Tertiary Syphilis Deaths -- South Florida

From January 1984 through July 1986, CDC received reports from three counties in south Florida of 18 persons considered to have evidence of tertiary syphilis at autopsy. Based on histologic review at CDC, eight had evidence strongly suggestive of syphilitic aortitis, and three showed cerebral chronic perivascular inflammation consistent with central nervous system syphilitic involvement. Seven were not confirmed on histologic review at CDC. Of the 11 cases consistent with tertiary syphilis, nine were reported by the medical examiners of Broward County, one by the medical examiner of Collier County, and one by a pathologist in Dade County. The Broward County cases were reported when the overall proportion of tertiary syphilis among persons autopsied by the medical examiners was 4 per 1,000.

The 11 decedents with evidence of tertiary syphilis ranged from 32 to 69 years of age at the time of death. Three of them were female. Six were white, and five were of other races. Seven of the 11 decedents had reactive postmortem microhemagglutination-Treponema pallidum (MHATP) serologic tests, and four had positive postmortem enzyme-linked immunoassay and Western blot tests for antibody to the human immunodeficiency virus (HIV). No postmortem blood was tested for one of the decedents.

To determine what factors may have been associated with evidence of tertiary syphilis at autopsy, a case-control study was performed. Data on the 11 reported decedents were compared with data on 29 autopsied decedents with positive postmortem MHATP tests but no evidence of tertiary syphilis. The two groups were not significantly different in terms of age, race, sex, or intravenous drug use. HIV infection was not significantly associated with tertiary syphilis--four of the decedents with tertiary syphilis and 10 of those in the comparison group had serologic evidence of HIV infection confirmed by Western blot (odds ratio (OR) = 1.3, exact 95% confidence interval (CI) =0.2, 6.9) (Table 1).

The names of persons in both groups were cross-checked with the state syphilis registry; only three with tertiary syphilis and two in the control group were known to have received treatment in Florida for late syphilis (late latent in two and cardiovascular syphilis in one). These three decedents also had HIV infection. Reported by: L Tate, MD, R Wright, MD, Broward County Medical Examiners Office; H Schmid, MD, Collier County Medical Examiners Office; G Hensley, MD, Dept of Pathology, University of Miami/Jackson Memorial Medical Center; J Hill, Florida STD Control Program; C Konigsberg, MD, Broward County Public Health Unit; JJ Witte, MD, MJ Wilder, MD, Acting State Epidemiologist, Florida Dept of Health and Rehabilitative Svcs. Treponema Research Br, Sexually Transmitted Diseases Laboratory Program; Experimental Pathology Br, Div of Host Factors; AIDS Program, Center for Infectious Diseases; Epidemiology Research Br, Div of Sexually Transmitted Diseases, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: This study does not support the hypothesis that HIV infection modifies syphilis infection (1), as it appears to modify clinical manifestations of tuberculosis (2). While severe manifestations of late syphilis in persons with HIV infection have been observed previously (3,4), such manifestations have also been observed among other persons (5). Moreover, while iatrogenic and other non-HIV- related causes of immunosuppression often reactivate tuberculosis (6), rapid progression to and early mortality from tertiary syphilis have not been demonstrated in similar clinical circumstances. Animal experimentation and anecdotal case reports, however, suggest that suppression of cell-mediated immunity may result in an unusual distribution of syphilitic lesions (7) and possibly other unusual manifestations of syphilis (1,4).

A history of syphilis infection is common among persons with HIV infection. For example, homosexual men with AIDS have been shown to be significantly more likely to have a history of syphilis than are homosexual men without AIDS (8). This association has been interpreted to reflect behaviors that are likely to expose patients to HIV infections (9), although excess risk independent of such behaviors has been reported (8). Since these infections are common in the same populations, evidence of both at death, as found in the study presented here, would be expected to be a common event.

It is not unusual, particularly among persons autopsied by medical examiners and even in areas with a low prevalence of syphilis, to find evidence of tertiary syphilis at autopsy despite its being unsuspected during the decedent's life (10). In one study, 1% of a series of decedents autopsied by Danish medical examiners had evidence of active syphilitic aortitis (10). Cardiovascular syphilis diagnosed on autopsy may occur among relatively young persons (in two series of autopsies, the mean ages were 36 (11) and 52 (12)). However, as appreciated in the preantibiotic era (12) and noted in this series, the diagnosis may be difficult to confirm.

The possibility that penicillin treatment for syphilis may have failed in two HIV-seropositive patients during latency is disturbing. Failures of penicillin treatment to arrest syphilis infection are considered rare in early disease, though such failures have been reported (4,13). They have also been reported in treatment of late infection (14), when treatment failure is probably more common. Studies are currently underway 1) to identify risk factors for failure of the treatment for syphilis to prevent or effectively treat tertiary syphilis and 2) to evaluate the clinical and serologic responses to treatment for syphilis of persons with HIV infection.

Physicians who have diagnosed central nervous system, cardiovascular, or other unusual manifestations of syphilis in persons less than55 years of age are encouraged to report these findings through their state and local health departments to the Division of Sexually Transmitted Diseases, Center for Prevention Services, CDC. Pathologists diagnosing tertiary syphilis on autopsy are also encouraged to report such cases.

References

1. Johns DR, Tierney M, Felsenstein D. Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med 1987;316: 1569-72.

2. Rieder HL, Snider DE Jr. Tuberculosis and the acquired immunodeficiency syndrome (Editorial). Chest 1986;90:469-70.

3. Zaidman GW. Neurosyphilis and retrobulbar neuritis in a patient with AIDS. Ann Opthalmol 1986;18:260-1.

4. Berry CD, Hooton TM, Collier AC, Lukehart SA. Neurologic relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med 1987;316:1587-9.

5. Hoffman BF. Neurosyphilis in a young man. Can J Psychiatry 1981;26:68-70.

6. Sahn SA, Lakshminarayan S. Tuberculosis after corticosteroid therapy. Br J Dis Chest 1976;70:195-205.

7. Pacha J, Metzger M, Smogor W, Michalska E, Podwinska J, Ruczkowska J. Effect of immunosuppressive agents on the course of experimental syphilis in rabbits. Arch Immunol Ther Exp 1979;27:45-51.

8. Moss AR, Osmond D, Bacchetti P, Chermann J, Barre-Sinoussi F, Carlson J. Risk factors for AIDS and HIV seropositivity in homosexual men. Am J Epidemiol 1987;125:1035-47.

9. Valdiserri RO, Brandon WR, Lyter DW. AIDS surveillance and health education: use of previously described risk factors to identify high-risk homosexuals. Am J Public Health 1984;74:259-60.

10. Asnaes S, Paaske F. Uncertainty of determining mode of death in medicolegal material without autopsy--a systematic autopsy study. Forensic Sci Int 1980;15:3-17.

11. Reddy DB, Ranganayakamma I. Syphilitic aortitis. Indian Heart J 1967;19:86-95.

12. Rosahn PD. Autopsy studies in syphilis. Atlanta, Georgia: US Department of Health, Education, and Welfare, Public Health Service, CDC, 1950.

13. Bayne LL, Schmidley JW, Goodin DS. Acute syphilitic meningitis: its occurrence after clinical and serologic cure of secondary syphilis with penicillin. G. Arch Neurol 1986;43:137-8.

14. Jorgensen J, Tikjob G, Weismann K. Neurosyphilis after treatment of latent syphilis with benzathine penicillin. Genitourin Med 1986;62:129-31.

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