Braz Dent J (1999) 10(2): 117-121  ISSN 0103-6440

| Introduction | Case report | Discussion | Acknowledgments | References |

This paper describes a case of benign tertiary syphilis represented by a solitary hypertrophic lesion on the dorsum surface of the tongue. The diagnosis was confirmed by serologic tests (VDRL and FTA-ABS). Histopathological analysis of biopsy specimens revealed, in the lamina propria, the presence of well-developed granulomas associated with necrotic areas (gummatous lesion). Currently, tertiary syphilis is rarely seen; however, this case emphasizes that it still exists and must be considered in the differential diagnosis of inflammatory oral lesions.

Key words: tertiary syphilis, tongue, granuloma.

Introduction

Acquired syphilis in adults has once again become an important public health problem. The disease has become more common and has been linked epidemiologically with human immunodeficiency virus (HIV) infection (Brandt, 1988; Felman, 1989; Singh et al., 1999). For therapeutic procedures, syphilis is divided into a series of clinical stages. Primary syphilis, the earliest stage, is characterized by the presence of lesions at the site of Treponema pallidum entry and subsequent development of regional lymphadenopathy. In secondary syphilis, which occurs about 2 to 10 weeks after infection, hematogenous dissemination of Treponema pallidum causes several systemic findings, including fever, malaise, generalized lymphadenopathy and mucocutaneous lesions (papular, macular, annular or follicular lesions). The signs and symptoms of primary and secondary syphilis resolve spontaneously and patients then enter the latent stage of infection (Anderson et al., 1989; Hutchinson and Hook, 1990). After a variable period of latency, tertiary or late stage disease develops in about one third of untreated patients. Manifestations may take up to 10 years to appear and then present themselves as benign tertiary (gummatous lesions), cardiovascular syphilis, or neurosyphilis (Hook and Marra, 1992). Fortunately, manifestations of tertiary syphilis have become rare due to the development of programs that control sexually transmitted diseases and the inadvertent therapy with antibiotics administered for other pathologic conditions.
In this report, we describe a case of benign tertiary syphilis represented by a solitary lesion of the tongue which was difficult to diagnose because it seldom occurs.

Case Report

A 35-year-old man with a chronic hypertrophic lesion on the dorsum surface of the tongue was referred to the School of Dentistry of the Federal University of Juiz de Fora, State of Minas Gerais, Brazil. The patient reported that he had noted the presence of the lesion one year before and immediately sought medical care at a private dermatology clinic. At that time, an incisional biopsy was made and after histopathological analysis the lesion was interpreted as a possible manifestation of Paracoccidioidomycosis (South American Blastomycosis), a granulomatous inflammatory fungal disease that is found particularly in Brazil, where it can be endemic in the states of São Paulo, Rio de Janeiro and Minas Gerais. However, therapy with itraconazole did not show a significant clinical result.
The patient’s medical history revealed the presence of periodic manifestations of herpes simplex labialis recurrent. The patient denied a history of blood transfusion or intravenous use of drugs. He related that he had only his wife as a sexual partner for the last 10 years. No lymphadenopathy, fever or skin lesions were observed.
The oral examination revealed the presence of a hypertrophic, red, painful and circumscribed tongue lesion (Figure 1). Biopsy for histopathologic examination and smears for bacterial and fungal cultures were taken. No microorganisms were seen with either Gram’s or periodic acid Schiff stain of the smears. No fungus was detected by culture. However, the microscopic analysis of the histologic slides, stained with hematoxylin-eosin, revealed the presence of well-developed granulomas in the lamina propria, which were formed by groups of macrophages associated with epithelioid cells surrounded by cuffs of lymphocytes. Furthermore, frequently the presence of multinucleated giant cells and necrotic areas in the middle of granuloma were observed (Figure 2). No microorganisms were detected by additional histological stains including Grocott, Silver stain and Ziehl-Nielsen.
Although there was no direct evidence of an epidemiologic history of acquired immunodeficiency syndrome (AIDS), an enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was performed. The patient was HIV seronegative and there were no episodes of other forms of immunosuppression detected during his medical history. The Mantoux test (PPD) was not reactive. The VDRL serologic test showed a positive result (1:8). To confirm the serologic diagnosis, the fluorescent treponemal antibody absorption test (FTA-ABS) was performed and also showed a positive reactivity. Standard therapy specific to tertiary syphilis was initiated immediately (2.4 million units of penicillin G benzathine per week for 3 weeks for a total of 7.2 million units). A reduction of 80% of the lesion and disappearance of the clinical signs of inflammation were observed a week later. Additional clinical and laboratory examinations were performed for both the patient and his family. The patient did not present manifestations of cardiovascular or neurological syphilis. The patient’s wife’s VDRL and FTA-ABS tests were negative. After 2 years of follow-up, the patient did not present clinical or laboratory evidence of syphilis.

Discussion

Conclusive diagnosis of syphilis infection is based on confirmation of the clinical signs and symptoms with laboratory tests (Hart, 1986). This case presented diagnostic difficulties because of its clinical and histopathological resemblance to other pathologic conditions. Our diagnosis was confirmed by two serologic tests (VDRL and FTA-ABS). However, these tests are subject to occasional false positive results in patients without syphilis (Sparling, 1971). Several acute and chronic infections (tuberculosis, leprosy, malaria, viral hepatitis, mumps, measles, leptospirosis and bacterial endocarditis) may be associated with false positive reaginic tests (Hart, 1986). After a positive result with reaginic tests, sequential use of specific treponemal tests such as the fluorescent treponemal antibody absorption test (FTA-ABS), the microhemagglutination assay to Treponema pallidum (MHA-TP), and the hemagglutination treponemal test for syphilis may be indicated to confirm diagnosis.
In the present case, the data obtained from patient anamnesis indicated that the Treponema pallidum transmission occurred at least 10 years before the patient had noted the first signs of the disease. Patients with tertiary syphilis may have no remembrance of lesions during earlier stages of the disease, because in many cases the lesions of primary and secondary syphilis may not have significant clinical findings. Furthermore, this patient reported the presence of herpes simplex labialis recurrent, thus it is possible that he recognized syphilitic lesions as a herpes simplex virus (HSV) manifestation.
Treponema pallidum is usually transmitted through sexual intercourse. Epidemiological studies with the sexual partners of patients with syphilis reveal an estimated infection risk in about one third of individuals exposed to patients with primary or secondary stage disease. On the other hand, sexual contact with patients who have latent and tertiary syphilis presented a lower infection risk (Schober et al., 1983; Schrijvers et al., 1989). The absence of Treponema pallidum infection in the patient’s wife may be explained by this low infection risk during sexual contact with tertiary syphilis patients.
The oral manifestations of primary and secondary syphilis are well described in the scientific literature (Raposo and Zallen, 1997). The apparent increase in orogenital sexual activity has resulted in an increase in primary oral lesions. Although the lesion formed at the site of Treponema pallidum entry may develop on the tongue, tonsils, hard and soft palate and buccal mucosa, the lips are the predominant sites. This lesion, called chancre, is characterized by the presence of a chronic painless encrusted ulcer, that heals spontaneously after some weeks and is highly infective. Maculopapular lesions and ulcers covered by mucous membranes are the most observed oral manifestation of secondary syphilis (Mani, 1982). The histopathological findings of primary and secondary syphilis lesions consist of a lymphohistiocytic infiltrate containing a variable proportion of plasma cells and proliferative endarteritis. In these stages of disease, the spirochetes in tissue can be easily detected by traditional silver stains, immunofluorescence, immunoperoxidase method using monoclonal antibodies against Treponema pallidum or electron microscopy (Jeerapaet and Ackerman, 1973).
Several studies have shown that syphilis may manifest as unusual skin and mucosal lesions in the HIV-infected patient usually associated with aggressive evolution of the disease (Glover et al., 1992; Anders et al., 1998). These unusual manifestations of syphilis are also often associated with unusual clinical and laboratory findings. It is possible that HIV-infected patients with proven secondary syphilis may have a negative serological test reactivity. Because of the unusual clinical findings and of the potential for altered results of serologic tests, it is frequently necessary to obtain a biopsy and subsequent identification of Treponema pallidum in tissue to confirm diagnosis (Tikjob et al., 1991). The oral presentation of syphilis in HIV-infected patients may also be atypical. Ficarra et al. (1993) reported a case of syphilis maligna in an HIV-infected patient that presented multiple coalesced ulcerations on the gum which progressed to form large crateriform ulcerations. This HIV-infected patient also presented skin ulcerations, fever, malaise, chills, and pain at the site of the oral lesions.
Manifestations of tertiary syphilis may appear after several years of no treatment of the disease with cardiovascular and neurologic involvement including severe manifestations of general paresis and aneurysm of the aorta. Furthermore, there is benign tertiary syphilis which is characterized by the tissue immunological reaction that leads to a specific lesion designed as gumma. These lesions are expressions of a destructive granulomatous inflammation that may develop in any organ (Hook and Marra, 1992). In the present case, the nodular lesion observed in the dorsum surface of the tongue was an expression of “gummatous inflammation” of tertiary syphilis. The histopathological examination of the tongue lesion biopsy stained with hematoxylin-eosin revealed the presence of many granulomas associated with the presence of necrotic areas which is a characteristic microscopic finding of gummas. In this type of syphilitic lesion, Treponema pallidum is considerably reduced which can explain the absence of microorganisms observed by us during histopathological analysis of the tongue biopsy stained with special silver stain. Finally, we emphasize that although tertiary syphilis is rare today it still exists and must be considered as one of the differential diagnoses of oral lesions.

Acknowledgments

The authors received a CNPq grant for this study.

References

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Correspondence: Prof. Dr. Fernando M. Aarestrup, Laboratório de Imunologia, Instituto de Ciências Biológicas (ICB), Universidade Federal de Juiz de Fora, Cidade Universitária, 36036-330 Juiz de Fora, MG, Brasil. Tel: +55-32-229-3851. E-mail: fmastrup@odonto.ufjf.br

Accepted May 25, 1999
Eletronic publication: April, 2000