Syphilitic osteomyelitis in a patient with headache and lytic lesions

Discussion

Syphilis, an STI caused by the spirochete Treponema pallidum, is often referred to as “the great imitator,” given its propensity for causing varied disease manifestations that can mimic other clinical syndromes.1 Syphilis infection is classically divided into 4 stages: primary, secondary, tertiary, and latent.2 Primary syphilis can present with a painless, clean-based, well-demarcated ulcer at the site of inoculation, which can include tongue, oral mucosal, vaginal, and penile lesions. It is usually associated with nontender regional adenopathy. Within 3–6 weeks, the spirochete can disseminate to cause secondary syphilis, typically associated with a rash involving the palms and soles. This can be accompanied by mucocutaneous changes, generalized uveitis, and hepatitis; arthralgias and periostitis are less commonly observed. If left untreated, the disease may evolve to tertiary syphilis 1–10 years after initial infection, with cardiac, neurologic, and gummatous lesions. Asymptomatic disease is classified as early or late latent — this distinction is important. Late latent syphilis requires 3 weekly doses of benzathine penicillin, compared with 1 dose for patients with early latent disease. Finally, neurosyphilis (including ocular or otitic manifestations) may occur at any stage and is more likely in people living with HIV.

Syphilitic osteitis and osteomyelitis have historically been rare complications of early (primary and secondary) syphilis and are more commonly described in congenital and tertiary disease. 2 In a previous case series on patients with early syphilis, from 1919 to 1940, only 15 of 10 000 patients had bony lesions.3 In a more recent systematic review of bony manifestations in secondary syphilis, only 36 cases of secondary syphilis with bone involvement were identified from 1964 to 2014.4 An increasing number of case reports of syphilitic osteitis in early syphilis, particularly in people living with HIV, suggests that osteitis may be a more common manifestation of syphilis than previously described.5^–9 The increased relative prevalence is potentially secondary to advanced imaging techniques, as well as the increased number of people living with HIV.

Osteitis, periostitis, and osteomyelitis likely result from hematogenous dissemination of spirochetes during secondary syphilis with deposition into the periosteum, Haversian canal, and bony medulla, leading to an inflammatory reaction with periostitis and subsequent osteolytic lesions.3^,4 The long bones, skull, sternum, and clavicle are the most frequently affected bone sites. Patients with osseous syphilis typically present with localized pain, erythema, or chronic headaches, but can also be asymptomatic.4 On CT imaging, these osteolytic lesions have typically been described as “worm-eaten bone.”10 Magnetic resonance imaging and nuclear medicine studies are more sensitive for osteomyelitis. Magnetic resonance imaging has the advantage of better delineation of soft tissue, marrow, and intracranial findings.

The diagnosis of syphilitic osteitis is often made through a combination of clinical, serologic, and radiographic findings.3^,4 Bone biopsy can be used to confirm a diagnosis, as spirochetes may be visible, but empiric therapy with monitoring of clinical and radiologic response has been described in the literature.1^,9 When biopsy is performed, pathologic findings show fibrous proliferation with lymphoplasmacytic infiltration. Spirochetes may also be identified using the Warthin–Starry stain but is of low sensitivity, and polymerase chain reaction testing of tissue specimens has also been used to make a microbiologic diagnosis.

In our patient, clinical and ongoing radiographic response to treatment and typical radiologic features supported the diagnosis and obviated the need for an invasive biopsy. However, we observed worsening of osseous changes on CT imaging after treatment was initiated despite simultaneous improvement in the patient’s clinical condition and serology. The soft tissue and dural findings on imaging indicated a clinical-radiologic lag. This lag likely reflected ongoing localized inflammation without new bone deposition, and serial imaging out to 2 years showed ongoing improvement. Recognizing that clinical improvement often precedes radiologic improvement may prevent premature discontinuation when treating syphilitic osteitis, periostitis, or osteomyelitis.

Optimal treatment of syphilitic osteitis and osteomyelitis is not well established in the existing literature, and no definitive guidelines exist. Both IM and IV penicillin have been used, and suggestions for duration of therapy are widely variable. These have ranged from 2 to 3 weeks of IV penicillin G when osteitis is associated with early syphilis, to 3 weeks of IM benzathine penicillin, or 6 weeks of IV penicillin or doxycycline when bony changes are found in association with later stages.1^,9 Other variations have included 3 weeks of ceftriaxone, or a combination of IV penicillin for 2 weeks followed by 3 weeks of weekly IM penicillin, similar to the regimen used in our patient, who preferred to avoid prolonged IV therapy.9 Rapid symptomatic relief is common with treatment, but osseous lesions can persist for as long as 1 year; in some case studies, no substantial radiographic changes in lesions were observed after therapy.5^,10 For treatment monitoring, most patients are followed with serial chemiluminescent microparticle immunoassays to ensure a fourfold decrease within 12–24 months.

The differential diagnosis for calvarial lesions is broad (Box 1).11 These alternative causes should be considered and evaluated as appropriate, based on a full history, physical examination, and review of systems. Bony involvement of early-stage syphilis should be considered, as incidence may be higher than previously appreciated. This may be related to increased ease of diagnosis based on improved radiologic modalities, along with potential increase in osseous syphilis in people living with HIV. It is important to consider syphilitic osteitis when assessing patients with bony pain, as misdiagnosis and delayed treatment can lead to permanent bony destruction. Frequent screening (i.e., every 3–6 months, considering high-risk encounters, immune status, and sexual practices) for syphilis is also important to identify the disease early on in its clinical course, given that many patients may present asymptomatically, especially as the incidence of syphilis continues to rise in Canada. Lastly, concomitant STIs like gonorrhea, chlamydia, and HIV are common and should be screened for. A diagnosis of syphilis should also prompt discussion of other preventive measures like HIV preexposure prophylaxis.