M- Genital Ulcers Flashcards
A 30 year old man presents with multiple painful lesions on his penis for 7 days.
He has never had this before.
He has a low grade fever, and some burning when urinating.
He has a h/o unprotected sex with female partners and is HIV neg.
What is the most likely diagnosis?
Primary HSV2
A 30 year old man presents with a painful ulcer. He is HIV neg. His last sexual encounter was 3 weeks ago with a female.
A week after sex, he noticed a papule, which became pustule then ulcerated.
On exam you note:
-irregular borders
-granulomatous base
- purulent exudate
- painful inguinal lymphadenopathy.
What is the most likely diagnosis?
Chancroid - H. ducreyi
A 30 year old AA male presents with painful, tender inguinal lymphadenopathy with some areas of drainage.
He vaguely remembers a painless small ulcer on his penis about 6 weeks ago but it spontaneously healed. He is MSM, and does not use condoms.
If he continues to leave it untreated, it can cause proctocolitis with rectal pain and tenesmus.
What is the most likely diagnosis?
lymphogranuloma venerum
What organism causes the following venereal disease?
- syphilis
- Herpes
- LGV
- Granuloma inguinale
- Chancroid
- T. pallidum
- HSV1 and HSV2
- Chylamydia trachomatis
- klebsiella granulomatis
- H. ducreyi
What are the infectious causes of genital ulcers?
- herpes
- syphilis
- chlyamdia trachomatis [LGV]
- chancroid
- donovanosis - G. inguinale
- RARELY CMV, HIV, S. aureus
What are the non-infectious causes of genital ulcers?
- medications/drug reactions
- Bechet’s disease
- cancer
- trauma
Which infectious causes of genital ulcers tend to be painful?
- Herpes
2. Chancroid
Which infectious causes of genital ulcers tend to be painless?
- syphilis
- LGV
- g. inguinale
What cause of genital ulcers present with constitutional symptoms?
- secondary syphilis
- primary HSV
- secondary LGV [mistaken for IBD]
Which infectious agents cause:
- single genital ulcers
- multiple genital ulcers
- single or multiple ulcers
Single:
- syphilis
- LGV
Multiple:
- HSV
- Chancroid
Single or Multiple:
1. G. inguinale
Which infectious agents cause:
- nontender-rubbery lymphadenopathy
- tender lymphadenopathy
- matted/suppurative nodes with painful buboes
- late primary syphilis
- HSV, chancroid, g. inguinale [secondary] and LGV
- LGV, chancroid
What diagnostic tests are used to diagnose syphilis?
Serologies:
- non-specific RPR, VDRL
- specific MHA-TP, TP-PA, FTA-ABS
What diagnostic tests are used to diagnose HSV?
- viral cultures
2. PCR/DFA
What diagnostic tests are used to diagnose Chancroid?
It is really difficult to diagnose chancroid and most often it is a diagnosis of exclusion.
MAYBE
- culture for H. ducreyi
- PCR
What is diagnostic testing for LGV?
- serology
2. Nucleic Acid Amplification Test for chlamydia
What is the diagnostic testing for granuloma inguinale?
Biopsy with a stain for Klebsiella
Describe the structure of the Herpes virus.
- large
- enveloped [lipoprotein]
- icosahedral capsid
- dsDNA, linear
What are the 3 major families of Herpes viruses? When cell type does each infect?
Where does each have its latency?
- Alpha
- HSV1, HSV2, varicella zoster
- infects mucoepithelial cells
- latency in neurons at the dermatome of the infection site - Beta
- CMV, HHV6, HHV7
- infects T cells and macrophages
- latency in T cells and macrophages - Gamma
- EBV, HHV8/KSHV [karposi’s sarcoma]
- infects B cells
- latency in B cells
After HSV1 or HSV2 infects and replicates in a mucoepithelial cell, what are the 3 things that can happen?
- Lytic infection
- persistent infection in lymphocytes and macrophages
- Latent infections in the innervating neurons [get to the ganglion by retrograde transport]
What are the 5 stages from primary infection leading to latency/reactivation in HSV infections?
- acute mucocutaneous infection
- spread to local sensory nerve endings
- est. and maintain neural latency
- reactivation of virus and distal spread
- recurrent cutaneous infection
How do HSV1 and HSV2 differ in terms of where they typically est. latency?
HSV1 tends to infect “above the belt” so latency is in the trigeminal ganglia
HSV2 tends to infect “below the belt” and latency is in the sacral or lumbar ganglia [mainly sacral]
What are inducers of reactivation for herpes simplex virus?
When the virus is reactivated, where does it go?
How will the reinfection present?
Sunlight Stress Menses Fever Trauma immunocompromise
Reactivated viruses go to the initial site of infection and can be:
- asymptomatic
- vesicular lesions containing infectious virion [dew on a rose petal]
What are the 2 main ways by which HSV evade the immune system?
What branch of the immune system is important in controlling the herpes virus?
CMI is crucial for controlling herpes virus. Suppression of cell-mediated immunity leads to reactivation, spread and severe disease.
Immune Evasion occurs by:
- obstructing the pathway leading to CD8 T-cell recognition
- directly spread cell-to-cell avoiding Ab neutralization
What are the antigenic differences between HSV1 and HSV2?
Why is this important?
HSV1- enveloped glycoprotein gG1
HSV2- enveloped glycoprotein gG2
[partial antigenic similarity allows for partial protection against each other]
This is the basis for serological testing like EIA and western blot
What are the epidemiological differences between HSV1 and HSV2?
- serology
- transmission
Seroprevalence:
HSV1 = 90% [most infected by age 30], higher prevalence in low SES locations
HSV2 = 20-30% [incrases with number of sex partners, age, Af. American]
Transmission:
HSV1- during childhood through saliva from kissing family members, kid-to-kid
HSV2 - sexually transmitted in young adulthood
Describe the primary infection of HSV1.
What is the incubation period?
Are there constitutional symptoms?
Where is latency established?
Describe what symptoms are associated with relapse.
Median incubation is 6-8 days.
It replicates in the oral mucosa causing:
1. fever
2. sore throat
It ascends sensory nerves to the trigeminal ganglion where it est. latency.
Relapse:
- Prodrome - tingling, burning, itching, “pins and needles” precedes appearance of the lesion
- Lesion is a clear vesicle on an erythematous base [dewdrop on a rose petal]. Often at vermillion border of mouth
- unilateral lesion, no systemic signs
Describe the primary infection of HSV2.
What is the incubation period?
What are the local and constitutional symptoms?
Where is latency est.?
What is the duration of the primary phase?
Describe relapse of HSV2 infection.
HSV2 infections have a 3-7 day incubation [shorter than HSV1]
Local symptoms:
1. dew on rosepetal, PAINFUL vesicles
Constitutional:
1. regional lymphadenopathy- bilateral, tender
2. +/- systemic manifestations [malaise, fever, anorexia, headache]
Latency in the sacral root ganglia
Primary duration is about 2 wks
Relapse :
- frequent, associated with prodrome
- lesion lasts for less time than primary infection [5-10 days]
- unilateral, no systemic signs
What is herpetic keratitis?
Is it more likely to be caused by HSV1 or 2?
It is where the herpes virus goes down the opthalmic branch of the trigeminal nerve forming a dendritic pattern seen with a slit-lamp.
Untreated [with topical acyclovir] it can lead to liquefaction of the cornea leading to perforation–>cataracts–>blindness
Because it originates from the trigeminal ganglia, we know that it is probably HSV1
What is herpetic whitlow?
Is it more likely to be cause by HSV1 or 2?
It is a herpes lesion on the finger.
It is typically seen on the fingers of dentists, hygenists, anesthesiologists due to inoculation from the patients saliva.
BOTH cause whitlow
What is herpes gladiatorium? Is HSV1 or 2 more likely to cause it?
It is a disease that follows contact to the skin lesion of an infected individual [wrestlers, football players]
BOTH HSV1 and 2
Which herpes strain is more likely to cause encephalitis?
Meningitis?
Encephalitis= HSV1 Meningitis= HSV2
What diseases are caused by HSV1?
- gingivostomatitis
- orolabial herpes
- herpetic keratitis
- herpatic whitlow
- herpatic encephalitis
- Mollaret’s aseptic meningitis
- esophagitis
- hepatitis
What disease are caused by HSV2?
- genital herpes
- oropharyngeal herpes
- neonatal/congenital herpes
- aseptic meningitis [Mollaret’s meningitis»_space;»than HSV1]
- autonomic neuropathy
Recent data suggests that 60-70% of contacts did not have what when they transmitted the herpes?
A noticable lesion!
How is the neonatal acquisition of herpes different from syphilis?
What characteristics of the mother make it most likely for viral transmission?
Syphilis- the spirochete crosses the placenta and enters the baby’s circulation during gestation
Risk of transmission is in women who have had syphilis for 2 years or less [still in latency]
HSV- transmitted most commonly DURING childbirth [although it technically can occur in utero and postnatally].
Risk of transmission is highest when the mother has a recently acquired primary HSV2 infection NEAR TERM.
[decreased risk if recurrent lesion, or prior HSV1 infection due to the Antibodies]
What are the 2 ways the baby acquires HSV2 infection during childbirth?
What are the 3 major sequelae of a congenital HSV2 infection?
What is treatment?
IF you know the mother has a current primary infection [new], what can you do to lower the incidence of spread to the baby?
The baby acquires the virus via:
- aspiration of the vaginal contents
- contact through skin
Major sequelae:
- HSV pneumonia
- HSV encephalitis [diff from adult version because it is DIFFUSE, not focal temporal due to retrograde migration from the trigeminal ganglia]
- HSV hepatitis
Treatment is IV acyclovir
If you know the mother has a new infection at the due date, deliver the baby by C-section before thre rupture of the placental membrane
What are the 6 possible ways HSV can be diagnosed?
What 3 are used most often?
What is the gold standard?
- clinical appearance of the lesion
- viral culture with typing [gold standard, often used]
- Tzanck prep - scraping from base of lesion, stained with giemsa on direct microscopy
- ELISA, DFA, IFA [often used]
- PCR [often used]
- type-specific serology [used for primary infection and epidemiology. recurrence does not correlate with a rise in titer]
What on Tzanck prep would clue you in to HSV?
Why is it not “gold standard” for diagnosis?
You take a scraping from the ulcer, stain it with Giemsa and look at it with direct microscopy.
You should see:
- Intranuclear inclusions
- Giant cells
These findings are not specific and would be the same for varicella zoster so it is not gold standard.
What is IFA, DFA, ELISA?
Techniques where you take scrapings and stain them using antisera or monoclonal antibodies to distinguish between the different herpes viruses
How is genital herpes managed to reduce spread to new people?
- counseling- natural history, risk of sex/perinatal, barrier methods
- antiviral chemotherapy
- decreases freq and severity of recurrence
- does NOT eradicate laten virus
What are the drugs of first choice for HSV?
What is their mechanism of action?
How has viral resistance occurred?
If there is viral resistance, what drugs are used?
Acyclovir, valacyclovir, famciclovir
All are prodrugs that :
- get phosphorylated by viral thymidine kinase
- become substrate for DNA pol
- incorporate into viral DNA preventing chain elongation
Viral resistance occurs via mutation to the thymidine kinase.
Second line: foscarnet, cidofovir [lots of side effects]
What organism is the cause of chancroid? What is the incubation period? Is the ulcer: 1. painful or painless, single or multiple 2. indurated or not? 3. smooth or rough edges? 4. associated with lymphadenopathy?
H. ducreyi causes chancroid. It has a 5-7 day incubation period after which it progresses from:
Tender papule-> ulceration[w/in 48hrs]-> painful ragged lesion
The ulcer is:
- painful and multiple [kissing lesions]
- non-indurated
- rough edges that can be lifted off the underlying tissue
- bilateral tender adenopathy that look like buboes and can rupture
Describe the H. ducreyi organism and its nutritional requirements.
What is the characteristic feature seen on gram stain?
What gives a definitive diagnosis?
What are clues for probably diagnosis?
It is a G- coccobacillus that is fastidious.
To grow it you need:
- choc agar for factor X, vancomycin
- high CO2
Gram stain = “school of fish”
Definitive diagnosis is by culture
Probable:
1. one or more painful ulcers with consistent clinical picture
2. syphilis ruled out by dark stain microscopy or serology
3.HSV ruled out
Regionally, where are chancroids most commonly found?
Africa and SE Asia.
In the US there are a few cases in the south.
Most US cases are due to returning travelers
What 4 drugs are options for the treatment of chancroid?
How do you determine an appropriate regimen?
If the drugs don’t work, what 5 questions do you need to ask?
- azithromycin
- ceftriaxone
- ciprofloxacin
- erythromycin
Give them a drug and re-examine at 3-7 days. If it is successful, there will be symptom improvement. If the drug doesn’t work consider:
- correct diagnosis?
- coinfected?
- HIV?
- treatment not used as instructed?
- resistant H. ducreyi strain
What organism is responsible for donovanosis [granuloma inguinale]?
How is it definitely diagnose?
Klebsiella granulomatis
To diagnose, you must do a biopsy and stain it to show Donovan bodies [which look like safety pins] inside of cells derived from monocytes [most often macrophages, but occasionally neutrophils]
Where is granuloma inguinale endemic?
papa new guinea Caribbean S. America India Vietnam Australia
Describe the progression of g. inguinale infection.
Incubation is 3 months.
- Genital papule–> ulcerative lesion
- ulcer bleeds and extends beyond the border of the ulcer to become multiple and large “beefy red lesions with white borders”
- grow within macrophages
- cause granulomatous inflammation
PAINLESS unless there is a secondary infection
What is treatment for g. inguinale?
- doxycycline
2. macrolides, cipro, TMP-SMX
What organism is responsible for lymphogranuloma venereum?
What areas are endemic for this infection?
Chlamydia trachomatis serobar L1-3
It is endemic in Africa, Latin America, MSM in US
What is the disease progression of LGV?
Incubation 1-4 weeks
- Painles papule [single] –> ulcerates.
- ulcer goes away/was very short lived
- MASSIVE inguinal lymphadenopathy that is tender and painful [buboes]
- . If untreated –> proctitis, tenesmus, ano-fistulas
What are the sequelae of an untreated LGV infection?
- direct extension from infection site to draining lymph nodes causes
- necrosis and abscess formation
- infects macrophages
- buboes suppurate and rupture - Granulomatous inflammation
- late stage LGV
- fibrosis
- strictures in anogenital tract
- genital elephantitis, infertility, proctitis
How is LGV diagnosed?
Clinically
Culture- ulcer is often missed due to painless/short nature
NAAT- not FDA cleared for rectal specimen
Serology- can’t tell the difference between serovars
PCR- not widely available
What is treatment for LGV?
Doxy or azithro for 21 days
Genital ulcer is recurrent, painful and looks like dewdrops on rosepetals. What is it?
HSV
An immigrant from Papa New Guinea presents with painless ulceration, destruction of glans.
Biopsy show intracytoplasmic inclusions of Wright stain.
What is the disease and causative organism?
Donovanitis [G. inguinale] caused by Klebsiella granulomatis
A man presents with a ragged, indurated ulcer. He is from the southern US and has been traveling. He has bilateral tender inguinal lymphadenopathy [buboes]. What does he have and what is the causative organism?
Chancroid - H. ducreyi
A man presents with recurrent aseptic meningitis [Mollaret’s]. What organism are you suspicious of?
HSV2
A man says a week ago he had a small painless ulcer but it went away. Now he has severely painful inguinal lymphadenopathy that is draining and suppurative. What does he have?
LGV - Chlamydia trachomatis L1-3
