only one symptomatic bone, diagnosis is difficult and the lesion is often confused with suppurative osteomyelitis because of the similarity of the clinicopathological findings [2]. Patients often receive long-term administration of antibiotics combined with surgery, such as saucerisation, decortication and partial resection of the affected bones, which are usually less effective and cannot cure the disease [68]. Conservative and expectant treatments are recommended for osteomyelitis in SAPHO syndrome [915]. Because pain may be severe and continue for several years, early diagnosis is of great importance in preventing unnecessary procedures and selecting an effective treatment. Radiographic examination is a convenient and non-invasive method of evaluating the osteomyelitic lesion. We performed a radiographic study to find possible diagnostic points for osteomyelitis in SAPHO syndrome.


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TABLE 1. Diagnostic criteria for SAPHO syndromea (From Kahn and Kahn, 1994)

 

    Methods
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 Methods
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The patients consisted of 52 with mandibular suppurative osteomyelitis and 25 with mandibular osteomyelitis of SAPHO syndrome. In suppurative osteomyelitis cases, the male:female ratio was 33:19 and the mean age was 52.3 yr (range 11–79 yr), and in SAPHO syndrome cases the corresponding values were 9:16 and 40.5 yr (13–72 yr). In all cases, the presence of osteomyelitis was confirmed by the clinical findings of pain and/or swelling and radiographic evidence of osteomyelitis (osteolytic and/or osteosclerotic change with variable amounts of periosteal reaction). Histological examination was performed in 39 suppurative osteomyelitis cases and in 16 SAPHO syndrome cases, and a non-specific inflammatory condition was confirmed. In cases without biopsy, the possibility of other lesions, such as malignancies, was rejected by complete resolution of the symptoms in suppurative osteomyelitis cases and by follow-up for more than 3 yr in SAPHO syndrome cases. Suppuration or a quick response to antibiotic treatment was a diagnostic point for suppurative osteomyelitis. In 11 of 25 SAPHO syndrome patients, diagnosis was obtained on the basis of diagnostic criteria (Table 1). In the remaining 14 patients, whose symptomatic site was the mandible alone, the lesion revealed recurrent bouts of symptoms without suppuration, continuing for more than 6 months despite long-term antibiotic therapy, and the diagnosis was diffuse sclerosing osteomyelitis of the mandible (DSOM) [16]. DSOM was recognized recently as a mandibular manifestation of SAPHO syndrome [2, 17, 18].

The type of radiographic examination in each patient was determined by the physician in charge according to the site of the lesion, the patient's condition and the facilities which could be used at the time of examination. Panoramic and intra-oral radiographs were taken in all cases. A postero-anterior projection was taken when the lesion involved the ramus of the mandible. CT examination was performed in 28 suppurative osteomyelitis cases and in 13 SAPHO syndrome cases. Using all radiographs obtained at the initial examination and during the follow-up period, various findings, such as osteolysis, osteosclerosis and periosteal reaction, and their extents and relationships, were carefully observed. Finally, the radiographic type of the lesion was evaluated by classifying it as showing an osteolytic pattern or a mixed pattern [19]. The osteolytic pattern was characterized by bone resorption with no or a small amount of osteosclerosis. The mixed pattern was a diffuse bone abnormality in which osteosclerosis and osteolysis were intermingled, which was often accompanied by extensive cortical bone resorption. Periosteal reaction was assessed and classified into three types: lamellated, solid and mixed [16, 20]. The lamellated type was a lamellar radio-opacity separated by a radiolucent zone from the underlying cortex or periosteal new bone. The solid type was an even, uniform, radio-opaque appearance on the cortex. When both types were observed, it was evaluated as the mixed type. The presence of other findings previously reported in osteomyelitis cases, such as external bone resorption and bone enlargement, was also investigated.

In this study, ethical approval and informed patient consent were not obtained because all of our data had been obtained during the treatments for the patients and there was no identifiable data.


    Results
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 Abstract
 Introduction
 Methods
 Results
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Radiographic findings in suppurative osteomyelitis cases
Bone resorption was the main feature and radiographs showed an osteolytic pattern (Fig. 1). Sclerotic change was slight and did not progress during the course. On CT images, osteolytic lesions in the bone were continuous, not scattered, and perforated the cortical bone. The margin of resorbed cortical bone was relatively well defined, and the density of the remaining cortical bone was almost normal (Fig. 2). Slight sclerotic change was observed at the cancellous part around the osteolytic lesion. Periosteal reaction was confirmed in 25 cases on conventional radiographs and in seven cases on CT images. In most cases it was the lamellated type and was related to the cortical bone perforation (Fig. 3, Table 2).



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FIG. 1. Cropped panoramic radiograph of suppurative osteomyelitis at the right mandible. Osteolytic change is observed from around the molar tooth roots to the body of the mandible (arrows).

 


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FIG. 2. Axial CT image (bone window) through the mandibular body affected by suppurative osteomyelitis. Osteolytic lesion perforates the cortical plate (white arrow). Slight sclerotic change (black arrows) is observed around the osteolytic lesion. The density of the remaining cortical bone is almost normal.

 


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FIG. 3. Lamellated-type periosteal reaction (short arrows) and cortical bone perforation (long arrow) observed in a case of suppurative osteomyelitis.

 

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TABLE 2. Number of patients with each radiographic type of periosteal reaction observed on conventional radiographs and CT images

 
Radiographic findings in SAPHO syndrome cases
Abnormal findings were more diffuse and extensive compared with those of suppurative osteomyelitis. Resorption of cortical and trabecular bone, sclerosis of cancellous bone and periosteal reaction spread to a wide area (Fig. 4). In two cases, the mandibular bone was totally involved by the lesion during the late stage. Osteolytic change was prominent during the early stage as well as at the time or site of flare-up of the symptoms. Sclerotic change advanced gradually during the course of the disease and the osteolytic lesion became diminished and restricted to relatively small areas. A radiographic mixed pattern was typically observed during the late stage (Fig. 5). On CT images, the density was often identical among the parts of the resorbed cortical bone, sclerotic cancellous bone and periosteal reaction. Low-density areas (osteolytic lesions) were scattered within them (Figs 6 and 7). A periosteal reaction was observed in 21 cases on conventional radiographs and in nine on CT scans. It was more prominent during the early stage and was of the solid type in most cases. (Table 2, Figs 6 and 7). External bone resorption was confirmed in four cases at the time of the initial examination and in 13 during follow-up. When this finding was confirmed, the symptoms had already been present for more than 1 yr in all cases but one. It was usually seen on panoramic radiographs at a location between the inferior border of the mandibular body and the posterior border of the mandibular ramus (Fig. 8). Bone enlargement was confirmed in three cases on CT images. The original cortex was almost or entirely disrupted, and a cortex-like radio-opaque zone was probably formed by a periosteal reaction observed outside the original cortex. The mandibular bone was enlarged (Fig. 9). In two cases, the possibility of establishing bone enlargement was suggested because the density of periosteal bone was higher than that of resorbed cortical bone (Fig. 10).



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FIG. 4. Panoramic radiograph of mandibular osteomyelitis of SAPHO syndrome. Diffuse bone abnormality is observed from the right premolar to the ramus region. Cortical bone is resorbed widely (arrows). The lesion involved the whole body of the mandible at the late stage.

 


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FIG. 5. Panoramic radiograph of SAPHO syndrome. A long-standing lesion that continued for more than 5 yr reveals the mixed pattern. Spotted osteolyses (arrows) are observed in the sclerotic lesion.

 


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FIG. 6. CT image of SAPHO syndrome. Diffuse cortical bone resorption and spotted osteolyses (arrows) are observed.

 


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FIG. 7. CT image of SAPHO syndrome. Solid-type periosteal reaction and extensive cortical bone resorption are seen. Differentiation of cancellous, cortical and periosteal new bone is not clear.

 


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FIG. 8. Panoramic radiograph of SAPHO syndrome reveals external bone resorption of the left mandible (arrows).

 


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FIG. 9. CT image of SAPHO syndrome through the level of the mandibular canals (long arrows) shows the enlarged left mandible (short arrows).

 


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FIG. 10. CT image of SAPHO syndrome. Cortex-like radio-opaque band (short arrows) is more distinct than the resorbed original cortex (long arrows).

 

    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conflict of interest
 References
 
Early diagnosis of SAPHO syndrome is very important in preventing repeated examination and invasive procedures. In the study by Hayem et al. [10] of 120 SAPHO patients, the mean interval between the onset of the lesion and the diagnosis was about 9 yr. The present investigation disclosed characteristic radiographic findings of the mandibular lesion: these were the mixed pattern, solid-type periosteal reaction, external bone resorption, and bone enlargement. In previous studies, these findings were reported in mandibular osteomyelitis in SAPHO syndrome [16, 18, 2123] but not in suppurative osteomyelitis. While we studied only the mandible, these findings apply to the osteomyelitic lesion of SAPHO syndrome in other bones. Progression of initial osteolyses to diffuse sclerosis, mixed pattern, bone enlargement with extensive cortical bone resorption, and solid-type periosteal reaction have been reported frequently in osteomyelitis in SAPHO syndrome [3, 4, 2427]. On the other hand, lamellated periosteal reaction and cortical bone perforation is the characteristic finding in suppurative osteomyelitis [20, 2830].

We suggest that the original site of osteomyelitis in SAPHO syndrome is not the bone but the periosteum. The following are our hypotheses. Some factors (probably cytokines, such as transforming growth factor, interleukin and tumour necrosis factor) are produced in the inflamed periosteum and irritate the osteoblastic and osteoclastic cells, promoting periosteal bone formation in addition to cortical bone resorption. A large amount of cytokines, such as bone morphogenetic protein, transforming growth factor and insulin-like growth factor, which are stored in the cortical bone matrix [31], is released from the resorbed cortical bone and induces endosteal bone formation. Scattered osteolysis in the sclerotic lesion is probably seen when bone remodelling is not uniform. Periosteal bone formation was prominent at the early stage and external bone resorption was confirmed later. This is explained by the different numbers of osteoblastic and osteoclastic cells. During the early stage, abundant and active osteoblastic cells in the periosteum produce new bone; these cells are derived from stroma cells in the periosteum and are exhausted or severely injured by long-standing inflammation. On the other hand, blood-borne osteoclastic cells continue to be derived from granulocyte–macrophage-committed progenitor cells as long as the inflammation continues. As a result, periosteal bone formation may tend to decelerate and external bone resorption may become prominent during the late stage. Diffuse extensive cortical bone resorption and a high recurrence rate after decortication treatment or partial resection of the affected bone [8, 32, 33] are also compatible with this consideration; the periosteum is the original site of the lesion. If the bone itself or an infection of the bone were the cause of the disease, surgical treatments would be more effective. The direct cause of the periosteal inflammation in SAPHO syndrome cannot be identified at present. It is suggested that the main cause is not a bacterial infection but an allergic reaction or an autoimmune disorder, because corticosteroids are more effective than antibiotics in reducing the symptoms [2]. The present study was based on a radiographic investigation alone. Further studies on the periosteum using histological and immunological techniques are necessary to clarify the aetiology and to explore more effective treatment methods for SAPHO syndrome.


    Conflict of interest
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 Abstract
 Introduction
 Methods
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 Discussion
 Conflict of interest
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The authors have declared no conflicts of interest.



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  1. Trobs R, Moritz R, Buhligen U et al. Changing pattern of osteomyelitis in infants and children. Pediatr Surg Int 1999;15:363–72.[CrossRef][ISI][Medline]
  2. Kahn MF, Khan MA. The SAPHO syndrome. Bailliere's Clin Rheumatol 1994;8:333–62.[ISI][Medline]
  3. van Doornum S, Barraclough D, McColl G, Wicks I. SAPHO: rare or just not recognized? Semin Arthritis Rheum 2000;30:70–7.[CrossRef][ISI][Medline]
  4. Handrick W, Hormann D, Voppmann A et al. Chronic recurrent multifocal osteomyelitis—report of eight patients. Pediatr Surg Int 1998;14:195–8.[CrossRef][ISI][Medline]
  5. Sonozaki H, Mitsui H, Miyanaga Y et al. Clinical features of 53 cases with pustulotic arthroosteitis. Ann Rheum Dis 1981;40:547–53.[Abstract]
  6. Eyrich GKH, Harder C, Sailer HF, Langenegger T, Bruder E, Michiel BA. Primary chronic osteomyelitis associated with synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO syndrome). J Oral Pathol Med 1999;28:456–64.[ISI][Medline]
  7. Suei Y, Taguchi A, Tanimoto K, Yamada T, Otani K, Fukuda T. Case report. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. Dentomaxillofac Radiol 1996;25:287–91.[Abstract]
  8. Jurik AG, Moller BN. Chronic sclerosing osteomyelitis of the clavicle: a manifestation of chronic recurrent multifocal osteomyelitis. Arch Orthop Trauma Surg 1987;106:144–51.[ISI][Medline]
  9. Beretta-Piccoli BC, Sauvain MJ, Gal I et al. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in childhood: a report of ten cases and review of the literature. Eur J Pediatr 2000;159:594–601.[CrossRef][ISI][Medline]
  10. Hayem G, Bouchaud-Chabot A, Benali K et al. SAPHO syndrome: a long-term follow-up study of 120 cases. Semin Arthritis Rheum 1999;29:159–71.[ISI][Medline]
  11. Yoshii T, Nishimura H, Yoshikawa T et al. Therapeutic possibilities of long-term roxithromycin treatment for chronic diffuse sclerosing osteomyelitis of the mandible. J Antimicrob Chemother 2001;47:631–7.[Abstract/Free Full Text]
  12. Montonen M, Kalso E, Pylkkären L, Lindström B-M, Lindqvist C. Disodium clodronate in the treatment of diffuse sclerosing osteomyelitis (DSO) of the mandible. Int J Oral Maxillofac Surg 2001;30:313–7.[CrossRef][ISI][Medline]
  13. Soubrier M, Dubost JJ, Ristori JM, Sauvezie B, Bussiére JL. Pamidronate in the treatment of diffuse sclerosing osteomyelitis of the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:637–40.[CrossRef][ISI][Medline]
  14. Olivieri I, Padula A, Ciancio G, Salvarani C, Niccoli L, Cantini F. Successful treatment of SAPHO syndrome with infliximab: report of two cases. Ann Rheum Dis 2002;61:375–6.[Free Full Text]
  15. Marshall H, Bromilow J, Thomas AL, Arden NK. Pamidronate: a novel treatment for the SAPHO syndrome? Rheumatology 2000;41:231–3.
  16. Suei Y, Taguchi A, Tanimoto K. Radiographic evaluation of possible etiology of diffuse sclerosing osteomyelitis of the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:571–7.[ISI][Medline]
  17. Suei Y, Taguchi A, Tanimoto K. Diffuse sclerosing osteomyelitis of the mandible: Its characteristics and possible relationship to synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. J Oral Maxillofac Surg 1996;54:1194–9.[ISI][Medline]
  18. Kahn MF, Hayem F, Hayem G, Grossin M. Is diffuse sclerosing osteomyelitis of the mandible part of the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome? Analysis of seven cases. Oral Surg Oral Med Oral Pathol 1994;78:594–8.[ISI][Medline]
  19. Yoshiura K, Hijiya T, Ariji E et al. Radiographic patterns of osteomyelitis in the mandible. Plain film/CT correlation. Oral Surg Oral Med Oral Pathol 1994;78:116–24.[ISI][Medline]
  20. Edeiken J. New bone production and periosteal reaction. In: Edeiken J (ed.) Roentgen diagnosis of diseases of bone. 3rd edn. Baltimore: Williams & Wilkins, 1981:11–29.
  21. Garcia-Marin F, Iriarte-Ortabe JI, Reychler H. Chronic diffuse sclerosing osteomyelitis of the mandible or mandibular location of SAPHO syndrome. Acta Stomatol Belg 1996;93:65–71.[Medline]
  22. Kanemoto K, Suzuki R, Okano T, Nagumo M. Osteomyelitis of the mandibular condyle: report of a case. J Oral Maxillofac Surg 1992;50:1337–9.[ISI][Medline]
  23. Schuknecht BF, Carls FR, Valavanis A, Sailer HF. Mandibular osteomyelitis: evaluation and staging in 18 patients, using magnetic resonance imaging, computed tomography and conventional radiographs. J Craniomaxillofac Surg 1997;25:24–33.[ISI][Medline]
  24. Jurriaans E, Singh NP, Finlay K, Friedman L. Imaging of chronic recurrent multifocal osteomyelitis. Radiol Clin North Am 2001;39:305–27.[ISI][Medline]
  25. Kothari NA, Pelchovitz DJ, Meyer JS. Imaging of musculoskeletal infections. Radiol Clin North Am 2001;39:653–71.[ISI][Medline]
  26. van Holsbeeck M, Martel W, Dequeker J et al. Soft tissue involvement, mediastinal pseudotumor, and venous thrombosis in pustulotic arthro-osteitis. A study of eight new cases. Skeletal Radiol 1989;18:1–8.[ISI][Medline]
  27. Kawai K, Doita M, Tateishi H, Hirohata K. Bone and joint lesions associated with pustulosis palmaris et plantaris. A clinical and histological study. J Bone Joint Surg Br 1988;70:117–22.[ISI][Medline]
  28. Edeiken J. Osteomyelitis. In: Edeiken J (ed.) Roentgen diagnosis of diseases of bone, 3rd edn. Baltimore: Williams & Wilkins, 1981:727–827.
  29. Wing VW, Jeffrey RB, Federle MP, Trafton P. Chronic osteomyelitis examined by CT. Radiology 1985;154:171–4.[Abstract]
  30. Worth HM. Infections of the jaws. In: Worth HM (ed.) Principles and practice of oral radiologic interpretation. Chicago: Year Book Medical Publishers, 1963:213–74.
  31. Mundy GR. Bone remodeling and its disorders. London: Martin Dunitz, 1995:1–65.
  32. Montonen M, Iizuka T, Hallikainen D, Lindqvist C. Decortication in the treatment of diffuse sclerosing osteomyelitis of the mandible. Retrospective analysis of 41 cases between 1969 and 1990. Oral Surg Oral Med Oral Pathol 1993;75:5–11.[ISI][Medline]
  33. Suei Y, Tanimoto K, Miyauchi M, Ishikawa T. Partial resection of the mandible for the treatment of diffuse sclerosing osteomyelitis. Report of four cases. J Oral Maxillofac Surg 1997;55:410–4.[ISI][Medline]
Submitted 24 December 2002; Accepted 3 April 2003