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Polyostotic Osteitis in Secondary Syphilis in an HIV-Infected Patient

Boix, Vicente MD, PhD; Merino, Esperanza MD; Reus, Sergio MD, PhD; Torrus, Diego MD, PhD; Portilla, Joaquín MD, PhD

doi: 10.1097/01.OLQ.0000431351.50346.20
Case Report

We herein describe a case of secondary syphilis in a patient with HIV infection that presented with an unusually diffuse polyostotic osteitis with skull involvement. Syphilis has to be added to the differential diagnosis of extensive inflammatory bone pain in patients at risk, especially if pain worsens at night.

Secondary syphilis in a patient with HIV infection that presented as widespread polyostotic osteitis with skull involvement was described.

From the Unidad de Enfermedades Infecciosas, Hospital General Universitario de Alicante, Alicante, Spain

Conflicts of interest and source of funding: None declared.

Correspondence: Vicente Boix, MD, PhD, Unidad de Enfermedades Infecciosas, Hospital General Universitario de Alicante, Maestro Alonso 109, 03010 Alicante, Spain. E-mail

Received for publication February 8, 2013, and accepted May 7, 2013.

Syphilis remains a global problem with an estimated annual incidence of 12 million cases worldwide.1 In recent years, there has been a major resurgence in developed countries, in part, fueled by the epidemic of HIV infection.2 Clinical manifestations of syphilis were described in detail in the preantibiotic era, even defining the frequency of rare events such as osseus involvement.3 However, post-1950, these unusual manifestations became so exceptional that a clinician would rarely see any of them throughout his/her professional career. Moreover, the radiological characteristics of syphilitic lesions have only been described in detail in recent years.

We report a case of secondary syphilis in a patient with HIV infection that presented as polyostotic osteitis with skull involvement. That he was allergic to β-lactams (history of severe allergy and strongly positive allergic tests) turned treatment outcome very uncertain.

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A 40-year-old man of Cuban origin consulted in January 2012 for fever and headache. He had been diagnosed as having HIV infection in 2007, with a CD4 nadir in November 2008 (76/mm3) and was receiving tenofovir-emtricitabine and raltegravir. The CD4 count was 248/mm3, and the viral load was less than 20 copies/mL. The patient was allergic to penicillin with a history of Stevens-Johnson syndrome induced by oral amoxicillin. Syphilis serology result had been negative in 2007 and 2008.

In the last 2 months, daily episodes of throbbing holocraneal headache had appeared, mainly in the evening, followed by fever and sweating. He had lost 8 kg during this time, approximately 10% of his weight, and had been getting worse with neck tenderness and pain in ulnar and tibial regions and on the anterior half of the skull that became much worse with the onset of evening fever.

On physical examination, his temperature was 37.9°C, he was alert and oriented but in moderate discomfort. Multiple lymph nodes could be palpated all around his neck, less than 1 cm but exquisitely tender to palpation. Cervical motion was extremely painful, but the neck was supple. No skin lesions were found, but the painful areas in the scalp seemed faintly bulging. Laboratory test results were as follows: C-reactive protein was 13.3 mg/dL and CD4 was 343/mm3 (26%). Blood cultures were sterile. Syphilis serology results were as follows: rapid plasma reagin (RPR) was positive 1/256, syphilis IgM was positive, and fluorescent treponemal antibody absorption (FTA ABS) was positive. A lumbar puncture showed clear cerebrospinal fluid with proteins of 40 mg/dL, glucose of 57 mg/dL, leukocytes of 4 cells/mm3 (50% mononuclear cells), erythrocytes of 300 cells/mm3, FTA ABS being positive, and RPR being negative. A cranial computed tomography showed multiple lesions on the frontal bone with destruction of the outer table, of approximately 1 cm in diameter each (Fig. 1). Brain magnetic resonance imaging confirmed multiple, ill-defined, osteolytic lesions in the cranial vault with extension to adjacent subcutaneous tissue and thickening and contrast enhancement of the meninges. The finding of cranial lesions and pain in arms and legs led us to perform a bone scintigraphy with techetium 99m hydroxymethylene diphosphonate that showed pathological radiotracer uptake in the cranial vault, humerus, and ulna—in both medullar and cortical bone tissue—and also a bilateral cortical tibial uptake suggestive of hypertrophic osteoarthropathy.

Figure 1

Figure 1

Given the history of Stevens-Johnson syndrome induced by oral amoxicillin, an allergologic study was undertaken: skin test results were positive to aminopenicillins with delayed onset, at 6 to 7 hours, of intense dermatitis lesions with vesicle formation; cephalosporins and meropenem were negative. Tests were repeated after 7 days with minor antigenic determinants mixture of penicillin, cefazolin, and cefotaxime clear positivity and dermatitis occurrence of vesicles across the forearm surface. Meropenem skin test results were negative. Considering the uncertain negative predictive value of skin tests to meropenem, it was recommended to avoid all β-lactams. The patient was treated with doxycycline 100 mg by mouth twice a day for 16 weeks and azithromycin 1 g by mouth once a day in the first 10 weeks. Fever disappeared in a few days, but pain improved slowly over several weeks. Bone scan was repeated after finishing treatment and showed resolution of all foci of increased uptake. The final diagnosis was secondary syphilis with polyostotic osteitis involving the skull, humerus, ulnas, and tibias and A3 HIV infection. Serology was repeated 6 months after finishing treatment, RPR title had fallen to positive 1/2, syphilis IgM had turned negative, and FTA ABS remained positive.

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Bone involvement is common in treponemal infections and is a usual finding in congenital syphilis. It is also common in the secondary stage of yaws, where polyostotic periostitis and osteitis affect especially the radius, ulna, and phalanges, and has been reported to be present in 15% of patients.4 However, bone disease is rare, although well known, in acquired syphilis.

Secondary syphilis usually presents with rash, fever, and lymphadenopathy. During the early syphilis, spirochetes can produce hematogenous spread and reach the periosteum, Haversian canals, and bone marrow, resulting in periostitis, osteitis, or osteomyelitis.5 In 1942, a series of 10,000 cases of early syphilis found only 15 cases of destructive bone lesions (0.15%), and of these only 8 had cranial involvement.6 The incidence of bone disease in early syphilis was confirmed in more recent years. In other retrospective series of 854 patients diagnosed as having secondary syphilis for 20 years, only 2 cases were found (0.2%).7 In a series without radiological confirmation, the reported incidence of bone syphilis is higher, ranging from 4% in the antibiotic era8 to 24% in 1916.3 In recent years, more than two thirds of bone syphilis cases have been described in HIV-infected patients.9

Skeletal involvement generally affects long bones and manifests as pain, especially on the shins; cranial involvement is less common. Relatively constant symptoms are the worsening of bone pain at night and febrile accesses.10

The usual treatment of secondary syphilis is with benzathine penicillin G, but patients with severe allergy to penicillin represent a clinical challenge.11 Doxycycline and azithromycin are among the alternatives. There are no specific recommendations for the treatment of bone syphilis. In the few cases reported in recent times, there seems to be a tendency to prolong treatments: penicillin G intravenously for 4 weeks12 or 6 weeks,9 although other authors report good results with the standard approach.13–15 American recommendations for latent syphilis in patients allergic to penicillin support doxycycline for 4 weeks.11 For patients with advanced syphilis or pregnant female patients who are allergic to penicillin, desensitization is recommended, but in our case, desensitization was considered inadvisable because of severe risk. Given the extent of the disease, the HIV-associated immunosuppression, that neurological involvement could not be excluded with absolute certainty, that symptoms improved slowly (for 4 weeks), and the occasional resistance to azithromycin, we decided to use 2 antibiotics for a long time. This is, to the best of our knowledge, the first case of secondary bone syphilis treated and cured without β-lactams.

In summary, bone-affecting secondary syphilis is not entirely uncommon, especially in patients with HIV infection, and cranial involvement can happen—although not the most common. Polyostotic disease can occur, resulting in a very painful, disabling condition. Syphilis has to be added to the differential diagnosis of extensive inflammatory bone pain in patients at risk, especially if pain worsens at night.

In cases of severe allergy to penicillin and in the absence of β-lactam antibiotics, long antibiotic courses may be needed, although cure is possible.

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1. Gerbase AC, Roxley JT, Heymann DH, et al. Global prevalence and incidence estimates of selected curable STDs. Sex Transm Infect 1998; 74 (suppl 1): S12–S16.
2. Fenton KA, Breban R, Vardavas R, et al. Infectious syphilis in high-income settings in the 21st century. Lancet Infect Dis 2008; 8: 244–253.
3. Wile UJ, Senear FE. A study of the involvement of bones and joints in early syphilis. Am J Med Sci 1916; 152: 689–693.
4. Mitja O, Hays R, Lelngei F, et al. Short report: Challenges in recognition and diagnosis of yaws in children in Papua New Guinea. Am J Trop Med Hyg 2011; 85: 113–116.
5. Ehrlich R, Kricun ME. Radiographic findings in early acquired syphilis: Case report and critical review. AJR Am J Roentgenol 1976; 127: 789– 7 92.
6. Reynolds F, Wasserman H. Destructive osseous lesions in early syphilis. Arch Intern Med 1942; 69: 263–276.
7. Mindel A, Tovey SJ, Timmins DJ, et al. Primary and secondary syphilis, 20 years’ experience. 2. Clinical features. Genitourin Med 1989; 65: 1–3.
8. Waugh MA. Bony symptoms in secondary syphilis. Br J Vener Dis 1976; 52: 204–205.
9. Liu ZY, Zhang Y, Qiu KF, et al. Osteomyelitis as the only manifestation of late latent syphilis: Case report and literature review. Int J STD AIDS 2011; 22: 353–355.
10. Samarkos M, Giannopoulou C, Karantoni E, et al. Syphilitic periostitis of the skull and ribs in a HIV-positive patient. Sex Transm Infect 2011; 87: 44–45.
11. Workowski KA, Berman SCenters for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines 2010. MMWR Recomm Rep 2010; 59 (RR-12): 1–110.
12. Huang I, Leach JL, Fichtenbaum CJ, et al. Osteomyelitis of the skull in early-acquired syphilis: Evaluation by MR imaging and CT. AJNR Am J Neuroradiol 2007; 28: 307–308.
13. Coyne K, Browne R, Anagnostopoulos C, et al. Syphilitic periostitis in a newly diagnosed HIV-positive man. Int J STD AIDS 2006; 17: 421–423.
14. Gurland IA, Korn L, Edelman L, et al. An unusual manifestation of acquired syphilis. Clin Infect Dis 2001; 32: 667–669.
15. Kang SH, Park SW, Kwon KY, et al. A solitary skull lesion of syphilitic osteomyelitis. J Korean Neurosurg Soc 2010; 48: 85–87.
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