Syphilis clinical features
Syphilis differential diagnosis
Syphilis diagnostic procedure
Syphilis has been a persistent public health challenge for
centuries, and is once again the focal point of study because
of its co-infection association with HIV. It is a systemic disease
caused by the spirochete Treponema pallidum. Spirochetes are
slender, spiral, motile bacteria of the order Spirochaetales,
most of which are pathogenic. Syphilis is passed from person-to-person
through direct contact with a syphilis sore called a chancre.
Chancres mainly occur on the external genitals, but may also
occur on the lips and in the mouth. If untreated or ignored,
the condition can progress to a chronic systemic disease.
The frequency of syphilis in the general population goes in
cycles. During the latter half of the 1980s, the most recent
syphilis epidemic peaked throughout the United States. This
particular syphilis epidemic was apparently associated with
increased crack cocaine use. In 1991, the number of reported
cases of primary and secondary syphilis began to decline for
the first time since 1985. With a national awareness drive,
the number and rate of syphilis cases dropped and the number
of cases reported in 1999 were the lowest ever reported in the
At least four factors may have contributed to the recent decline
- Increased state and federal programs for syphilis control
- Implementation of HIV prevention activities
- Decrease in the use of crack cocaine
- The presence of acquired immunity in the at-risk population following the epidemic.
Syphilis typically has three stages – primary, secondary,
and late (tertiary), with different symptoms at each stage of
the infection. Scalp hair loss does not occur in primary syphilis
unless there is a primary lesion (usually an eruption comprising
of papules and scales) on the scalp. This imperceptible hair
loss can easily be overlooked by the patient, and careful evaluation
of hair loss by the experienced clinician is of utmost importance
to diagnosis. However, in the secondary and tertiary stages
of syphilis, hair loss is common and obvious.
“Moth-eaten” alopecia is the most typical look
of secondary syphilis on the scalp. This hair loss in its classic
form resembles a somewhat diffuse and patchy alopecia areata
(patches of hair loss with ragged edges to the alopecia spots).
There may be hair loss from the eyebrows, and a patchy alopecia
in the beard and other hair-bearing areas of the body is also
Apart from the recognizable moth-eaten alopecia of secondary
stage of syphilis, a less well-known pattern of diffuse hair
loss associated with secondary syphilis is called essential
syphilitic alopecia. This type of hair loss occurs in the absence
of any other cutaneous signs of syphilis and resembles the diffuse
hair loss pattern as seen in telogen effluvium.
A third form of hair loss is associated with the nodulo-ulcerative
cutaneous lesions found in patients with lues maligna. Lues
maligna is a rare ulcerative form of secondary syphilis characterized
by papulopustular skin lesions that rapidly enlarge and evolve
into round or oval ulcers with sharp borders, centrally covered
by a dark crust. This noduloulcerative or papulopustular presentation
of secondary syphilis may affect the scalp as well as other
areas of the body. From the histological aspect, this condition
is a necrotizing vasculitis and occurs more in patients with
HIV infection. When scalp involvement is severe, destruction
of the hair follicle with subsequent scarring may occur. There
also seems to be a correlation between the papulopustular type
and the development of neurosyphilis, which is syphilis that
has reached the central nervous system.
Tertiary or advanced stage of syphilis is characterized by
gumma which are small, rubbery granuloma in the skin having
a necrotic center and an inflamed, fibrous capsule. In such
cases, hair loss occurs in the area overlying the gumma.
The irregular moth-eaten type of alopecia on the scalp seen
in secondary syphilis resembles the diffuse pattern of hair
loss of patchy alopecia areata. The type of hair loss seen in
essential syphilitic alopecia occurs without any cutaneous signs
of syphilis and mimics the diffuse hair loss as seen in telogen
Microscopic examination of an area of patchy or diffuse alopecia
in a patient with secondary syphilis reveals an inflammatory,
non-scarring alopecia. Follicular changes include a decrease
in the percentage of hairs in the anagen (active) phase and
a corresponding increase in catagen (transitional stage of hair
cycle) and telogen (resting phase of hair cycle) hairs. The
infiltrate is described as a sparse, predominantly peribulbar,
lymphocytic, superficial perivascular infiltrate with scattered
plasma cells and fibrous tract formation.
In histologic examination of the scalp alopecia of lues maligna,
the nodulo-ulcerative form syphilis, the entire dermis shows
a perivascular, lymphohistiocytic infiltrate with epithelioid
histiocytic granulomata. In the center of the dermis, there
is a zone of degenerated collagen and an infiltrate consisting
of lymphocytes, histiocytes, neutrophils, and fragmented nuclear
particles. This pattern follows vessels that show varying degrees
of degeneration and necrosis of vessel walls. Throughout the
whole inflammatory reaction, plasma cells are predominant, and
the Warthin-Starry stain demonstrates many spirochetes.
Diagnosis of syphilis begins with a medical history and physical
exam. There are two classes of tests used for screening syphilis:
treponemal tests and non-treponemal tests.
Initial screening for syphilis is performed
with one of the non-treponemal antibody tests, the Venereal
Laboratory (VDRL) test, or the Rapid Plasma Reagin (RPR)
test. These tests are very sensitive, but not necessarily
for syphilis. Treponemal test antibody titers correlate
poorly with disease activity and should not be used to assess
response. False-positive non-treponemal results can also
occur in patients with connective tissue diseases.
- The specific treponemal tests include the Fluorescent
Treponemal Antibody Absorbed (FTA-ABS) and the Microhemagglutination
Assay for Antibody to T. pallidum (MHA-TP) tests. Compared
with non-treponemal tests, treponemal tests may be positive
in the course of infection.
However, the definitive method to detect T. pallidum is direct
visualization of the organism by dark field examinations
and direct fluorescent antibody tests of lesion exudates or
The direct fluorescent antibody test has greater specificity
and sensitivity than dark field examination.
The primary goals of clinicians in syphilis treatment are to
avoid disease progression and to prevent transmission. Penicillin
as a treatment option has been used in clinical settings for
a long time, and remains the cornerstone of syphilis therapy.
The standard recommendation for treatment
of all stages of syphilis is a weekly intramuscular injection
penicillin G of 2.4 million units for 1 to 3 weeks. Clinical
staging or serological staging (e.g. RPR or VDRL titers)
determines the treatment regime.
For patients with HIV co-infection,
2.4 million units penicillin
G intramuscularly is usually recommended plus anti-retroviral
drugs against the HIV.
Patients should be informed about
the possible adverse reaction called the Jarisch-Herxheimer
reaction. This is an acute
febrile reaction frequently accompanied by headache and other symptoms
that usually occur within the first 24 hours after any
therapy for syphilis. This reaction can usually be controlled with
corticosteroids or indomethacin.
Doxycycline 100 mg orally twice daily or
tetracycline 500 mg orally four times a day for 2 weeks
is a recommended
treatment option for patients who are allergic to penicillin, as an
alternative treatment regime.
Follow-up cultures or serologic studies
should be obtained after completion of therapy. If signs
or recur, or if there is a sustained increase in non-treponemal test
titers, the treatment has most likely failed to cure the patient;
it may also suggest that the patient has become re-infected
and requires re-treatment.
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