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Establishing a diagnosis of syphilis, whatever the stage
of the disease, can be difficult because syphilis is a great
mimic in clinical morphology and histology. Many patients
infected with venereal diseases have oral manifestations,
but very few dentists and physicians have the proper experience
to diagnose syphilis or other STDs from oral lesions. Oral
secondary syphilis appears to be very uncommon, and few cases
have been reported over the recent past. We present 4 patients
who developed secondary syphilis-related oral lesions of moist
ulcers, irregular linear erosions termed 'snail-track' ulcers,
or erythematous mucous patches on the labial mucosa, buccal
mucosa, palate, or tongue. Concurrent human immunodeficiency
virus (HIV) infection was diagnosed in 1 patient. The histological
examination in 2 patients showed dense subepithelial inflammatory
cell infiltration comprised predominantly of plasma cells,
and it was of practical help in the diagnosis of syphilis.
The diagnostic value of a histological examination, serologic
tests, and treatment of syphilis are discussed. Obviously,
coinfection with HIV will complicate the clinical presentation,
diagnosis, and management of syphilis. Concurrent HIV infection
should be considered in any patient with a sexually transmitted
disease including syphilis. (Chang Gung Med J 2002;25: 683-8)
Key words: sexually transmitted disease, syphilis, oral ulcer,
HIV.
Present trends show a dramatic increase in sexually transmitted
diseases (STDs) in Taiwan, including herpes simplex virus
types 1 and 2, syphilis, gonorrhea, chlamydia, and HIV. A
great challenge to the dental profession is that many patients
infected with venereal diseases have oral manifestations.
Unfortunately very few dentists and physicians have the proper
experience to diagnose syphilis or other STDs from oral lesions.
A person with an STD is also at a high risk of HIV infection.
In addition the increased susceptibility to HIV infection,
persons coinfected with HIV and a STD are theoretically more
likely to transmit HIV to others. One reason for that is an
increase in vaginal and urethral discharge that occurs in
many patients with STDs. These discharges contain large numbers
of HIV-infected T-cells, which may make transmission of HIV
easier. In this study, we report on 4 patients with secondary
syphilis-related oral lesions, including 1 coinfected with
HIV.
CASE REPORTS
Case 1
A 58-year-old married man complained of a 4-week history of
ulceration of the lower labial mucosa on the left buccal mucosa.
The ulcers persisted despite treatment by other otorhinolaryngologists
and dentists. He developed a maculopapular skin rash close
to the external genitals at the same time. There was no other
relevant medical history.
Oral examination revealed moist ulcers on the lower labial
mucosa, irregular serpiginous linear erosions and ulcers with
a 'snail-track' appearance along the left buccal mucosa, and
an erythematous patch on the left border of the tongue (Figs.
1, 2). The lesions showed numerous small nodules below the
surface of the ulcers on palpation. He had cervical lymph
node enlargement on the left side and was afebrile. The histological
study revealed ulcers with superficial, bandlike, deeply perivascular,
diffuse, dense inflammatory infiltrate composed mainly of
plasma cells (Fig. 3A, B). This aroused suspicion of syphilis,
and the serological tests showed a positive venereal disease
research laboratory test (VDRL) (1:256) and Treponema pallidum
hemagglutination test (TPHA) (1:5120). This was consistent
with a diagnosis of secondary syphilis. The patient was referred
to the Division of Infectious Diseases, and his wife also
received penicillin treatment. Because of the social stigma
in dealing with venereal diseases and poor patient compliance,
he defaulted from follow-up after initial treatment.
Case 2
A 30-year-old unmarried man complained of a 1-year history
of recurrent erythematous mucous patches on the left buccal
mucosa and received many treatments without permanent relief.
He denied any systemic diseases. Both palms showed a deep-red
skin rash. He served as a bartender in a pub and had once
experienced unprotected sexual intercourse.
An oral biopsy was done with dense subepithelial inflammatory
cell infiltration comprised predominantly of plasma cells.
Serological tests of syphilis (STS) were positive by VDRL
(1:64) and TPHA (1:640). A secondary syphilis-related oral
lesion was diagnosed. He was referred to the Division of Infectious
Diseases. The oral lesion and skin rash resolved 2 months
later after weekly injections of 2.4ĦÑ106 units of Benzathine
penicillin G (BZN-PCN) for a total of 3 doses.
Case 3
A 38-year-old married woman complained of recurrent sore throat
and erythematous patches on the palate for several months.
She suffered from syphilis and had received an initial treatment
of 3 doses of 2.4ĦÑ106 units BZN-PCN by intramuscular injection
8 months previous. Another 2 courses of 3-week oral erythromycin
(250 mg 4 times daily) were given 4 and 6 months later due
to relapse of clinical symptoms and increased VDRL titer.
The STS showed positive VDRL (1:32) and TPHA (1:640) at that
point. She was referred to the Division of Infectious Diseases
to restart the entire 3-week course of BZN-PCN injections.
The oral lesions and sore throat resolved, with the VDRL declining
to 1:4 after 1 month.
Case 4
A 35-year-old man complained of a 5-month history of recurrent
oral ulcers and intermittent fever and diarrhea. Oral findings
showed irregular erythematous patches on the palate and left
buccal mucosa, linear erosion on the right buccal mucosa with
superinfection by miliary candidiasis, and heavy thrush on
the dorsal surface of the tongue. Herpes zoster on the left
thigh had been noted for several days.
He denied any previous systemic diseases. He had visited Chang
Gung Memorial Hospital due to pneumonia 7 months previous,
when atypical pneumonia was diagnosed. At that time, clarithromycin
was given, and his fever had subsided for several weeks. But
the fever recurred afterwards, and oral ulcers and thrush
bothered him very much during that period. He usually went
to local clinics for help, and a common cold was diagnosed.
Then he was referred to the Department of Oral Medicine of
Chang Gung Memorial Hospital. STDs were highly suspected.
He used to live in Japan and had had unprotected sexual exposure
with many prostitutes there. The laboratory tests were positive
for HIV, VDRL (1:8), and TPHA (1:160). Blood tests showed
mild anemia, mild leukopenia, low CD4 counts of 59 cells/mm3,
and a very low CD4/CD8 ratio of 0.08. A diagnosis of AIDS
with syphilis was made. He was referred to the Division of
Infectious Diseases for antiretroviral therapy and BZN-PCN
injection. We recommended that his wife and previous sexual
partners be screened for possible HIV and syphilis infection.
After treatment, the oral lesions resolved, but oral candidiasis
recurred whenever the antifungal therapy was discontinued.
He is now hospitalized for further management.
DISCUSSION
The 4 cases illustrate the need for vigilance with suspected
STDs in the differential diagnosis of oral ulceration. It
is also important to exclude the possibility of more than
1 STD presenting at the same time. Other STDs often have a
much shorter period between infection and symptoms than HIV,
and they can serve as a marker for those more vulnerable to
HIV infection. Coinfection with HIV will complicate the oral
features of syphilis or other STDs and make a diagnosis more
difficult.(1-3) Oral health providers should have an understanding
of the natural history, oral manifestations, and management
of syphilis and HIV infection.
After initial exposure to infection with Treponema pallidum,
the primary chancre develops at the site of entry after an
incubation period of about 3 to 4 weeks. The chancre is a
round or oval ulcer with an indurated base which spontaneously
heals 1 to 5 weeks after appearing. Secondary syphilis-related
oral lesions usually manifest 6 to 8 weeks after disappearance
of the primary chancre and are often accompanied by systemic
symptoms and signs including fever, sore throat, anorexia,
headache, generalized lymphadenopathy, and a maculopapular
skin rash. It can be recurrent during a period of 8 weeks
to 3 years after initial infection if treatment is not sufficient.
Then it becomes latent and enters the tertiary syphilis or
neurosyphilis stage. The oral features of secondary syphilis
can be painless or painful erythematous lesions, grayish-white
mucous patches, or irregular linear erosions termed 'snail-track'
ulcers.(4-7) They are often confused with aphthous ulcers,
infectious diseases, or nonspecific erosions and ulcers. Secondary
syphilis-related oral lesions are highly contagious. It is
wise for clinicians to wear protective rubber gloves while
examining patients presenting with undiagnosed oral lesions
in order to avoid not only syphilis, but also other infections
including AIDS. The common oral features of HIV infection
are oral candidiasis, hairy leukoplakia, HIV-associated gingivitis/periodontitis,
and Kaposi's sarcoma. In this report, case 4 presented with
recurrent erosion on the bilateral buccal mucosa and erythematous
patches on the palatal mucosa, which were superinfected with
Candida, leading to a diagnosis of coinfection of HIV.
A diagnosis of syphilis, at whatever stage of the disease,
might not be easy because it is a great mimic clinically and
histologically. Alessi et al. reported that there was an excellent
correlation among histologic findings, clinical appearance,
and duration of syphilis in their 33 cases.(8) In the early
stage, plasma cells were absent, and there was only sparse
superficial infiltrate; but as the disease progressed, dense
superficial and deep infiltrate with abundant plasma cells
became predominant.(9) The pathological findings of the 2
patients in that study illustrated the importance of oral
biopsy in the diagnosis of secondary syphilis.
STS are absolutely necessary to establish a diagnosis of syphilis
at any clinical stage. But a diagnosis of syphilis cannot
be made on the basis of only 1 set of STS alone. Which of
these tests appears positive depends on the clinical stage
of syphilis. The STS are either non-specific (nontreponemal
test) or specific (treponemal test). Commonly used for nonspecific
tests is VDRL and the Rapid Plasma Reagin (RPR) test. The
specific tests include TPHA and the fluorescent treponemal
antibody absorption (FTA-ABS) test. The best combination of
tests for screening of syphilis is VDRL/RPR plus TPHA or VDRL/RPR
plus TPHA and FTA-ABS once per month for at least 4 months,
because 35% latent syphilis shows a negative VDRL test, and
primary syphilis often is seronegative except FTA-ABS.(10-13)
A rising titer of VDRL or RPR may be indicative of a recently
acquired infection, a reinfection, a relapse in sero-fast
individuals, or late syphilis. The findings of a clinically
suspicious lesion and a reactive nontreponemal test are sufficiently
specific for syphilis that a routine confirmation test is
not necessary. Following therapy, the VDRL or RPR titer tends
to become negative and is useful for monitoring treatment.
However, unlike the VDRL test, the specific tests often stay
positive for life in spite of adequate treatment and cannot
be used to monitor response to treatment. This condition is
called a serological scar. Therefore, a definite diagnosis
of syphilis will depend on correlating all the historical,
clinical, and STS results and histological findings if possible.
In this study, the variable values of VDRL and TPHA accompanied
by different degrees of clinical symptoms in these 4 patients
were compatible with a diagnosis of secondary syphilis.
The category "early syphilis" includes primary,
secondary, and latent syphilis of less than 1-year's duration.(14)
Treatment failure in early syphilis is defined as failure
of the nontreponemal test to decline 4-fold (equivalent to
2 dilutions; for example, from 1:16 to 1:4, or from 1:64 to
1:16) within 6 to 12 months after treatment, or a 4-fold increase
in titer at any time; a patient with this situation should
undergo serologic follow-up at 6, 12, 18, and 24 months after
completion of treatment. Many retrospective studies on the
results of treatment with BZN-PCN in patients with primary
or secondary syphilis cited a failure rate of 5.0%.(15-17)
HIV-infected persons with early syphilis should receive the
same therapy as an HIV-seronegative individual.(18-20) A stable
or rising titer during the observation period may suggest
inadequate therapy, reinfection, or a false-positive serology.
However, patients treated for latent or late syphilis may
be sero-fast, so that failure to observe a titer fall in these
patients does not indicate a need for retreatment except when
clinical symptoms recur, as with patient 3 in this study.
Syphilis is well known for its diversity of clinical manifestations.
For this reason oral syphilis needs to be considered and investigated
in any patient who presents with what might at first look
like a common clinical problem, such as a nonspecific oral
ulceration or rash. Furthermore, it is emphasized that coinfection
with HIV is not uncommon in patients with other STDs.
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