An Epidemiological Study of Syphilis Incognito, an Emerging Public Health Problem in Greece

Background  Syphilis incognito is a subtype of latent syphilis (early or late) characterized by no signs or symptoms of primary or secondary syphilis and diagnosed by positive serologic results for syphilis during routine screening.

Objective  To study the epidemiological characteristics, causes, and implications of syphilis incognito in Greece.

Patients and Methods  All new adult patients diagnosed as having syphilis in Andreas Sygros Hospital for Skin and Venereal Diseases, Athens, Greece, from 1989 through 1996 were studied prospectively and retrospectively (history, physical examination, serologic tests, cerebrospinal fluid examination, and imaging) to determine the stage of their disease. The epidemiological, clinical, and serologic characteristics of patients with syphilis incognito were recorded and analyzed.

Results  During the 8-year period, 711 new syphilis cases were detected; of these, 480 cases (67.5%) fulfilled the definition criteria of syphilis incognito. The male-female ratio was 1.8:1. Patients with syphilis incognito were most commonly heterosexual, had a median socioeconomic status, and were aged 20 to 39 years, and their conditions were diagnosed during routine screening for syphilis (prenatal care, hospital admission, or blood donation). However, the number of syphilis incognito cases appeared to decline during the period studied.

Conclusions  The incidence of syphilis in Greece has decreased dramatically, following the trends in western Europe. The most common form of syphilis is syphilis incognito, affecting adults who are older and have a higher socioeconomic status than those in the past. Improved hygiene and wide use of antibiotics that minimize or abolish symptoms of early disease may have contributed to the frequency of syphilis incognito in recent years. Screening of asymptomatic persons, especially those at high risk, should continue and be reenforced to prevent the devastating consequences of unrecognized and untreated syphilis.

DESPITE THE availability of an effective treatment, the development of reliable diagnostic techniques, and the implementation of broad-based preventive strategies, the eradication of syphilis still appears unattainable. During the second half of the 20th century, the overall global incidence rates of syphilis have been decreasing.¹ However, a resurgence of syphilis occurred in the United States in the late 1980s, and in the Third World, sexually transmitted diseases (STDs), including syphilis, represent a significant, ever-present public health issue.^2,3

Following the trends in western Europe, the incidence of syphilis in Greece has been declining since the 1950s.⁴ However, the presentation of the "great imitator" appears to have changed. In recent years, the majority of patients diagnosed as having syphilis in our hospital were completely unaware of when, where, how, or by whom they had been infected, reported no signs or symptoms consistent with primary or secondary syphilis, and were diagnosed as having syphilis accidentally during routine serologic screening. This subtype of latent syphilis (early or late), which runs a subclinical course from the time of infection until its diagnosis by routine serologic screening, has been referred to as syphilis incognito. Syphilis incognito is not a new variant of syphilis but represents an emerging problem that has not yet received the appropriate attention. The aims of the present study were to record the sociodemographic characteristics of patients with syphilis incognito and to discuss the magnitude, the causes, and the implications of the evolving clinicoepidemiological profile of syphilis.

We retrospectively and prospectively studied all new cases of syphilis in adults presenting to Andreas Sygros Hospital for Skin and Venereal Diseases in Athens, Greece, from January 1, 1989, to December 31, 1996. Individuals were either outpatients referred to us by various sources (dermatologists, STD clinics, general or maternity hospitals, or blood banks) or inpatients whose conditions were diagnosed from the results of laboratory workup at admission. Andreas Sygros Hospital for Skin and Venereal Diseases is the major referral center of STDs not only for the Athens metropolitan area but also for the entire country, particularly southern and central Greece. Syphilis screening in Greece continues to be broadly applied according to an obsolete law and occurs before blood donation, at admission to any general hospital, and before employment in food-handling services. Prenatal syphilis testing is not obligatory, but it is recommended by most obstetricians. In our hospital, all inpatients and outpatients with STDs are screened for syphilis.

Syphilis screening was performed using the Venereal Disease Research Laboratory (VDRL) test in combination with the qualitative microhemagglutination–Treponema pallidum (MHA-TP) test. The diagnosis was confirmed by both the fluorescent treponemal antibody–absorption (FTA-ABS) test and the quantitative MHA-TP test.

The evaluation of patients included obtaining a detailed history; conducting a clinical examination; investigating for T pallidum in serous transudate from lesions of early syphilis (if present) using a dark-field microscope; conducting qualitative and quantitative serologic tests for T pallidum using both cardiolipin and treponemal antigen tests; and, in patients with disease of unknown duration (presumably more than 2 years), performing posteroanterior and left oblique chest radiographs, cardiovascular examination, ophthalmologic and neurologic evaluation, and cerebrospinal fluid examination (cell profile, VDRL, and FTA-ABS). In those patients who had given their informed consent, a test for human immunodeficiency virus (HIV) antibodies was performed using enzyme-linked immunosorbent assay for screening and Western blot analysis for confirmation.

Disease stage was determined on the basis of history, clinical findings, and antibody titers. Asymptomatic patients with positive serologic results for syphilis were diagnosed as having latent syphilis, either early (duration less than 2 years) or late (duration more than 2 years). The diagnostic criteria for syphilis incognito included a diagnosis of latent syphilis based on the results of routine serologic screening, no history of signs or symptoms of early disease, negative results of a cerebrospinal fluid examination for neurosyphilis, and absence of cardiovascular or other tertiary disease manifestations.

For patients diagnosed as having syphilis incognito, the sociodemographic characteristics, sexual orientation and behavior, antibody titers, and sources of referral were recorded and analyzed.

From 1989 to 1996, 494 718 dermatovenereologic visits were recorded in the inpatient and outpatient clinics of Andreas Sygros Hospital for Skin and Venereal Diseases. During the 8-year period, 711 new syphilis cases were reported. The mean rate of syphilis among patients with venereal diseases was 2.2%, decreasing from 2.15% in 1989 to 0.9% in 1996.

Of the 711 patients with syphilis, 92 (12.9%) had primary syphilis, 64 (9.0%) had secondary syphilis, 528 (74.2%) had latent syphilis (early or late), 24 had neurosyphilis (3.4%), of whom 22 had asymptomatic neurosyphilis, and 3 (0.4%) had cardiovascular syphilis. Of those patients with latent syphilis, 480 (67.5%) had syphilis incognito.

Table 1 presents the distribution of cases of syphilis incognito by year of diagnosis. A declining trend is evident and agrees with the decreasing rates of syphilis in Greece. There were 309 men (64.4%) and 171 women (35.6%). The mean male-female ratio was 1.8:1, dropping from 3.4:1 in 1989 to 1.3:1 in 1996 (Table 1). Of the men, 287 were heterosexual and 22 were homosexual. In the cohort, 245 patients (51.0%) were married and 235 (49.0%) were single or divorced. Most patients were between 18 and 29 years (32.9%) and between 30 and 39 years (30.4%). The age distribution of the 480 patients with syphilis incognito is presented below.

Syphilis rates gradually tapered with age, except in patients older than 60 years. The occupation and sex of the patients with syphilis are displayed in Table 2. Among men, employees, sailors, and self-employed individuals predominated, while 14.4% were unemployed and 7.3% were prisoners. The majority of women were housewives (55.5%). The screening settings where the serologic diagnosis of syphilis was initially made are listed below. A notable proportion of patients were referred to us from general or maternity hospitals and blood banks, where screening for syphilis is a routine practice.

The results of the MHA-TP test were positive for syphilis in all 480 patients with syphilis incognito, while the results of VDRL were negative (false-negative) in 30 of the patients with syphilis incognito. The distribution of VDRL and MHA-TP titers at the time of diagnosis is presented below. Most patients had high MHA-TP titers, suggesting a relatively recent infection.

All patients with syphilis incognito had normal results of clinical and laboratory evaluations that included chest radiographs and cerebrospinal fluid, cardiovascular, ophthalmologic, and neurologic examinations.

Of the 480 patients, 6 (1.2%) declined HIV testing. Among those tested, there were 7 HIV-positive individuals (1.5%).

As the analysis of our results indicates, a majority of new adult cases of syphilis in Greece fulfill the diagnostic criteria of syphilis incognito. Our observations are in agreement with other reports in the literature. Only 35% of patients diagnosed as having early syphilis in Houston, Tex, reported noticing some symptoms of the disease.⁵ Thus, the remainder may be regarded as patients with syphilis incognito.

Despite a resurgence in the 1960s and a shorter and lower peak in the early 1970s, the incidence of syphilis in Greece decreased from 1953 to 1974.⁴ Data regarding early syphilis cases reported in our hospital from 1974 to 1998 indicate that the incidence rate remained low until 1982 and has dramatically declined thereafter, especially since 1991.⁶ In the past, syphilis in Greece was 3.6 times more common in males than in females. Young adults (younger than 25 years), especially sailors and workers, were predominantly affected.⁴

Our patients with syphilis incognito exhibited special sociodemographic characteristics. They were mostly heterosexual, middle-class, young adults, not only in their 20s, but also in their 30s. Male predominance was weak and decreasing. The disproportionate increase of women with syphilis incognito is probably an artifact phenomenon due to the implementation of preventive programs for congenital syphilis. Furthermore, women are more often identified through screening because they do not commonly have symptoms and, therefore, are less likely to seek medical advice. Half of the patients were married. A notable percentage of the patients were of median or high socioeconomic status. No association with homosexual orientation or illicit drug use was noted.

What causes the absence or masking of early syphilis manifestations in patients with syphilis incognito is still unclear. On the one hand, personal hygiene has improved, supporting the speculation that soaps or topical antiseptics may cause the primary chancre to stop developing or to heal rapidly. Coincidental use of antibiotics for some intervening cause may minimize or abolish symptoms of early disease, but the dose may be insufficient to cure syphilis. Despite educational efforts by physicians, antibiotics in Greece can be obtained without prescription and many individuals use them even in the absence of any clear indication. On the other hand, a subgroup of the patients with syphilis who do not report any signs or symptoms of early disease may not represent true syphilis incognito cases. Patients' memories are not always reliable; painless ulcers may be overlooked by women and homosexual men; and clinical manifestations of primary or secondary syphilis may be easily misdiagnosed by an inexperienced physician.

In general, the incidence of syphilis in Europe is low. A rise in the 1970s has been associated with homosexual transmission, and the decrease that followed resulted, probably, from changes in sexual behavior due to the acquired immunodeficiency syndrome epidemic.⁷ Resurgence of heterosexually acquired syphilis has been reported recently in areas of London, England, and Amsterdam, the Netherlands.⁸ In Russia, the incidence of syphilis showed a rapid and substantial increase during the 1990s. This increase may be due to socioeconomic perturbations leading to changes in sexual behavior and deterioration in STD surveillance and management.⁹ In the United States, an epidemic occurred in 1986-1987 that peaked in 1990 at a rate of 20.3 cases per 100 000.¹⁰ Syphilis has disproportionately affected urban minority populations, especially in the southern parts of the United States. Poverty, limited access to health services, prostitution, and illicit drug use have been recognized as important contributing factors.^2,11 Although the national rate for syphilis decreased to 8.1 by 1994, outbreaks continue to occur in the United States.¹²

The natural course of untreated syphilis may span the remainder of an individual's life.¹³ Latent-stage disease may persist or may give rise to clinical manifestations of tertiary syphilis after several years or decades (Figure 1). According to the Oslo study¹⁴ of patients with syphilis who were isolated, but otherwise received no treatment, in a hospital in the late 19th to the early 20th century, 15% of the patients developed late benign gummatous syphilis later in their lives, 10% had cardiovascular syphilis, and 8% experienced neurosyphilis. Nowadays, this progression appears to be less common, probably because of the wide use of antibiotics. Nevertheless, the international experience indicates that late syphilis still exists and appears to have increased during the last decade, often presenting in atypical unrecognized forms.¹⁵ Although syphilis is most infectious in its early stages, the long-term consequences of syphilis incognito, if it remains unrecognized and untreated, can be devastating since active disease will develop in as many as one third of the patients.¹⁴ Furthermore, detection and treatment of syphilis incognito in women is of paramount importance because of the risk of vertical transmission.¹⁶

Because of the declining incidence of syphilis in the developed countries, some authors have questioned the value of traditional routine screening of selected populations.^17,18 Snyder¹⁹ showed that serologic diagnosis of syphilis may not be reliable and cost-effective in groups with very low prevalence of the disease. In contrast, the emergence of syphilis incognito emphasizes the need for continuation of syphilis screening among asymptomatic individuals, especially those at high risk, such as sailors, military personnel, prostitutes, illicit drug users, homosexuals, patients with STDs, and pregnant women. Syphilis in most of the 480 patients in the present study probably would have remained undetected if the screening practices did not exist. To prevent and control syphilis effectively we must take into consideration the new clinicoepidemiological profile of syphilis and design programs and interventions that address the disease in the context of these changes.

Accepted for publication March 24, 2000.

Corresponding author and reprints: John D. Stratigos, MD, 28 Voukourestiou St, Athens 10671, Greece.