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Case report

A 69-year-old white woman was transferred to our facility for a higher level of care after initial evaluation at her local emergency department with complaints of decreased level of consciousness and weakness. Her family reported anterior neck swelling and erythema of 3-day duration. Her medical history included prior administration of the bisphosphonate zolendric acid to treat bone metastasis from breast cancer. Six months prior, she had developed osteonecrosis of the jaw (ONJ) after tooth extraction, which had been conservatively treated with several sequestrectomies in the office.

Clinical examination revealed an acutely ill patient with a decreased level of consciousness, tachycardia, tachypnea, and fever of 100.8°F. Erythema, edema, and tenderness to the anterior neck were also present. In the oral cavity, there was a 3-cm area of eroded bone on the right side of the mandibular body ( Fig. 1 ). Her white blood cell count was 24.4. An outside computed tomographic scan of the neck without contrast revealed significant free air in the tissues of the submental and submandibular spaces ( Fig. 2 ). A clinical diagnosis of necrotizing fasciitis (NF) was made.

Intraoral view: osteonecrosis of the right mandibular body.

Computed tomographic scan of the neck without contrast demonstrating significant free air in the soft tissues of the submental and submandibular spaces.

After treatment options were discussed extensively with her family including radical surgical debridement, the patient’s family elected to proceed and the patient was taken to the operating room immediately. Incision, drainage, and debridement of the anterior neck, including resection of necrotic strap muscles, platysma, parts of the sternocleidomastoid, and digastric muscles up to the mylohyoid, were performed. Sequestrectomy of the mandible and copious irrigation with bacitracin was also performed. The wound was packed with the incision left open and intravenous antibiotics were started. She was transferred to the intensive care unit, and dressing changes were instituted. Histologic examination of the tissue was consistent with NF: acute inflammatory necrosis of soft tissue and skeletal muscle with abundant bacterial colonies. Intraoperative aerobic cultures were positive for Streptococcus constellatus , Streptococcus viridans group, and the anaerobic culture was positive for Peptostreptococcus species, Prevotella ( Bacteroides ) species, and Fusobacterium nucleatum . Intensive postoperative care was successful in keeping the wound clean, and further necrosis did not develop. Over the next several weeks, the wounds slowly granulated and healed by secondary intention. The patient was eventually discharged home. She subsequently died several months later as a result of complications of her metastatic breast cancer but had not had any further problems with her ONJ or neck infection.

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Discussion

Cervical NF is an uncommon polymicrobial soft tissue infection characterized by gas formation and extensive tissue necrosis, which is often fatal. Predisposing factors include systemic diseases such as neoplasia and immunocompromised states . It is a fulminate infectious process, affecting deep and superficial fascia while sparing the overlying skin and underlying muscle . Clinically, the overlying skin can become tender to palpation; however, cutaneous nerve involvement can also result in an anesthetized area. Gas formation within the soft tissue has been noted on radiographic examination and has been reported in 50% of cases of NF involving the head and neck .

Most cases of NF are polymicrobial with the most common organism being Streptococcus ( Streptococcus milleri ), followed by Staphylococcus and gram-negative rods. In one study, one third of the cases included Bacteroides species, Peptostreptococcus , Eubacterium , Propionibacterium , and Fusobacterium , many of which were isolated in this case.

Treatment of NF can be very challenging, and keys to successful management seem to include early recognition, high doses of appropriate antimicrobial therapy, and early surgical intervention with radical debridement of necrotic tissue. The clinical outcome in this case supports the regimen of aggressive surgical debridement with immediate initiation of IV antibiotics as has been previously reported .

Bisphosphonates are used in the treatment of many skeletal disorders including bone metastases, osteoporosis, hypercalcemia of malignancy, Paget disease, multiple myeloma, and bone pain . The drug’s primary mode of action is the inhibition of bone resorption caused by decreasing the function of osteoclasts. One of the known complications of this medication is ONJ, previously known as drug-induced avascular necrosis. Histologically, it is similar to radiation-induced osteonecrosis. Woo et al recently completed a meta-analysis in which 368 reported cases of bisphosphonate-associated ONJ were reviewed. Ninety-four percent of patients were treated with intravenous bisphosphonates, and most patients (85%) had multiple myeloma or metastatic breast cancer .

Several hypotheses exist attempting to explain the susceptibility of the jaw to osteonecrosis. One of these hypotheses emphasizes the thin mucosa and periosteum as well as persistently high bacterial counts in these areas that produce a fragile barrier. Medications such as bisphosphonates cause marked suppression of bone metabolism that results in physiologic microdamage that when compounded with any trauma or infection results in increased need for osseous repair that exceeds the capacity of the hypodynampic bone leading to bony necrosis . Others hypothesize that the combination of osteoclast and keratinocyte apoptosis, which reduce and compromise the immune keratinocyte barrier of oral mucosa, represents a possible pathway leading to ONJ. Another hypothesis emphasizes secondary infection from dental work that can result in an acidic environment where bisphosphonates may be released from bone surfaces and result in high concentrations and an increased apoptotic rate . As in the case presented here, previous dental extraction is a common predisposing factor in up to 60% of patients . Another possible mechanism described for bisphosphonate-induced ONJ emphasizes the antiangiogenesis effect that leads to avascular necrosis and the suspected decreased vascular endothelial growth factor .

Our approach to the treatment of ONJ is conservative with serial debridements (sequestration) and increased oral hygiene with aggressive operative intervention reserved for long-term failures. Bedogni et al has advocated complete excision of the diseased areas with reconstruction as indicated when the disease is symptomatic, progresses, and fails conservative therapy. Hyperbaric oxygen and oral antibiotics have also been recommended by some but remains controversial . The incidence of soft tissue infections as a result of ONJ is unknown, and no reports of such have been found in the literature to this point as ONJ has traditionally been considered a bony problem. This emphasizes the uniqueness of this report as it demonstrates an aggressive soft tissue infection as a result of ONJ. Necrotizing fasciitis is a rare but serious complication of bisphosphonate-induced ONJ, which was managed successfully in this case with aggressive debridement and intravenous antibiotics.