HSV & External Genital Warts & Syphilus

Question 1

Which strand of HSV is the most common cause of genital herpes?

HSV-1
HSV-2
HSV-3
HSV-8
HSV-16

Answer 1

Which strand of HSV is the most common cause of genital herpes?

HSV-1
HSV-2
HSV-3
HSV-8
HSV-16

Question 2

Which strand of HSV is the most common cause of recurrent genital herpes?

HSV-1
HSV-2
HSV-3
HSV-8
HSV-16

Answer 2

Which strand of HSV is the most common cause of recurrent genital herpes?

HSV-1
HSV-2
HSV-3
HSV-8
HSV-16

Question 3

After the initial infection, HSV is able to enter a dormant latent phase within []

There are typical locations of HSV in both oro-labial and anogenital herpes:

Oro-labial herpes: [] ganglia
Anogenital herpes: [] ganglia

Answer 3

After the initial infection, HSV is able to enter a dormant latent phase within nerve cell ganglia.
There are typical locations of HSV in both oro-labial and anogenital herpes:

Oro-labial herpes: trigeminal ganglia
Anogenital herpes: sacral nerve root ganglia

Question 4

Describe how the transmission of HSV occurs [1]

Answer 4

It can only be transmitted when an already infected individual is shedding virus, which happens sporadically
and not necessarily in association with symptoms (asymptomatic shedding).

Question 5

Describe the initial presentation of HSV-1 infection [7]

Answer 5

Genital lesions - initial infection:
- Grouped painful blisters which burst after 2-3 days, resulting in crusted erosions and ulcers on the external genitalia.
- Lesions can also occur on the thigh, buttocks, cervix and rectum.
- These can be extremely painful, making urinating and even sitting down painful (especially in women).
- Febrile illness (prodrome) lasting 5–7 days
* Dysuria, urinary frequency
* Painful inguinal lymphadenopathy
* Primary episodes can last up to 20 days.

Question 6

Describe the presentation of recurrent HSV-1 infection [7]

Answer 6

Prodrome:
- Tingling and burning sensation in the genitals.
- May precede the appearance of lesions by up to 48 hours.

Genital lesions:
- Usually recur in the same area but lesions less severe than in the initial episode.

Duration:
- Lesions crust and heal within 10 days.

Question 7

Complications usually occur with the first episode and the risk is reduced if given antiviral
therapy. They include: [3]

Answer 7

• Acute urinary retention (occurs predominantly in women)
• Constipation (may be a risk with first episode peri-anal disease)
• Aseptic meningitis

Question 8

Describe how you dx genital HSV [3]

Answer 8

Polymerase chain reaction (PCR):
- Nucleic acid amplification tests (NAAT) are a type of PCR.
- A negative test does not exclude herpes (may be taken too late in an attack).

Viral culture:
- If NAAT unavail

Serology:
- BASHH 2014 guidelines state virus typing should be done via serology in all patients with a new diagnosis of genital herpes (in addition to NAAT or culture).
- To test for HSV type-specific antibodies (IgG).

Question 9

DDx of genital HSV?

Answer 9

Primary syphilis
- Differences: singular, usually painless ulcer.

Chancroid (Haemophilus ducreyi bacterium)
- Differences: single, deep ulcer.

Lymphogranuloma venereum
- Differences: lymphadenopathy is unilateral, lack of vesicles, single or few ulcers.

Bechets:
- Differences: absence of vesicles, coexistence of oral, eye, skin or neurological involvement.

Question 10

Describe the management of genital HSV:

• initial infection
• recurrent episodes
• repeated recurrent infections

Answer 10

Commence treatment immediately if within five days of lesions developing, new lesions are still forming, or if systemic symptoms are present.

Primary infection:
o Aciclovir 400mg TDS
o Valaciclovir 500mg BD
o Analgesia: paracetamol, ibuprofen, topical 5% lidocaine ointment

Recurrent infection:
o Usually self-limiting

Repeated recurrent infections (6+ a year)
o Duration of therapy is commonly 6 months to 1 year.

Anti-virals all reduce the severity and duration of symptoms. They do not alter the natural
history of the disease in that frequency or severity of subsequent recurrences remains
unaltered

Question 11

Specialist management is important during pregnancy to reduce the risk of transmission to the baby.

What is this?

NB: depends on when the infection is during the pregnancy

Answer 11

Management:
If the first episode is BEFORE week 28 of the pregnancy, offer the mother antiviral therapy at that time, and then again from 36 weeks until the birth.

If the first episode is at or AFTER week 28 of the pregnancy, advise the mother to take antiviral treatment from then until the birth.

Question 12

Specialist delivery is important during pregnancy to reduce the risk of transmission to the baby.

What is this?

Answer 12

If the first episode is within 6 weeks of the due date, offer an elective caesarean section to reduce the risk of neonatal herpes.

If the first episode is earlier in the pregnancy, normal vaginal birth is advised as the risk of transmission is very low.

Question 13

Describe how neonatal HSV manifests

Answer 13

Can cause neonatal fever, seizures, sepsis or vesicular blisters.

Question 14

Anogenital warts are caused by [].

Answer 14

Anogenital warts are caused by human papillomavirus.

Question 15

Describe the presentation of external genital warts

Answer 15

Genital lumps, which vary in size, shape and colour, and range from solitary to
multiple
* Irritation or discomfort
* Bleeding, especially urethral
* Occasionally itchy
* Sometimes, hyper pigmentation is present

Question 16

What is the managment for
- simple external warts [2]
- cervical warts [1]
- oral warts [1]

Answer 16

Simple external warts
o Podophyllotoxin cream or solution (avoid in pregnancy)
o Imiquimod cream 5%,
o Weekly cryotherapy, if available or Electrocautery, Excision

Cervical warts
o Colposcopy

Oral warts
o Cryotherapy

Question 17

Describe how choose between podophyllotoxin, imiquimod and TCA to treat genital warts [3]

NB: depends on the type of warts

Answer 17

Podophyllotoxin (e.g. Warticon):
- Good against soft lesions and can be self-applied at home.
- Disrupts cellular division. Clearance rate 43-70% and recurrence rate 6-55%.

Imiquimod:
- Good against both hard and soft lesions.
- Can be self-applied at home. Stimulates a local immune response by activating macrophages. Clearance rate 35-68% and recurrence rate 6-26%.

TCA (80-90% solution):
- Good against both hard and soft lesions.
- Applied in specialist setting. Essentially corrodes skin leading to necrosis. Clearance rate 56-81% and recurrence rate 36%.

Question 18

The majority of anogenital warts are caused by the HPV genotypes [] and [].

HPV genotypes [] and [] are predominantly responsible for development of anogenital malignancies (e.g. cervical cancer).

Answer 18

The majority of anogenital warts are caused by the HPV genotypes 6 and 11.

Genotypes 16 and 18 are predominantly responsible for development of anogenital malignancies (e.g. cervical cancer).

Question 19

Describe what is meant by HPV intraepithelial neoplasia

Answer 19

Patients infected with genotypes that have malignant potential (e.g. 16 and 18) can present with lesions that have evidence of intraepithelial neoplasia on biopsy/cytology. These areas may be subclinical and only detected on biopsy/cytology.

A small proportion of these lesions progress to invasive cancer

Question 20

Syphilis is caused by an infection with the spirochete bacterium []

Answer 20

Syphilis is caused by an infection with the spirochete bacterium Treponema pallidum

Question 21

Syphilis is categorised into which four stages: [4]

Answer 21

• Primary
• Secondary
• Latent: divided into early latent and late latent
• Tertiary

Question 22

Describe the basic pathophysiology of primary, secondary and tertiary syphilis [3]

Answer 22

Primary:
- The primary ulcer contains the Treponema pallidum bacterium in a
chancre
- Infiltration appears to coincide with the resolution of the primary chancre which occurs over 3-6 weeks

Secondary syphilis
- haematogenous spread of the bacterium resulting in endarteritis obliterans.
- Mucocutaneous lesions in secondary syphilis also contain treponemes

Approximately 15-40% of patients with untreated secondary syphilis progress to late syphilis involving:
- Neurosyphilis
- Gummatous syphilis
- Cardiovascular syphilis

Question 23

Describe the clinical presentationf of primary, secondary, latent and tertiary syphilis [3]

Answer 23

Primary:
* Chancre
* A single ano-genital ulceration
* It is painless and indurated with a clean base, non-purulent
* Can be multiple, painful, and purulent (usually extra-genital)
* Resolve over 3-8 weeks

Secondary syphilis - signs are multisystemic:
* Symmetrical maculopapular rash , typically on the trunk, face, palms or soles
* Fever, malaise, myalgia, fatigue, and arthralgia (25%)
* Lymphadenopathy
* Neurological complications
* Glomerulonephritis
* Splenomegaly

Latent disease:
* Secondary syphilis will resolve spontaneously in 3–12 weeks and the disease enters an
asymptomatic latent stage. Approximately 25% of patients will develop a recurrence of
secondary disease during the early latent stage

Late (tertiary) disease
- In the late stage, the disease may damage the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints

Question 24

Describe what this presentation of secondary syphilis is called [1]

Answer 24

Condylomata lata (appear like genital warts)

Question 25

Describe what this presentation of secondary syphilis is called [1]

Answer 25

Snail track ulcer

NB: very specific to syphilus

Question 26

Which neurological complications can occur from secondary syphilis infection? [5]

Answer 26

Neurological complications
o Acute meningitis
o Cranial nerve palsies
o Uveitis
o Optic neuropathy
o Interstitial keratitis and retinal involvement

Question 27

Describe how you investigate for syphilis

Answer 27

PCR swab for HSV and syphilis

Treponemal tests: - Detects antibodies that react to specific treponemal antigens
- Examples include T. pallidum particle agglutination assay (TPPA) and enzyme immunoassay (EIA)
- A positive result suggests exposure to the bacteria but does not distinguish between current or past infection.

Non-treponemal tests: - This refers to two different tests:
* Rapid plasma reagin (RPR)
* Venereal Disease Research Laboratory (VDRL)
- measure the response to cellular damage caused by the infection rather than directly detecting the bacterium
- correlate with disease activity.

Dark ground microscopy
- primary syphilis if there is a visible lesion such as a chancre. A sample from the lesion can be examined under dark-field microscopy to look for Treponema pallidum.

CSF examination if ? neurosyphilis

Question 28

Describe the different serological testing performed in syphilis investigations

Answer 28

Treponemal tests: - all have A in them - TPPA, EIA, CMIA - Detects antibodies that react to specific treponemal antigens
- A positive result suggests exposure to the bacteria but does not distinguish between current or past infection. These will almost always stay positive after infection

Non-treponemal tests - R - RPR, VDRL
* rise in recent infection
* Level will fall over time even without treatment

Question 29

Describe how you interpret RPR tests [2]

Answer 29

Lab test for RPR on neat serum and then dilute it to see if the test still remains positive

The bigger the second number the higher the RPR because it has stayed positive even though very dilute

RPR margin of error:
- Adequate response of treatment - want to see RPR / 4 by 6 months
- If RPR increases by 2 fold, generally not enough to increase to dx (as there might be variability in the tests), but if 1:2 —> 1:8 /16 then worry
- RPR might never fully become negative

Question 30

Describe the difference in timing between primary, secondary and tertiary syphilis

Answer 30

Primary syphilis is characterised by generalised lymphadenopathy and a chancre

Secondary syphilis occur 3-12 weeks after appearance of the initial chancre and is characterised by systemic features, skin lesions, alopecia, and mucous patches
Early latent syphilis is serological confirmation of infection in the absence of clinical features

Tertiary or late syphilis occurs after 2 years of infection (typically 15-40 years)
- Tertiary syphilis may present with gummatous syphilis, cardiovascular syphilis or neurosyphilis
- Tertiary latent syphilis is serological confirmation of infection in the absence of clinical features

Question 31

Describe what is meant by Jarisch-Herxheimer reaction [1]

What treatment is given in tertiary CV or neurosyphilis

Answer 31

This refers to an acute febrile illness that usually presents within the first 24 hours of treatment for syphilis with headache, myalgia, chills and rigors.

The reaction occurs after the initial dose of anti-treponemal treatment. It occurs in 10-35 % of patients and is most common in early syphilis. It usually self-resolves without intervention in 12-24 hours. Anti-inflammatory drugs can be used (e.g. NSAIDs).

Due to the potentially life-threatening nature of the reaction in patients with late tertiary cardiovascular or neurosyphilis, steroids are usually recommended (prednisolone 40-60 mg once daily). They are given for three days starting 24 hours before the initial dose of anti-treponemal antibiotics.

Question 32

Describe the medical management for early [1] late [2] (with CV or gummatous)

Answer 32

Early syphilis:
* Benzathine penicillin 2.4 Million units, IM single dose.

Late syphilis: (cardiovascular or gummatous):
* Benzathine penicillin 2.4 million units, IM weekly for three weeks (3 doses)
* Prednisolone 40-60 mg for three days if cardiovascular (see Jarisch-Herxheimer reaction)

The treatment of syphilis is with parenteral penicillin.

Question 33

Describe the medical management for neurosyphilis [3]

Answer 33

• Procaine penicillin 1.8-2.4 million units IM once daily plus probenecid 500 mg QDS for 14 days, OR
• benzylpenicillin 10.8-14.4 g daily, given as 1.8-2.4 g IV every 4 hours for 14 days.
• Prednisolone 40-60 mg for three days (see Jarisch-Herxheimer reaction)

Question 34

Describe the medical management for syphilis for pregnant patients [1]

Answer 34

Erythromycin 500mg/6h PO

Question 35

What are the three main types of teriary syphilus? [3]

Answer 35

gummatous syphilis, late neurosyphilis, and cardiovascular syphilis.

Question 36

What does this lesion of a patient with syphilis show? [1]

Answer 36

gummatous syphilis:
- gummas develop in the skin, bones, and organs. These lesions are a result of inflammation and contain different types of immune cells surrounded by fibrous tissue.

Question 37

What is meant by the manifestation of neurosyphilis called tabes dorsalis

Answer 37

progressive damage to the posterior part of the spinal cord, and this results in a loss of vibration sensation and proprioception

Question 38

Cardiovascular syphilis typically targets which blood vessel? [1]

Which cardiac pathologies can it cause?

Answer 38

Syphilis loves the aorta
* dilated thoracic aorta
* aortic valve regurgitation
* aortic aneurysm

Question 39

Painless genital ulcer in a question is most likely to indicate:

Gardnerella vaginalis
Syphilis
Behcet’s disease
Gentital herpes

Answer 39

Painless genital ulcer in a question is most likely to indicate:

Gardnerella vaginalis
Syphilis
Behcet’s disease
Gentital herpes

Question 40

Gardnerella vaginalis
Syphilis
Behcet’s disease
Gentital herpes

Answer 40

Gardnerella vaginalis
Syphilis
Behcet’s disease
Gentital herpes

inflammation in the blood vessels and artery/vein damage, and causing symptoms like mouth sores and skin

Question 41

A 30-year-old homosexual man develops a solitary, raised, firm, red papule which later erodes to form a painless ulcer. Non-tender inguinal lymphadenopathy is noted is a stereotypical history of [1]

Answer 41

Syphilis

Question 42

Multiple painful genital ulcers, sexually active in a question is most likely to indicate:

Answer 42

Genital herpes

Question 43

Linear scars at the angle of the mouth is most associated with:

Primary syphilis
Secondary syphilis
Tertiary syphilis
Congenital syphilis

Answer 43

Linear scars at the angle of the mouth is most associated with:

Primary syphilis
Secondary syphilis
Tertiary syphilis
Congenital syphilis

Question 44

What is the name for this congenital manifestation of syphilis? [1]

Answer 44

Saddle nose

Question 45

What is the name for this congenital manifestation of syphilis? [1]

Answer 45

hutchinson teeth

Question 46

condylomata lata is most associated with

Primary syphilis
Secondary syphilis
Tertiary syphilis
Congenital syphilis

Answer 46

condylomata lata is most associated with

Primary syphilis
Secondary syphilis
Tertiary syphilis
Congenital syphilis

Question 47

Name this sign [1]
Which is it most associated with?

Primary syphilis
Secondary syphilis
Tertiary syphilis
Congenital syphilis

Answer 47

Argyll Robertson Pupil
- do not constrict when exposed to bright light, but do constrict when focused on nearby object

Tertiary syphilis