Lecture 34: Genital Ulcers and Genital Lesions Flashcards
What is Syphillis caused by?
Syphilis is due to T. pallidum (a spirochaete)
Evasion of immune responses is important in the maintenance of latency:
- Immunologically priviledged sites (e.g. eyes/brain)
- Intracellular sites
- Little evidence that antibody is lytic
- Surface of organism is immunologically inert
Cell-mediated immunity (CMI) is critical and to control of proliferation of T. pallidum
Much clinical disease i_s due to the im_mune response to organism, e.g. vasculitis, destruction of surrounding tissue, fibrosis
What are the early manifestations of Syphilis?
Onset 9-90 days post-exposure
Common features of early disease include:
(1) anogenital ulceration
(2) rash;
(3) ocular lesions;
(4) neurological signs, e.g. cranial nerves 3, 6, 7, 8
Describe the Primary Syphilis features + diagnosis
Primary syphilis is the first stage of the disease. It causes one or more small, painless sores in or around the genitals, anus, or mouth. If you don’t get treatment for the primarystage of the disease, it may progress to the second stage, which is secondary syphilis.
Primary syphilis has onset of 14-21 days after inoculation
Primary lesion is initially papular (circumscribed, solid elevation of skin with no visible fluid), then ulcerates:
- Ulcer or ‘hard chancre’ 1-2 cm diameter with indurated margin
- Usually solitary; painless
- Less typical in non-genital sites (mouth, anus)
Rubbery inguinal node(s)- but unusual with genital lesions
Diagnosis by d_ark field microscopy_ or direct fluorescent antibody (DFA) test before serology positive
What are the early confirmation of diagnosis
Before serology positive, we use:
- Dark field microscopy (non-specific depending on site) (left figure)
- Direct fluorescent antibody (DFA) test (specific) (right figure)
Describe the features of Secondary Syphilis
- It is due to haematogenous spread therefore may have systemic symptoms
- __Haematogenous spread = originating in the blood. producing blood or components of blood. distributed orspread by way of the bloodstream, as in metastases of tumors or in infections; blood-borne.
- It can develop rash, which are:
- Macular (distinct spots); papular (solid elevation of skin with no visible fluid); papulosquamous
- Trunk, extremeties, palms and soles
- It may also have mucus membrane lesions (ulcers; condylomata lata), alopecia
Describe the features of Late Manifestations of Syphilis
Late disease is defined as when no longer infectious (but can reactivate beyond this point in immune compromise)
Common features of late disease include (commonly NONE):
- Aortic disease
- Papillary signs, optic atrophy
- Long tract signs, pyramidal signs
- Cognitive change
- Gummatous change
Describe Congenital Infection of Syphilis
Infection occurs as early as 9/40 gestational weeks, but no inflammatory response until ~18/40 onwards
More than 50% undergo mid-trimester abortion or perinatal death
- For early form, most changes appear 1-2 months of age
- For late forms, 80% of those liveborn who are infected are undetected early
Define “assay” in the context of medicine
An assay is an analysis done to determine: The presence of a substance and the amount of that substance.
Describe Syphilis Tests for Congenital Infection
Syphilis Tests (Remember Abbreviations)
- For syphilis tests, predictive value of tests is poor in low prevalence settings such as NZ
- Pregnancy is a significant cause of biological false positive (BFP) results
- Firstly, screening with e_nzyme-linked immunosorbent assay (EIA)_
- If positive, then confirmed using rapid plasma reagin (RPR) and treponema pallidum particle/hemagglutination agglutination assay (TPPA (or TPHA))
- False positives not associated with conventional BFP reactions
Describe the ELA test
- Enzyme-Linked Immunosorbent Assay (EIA) Test
Murex ICE*Syphilis is an EIA test which uses 3 recombinant proteins (some labelled) representing immunodominant epitopes from T. pallidum (applied as a coating to the wells of microtitre plate strips)
Utilises anti-human IgG and anti-human IgM
- Overall performance
- Sensitivity >99%
- Specificity >99%
- Primary syphilis
- Sensitivity 75%
- Specificity 61.1-81.3%
Describe the RPR test
- Rapid Plasma Reagin (RPR)Test
Rapid plasma reagin (RPR) is a non-specific or non-treponemal test, which:
- Detects antibodies (Ab) against lipoidal antigen (Ag) of syphilis (liposomes in suspension + unattached charcoal)
- Flocculation type, i.e. not complement dependent (charcoal particles trapped in lattice of Ag-Ab complex)
- Quantitative is used to follow treatment
Test is positive after 3-5 weeks post-exposure. It is highly specific in healthy people (false positive rate 1-10%)
VDRL is highly specific in CSF (but low sensitivity). Cerebrospinal fluid (CSF) venereal disease research laboratory (VDRL) test is a mainstay for neurosyphilis diagnosis. VDRL is similar to RPR.
Decsribe the TPPA test
- Treponema Pallidum Particle Agglutination Assay (TPPA) Test
Treponema pallidum particle agglutination assay (TPPA) is a specific, or treponemal test
It is indirect agglutination assay:
- Gelatin particles are sensitized with T pallidum Ag
- Patient serum is mixed with these particles
- I a positive assay the particles aggregate & clump
It is confirmatory. It can diagnose early and also late disease
- Primary syphilis has sens. 85-11%; spec. 98-100%
- Secondary syphilis and late-latent has sens. 98-11%
False positive reactions can occur due to presence of Ab against other treponemal organisms
What are the causes of some false positives in syphilis tests
Causes of _false positive in VDRL/RPR i_nclude:
- Technical
- Acute biological (fever, immunisation, pregnancy)
- Chronic biological (i.e. > 6 months) (chronic infection, autoimmune disease, IDU, debilitated states, advancing age)
Causes of false positive TPHA include:
- Systemic lupus erythematosus (SLE), infectious mononucleosis, leprosy
How do you treat Early Syphilis?
Treatment Of Early Syphilis
For pimary, secondary, or early latent (infected <2 years) syphilis, Rx is:
- Benzathine penicillin 2.4 MU IMI stat (Bicillin Long Acting Injection 900mg/2.3ml prefilled syringe x2)
In epidemiological (contacts), Rx is the same.
For penicillin allergy, Rx replace with doxycycline 100mg twice daily for 14 days
For pregnancy:
- General Rx is benzathine penicillin 2.4 MU IMI
- If in third trimester, give benzathine penicillin 1.8g (2.4 MU) followed by a second dose one week later
- If allergic to penicillin, desensitise (cannot use doxycycline )
Note that a Jarisch–Herxheimer reaction (usually not life-threatening) is a reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment. Efficacious antimicrobial therapy results in lysis (destruction) of bacterial cell membranes, and in the consequent release into the bloodstream of bacterial toxins, resulting in a systemic inflammatory response.
How do you treat early syphilis in a pregnant individual
For pregnancy:
- General Rx is benzathine penicillin 2.4 MU IMI
- If in third trimester, give benzathine penicillin 1.8g (2.4 MU) followed by a second dose one week later
- If allergic to penicillin, desensitise (cannot use doxycycline )
