Secondary syphilis in an HIV positive patient

ORTEGA K, REZENDE NPM, WATANUKI F, ARAUJO N, MAGALHAES MHCG. SECONDARY SYPHILIS IN AN HIV POSITIVE PATIENT. MED ORAL 2004;9:33-8.

SUMMARY

The incidence of oral manifestations of HIV infection is changing markedly. Oral afflictions previously uncommon in HIV condition are now emerging in this scenario and may be underestimated.
Clinical characteristics of some oral diseases could change in the presence of HIV/AIDS infection and health care professionals must be made aware of such changes.
Oral lesions of secondary syphilis are rare, however they can occur and the dentist should be able to diagnose them. In some cases the anamnesis and the clinical features of the lesions are not enough to diagnose this disease. Histological features and an acute knowledge on laboratory exams, as well as its applicability and limitations are necessary to diagnose it.
The present report describes a case of secondary syphilis in an HIV positive patient. The patient showed red spots in the torso's skin and abdomen. The spots were also present on the hands but the color was darker. The oral mucosa had several ulcers, with variable shapes, sometimes recovered by a white and resistant membrane. They were present in the buccal mucosa, palate, gingiva, tongue and labial mucosa. Those clinical manifestations appeared 6 months earlier. Exams were performed (VDRL, FTA-abs, direct fungal exams in the skin and oral mucosa and a biopsy in the oral mucosa) but the diagnose remained unclear.
Clinical and laboratory features disagreed and postponed the final diagnosis and the treatment for more than 6 months.

Key words: Syphilis, HIV, AIDS, secondary syphilis, oral syphilis.

INTRODUCTION

For centuries humanity has been afflicted by syphilis, an infectious disease whose incidence has varied considerably over the last century in the global population (1,2). The incidence of syphilis has been reduced by the use of antibiotics, and the numbers of deaths and hospitalized patients with sequels of the infection have declined (3,4).

Many countries have implemented programs to eliminate syphilis, and have developed epidemiological surveillance systems to monitor the efficiency of such programs. For example, today, the United States has the lowest rate of syphilis notification since 1941, when notification started (2). Unlike the United States, other countries have encountered difficulty in syphilis management and control. In Brazil, sexually transmitted diseases are a public health problem recognized by the Ministry of Health. Despite the fact that the incidence of these diseases is increasing in an alarming manner, notification (with the exception of AIDS and congenital syphilis) is not mandatory. Even congenital syphilis, for which an elimination program was implemented only in 1993, has a very high rate of non-notified cases (4).

The prognosis of patients infected by Treponema Pallidum is directly related to an early diagnosis and efficacy of treatment. Dentists play a very important role in the diagnosis of acquired syphilis whether primary or secondary, and in the identification and management of manifestations of congenital syphilis (5,6).

When the global HIV/AIDS epidemics began, an increase in diagnosed syphilis cases was reported, and difficulty encountered by professionals to diagnose and treat this disease became more evident (7-14). Oral syphilis lesions are uncommon and may be confused with other pathologies that affect HIV patients more frequently (15). There are few reports in the literature, and difficulty in interpreting laboratory tests in patients with an altered immune system response may also be responsible for a late diagnosis, as well as for some undiagnosed cases (16).

The aim of this report is describe a case of secondary syphilis in an HIV positive man whose clinical and laboratory findings disagreed, leading to postponement of the final diagnosis and appropriate treatment for more than 6 months.

CASE REPORT

A 35 year-old, white male was referred by his doctor to the Special Care Dentistry Center of the School of Dentistry at the University of São Paulo (CAPE-FOUSP) in order to diagnose several oral lesions.

During the anamnesis, the patient reported being HIV seropositive since 1990. He related an episode of syphilis and gonorrhea 17 years previously and recently he suffered hepatitis, anemia and four episodes of pneumonia. Antiretroviral therapy was begun in 1992 with monotherapy (AZT) and was substituted in 1997 by two nucleoside reverse transcriptase inhibitors and a protease inhibitor, drugs that he is currently using. The patient noted that painful, vesicular and ulcerated lesions appeared in his mouth six months ago, three weeks after an important labial herpes episode. The lesions have persisted since then. Palm-plantar lesions, red spots on the torso, and genital lesions have followed the oral lesions. The patient reported that he had been treated by his physician for 6 months with thalidomide, acyclovir and topical and systemic corticoids, but no favourable change in his clinical features was noted. A blood cell count, VDRL, FTA-abs, blood culture for mycobacterium, direct fungal exams on the skin and oral mucosa, and a biopsy of the oral mucosa (with an immunohis-toquimical study for herpes) were performed. Unfortunately, after all these examinations, the diagnosis was still unclear.

During the exams performed at CAPE, light red spots on the skin of the torso and abdomen were observed (Figure 1-F). The hands exhibited intense red spots with central desquamations (Figure 1-E). A palpable soft, painless and mobile lymphnode of 1 cm in diameter was present in the cervical region. Scurf was noted in the moist portion of the lips (Figure 1-A). The oral mucosa presented several shallow ulcers, of irregulars contour although of definite limits and variable shape, sometimes covered by a white resistant membrane. The ulcers were present in the buccal mucosa, palate, gingiva, tongue and labial mucosa (Figure 1-B, C and D).

A biopsy was performed on an ulcerated lesion in the buccal mucosa: the clinical hypotheses were erythema multiforme and secondary syphilis. The material was fixed in formaldehyde and sent to the Surgical Pathology Laboratory of the Oral Pathology Department in the Dentistry School at the University of São Paulo.

The histopathological exam revealed an ulcerated epithelium with an underlying lamina propria exhibiting an increased number of vascular channels and an intense, chronic, inflammatory, perivascular reaction. The histopathological diagnosis was of an unspecific inflammatory process.

The VRL and FTA-abs tests were repeated in the patient. The result of the VDRL test was 1/128, and the FTA-abs test was positive. As a consequence of the clinical and laboratory features, a final diagnosis of secondary syphilis was made. The treatment proposed was 3 doses of penicillin G (2,400,000) once a week.

Six days after beginning treatment, the oral lesions disappeared completely, only the skin lesions remaining. The patient returned 20 days later (he had already received two doses of penicillin G) and, although less intense, the skin lesions persisted. One year after beginning treatment, the skin lesions disappeared, although the patient still had a positive VDRL titer of 1/64.

The patient's CD4 count was 329 cells/mm³ at the beginning of treatment and showed a gradual increase to 600 cells/mm³ after 6 months. The viral load was 2,900 copies/ml (log 3.46) before the syphilis lesions appeared, increasing to 21,000 copies/ml (log 4.32) when the first oral and skin lesions appeared, reaching 37,000 copies/ml (log 4.56) two months later.

Today the patient is clinically stabilized with CD4 counts 464 cells/mm³, a viral load of 14,000 copies/ml and a VDRL titer of 1/16.

DISCUSSION

The final diagnosis of any stage of syphilis is based on historical and clinical data supported by laboratory tests.

In secondary syphilis, the clinical features of the lesions and the patient's anamnesis can lead the professional to propose other diagnostic hypotheses. The main differential diagnoses include aphthous ulcer, candidiasis, lichen planus, lupus erythematosus, erythema multiforme, erythroleukoplakia, and squamous cell carcinoma. In the HIV positive patient, autoimmune diseases and hypersensibility reactions to drugs must be contemplated when oral lesions appear associated with skin lesions. These diseases and responses, particularly drug reactions, seem to be more common than secondary syphilis cases (17-20).

In the present case, the anamnesis suggested that two different factors may have been involved in the etiology of erythema multiforme: the herpetic infection and the change of antiretroviral drugs. The negative VDRL at the time of appearance of the lesions favoured the hypothesis of erythema multiforme.

It is important to emphasize certain characteristics of the laboratory exams for syphilis. Usually histological sections stained with hematoxylin-eosin are sufficient to diagnose primary syphilis. However, the non-specific, microscopic aspects of secondary syphilis emphasize the need for complementary exams. Darkfield examination is recommended to diagnose cases of skin syphilis lesions (mostly secondary syphilis), and this technique therefore should not be used on oral tissues. The large number of other spirochetes present in the oral mucosa and the difficulty in differentiating them from T. pallidum make this technique unsuitable for diagnosis in this location (21).

Nontreponemal reactions to syphilis are useful to identify a current infection, gradually decreasing their titers until cure of the patient. Treponemal reactions are positive for the patient's life, a fact which restricts its ability to make an indefication of previous infections: the reaction is not adequate to diagnose a current infection, even though the patient's first VDRL serological test may be negative. Some authors explain this fact in HIV positive patients by raising the hypothesis of circulating antibodies deficiency. An alternative explanation is the Prozone phenomenon, in which the quantity of antibodies produced is so high that the dilutions used in the nontreponemal tests are insufficient for diagnose. This hypothesis was more likely in the present case since the patient's second VDRL test titer was higher than 1/128 (22).

The variations seen in the plasma CD4 levels and in the HIV viral load suggest that opportunistic infections can disadvantageously alter the course of HIV infection.

Syphilis treatment must be followed by nontreponemal tests. After each administration of penicillin G, antibody titers must become lower, until they cannot be identified. This usually occurs within one year of beginning treatment. The HIV seropositive patient may exhibit greater difficulty in reacting favorably to treatment, and a greater number of doses may be necessary until cure. These patients require continued observation and periodic testing since immunodepression may reactive the syphilis, even after treatment.

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