ReportofaCase SouichiYanamoto,DDS,PhD,*GoroKawasaki,DDS,PhD,†IzumiYoshitomi,DDS,PhD,‡andAkioMizuno,DDS,PhD§ DiffuseChronicSclerosingOsteomyelitisoftheMandibleWithSynovitis,Acne,Pustulosis,Hyperostosis,andOsteitis:ReportofaLong-TermFollow-UpCase

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19. Scaglietti O, Marchetti PG, Bartolozzi P: Final results obtained in the treatment of bone cysts with methylprednisolone acetate

(depo-medrol) and a discussion of results achieved in other bone lesions. Clin Orthop Relat Res 165:33, 1982

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Report of sixty-six cases. Oral Surg Oral Med Oral Pathol 37:

899, 1974

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22. Oppenheim WL, Galleno H: Operative treatment versus steroid injection in the management of unicameral bone cysts. J Ped Orthop 4:1, 1984

23. Yu CL, D’Astous J, Finnegan M: Simple bone cysts. The effects of methylprednisolone on synovial cells in culture. Clin Orthop Relat Res 34, 1991

J Oral Maxillofac Surg 68:212-217, 2010

Diffuse Chronic Sclerosing Osteomyelitis of the Mandible With Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis:

Report of a Long-Term Follow-Up Case

Souichi Yanamoto, DDS, PhD,* Goro Kawasaki, DDS, PhD,†

Izumi Yoshitomi, DDS, PhD,‡ and Akio Mizuno, DDS, PhD§

Mandibular osteomyelitis is one of the most common infectious diseases and is usually odontogenic or traumatic in origin. Meanwhile, mandibular osteomyelitis caused by a process of unknown etiology is known to develop during the clinical course. In 1987, Chamot et al¹described a syndrome associated with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO syndrome), which is characterized by osteoarticular and dermatologic symptoms.²The most prevalent site of bone lesions is the anterior chest wall with involvement of other locations including the sternum, clavi-

cles, ribs, spine, and peripheral long and flat bones.^1-4 Bone lesions in SAPHO syndrome demonstrate clinical and radiologic features similar to diffuse sclerosing osteomyelitis.⁵Clinical diagnosis of SAPHO syndrome is defined as the presence of any one of the following:

1)multifocal osteitis with or without skin manifesta- tions; 2) sterile acute or chronic joint inflammation associated with pustules or psoriasis of palms and soles, or acne, or hidradenitis; or 3) sterile osteitis in the presence of one of the skin manifestations.⁶Other investigators have suggested that early diagnosis of this condition is crucial to avoid repeated examina- tions and invasive procedures; however, the etiology of SAPHO syndrome remains unknown.^1,2,5-7 Treat- ment has therefore been difficult and focuses on symptoms only.^3,5,7

This report presents the long-term follow-up of a case of SAPHO syndrome in the mandible of a patient who received nonsteroid anti-inflammatory drugs (NSAIDs) and long-term administration of macrolides in combination with surgical procedures.

Report of a Case

A 51-year-old woman was referred to the Department of Oral and Maxillofacial Surgery, Nagasaki University Gradu- ate School of Biomedical Sciences (Nagasaki, Japan) in No- vember 1998 because of a painful swelling of the right Received from the Department of Oral and Maxillofacial Surgery,

Unit of Translational Medicine, Course of Medical and Dental Sci- ences, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.

*Senior Assistant Professor.

†Associate Professor.

‡Assistant Professor.

§Professor and Chairman.

Address correspondence and reprint requests to Dr Yanamoto:

Department of Oral and Maxillofacial Surgery, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki Univer- sity Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Na- gasaki, 852-8588, Japan; e-mail:syana@nagasaki-u.ac.jp

doi:10.1016/j.joms.2009.04.121

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cheek associated with limited mouth opening for at least 3 weeks. She did not have weakness or fever. At that time, the patient reported no use of medications or previous treatment for these conditions. Her medical history was unre-

markable. There was no history of trauma to the maxillofacial complex.

Clinical examination showed a bony hard swelling in the region of the right parotid-masseter and the right temporomandibular joint (TMJ) without suppuration and cervical lymphadenopathy (Fig 1). Intraorally, no alterations were seen in the oral mucosa. Fever did not increase during the course. In laboratory data, C-reactive protein was slightly elevated (2.3 mg/dL); however, blood counts and other laboratory tests were within normal limits.

Panoramic radiogram and coronal TMJ tomogram showed destruction of the condyle and reactive sclerosis of the articular process of the mandible (Figs 2A,B). Coronal contrast-enhanced T1-weighted magnetic resonance image showed a low intensity signal of the bone marrow of the condyle and ascending ramus (Figs 3A,B). Based on a diagnosis of mandibular osteomyelitis, antibiotic and NSAID therapy was given for 1 week, but it failed to improve the symptoms. Partial resection of the condyle with an open biopsy was performed under general anesthesia. The histopathologic examination showed fibrous granulation tissue and mature lamellate cellular bone (Fig 4). Microbiologic culture from the biopsy specimen was negative.

Two years later, the patient also experienced pain and swelling in the right mandibular body, but no evidence of recurrence of the mouth-opening limitation. At that time, panorama radiogram showed bone sclerosis with scattered osteolyses of the ascending ramus (Fig 5A). Coronal TMJ tomogram showed cortex formation of the condyle; however, the progressive sclerotic change and periosteal reaction were predominant in the ascending ramus (Fig 5B).

Coronal contrast-enhanced T1-weighted magnetic resonance image demonstrated extension of the low intensity FIGURE 1. Extraoral photograph shows a bony hard swelling in

the region of the right parotid masseter.

Yanamoto et al. Mandibular Osteomyelitis in SAPHO Syndrome.

J Oral Maxillofac Surg 2010.

FIGURE 2. Panoramic radiogram (A) and coronal TMJ tomogram (B) show destruction of the condyle and reactive sclerosis of the articular process of the mandible.

Yanamoto et al. Mandibular Osteomyelitis in SAPHO Syndrome. J Oral Maxillofac Surg 2010.

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signal of the bone marrow to the mandibular angle, and the periosteal reaction was observed outside the original cortex (Fig 6). Bone scintigram (technetium 99m) showed enhanced uptake in the right ascending ramus and sternoclavicular joint (Fig 7). In laboratory data, as in the first exam- inations, C-reactive protein was slightly increased (0.55 mg/

dL); however, other laboratory test results were within normal limits. In addition, she was negative for rheumatoid factor and antinuclear antibody. Serum immunoglobulin levels and immunoglobulin G subclasses were normal. HLA antigen typing was positive for A11, A24, B55, B52, and Cw1. Based on the clinical manifestations, laboratory exam- inations, and radiologic findings, a diagnosis of SAPHO syndrome was established.

Extensive decortication of the ramus was performed to decrease swelling of the mandible. Histopathologic findings showed fibrous granulation tissue and bone fragments, as in the first surgical treatment. Microbiologic culture of the biopsy specimen was also negative. The patient subsequently received long-term administration of clarithromycin (400 mg/d) and etodolac (200 mg/d) for at least 3 months.

During that time, she had a long symptom-free period. At this point, the antibiotic and NSAID treatments were stopped.

After 6 months, she again experienced pain and swelling in the right mandibular body; however, the degree of pain and swelling were markedly decreased. Subsequently, these symptoms appeared every 3 months and the patient was discontinuously administered clarithromycin (400 mg/d) and etodolac (200 mg/d). This symptomatic treatment has been continuing for the past 8 years, resulting in sufficient relief of pain and swelling. At the last radiologic examination, panoramic radiogram showed slight enhancement of sclerosis of the ascending ramus (Fig 8A). Coronal TMJ tomogram showed slight enlargement of the ascending ramus (Fig 8B). Coronal contrast-enhanced T1-weighted magnetic resonance image re- mained almost unaltered (Fig 9).

Discussion

SAPHO syndrome is a rare disease of unknown infectious origin; however, its incidence is underesti- mated. A pediatric subset of SAPHO syndrome is referred to as chronic recurrent multifocal osteomyelitis,⁸ which is the most severe form of sterile bone inflammation in children.⁹ Moreover, SAPHO syndrome may be misdiagnosed if the location is atypical or if the clinical presentation is unusual. In fact, chronic recurrent multifocal osteomyelitis and SAPHO syndrome share several features: osteitis, unifocal or multifocal presentation, pustulosis, hyperostosis, and a good general state of health without spiking fevers, organomegaly, weight loss, or fatigue.⁸

A sternocostoclavicular lesion is the most frequent site of SAPHO syndrome, followed by the sacroiliac joint and the spine.^10,11 Diffuse sclerosing osteomyelitis of the mandible is a well-known bone lesion of SAPHO syndrome. Hayem et al¹¹ reported 13 cases (10.8%) of mandibular osteomyelitis in 120 patients with SAPHO syndrome. Moreover, in a series of 85 patients with SAPHO syndrome, 7 had mandibular lesions (8.2%).⁶ Despite previous reports of SAPHO

FIGURE 4. Histopathologic examination shows fibrous granula- tion tissue and mature lamellate cellular bone.

FIGURE 3. Coronal contrast-enhanced T1-weighted magnetic res- onance image shows a low intensity signal of the bone marrow of the condyle (A) and ascending ramus (B).

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syndrome in the literature,^6,7,11-13only 4 cases involving the TMJ have been reported.^7,11-13 These cases presented various complications such as TMJ ankylosis⁷and inflammatory spread to the temporal bone causing deafness.¹² Although our case also involved the TMJ and showed destruction of the condyle and reactive sclerosis of the articular process of the man-

dible, good progress was achieved by partial resection of the condyle as the initial surgical procedure.

Suei et al⁵recommended that mandibular osteomyelitis lesions should be classified into bacterial osteomyelitis and osteomyelitis in SAPHO syndrome. Diagnos-

FIGURE 7. Technetium 99m bone scintigram shows enhanced uptake in the right ascending ramus and sternoclavicular joint.

FIGURE 5. Two years after first surgical treatment. A, Panoramic radiogram shows bone sclerosis with scattered osteolyses of the ascending ramus. B, Coronal TMJ tomogram shows cortex formation of the condyle; however, progressive sclerotic change and periosteal reaction is predominant in the ascending ramus.

FIGURE 6. Coronal contrast-enhanced T1-weighted magnetic res- onance image shows extension of the low intensity signal of the bone marrow to the mandibular angle, and the periosteal reaction is observed outside the original cortex.

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tic features of bacterial osteomyelitis are suppuration and osteolytic radiographic change with lamellar-type periosteal reaction. In contrast, mandibular osteomyelitis in SAPHO syndrome is characterized by nonsup-

puration and a mixed radiographic pattern accompanied by solid-type periosteal reaction, external bone resorption, and bone enlargement.^5,10,14Moreover, in SAPHO syndrome, progressive bone sclerosis with scattered osteolyses (mixed type) is a common fea- ture⁵; however, bone resorption may be prominent in the early stage, whereas sclerotic changes may be observed in a more quiescent chronic reaction.⁵ In accordance with these radiologic features, our case showed bone resorption of the condyle in the early stage, and sclerotic changes were observed with chronic inflammation in recent years.

Skin lesions typically seen in SAPHO syndrome are palmoplantar pustulosis and acne; however, not all of these manifestations necessarily occur. The incidence of skin lesions such as palmoplantar pustulosis and acne in patients with SAPHO syndrome has been reported as 84%.¹¹ Moreover, Kahn et al¹⁵ reported the occurrence of long intervals between the devel- opment of skin and bone lesions; however, our case had no history of skin lesions.

SAPHO syndrome shows various immunogenetic backgrounds; however, its genetic basis remains unknown.¹⁶Although some studies have suggested that antigen HLA B27 is associated with SAPHO syndrome,^1,6 some recent reports have supported the idea that the HLA B27 phenotype could not be associ-

FIGURE 8. Eight years after second surgical treatment. A, At the last radiologic examination, panoramic radiogram showed slight enhancement of sclerosis of the ascending ramus. B, Coronal TMJ tomogram showed slight enlargement of the ascending ramus.

FIGURE 9. Eight years after second surgical treatment. Coronal contrast-enhanced T1-weighted magnetic resonance image re- mained almost unaltered from that seen inFigure 6(2 yrs after first surgical treatment).

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ated with the pathogenesis of SAPHO syndrome.^11,16 Our patient did not have the HLA B27 phenotype.

In SAPHO syndrome, therapeutic modalities such as antibiotic administration, hyperbaric oxygen, cu- rettage, saucerization, decortication, and partial resection of the affected bones have been reported by some investigators^3,7,11,13; however, these modalities have very limited efficacy and cannot cure the disease.^5,13Although surgical procedures such as decortication and removal of necrotic tissue may be useful in the early stages of the disease, it is well known that surgical treatment of osteomyelitis with SAPHO syndrome often has no or only short-term success.^17,18 Up to now, treatment for SAPHO syndrome has fo- cused only on symptoms. NSAIDs seem to be the treatment of first choice, in combination with anti- biotics.3,7,11,13,18 Corticosteroid therapy is accept- able for patients with a poor clinical response to NSAIDs.^11,13In almost all cases, long-term administration of macrolides and conservative treatment with NSAIDs have been recommended.^5,7,11,18 Recently, treatment with pamidronates or bisphosphonates has been reported to be effective¹¹; however, the effects of these drugs have to be evaluated, because there are no long-term data on the outcome with these drugs.

In our case, NSAIDs (etodolac 200 mg/d) and long- term macrolides (clarithromycin 400 mg/d) were administered. Moreover, surgical treatment in the early stage seemed effective to repress disease progression.

In conclusion, mandibular osteomyelitis in SAPHO syndrome is characterized by nonsuppuration and a mixed radiographic pattern accompanied by solid- type periosteal reaction, external bone resorption, and bone enlargement. SAPHO syndrome should be considered when a patient presents with osteomyelitis in other bones, arthritis, or skin diseases.

Acknowledgment

We thank the staff of the Department of Radiology and Cancer Biology and the Department of Oral Pathology and Bone Metabo- lism, Nagasaki University Graduate School of Biomedical Sciences.

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