INTRODUCTION
Osteomyelitis is an inflammatory condition of bone marrow, which in almost all cases extends to involve the bony cortex and periosteum of the infected area.1 Chronic osteomyelitis may be a persistant sequela of acute osteomyelitis, or it may represent a long-standing, low grade inflammatory infection without a clinically evident acute phase.2 The Zurich classification of osteomyelitis divides the disease entity into three distinct types. Acute and secondary chronic osteomyelitis are essentially the same disease, arbitrarily separated by one month from the beginning of symptoms.3 They consist of suppuration, fistulas and sequestra formation, and constitute a true bacterial infection. They are analogous to chronic suppurative osteomyelitis, according to Marx4 and Topazian.5 Primary chronic osteomyelitis is a rare condition of the jaw, presenting as a nonsuppurative, chronic inflammation of unknown cause. It can manifest as early or adult onset and characterized by lack of pus formation, fistula or sequestra formation.3 Predominantly, mandibular cases of osteomyelitis can be further subdivided into those cases accompanied by extragnathic dermatoskeletal signs of synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO syndrome), or cases showing periodic flare-ups and remissions over multiple years as chronic recurrent multifocal osteomyelitis (CRMO). Chronic diffuse sclerosing osteomyelitis has been shown to be caused by Actinomyces species and Eikenella corrodens which induce sclerosis.6 Although this disease is seen less commonly today due to widespread antibiotic use, it still has an intractable course, and continues to be a relatively common sequela after third molar surgery.7,8 We describe five cases of secondary chronic osteomyelitis after third molar surgery, in which two cases resulted in pathologic jaw fractures.
CASE 1
An otherwise healthy 21-year-old female presented for the removal of one erupted and three impacted third molars. She was a controlled asthmatic taking Advair, Ventolin and Flovent. She had multiple food and drug allergies, including peanuts, peas, lentils, Amoxil, Erythromycin, Septra and Keflex. In January 2007, she underwent the uneventful removal of her four third molars under office general anaesthesia. One week follow-up was unremarkable. Seven weeks postoperatively, she presented with swelling and pain in the previous #48 site. A subperiosteal abscess was drained, a medicated dressing was placed and she was given oral Clindamycin 300mg QID. The medicated dressing was removed two days later and she was followed weekly for three weeks, showing improved healing and good oral hygiene. However, at week four (three months after extractions) she presented with recurrent symptoms of increasing swelling, pain and, in addition, difficulty with jaw opening. Panorex radiograph showed increased areas of radiolucency in the right angle of the mandible, with diffuse erosion at the socket base (Fig. 1). Complex cranial CT of the mandible (Figs. 2-4) with Multiplanar Reconstruction (MPR) imaging without contrast (Fig. 5), showed cortical lucencies in the lateral cortical margin, with overlying periosteal new bone formation along the lateral aspect of the right angle of the mandible. Swabs were taken for Gram stain, culture and sensitivity for aerobic and anaerobic organisms, showing 4+ growth of a mixed population including mixed anaerobes, with no predominant organism. Incisional hard and soft tissue biopsies, along with sequestra and inflammatory tissue from the socket, were sent for examination. These showed granulation tissue with marked acute inflammation and hyperplastic squamous epithelium with underlying inflammation and fibrosis. Total body bone scan showed very intense uptake involving the angle of the right mandible. Gallium scan of the head and neck showed a focus of Gallium uptake in the region of the right angle. CBC revealed a white cell count of 11.3. These findings were consistent with a diagnosis of osteomyelitis.
She was started on intravenous Clindamycin 600mg Q8H, Flagyl 500mg Q8H and Gentamycin 300mg Q24H. She was not able to tolerate Levaquin and this was discontinued. The medicated dressing was changed. A PICC (peripherally inserted central catheter) line was inserted. She was then taken to the operating room for an intraoral sequestrectomy and repeat hard and soft tissue biopsies. A Gentamycin impregnated cement cone was placed into the socket. Results showed no evidence of actinomyces or acid-fast bacilli. She had some initial improvement, but one week later presented to the Emergency Department with significant right submandibular swelling, pain and trismus. Her white cell count was 14.0. A CT scan showed increased mottling and bony destruction. She was returned to the operating room and underwent an extraoral incision and drainage of a right submandibular abscess, removal of the antibiotic impregnated cement cone, and sequestrectomy and saucerization for osteomyelitis. Vancomycin 1g Q12H was substituted for Flagyl. Cultures grew a Clindamycin resistant Streptococcus intermedius. She finally began to show much improvement with decreased pain and increased jaw opening. Packing changes every three days were continued for the following two months. Intravenous antibiotics were continued for at least seven weeks after which her PICC line was removed. A follow-up bone scan of the skull and neck showed a persistent but decreased focus of tracer activity, indicating a positive response to treatment. She was finally discharged from care six months after her third molar surgery.
CASE 2
A healthy 25-year-old male presented for the removal of four impacted third molars after a bout of pericoronitis involving tooth #48. In January 2007, he underwent the uneventful removal of his four third molars under office general anaesthesia. His one week follow-up visit was unremarkable. In April 2007, 14 weeks after surgery, he presented with left facial swelling and jaw pain. An intraoral exploration of #38 site showed significant granulation tissue, which was curetted and the area packed with a medicated dressing. Oral Penicillin and Flagyl were started. Two days later, the dressing was changed but the patient complained of increased pain and trismus. Panorex radiograph showed evidence of lack of bony fill and outline of a non-healing socket (Fig. 6). CT scan of the mandible show no evidence of lytic lesions. Multiplanar Reconstruction revealed localized bony destruction in the extraction #38 site (Fig. 7). Total body bone scan showed slight increased uptake in #38 site, suggesting osteomyelitis. He was admitted to hospital for intravenous Penicillin and Flagyl, but without any improvement after four days, he was taken to the operating room. He underwent an open debridement, Gram stain, culture and sensitivity, hard and soft tissue biopsies and sequestrectomy and saucerization for osteomyelitis. White cell count was 9.3. A PICC line was inserted and he was placed on Clindamycin and Ceftriaxone. Surgical pathology reports showed mixed inflammation and fibrosis consistent with osteomyelitis. He had medicated dressing changes every three days for the following eight weeks, after which he began to show improvement. Follow-up panorex radiograph ten months after surgery showed excellent bony healing of the socket.
CASE 3
A 37-year-old male presented in July 2007 with pericoronitis related to a partially impacted #38, limited jaw opening and numbness of the left chin. He was allergic to Penicillin and cheese. He took multiple medications including Ativan, Gemfibrozil, Trazodone, Pariet, Percocet, Ramipril, Cotazym, OxyContin and Cytomel. He had a long history of recurrent admissions to hospital for alcoholic-induced pancreatitis. He continued to smoke and drink heavily. He had a hernia repair in the past. He was placed on oral Clindamycin and underwent an incision and drainage in the lower left third molar site. His panorex radiograph did not show any
significant bony changes around the partially impacted #38. After gradual improvement of his trismus, #38 was removed under local anaesthesia in September 2007. During the extraction, copious amounts of mucopurulence drained from the surrounding marrow cavity around the socket. He was admitted to the hospital for high-dose intravenous antibiotics and Gram stain, culture and sensitivity. A CT scan and bone scan were performed. The CT scan was not conclusive for osteomyelitis, although an early osteomyelitis could not be excluded. However, the bone scan showed a focus of intense uptake in the left mandibular condyle and a low grade uptake in the entire ramus and body of the mandible, extending to the midline. These findings were consistent with a diagnosis of osteomyelitis. A PICC line was inserted and he was placed on Clindamycin and Cefuroxime. He underwent multiple medicated dressing changes of the third molar socket over the following eight weeks. With eventual granulation of the socket, he went on to heal and was subsequently lost to follow-up.
CASE 4
A 55-year-old female presented in May 2009 with pericoronitis related to a partially impacted #38. Her past medical history showed bipolar affective disorder and asthma. She was allergic to Codeine and Percocet and her medications included Lithium, Ciprolex, Effexor, Wellbutrin, Synthroid, Eltroxin, Advair and Ventolin. Her past surgeries included bilateral carpel tunnel, three Caesarian sections and tubal ligation. In June 2009, she underwent the surgical removal of #38 under office sedation. There was a witnessed left mandibular nerve injury. At her one week follow-up, she complained of persistent intense pain since surgery and the socket was packed with a medicated dressing. One week later, she again presented with tender swelling of the left face, and the socket was explored without production of purulence. Ten days later, she had continued painful swelling of the left face, which had become indurated. She was then admitted to the hospital for intravenous Clindamycin and Flagyl, and an extraoral incision and drainage of a possible buccal space abscess under general anaesthesia. This was productive for small amounts of purulence. A swab was sent for Gram stain, culture and sensitivity. A postoperative CT scan did not show any bony erosive changes or periosteal new bone formation. Culture grew an alpha-hemolytic streptococcus. She began to show marked improvement with decreased swelling and pain. She was discharged on Clindamycin and Avelox.
One week later while chewing hard candy at a restaurant, she experienced a distinct crack of her jaw, accompanied by a sharp pain in the left mandible. Examination showed mucopurulence draining from the extraction socket of #38. Panorex radiograph showed an undisplaced fracture through the extraction socket of #38. A CT scan confirmed an undisplaced pathologic fracture through the angle of the left mandible and old extraction socket of #38. She was taken to the operating room and underwent a closed reduction of the mandibular fracture with maxillomandibular fixation (Fig. 8). A debridement and sequestrectomy of #38 socket for osteomyelitis was performed simultaneously. Gram stain showed gram positive cocci. A PICC line was inserted and she was started on Clindamycin and Ceftriaxone for at least six weeks. Healthy granulation of the socket gradually occurred. Six weeks later, the maxillomandibular fixation was removed and elastic traction placed. The patient was followed biweekly with panorex radiographs. Follow-up CT (Fig. 9), Multiplanar Reconstruction (Fig. 10), bone and Gallium scans showed a non-union of the fracture with intense uptake in the area of the left angle of the mandible with a small amount of periosteal new bone formation, suggesting residual infection and osteomyelitis. However, clinical healing continued to be apparent and by four months after the fracture, the mandibular segments were stable. Six months after the fracture event and seven months after the extraction, intraoral healing was complete, paresthesia had resolved and the mandible clinically stable. She was discharged from further follow-up.
CASE 5
A 42-year-old female presented for the removal of two erupted and one partially erupted and infected third molar. Her past medical history was positive for depression and anxiety, and she had been a recovered alcoholic for three years. She was a smoker and had an allergy to Penicillin. In September 2008, she underwent the removal of three third molars uneventfully. Four days postoperatively, the patient complained of increased pain in the lower third molar sites, which were then irrigated and packed with a medicated dressing. She also complained of left mental nerve paresthesia. The dressing was removed two days later without sign of infection. Four days after the packing removal, the patient returned with increasing pain in the extraction socket of #38. Examination showed no signs of infection, purulent discharge or trismus. She was again treated for an alveolar osteitis with a medicated dressing, which was removed four days later. Fifteen days later, she presented with limited jaw opening of 35 mm with severe tenderness in the left masseter muscle. She was treated for myofascial pain with Lorazepam at nighttime, but returned three days later with worsening pain and Toradol, Flexeril and Elavil was prescribed. Her symptoms subsided three days later and she felt a significant improvement. Two days later, the patient complained of a swelling with purulent discharge at the #38 extraction site. An incision and drainage was performed and Clindamycin 300mg QID was prescribed for one week. She had momentary improvement after three days, but subsequently, the swelling increased and the left submandibular space became involved. This was accompanied with significant pain and trismus, and an elevated white blood count of 12. A CT scan showed a collection of fluid at the posterior angle of the left mandible with bone mottling and destruction. She was taken to the operating room for an intraoral and extraoral incision and drainage. Swabs for Gram stain, culture and sensitivity for aerobic and anaerobic organisms were taken. They showed 3+ growth of a mixed population including mixed anaerobes, with no predominant organisms. Incisional biopsies of soft and hard tissue showed granulation tissue with marked inflammation and fibrosis, consistent with a diagnosis of osteomyelitis.
She was started on Ciprofloxacin 400mg q12h orally and Clindamycin 800mg q8h intravenously, as recommended by Infectious Disease consultation. Prior to hospital discharge, a PICC line was inserted. Due to a Clostridium difficile outbreak in the community, the patient was very worried about her situation and requested a different antibiotic. After consultation with ICU, it was agreed to have the patient undergo a desensitization procedure to Penicillin in the ICU. In this procedure, she was exposed to the antigen (Penicillin), until the recommended dose was reached, while being closely monitored in the ICU. She tolerated Penicillin for 24 hours after the dose had been reached. She was then discharged on Penicillin G 24 million units per 24 hour infusion, Flagyl 500mg TID orally, Hydromorphone for analgesia and Ativan at nighttime as a muscle relaxant. A postoperative panorex showed a non-displaced pathologic fracture of the left mandibular angle, which was confirmed with a CT scan. Her occlusion remained stable and she was treated with a soft diet. The patient began to slowly improve as her intravenous antibiotics were continued for seven months. A CT scan confirmed good bone healing across the fracture site and a bone scan showed no tracer activity, indicating a positive response to treatment. At that point, she was switched to Clavulin 875 mg BID orally for three months on the recommendation of Infectious Disease Service. She was discharged from care 18 months after her third molar surgery.
DISCUSSION
The pathogenesis of chronic osteomyelitis of the jaw oc
curs by bacterial invasion into the medullary space, resulting in eventual vascular compromise to the bony tissues. Recent microbiological studies of osteomyelitis of the mandible show organisms similar to odontogenic infections and include streptococci viridans, anaerobic cocci such as Peptostreptococcus spp, and anaerobic gram-negative rods such as Prevotella and Fusobacterium.1 When host defenses are intact, osteomyelitis rarely occurs. Co-morbidities such as alcoholism, smoking, substance abuse, malnutrition, HIV, diabetes, leukemia, sickle-cell disease and immunosuppression from cancer chemotherapy, are predisposing factors for osteomyelitis.9
Radiographic bone imaging using conventional plain dental or panorex radiographs require at least 30-50 percent loss of bone mineral density before disease detection, and therefore, may appear normal for up to three days or to as much as three weeks after onset of symptoms.10 Radiographic findings show bony destruction and increased radiolucency with a moth-eaten appearance. CT scans show impending cortical perforation (cortical bone thinning), sequestra, periosteal new bone formation, cortical interruption and involucrum (periosteal new bone formation surrounding a sequestrum).11 Bone and gallium scans combined have 98 percent sensitivity and can show changes as early as three days from onset of infection.12 Newer modalities, such as MRI and PET/CT, show promise in diagnosing osteomyelitis, especially in combination with other conventional imaging.
Early diagnosis of osteomyelitis of the jaw depends on a high index of clinical suspicion, along with a thorough examination and appropriate imaging. Early treatment reduces the morbidity and amount of surgical intervention required. Empirical antibiotics of choice include clindamycin, penicillin/metronidazole and fluoroquinolones and should be instituted aggressively for a minimum of six weeks. Hospitalization may be required for intravenous administration of antibiotics, after which home intravenous treatment can be given by a peripherally inserted central catheter, and then subsequently followed by oral therapy for several more months. It is always prudent to involve an infectious disease specialist to co-ordinate the pharmacologic agents in the more complex cases. Surgical treatment should also be early and aggressive and involve surgical debridement by removal of infected and non-vital teeth, affected soft tissue, and necrotic and chronically infected bone. Multiple procedures over several days or weeks may be required to control the infection, and include sequestrectomy, saucerization, decortication in refractory, nonresponsive cases to conservative surgical therapy, and eventually resection with reconstruction in persistent cases.11 Severe, long-standing refractory cases of osteomyelitis may benefit from hyperbaric oxygen treatment as an adjunct to improve oxygen tension in the wound and boost host defense. It has the greatest advantage in strictly anaerobic infections, but there are no large scale prospective human studies to date to validate its use in early or acute osteomyelitis.12
The risk of pathologic fractures of the mandible in the presence of long-standing osteomyelitis after wisdom tooth extraction has been reported.13-16 Closed reduction with arch bars and maxillomandibular fixation was the standard treatment.14,16 Open reduction with rigid internal fixation was not felt to be the treatment of choice, to avoid further vascular compromise by periosteal reflection. However, other authors advocate rigid internal fixation with strong plates, such as reconstruction plates, to ensure immobilization of the infected fractured site. It has proved to be a safe, predictable procedure with a good outcome.17 Case 4 is an example of a pathologic fracture occurring as a result of osteomyelitis after third molar removal, and was treated by closed reduction with arch bars, maxillomandibular fixation and antimicrobial therapy. In Case 5, the pain experienced by the patient was so excruciating that she refused a period of immobilization, knowing full well the risk of complications that this might have caused. The fracture went on to heal completely with conservative management involving a soft diet, close regular monitoring and long-term antibiotics.
CONCLUSION
All the reported cases in this article presented a challenge to the clinician in managing chronic mandibular osteomyelitis after third molar surgery. All cases required aggressive intravenous antibiotics via a peripherally inserted central catheter and prompt surgical debridement. Pathological fractures were treated conservatively. None of the cases in our series required jaw resection. The outcome of these cases highlights the fact that despite advances in modern medicine, the difficulty of managing this disease is still encountered and further research is required.OH
Katie Gilbertson is a dental hygienist in the Department of Paediatric Dentistry, University of Michigan School of Dentistry, Michigan. She can be reached at gilbertson13@gmail.com
Dr. Daisy Chemaly is an Oral and Maxillofacial Surgeon in private practice in Toronto, ON and on active staff at Peterborough Regional Health Centre and Sault Area Hospital. She can be reached at daisychemaly@gmail.com
Dr. Gordon B. Wong is an Oral and Maxillofacial Surgeon in private practice in Sault Ste. Marie, ON and on active staff at Sault Area Hospital. He can be reached at gbwong@shawbiz.ca
Oral Health welcomes this original article.
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