00:01
So let's look now, by pathogenesis,
at the first
2 herpesviruses: herpes simplex
viruses type 1 and 2.
00:09
These infections occur by initial
binding of either herpes
simplex virus 1 or 2
to their target mucoepithelial cells.
00:18
And again, depending on whether it's 1 or 2,
those typically have tropism for
the oral mucosa, conjunctiva mucosa,
or the genital mucosa.
00:29
The infections then set up a lytic process.
00:32
Some are going to go become latent,
but primarily after the replication process,
they create lysis of their target cells,
which then causes the inflammatory reaction
with all the cytopathic effects,
and we get the lesions which
we'll look at very shortly.
00:48
The latent infection primarily sets up in a
sensory or sensory neural ganglia.
00:53
Keep in mind that herpes
simplex types 1 and 2
develop latent infection in neurons.
They're neurotropic
after their primary infection in
the mucoepithelial cells.
01:07
When a patient has some sort of stressor,
and this could be physiologic,
it could be emotional, there even are
some foods in some people,
or certainly anybody who is
immunosuppressed,
then that latent infection within the
sensory ganglia can reactivate.
01:23
Reactivation causes a recurrence
of the lesions,
but in a distribution specific to
where the sensory ganglia,
which had the latent infection,
wherever those might be.
01:35
So, what do lesions look like?
Well, the lesions, in general,
have erythematous basis.
They typically occur
3 days or so after an initial
circulation or infection,
and they last for up to 2 weeks.
01:49
To identify herpes simplex virus 1 and 2,
one can do a Tzanck or Pap smear,
but increasingly one uses fluorescent anti-
body testing on viral culture specimens.
02:01
One also in pathology can look for syncytia
or Cowdry type A inclusion bodies,
which you can see as the densely stained
bodies toward the top of the
slide in front of you.
02:15
Diagnosis of HC infection can be cured in
multiple different ways.
02:19
Firstly, one can perform cytology of an
active lesion using either a zinc or pap
smear. The psychopathic effects seen on
these smears would include such things as
multi nucleotide giant cells.
02:30
However, these are not very sensitive tests
and are definitely technique dependent.
02:34
The most sensitive test and even specific
would be polymerase chain reaction PCR,
which accurately and sensitively detects the
the nuclear material of the viruses
themselves. One further can perform biopsy
of an active lesion looking for
such findings as syncytial cells or nuclear
inclusions, and also perform
immunohistochemistry on that specimen.
02:56
Direct fluorescent antibody can be formed as
can viral culture with a characteristic
psychopathic effect and then type specific
serologic tests also can be
done to distinguish HSV one versus HSV two,
especially in patients that may have
atypical presentation or to determine
whether they have active or old
disease. As we see
in this slide here, of a biopsy of a
herpetic skin lesion stained with HC
there are two distinct cytoplasmic effects
that one can demonstrate.
03:26
The first in Slide A is epithelial cells
with intra nuclear viral
inclusions. The second on the right, Slide B
demonstrates multi nucleated
epithelial cells.
03:37
These are findings typical typically seen in
HC infection.
03:44
Transmission of herpes 1. Now, we're
looking again specifically
at herpes simplex virus 1 which most
often is in the, sort of,
above the neck region. The transmission
is via secretions,
so you can imagine through saliva, through
kissing, through sneezing, sometimes.
04:02
This virus is everywhere, I'm sorry
to say. And in fact,
herpes simplex virus type 1
is a very common infection.
04:11
90% of people will be exposed to
this virus in childhood.
04:16
Not all develop disease. In fact, very
few will develop disease,
but it means that all of us might be at
risk for having a reactivation
with a lovely cold sore later on in life.
04:27
So, when the infection occurs and lysis of
the host mucoepithelial cells occurs,
then one can see lesions developing
in the mouth, or in the finger, or other
places, as we'll talk about in just a second.
04:42
The latency, where the virus
goes to sleep or hides,
is almost always in the trigeminal ganglia.
04:49
That is important
because that particular ganglia can also
backtrack to the temporal lobe.
04:55
So if you think about neurologic structures,
trigeminal, going back to the
frontal and temporal lobe
is where encephalitis with
herpes type 1 occurs.
05:06
It travels backwards to cause
a CNS infection.
05:10
So, the diseases that we see with
herpes simplex virus type 1
are the herpes labialis, a cold sore,
which you can see in the image on
the upper part of the slide.
05:21
Very prominent.
05:23
Everybody knows you've got one.
They're so common.
05:25
There shouldn't be any shame
about it, but of course,
all of us try and cover those things up
and do topical treatments, etc.
05:33
There also is, along the lines,
a gingivostomatitis,
which typically is the primary infection,
the first mucoepithelial disease.
05:43
And that typically occurs inside the mouth
on the gingiva, so the sides of the mouth,
the gums themselves, sometimes, the
tongue. Very painful, very prominent,
but it also can be quite silent
as the primary infection.
05:56
One can then self-inoculate to the conjunctiva,
causing a keratitis or a uveitis.
06:03
Herpetic whitlow, that is the image on
the lower left side of a finger
with a white vesicle related.
06:10
That typically comes from inoculation
from the mouth to the finger.
06:15
Classically, you'll see this in infants
to sometimes toddlers,
because an adult -- and it's almost
always grandma --
has an active cold sore, and that just
has to nibble on those cute little fingers,
like those tiny little hangers-on to the
fingernails. You've all seen it happen.
06:31
In fact, we've all probably done it. So
you just sort of -- nibble on that,
and that inoculates herpes from
the cold sore active mouth
into or on the finger,
and then you have secondary infections
causing herpetic whitlow.
06:44
The gingivostomatitis, we talked about.
06:47
The encephalitis we've talked
about, temporal lobe.
06:50
Typically presenting with confusion,
and if you think about your neural mapping,
what happens in the temporal lobe?
Speech and understanding. So
patients will be confused,
and they will most likely have an expressive
or even a Broca's aphasia.
07:06
They can't get their words out.
07:07
Those would be warning signs, in
combination with fever,
that the patient has a sporadic or
an acquired herpes encephalitis.
07:17
And then finally, erythema multiforme.
07:19
Now, this rash is a reactive or
a hypersensitivity rash.
07:24
It is not caused by any viral
specific effects,
but the body's immune reaction to
herpes simplex virus 1
will cause this hypersensitivity
rash in many people.
07:36
And keep in mind that that rash,
although not pictured here, has
flat, erythematous macules,
which will have a variable border,
the look and different shapes.
07:46
Some might even look a bit targetoid or so.
07:50
And this is an important question to
remember for those standardized exams.
07:54
Herpes simplex virus number 1 is
the most common cause
of erythema multiforme worldwide.
Remember that.
08:03
Okay. Herpes simplex virus type 2.
08:05
Now going down to the other
part of the body.
08:07
So keeping in mind that this virus
mostly has tropism for genital
mucoepithelial cells.
08:14
Transmission, therefore, of course
is sexual contact,
or exposure to the perineal region,
therefore, perinatal disease can occur.
08:24
This is slightly less common, although still
pretty darn common; 30% in adulthood.
08:30
Important to remember, especially if
one is dealing in pediatrics.
08:35
2 studies have shown that women
of childbearing age --
and we're talking ages 16 years
to 40 years, or so --
were studied to identify how prevalent
was herpes simplex virus type 2.
08:48
Both studies were done in the States.
08:51
Both studies show that 28% and
26%, both of them,
of women had serologic evidence of having
having had herpes simplex virus type 2.
09:04
However, on survey, fewer than half
of those positive women
knew, remembered that they had
had genital herpes.
09:12
So, there is fully a quarter to almost a
third of women of childbearing age
throughout the world who have had
herpes simplex virus 2 as a cause
of genital herpes,
but not that many women will actually
know about it. It was silent.
09:26
They didn't know about it, meaning, they're
still at risk for transmitting it to
their babies during childhood.
09:33
Mucoepithelial cells in the genital region
are the target, and when lysis occurs,
one gets lesions such as you
see on the picture
of the penis in the upper part of the slide.
09:44
Latency occurs in the sacral ganglia,
which means that reactivations'll typically
occur also in the sacral region,
again, most often in the genital mucosa.
09:56
The diseases. Herpes genitalia,
or herpes genitalis, will be
that primary lytic lesion of
the mucoepithelial cells,
causing painful, shallow, ulcerated lesions
on the genitalia, again, as you see on
the picture of the penis at the top.
10:13
Neonatal herpes occurs when the baby
is born through the cervix,
which itself has lesions. The cervical herpes
lesions are typically not painful.
10:24
They're silent. There's not primary
nerve fibers at that particular
part of the cervix.
10:30
So babies could be born unknowingly
to a mother with
or reactivated herpes and
be exposed to that.
10:37
And then within the first 2 weeks of life,
babies may develop skin lesions, such
as you see on the infant foot
in the lower part of the slide.
But most often,
look for herpes lesions in neonatal herpes
in the scalp, because, why?
Well, the scalp was the first thing exposed
to the cervix during a normal
head-first delivery.
11:00
If the baby also had a scalp electrode,
that is a high risk factor
for developing neonatal herpes in moms
who are herpes-positive themselves.
11:10
And those babies may develop
their first herpes lesions
right up at the scalp, right where
that scalp electrode was.
11:17
Other manifestations of genital herpes
can be keratoconjunctivitis,
again, through self-inoculation, and
then aseptic meningitis.
11:27
Now, this is not the severe encephalitis
which we talked about for herpes 1,
but an aseptic meningitis,
very similar to some other viral infections
where there's pain, headache,
neck pain, but it goes away on
its own after 5 to 7 days.