Syphilis – causes, symptoms, diagnosis, treatment, pathology

Treponema pallidum is a gram-negative bacterium
that causes syphilis. Syphilis is a sexually transmitted disease
that affects the skin and mucous membrane of the external genitalia, and also sometimes
the mouth. Treponema pallidum is an obligate parasite
bacteria, meaning they can’t survive outside a living body, more specifically outside of
a living body. To be more specific that’s the human beings
body. They belong to a group of bacteria called
spirochetes, which are long and thin, and contain endoflagella, which are a band of
protein filaments that coil within the spirochetes, and give them a spiral shape – kind of like
a curly fry, but less appetizing. The endoflagella also help the spirochetes
to move around by spinning or twisting, it’s a bit like a drill that’s slowly boring
into a piece of wood. People that have syphilis can transmit the
disease to others, in one of two ways. The first way is called acquired syphilis
and it’s when Treponema pallidum enters the body through body fluids. That can happen when there are tiny cuts,
or breaks in the skin or mucous membranes of the external genitalia or mouth and when
there’s sexual contact – including oral, anal, and vaginal sex. It can also happen when people share contaminated
needles, or when they have direct contact with a skin lesion on an infected person,
‘cause the lesion is covered in this fluid which is rich in spirochetes. The second way is called congenital syphilis
and it’s when a mother has syphilis and Treponema pallidum infects a baby either in
the uterus or while the baby exits through the vagina at birth. In acquired syphilis, there are three stages
to the infection. The first stage is called primary syphilis
or the early localized stage, and it usually starts 1 to 3 weeks after the T. pallidum
lands on the skin or mucous membrane. During this stage, the spirochetes destroy
the soft tissue and skin wherever they enter the body, and that results in the formation
of ulcers called syphilitic chancres. A syphilitic chancre is painless – and you
can remember that by dropping in a “u” to make it chan”cure” like you’re “cured”
of the pain. These chancres have a hard base, raised borders,
and are usually covered by a fluid rich in spirochetes, and this can spread to other
parts of the body as well as to other individuals. In individuals who acquire syphilis through
sexual contact, the primary chancre develops around the external genitalia. However, for individuals that acquire syphilis
by physically touching a lesion or in some other way, the primary chancre might appear
on the hands or some other part of the body. Syphilitic chancres typically heal on their
own over a few months, but during that time, some spirochetes go to nearby lymph nodes
where they cause lymphadenopathy, which is lymph node enlargement, and then they get
into the lymph and finally into the bloodstream. If syphilis is acquired through something
like a blood transfusion, then there may not be any early localized stage at all and no
primary chancre. The second stage is secondary syphilis, or
the dissemination stage, and it occurs about 6 to 12 weeks after the infection. During this stage, spirochetes enter the bloodstream,
which is called spirochetemia, and this causes generalized lymphadenopathy, which is when
spirochetes can be found in lymph nodes throughout the body. The spirochetes like to attach to and infect
endothelial cells in small capillaries near the skin. This causes a non-itchy maculopapular rash,
which are small bumps that are either flat or raised. The rash starts on the trunk and spreads out
to the arms and legs and eventually to the palms, soles, genitalia, and other mucous
membranes. These rashes can sometimes be pustular, which
is they’re filled with the white fluid pus, or they can be papulosquamous, which is when
they’re scaly and hard. In addition, there can be something called
condyloma lata, which are smooth, white, painless, wart-like lesions, and they appear on moist
areas like genitals, around anal region, and the armpits. So these various rashes can erupt all over
the body, and the lesions are chock-o-block full of spirochetes, making secondary syphilis
the most infectious stage. The rashes from secondary syphilis usually
resolve within a few weeks to months. Then after secondary syphilis, is a latent
phase, called latent syphilis. This is when the disease enters a dormant
or asymptomatic phase. During this phase, the spirochetes can mostly
be found in the tiny capillaries of various body organs and tissues. Latent syphilis can be further divided into
an early phase and a late phase. Early latent syphilis occurs within a year
of infection, and during that time the spirochetes can re-enter the blood – so this means that
during early latent syphilis they can still be found circulating in large numbers in the
blood, cause symptoms of secondary syphilis. However, the late latent phase is generally
after a year, and that’s because the spirochetes generally stay within the tiny capillaries
of various body organs and tissues. As it turns out, only a few spirochetes are
actually found in the capillaries of tissues and organs, but there is a severe immune response—so
severe, that it causes tremendous damage to the cells there. And that triggers the next phase which is
tertiary syphilis. In tertiary syphilis, there’s a type IV
hypersensitivity reaction, which means that there’s an immune response that’s mainly
led by the T cells and they recruit phagocytes like macrophages, and cause the release of
proinflammatory cytokines such as tumor necrosis factor, IL-1, and IL-6. All of this leads to local swelling or edema,
redness, and warmth as well as systemic symptoms like a fever. T. pallidum has three main antigens. These include group specific antigen, which
are present in all treponemes, species-specific antigen, which are specific to T. pallidum,
and cardiolipin, which is a lipid antigen, which interestingly, is present within the
spirochetes as well as the cells in our body. Now, plasma cells like to get themselves involved
in the immune reaction by producing antibodies against these antigens. In some cases, the immune cells start to huddle
around and form a granulomatous lesion called a gumma, and this has lots of different types
of immune cells that get surrounded by an outermost layer of fibroblasts. Often, funnily enough, there aren’t any
spirochetes at all in these lesions-it’s just like the immune cells are just getting
over excited and huddling up for no obvious reason. The tissue at the center of the gumma often
ends up without oxygen and that can lead to coagulative necrosis. In tertiary syphilis various organs get damaged,
like the heart and blood vessels, called cardiovascular syphilis, the brain and spinal cord, called
neurosyphilis, and also the liver, joints, and testes – which haven’t yet earned their
own special names yet. In cardiovascular syphilis, there’s endarteritis,
which is inflammation of the tiny arterioles called vasa vasorum, which supply blood to
large arteries like the aorta. The result is that parts of the aorta are
damaged, resulting in aortitis, or inflammation of the aorta, and this can cause aortic aneurysms. In neurosyphilis, the spirochetes set up camp
in the capillaries supplying the posterior or back part of the spinal cord, and this
can result in something called tabes dorsalis, which literally translates as wasting or loss
of the back of the spinal cord. The protective sheath which covers the nerves
running along the back of the spinal cord is damaged, and this results in a loss of
vibration sensation, and a loss of proprioception, which is the sense of position of the joints
and other body parts, like the hands and the foot. So that’s what happens when syphilis damages
the posterior spinal cord, but sometimes, the spirochetes invade the capillaries supplying
the anterior or front of the spinal cord, and that results in general paresis, which
causes loss of sensation, and weakness, or sometimes even paralysis, mostly in the legs. If spirochetes get into the capillaries serving
the brain then that can cause slurred speech, altered behavior, memory loss, difficulty
coordinating muscle movements, and even paralysis. Syphilis can even affect the eye, causing
an Argyll Robertson pupil, which is when the pupil loses its light reflex, but it does
still have its accommodation reflex, which means that the pupil constricts when there’s
a nearby object, it just doesn’t do anything when it’s too light. In congenital syphilis, the spirochetes can
infect the baby either via the placenta or during childbirth in the birth canal. In early disease, which is in the first two
years, the result can range from a baby being still-born, or dying within the womb to having
classic features like a maculopapular rash of the palms and soles of the feet, and snuffles,
which is when the nose is blocked by increased secretions, which contain spirochetes. Babies may also have organ damage to the liver
and spleen causing hepatosplenomegaly and damage to the eyes -as well – like optic neuritis. In late disease, which is after a child is
two years old, classic features often include a saddle nose which is bony destruction of
the nose, saber shins which is when the tibia gets bent, Hutchinson teeth which is when
the teeth develop little notches, and hearing loss. Diagnosis of acquired syphilis starts with
identifying spirochetes in the fluid from chancres, and this can be done using dark-field
microscopy. A dark field microscope shines thin slivers
of light on a slide so that the background appears dark, while the extremely thin spirochetes
light up, it’s a bit like you know how we can see dust particles better in a dark room
with just a stream of light shining through the door. It’s kind of like that. Now the diagnosis is confirmed with serological
tests, and these look for antibodies against the T. pallidum antigens. There are non-treponemal tests, like the Rapid
plasma reagin test, or RPR, and the Venereal Disease Research Laboratory test or VDRL as
well tests that detect anti-cardiolipin antibodies, called reagin, in the blood. The key, though, is that these are not specific
to syphilis, for example, cardiolipin is also released by damaged cells in our body. Then we have the treponemal tests, which includes
T pallidum–particle agglutination or TPPA, and fluorescent treponemal antibody absorbed
or FTA-ABS. These treponemal tests detect antibodies that
target T. pallidum. Diagnosing congenital syphilis, as you might
imagine is a bit different. In Congenital syphilis the diagnosis involves
looking at mother’s and baby’s results in parallel. For example, if a baby’s non-treponemal
serologic titer is four times greater than the mother’s titer, like if the baby’s
RPR is 1:16 and the mother’s is 1:64 then that suggests that the baby has congenital
syphilis. In general for any baby who’s mother was
inadequately treated for syphilis or is suspected of having congenital syphilis for a different
reason it’s helpful to get CSF fluid for VDRL, as well as cell counts, and protein. It’s also helpful to perform long bone X-rays,
as well as an eye exam, and a hearing screen. The main treatment for syphilis is penicillin,
but in some cases doxycycline can be used as well. When using penicillin, though, it’s important
to watch out for a Jarisch-Herxheimer reaction, which is when spirochetes die and break open
releasing a lot of antigens all at once, and making the immune system go into overdrive. When that happens, the it results in sudden
fevers, sweating, muscle and joint pains that may last for a few hours to few days. All right, so we’ve made it to the end of
the syphilis video. Now we’ve got time just to quickly recap
the main points. So, syphilis is a sexually transmitted disease
and it’s caused by the spirochete called Treponema pallidum. It can cause disease in three stages – the
first is localised primary syphilis, and this produces hard chancres. The second is disseminated secondary syphilis,
which produces widespread maculopapular rash, and the third is a systemic tertiary syphilis,
and it affects various organs. Syphilis can be diagnosed by using serological
tests and treated with antibiotics like penicillin.

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