Long-term Evaluation of Mandibular Reconstruction with Fibular Flap in SAPHO Syndrome: 18 Years Post-onset

Abstract

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a systemic inflammatory disease that involves mandibular osteomyelitis with diffuse sclerosis in 10% of cases. Drug therapy is the primary treatment choice; however, severe deformity resulting in restricted mouth opening requires mandibular reconstruction. We report a rare case of mandible reconstruction in a patient with SAPHO syndrome, using a vascularized fibular flap with long-term follow-up. One year after surgery, a fistula developed in the chin region following a rash on both lower extremities as a skin manifestation of SAPHO syndrome. Bone scintigraphy showed uptake in the remaining right mandible, although there was no uptake in the transplanted fibula bone. Five years after the surgery, the mandibular fistula was closed by removing the titanium plate. The transplanted vascularized fibula achieved osteosynthesis; however, further follow-up is required to identify early symptoms of relapse and determine the need for additional medications.

Introduction

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, first reported by Chamot et al. in 1987, is a rare systemic inflammatory disease of unknown etiology¹⁾. The diagnosis of SAPHO syndrome can be difficult because it relies on clinical features (sterile bone inflammation, arthritis, and inflammatory skin disease) and the exclusion of differential diagnoses²⁾. The incidence of mandibular involvement with diffuse sclerosing osteomyelitis is 10%, and it predominantly occurs in young women after dental procedures, which are a risk factor for the onset of SAPHO syndrome³⁾.

Severe mandibular deformity caused by a pathological fracture resulting in restricted mouth opening requires surgical intervention. Mandibular reconstruction using an alloplastic condyle⁴⁾, total joint prosthesis⁵⁾, iliac crest flap⁶⁾, and fibula flap⁷⁾ has been reported. Here, we report a case of mandibular reconstruction in a patient with chronic jaw inflammation due to SAPHO syndrome, with long-term follow-up for 12 years before surgery and six years after surgery.

Case

The patient was a 49-year-old woman. Her medical history included palmoplantar pustulosis and emphysema due to smoking. She visited a local dental clinic with swelling and pain in the left mandible. The mandibular left first molar was extracted with a diagnosis of periodontitis; however, the patient's symptoms did not improve. She was referred to the Department of Oral and Maxillofacial Surgery at our hospital. Panoramic radiography and computed tomography (CT) showed sequestration in the left mandible, and magnetic resonance imaging revealed widespread low signal intensity on T1-weighted images, leading to a diagnosis of osteomyelitis (Figure 1). The second premolar of the left mandible was extracted, and bone curettage was performed by the oral and maxillofacial surgeons along with hyperbaric oxygen therapy (HBOT). Bone scintigraphy during the disease course showed a decrease in accumulation due to the removal of the mandibular cortical bone at 50 years of age; however, osteomyelitis had expanded from the midline to the left angle at 51 years of age. HBOT was administered for six years (two atmospheres, 80 min, 15 sessions per course). The pain and inflammation in the lower jaw persisted and gradually worsened. It was unclear whether there was any definite effect (Figure 2).

Figure 1.

Findings at 49 years of age. (a) CT: left mandible, (b) CT: front view. (c) Panoramic radiography. (d) T1-weighted MRI: widespread low signal intensity leading to a diagnosis of osteomyelitis.

CT: computed tomography; MRI: magnetic resonance imaging

Figure 2.

Detailed schedule of HBOT. Images of bone scintigraphy at 49, 50, 51, and 53 years of age showing repeated changes in the uptake of exacerbations and relief.

HBOT: hyperbaric oxygen therapy

After 55 years of age, the patient was followed up at another dental clinic, but at 60 years of age, she was referred back to our hospital with complaints of severe pain and difficulty in opening her mouth. Panoramic radiography and CT revealed osteolytic changes extending from the mandibular midline to the left condyle, as well as diffuse sclerosis with pathological fractures. The left ramus and mandibular body were deviated toward the left at the fracture site. Bone scintigraphy revealed worsening osteomyelitis mainly at the left mandibular angle (Figure 3). Upon consultation with rheumatologists in our hospital, the patient was diagnosed with SAPHO syndrome, given the swelling of the right sternoclavicular joint and her history of palmoplantar pustulosis. However, they decided to observe without administering medicines such as corticosteroids because of the absence of arthritis.

Figure 3.

Findings at age 60 years of age. (a) Restriction of mouth opening. (b) The mandible deviated to the left overall. (c) CT: pathological fracture. (d) CT: severe deformity with atrophy. (e) Panoramic radiography: diffuse sclerosis with pathological fractures. (f) Bone scintigraphy: extending from the mandibular midline to the left condyle.

CT: computed tomography

At 61 years of age, she was referred to the Department of Plastic and Reconstructive Surgery for mandibular reconstruction to address her inability to open her mouth. In joint surgery with the Department of Oral and Maxillofacial Surgery, left hemimandibular resection (from the right lateral incisor to the left condyle of the mandible) and mandibular reconstruction using a vascularized fibular osteocutaneous flap were performed. The fibula was cut into three bone fragments measuring 2 cm, 5 cm, and 4 cm, and fixed with a 2.0-mm-thick titanium plate (Matrix Mandible angle reconstruction plate; Johnson and Johnson, New Brunswick, NJ, USA). The oral mucosa was closed directly, and a fibular flap skin island was used to replace the skin ulcer of the left mandible. A de-epithelialized skin flap was applied to cover the surface of the titanium plate and fill the submandibular dead space (Figure 4). The area around the mandibular fossa was filled with scar tissue due to years of inflammation; therefore, the tip of the fibula was positioned in the space where the atrophied coronoid process existed, with the expectation that the reconstructed mandible would move as a non-union false joint pattern. The peroneal artery and vein were microscopically anastomosed to the left facial artery, the left external jugular vein, and the left facial vein. Pathological findings confirmed destruction of bone trabeculae and proliferation of fibrous tissue, consistent with chronic osteomyelitis. Postoperative CT showed a mixture of bone union and bone resorption. The patient was able to open her mouth without pain (Figure 5).

Figure 4.

Intraoperative findings at age 61 years of age. (a) A fibular osteocutaneous flap elevated from the left lower leg. (b) A de-epithelialized area covered the plate and filled the dead space. (c) A cutaneous flap was placed in the ulcer area. (d) Occlusion was adjusted as much as possible.

Figure 5.

Postoperative course. (a) CT: 1 month after surgery. (b) CT: 1 year after surgery at 62 years of age. White arrows show irregular sclerosis and hyperostosis. (c) Frontal facial appearance 1 year after surgery. (d) Opening of mouth 1.5 finger widths possible. (e) A skin graft on the left lower leg, no functional impairment, no sensory impairment.

CT: computed tomography

At 62 years of age (one year after surgery), a sterile fistula appeared in the chin area. Although the doctor in the Department of Rheumatology suggested treatment with adalimumab (a tumor necrosis factor [TNF]-α blocker), she refused because of financial reasons (the treatment was not covered by insurance). At 64 years of age (three years after reconstructive surgery), multiple ulcers in the mandible and a rash appeared on both lower extremities (Figure 6). A biopsy of the lower leg revealed psoriasis vulgaris, which was considered a skin symptom of SAPHO syndrome. Bone scintigraphy showed worsening osteomyelitis in both sternoclavicular joints and uptake in the right mandible, although there was no uptake in the transplanted fibular bone. Adalimumab administration was suggested again; however, the patient refused treatment. CT findings indicated favorable bone union; therefore, we decided to remove the titanium plate at 66 years of age (five years postoperatively). Intraoperative findings also confirmed good union of the transplanted fibula and right mandible, and the wound was closed. At 67 years of age (six years postoperatively), she was able to open her mouth with two finger widths and consume soft food orally without mandibular fistulas (Figure 7). The mastication plane deviated due to the abnormal position of the left temporomandibular joint.

Figure 6.

Findings at 64 years of age. (3 years after surgery) (a) Sterile fistulas. (b) The mouth opening ability was maintained. (c) A skin rash was observed on both lower extremities; a biopsy showed psoriasis vulgaris. (d) Bone scintigraphy showing the uptake in the sternoclavicular joint. The uptake was observed in the right mandible, but not in the transplanted fibula. (e) Bone scintigraphy showing the whole body. No obvious uptake was observed in the other parts.

Figure 7.

Findings at 66 years of age (a, b) and at 67 years of age (c-g). (a) Fistula excision. (b) After the removal of the titanium plate, the bone union was good. (c) CT images. White arrows show irregular sclerosis and hyperostosis. (d) Frontal view. (e) Panoramic radiography. (f) Open mouth. (g) Elevation angle. (h) Right sole. White arrows show palmoplantar pustulosis.

CT: computed tomography

Discussion

This is a rare case in which the patient was not diagnosed with SAPHO syndrome for 12 years. The patient developed pathological fractures and severe deformity of the mandible during a long-term follow-up period of six years after reconstruction. SAPHO syndrome is characterized by repeated exacerbations and remissions of inflammation, which may improve within a few days or last several years. Not all patients display all clinical findings, and symptoms do not necessarily occur simultaneously⁸⁾. Bone lesions are sterile osteomyelitis/osteitis and have been reported to be osteolytic in the early stages and osteosclerotic in the later stages⁹⁾.

The etiology of SAPHO syndrome remains unknown and may result from a combination of genetic, infectious, and immunological factors. Bone manifestations such as hyperostosis intermixed with areas of osteolysis and arthritis are the most typical symptoms¹⁰⁾. Some cases with imaging findings similar to mandibular involvement in SAPHO syndrome have been reported under various names, such as chronic recurrent multifocal osteomyelitis, diffuse sclerosing osteomyelitis, and juvenile mandibular chronic osteomyelitis, some of which are considered to be included in SAPHO syndrome^11,12). Therefore, the key to diagnosing SAPHO syndrome is to identify both osteoarticular and skin manifestations¹³⁾. Palmoplantar pustulosis is a typical symptom; however, other dermatological manifestations such as psoriasis vulgaris and generalized pustula have been reported¹⁴⁾. In our case, three years postoperatively, a rash appeared on both lower extremities, which was diagnosed as psoriasis vulgaris.

Drug therapy is the first choice, and most patients with SAPHO syndrome respond well to combination therapy with non-steroidal anti-inflammatory drugs (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and bisphosphonates. TNF blockers are effective in patients who are refractory to NSAIDs and DMARDs¹⁵⁾. Recent reports have presented successful experiences using tofacitinib (a novel small-molecule biological agent that acts as a Janus kinase inhibitor) for the treatment of SAPHO syndrome^16,17). Surgery is not recommended because of the high recurrence rate; however, severe functional disorders still require mandibular reconstruction. Limited opening and severe pain due to pathological fractures or temporomandibular joint involvement are typical indications for mandibular reconstruction surgery⁵⁾. This is interpreted as a condition in which irreversible functional impairment occurs even if SAPHO syndrome progression can be controlled with drug therapy. Another difficulty in mandibular reconstruction surgery for SAPHO syndrome is the issue of bone flap donor sites⁶⁾. Osteomyelitis can also occur in the fibula and ilium. Although careful preoperative examination with bone scintigraphy is recommended, the possibility of future inflammation of transplanted bone cannot be completely ruled out.

If surgical treatment is selected, the patient must be continuously monitored to identify the relapse of symptoms¹⁸⁾. Our case showed fibula bone absorption and remodeling one year postoperatively, and the residual periosteum of the left mandible showed irregular sclerosis and hyperostosis postoperatively (Figure 5b and 7c). Bone scintigraphy did not show osteomyelitis in the transplanted fibula (Figure 6d); however, careful follow-up is required because there was a rare case of SAPHO syndrome with hyperostosis extending to the upper half of the fibula itself¹⁹⁾. We performed titanium plate removal surgery five years after the reconstruction surgery to address the delayed healing of the mandibular ulcer. This was done because we considered the possibility of a foreign body reaction to a metal or microinfection. However, the absence of signs of sequestration or infection during surgery made it unclear whether plate removal was necessary.

We report the long-term follow-up of a case of mandibular-related SAPHO syndrome: 12 years preoperatively and six years postoperatively. The transplanted vascularized fibula achieved good osteosynthesis; however, we observed sclerosis and hyperostosis in the residual left mandibular periosteum with irregular partial absorption of the fibula. Further follow-up is needed to identify early symptoms of relapse and to administer additional medications.

Author Contributions: I.T., T.W., and H.Y. performed the surgeries and treatment; M.K. and N.M. supervised the surgeries; I.T. and T.W. wrote the manuscript.

Conflicts of Interest: There are no conflicts of interest.

Ethical Approval: This is a case report; therefore, this paper does not require approval from our ethics committee.

Consent to Participate: The patient provided their written informed consent to participate in this study.

Consent for Publication: Written informed consent for publication of images and information about the patient was obtained.

Disclaimer: I.T. and N.M. are the Editorial Committee members of Journal of Plastic and Reconstructive Surgery. These authors were not involved in the peer-review or decision-making process for this paper.