SYPHILIS
Syphilis has been well described in the literature since the late 1400s. The history behind the discovery and treatment of the disease is a story of perseverance and the willpower of many scientists working separately and together to help treat one the most deadly diseases of their time. Philip Ricord, a French scientist, is given credit for describing the three stages of syphilis and differentiating it from other diseases such as gonorrhea. The infectious organism, Treponema pallidum, was described in 1905 by Fritz Schaudinn, a German zoologist, and Erich Hoffman, a German dermatologist. Soon after this discovery, the German scientist Paul Ehrlich developed the first specific therapy for syphilis. The oral medication he and his team discovered was initially called 606, because it was the 606th compound they had attempted to use to treat the disease. This organoarsenic molecule was soon renamed salvarsan. This medication is highly effective against T. pallidum.
T.
pallidum is
classified as a spirochete. Spirochetes are gram-negative bacteria that have a winding or coiled linear body.
There are three subspecies of T. pallidum; the one responsible for
syphilis is named Treponema pallidum pallidum. The other subspecies of T.
pallidum cause endemic syphilis or bejel, pinta, and yaws. Syphilis is a
highly infectious disease that is trans- mitted via sexual contact or
vertically from an infected mother to her unborn child. Syphilis has been
recognized to progress through three stages: primary, secondary, and tertiary.
Not all cases progress through all of the stages, and only about one third of
untreated cases eventually progress to tertiary syphilis. The secondary and
tertiary phases are interrupted by a latent phase of variable length.
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| SYPHILIS OF GENITALIA |
Clinical
Findings: Both historically and today, most cases of syphilis have been
transmitted via sexually intercourse. The disease is often seen in conjunction
with other sexually transmitted diseases (STDs), especially human
immunodeficiency virus (HIV) infection. The two infections may actually
facilitate each other’s infectious potential. There is no race or sex
predilection; the organism is able to infect any host with whom it comes in
contact. The initial infection in most cases results in clinical findings in
the genital region.
Primary
syphilis is marked by a nonpainful ulceration that begins as a red papule and
ulcerates over a period of a few days to weeks. The average time to onset of
the ulcer is 3 to 4 weeks after exposure, but it can occur 3 to 4 months later.
This primary ulcer, called a chancre, is firm to palpation. The ulcer can be found anywhere on the
genitalia, including the labia, vaginal introitus, and mons in females and the
glans, foreskin, and penile shaft in males. Lesions on the foreskin of males
often show the Dory flop sign. This occurs when one grasps the area of the
prepuce containing the ulcer and slowly retracts the proximal edge; after a
critical angle has been achieved, the entire ulcer flops over.
This occurs
because the ulcer is firm and does not bow under pressure. If left untreated,
these ulcers self-resolve within 1 to 3 weeks. After this occurs, the bacteria
hematogenously disseminate to other organ systems.
The timing
of secondary syphilis is variable: It can occur immediately after primary
syphilis or up to 6 months after the chancre of primary syphilis has healed.
The average
time frame is approximately 6 weeks after healing of the primary ulcer. Without
treatment, most if not all patients experience symptoms and skin lesions of
secondary syphilis. Patients universally complain of constitutional symptoms
such as malaise, fever, chills, fatigue, and weight loss. Cutaneous findings
can be multifaceted. The most prevalent skin finding is that of skin-colored to
red to slightly hyperpigmented papules and patches. The palms and soles are
characteristically involved, and this is a clue that the diagnosis of syphilis
should be entertained.
Condylomata
lata is
the name given to the moist plaques that develop in the groin region from
secondary syphilis. These lesions contain numerous T. pallidum organisms.
Adenopathy is almost always present. Some rare findings of secondary syphilis
include ulcers in the mouth, which can mimic aphthous ulcerations, and a
nonscarring alopecia. The alopecia has been described as having a “motheaten”
appearance. This is in reference to the random arrangements of patches of
alopecia. All the lesions of secondary syphilis contain the bacteria, and
samples can be taken and directly observed under darkfield microscopy. The
organisms are seen as mobile spirochetes with a spiral configuration. Patients
with secondary syphilis may have early central nervous system (CNS) involvement
and may complain of head- aches and other meningeal signs. Approximately 3 to 4
months after the first signs and symptoms of secondary syphilis appear, they
spontaneously resolve. This is the beginning of the latent phase, which is a
phase of wide variability. Some patients never develop tertiary syphilis, and
approximately 1 in 5 develop a recurrence of secondary syphilis.
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| SYPHILIS OF ORAL CAVITY |
Tertiary
syphilis follows the latent phase of syphilis in 30% to 40% of untreated
individuals. The average time from initial development to tertiary syphilis is
approximately 4 years. Tertiary syphilis can affect the skin, bone, and mucous
membranes. The characteristic skin finding is the gumma. Gummas appear
frequently as individual lesions, although a multitude of gummas may occur at
the same time. The gumma starts as a papule and then evolves into a nodule,
which ulcerates over the course of a few days to weeks. The ulceration is
caused by significant necrosis of the involved tissue. This leads to deep
ulcers with well-defined borders. The surface of the ulcer may be covered with
gelatinous exudates. Another form of tertiary syphilis is the nodular syphilid
skin lesion. These lesions are red to red-brown nodules that slowly enlarge and
can develop various
configurations, including serpiginous and annular formations. These lesions
rarely, if ever, ulcerate.
Unique forms
of syphilis that do not fit neatly into one of the categories already described
include neuro- syphilis, congenital syphilis, and late syphilis. Involvement of
the CNS by T. pallidum is termed neurosyphilis. Neurosyphilis can occur
during any of the numerous forms and stages of syphilis. It is caused by direct infection of the CNS by
the spirochete. Most patients with syphilis exhibit no signs of CNS
involvement, even when the bacteria can be isolated from the CNS. However,
almost all of these cases of asymptomatic neurosyphilis eventually progress to
symptomatic clinical illness. Some of the common symptoms of neurosyphilis are
headache, hearing difficulty, neck stiffness, and muscle weakness. As the
disease progresses untreated, patients develop seizures, delirium, and tabes dorsalis.
Tabes dorsalis results from degeneration of the posterior columns of the spinal
cord. The posterior columns are critical for proper sensation, and patients
with tabes dorsalis develop gait disorders, diminished reflexes, proprioception
abnormalities, pain, paresthesias, and a host of other neurological symptoms.
If neurosyphilis remains untreated, the patient dies of the disease. Therefore,
any patient who exhibits signs or symptoms of neurosyphilis should undergo a
spinal tap to evaluate the cerebrospinal fluid for involvement with T.
pallidum.
Congenital
syphilis occurs as the result of vertical transmission from an infected mother to her unborn fetus. Up to one
third of infected neonates die of the disease. In neonates who survive, the
disease manifests in many ways. Neonates may present with macerated erosions
associated with cachexia and failure to thrive. “Snuffles” is the term used to
describe the chronic runny nose with a bloody purulent discharge. Rhagades are
one of the most common signs seen in congenital syphilis; they appear as
scarring around the mouth and eyes. Many bony abnormalities have been reported,
including a saddle-nose deformity, the Higoumenakis sign (medial clavicular
thickening), saber shins, and Clutton’s joints. Teeth abnormalities include
Hutchinson’s teeth (notched incisors) and, less frequently, mulberry molars.
Histology:
Skin
biopsies of syphilis that are evaluated with routine hematoxylin and eosin
(H&E) staining show varying features depending on the stage and form of
disease being biopsied. A universal finding in all forms is the presence of
numerous plasma cells within the inflammatory infiltrate. Ulceration,
granulomas, and vasculitis are often encountered. The spirochetes cannot be
appreciated with routine H&E staining; special staining techniques are
required. The Steiner stain and the Warthin-Starry stain are the two most
commonly used stains. Immunohistochemical stains can also be used, and they
have been shown to be highly sensitive and specific.
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| SYPHILIS IN PREGNANCY |
Pathogenesis:
Syphilis
is caused by the spirochete, T. pallidum pallidum. This bacteria is
highly infective and is predominantly spread by sexual contact and by
transmission from an infected mother to her unborn child. Treatment: The
T. pallidum organism has very little antibiotic resistance, and the
therapy of choice is still penicillin. A single intramuscular dose of 2.4
million IU of benzathine penicillin G is recommended, and some now recommend a
follow-up dose—the same as the initial dose—at 1 or 2 weeks. Patients who
develop neurosyphilis need to be treated with intravenous penicillin for at least
2 weeks. Most patients who are treated for syphilis develop the Jarisch-Herxheimer reaction.
This reaction is the result of the decimation of the T. pallidum organisms
due to therapy with penicillin. As the scores of bacteria are killed, the dead
spirochetes induce an inflammatory reaction. This reaction may manifest as
fever, chills, fatigue, malaise, and rashes of varying morphology. It can often
make the rash of secondary
syphilis appear worse for a period of time. This reaction is not specific to T.
pallidum and has been reported with other infectious agents. It is critical
to follow patients long enough after therapy ensure adequate treatment as
measured by titers on rapid plasma reagin (RPR) or venereal disease research
laboratory (VDRL) testing. All patients with syphilis should be tested for HIV.
