The Great Imitator

Why a lecture on syphilis?

syphilis is an treatable disease control of syphilis is vital because of its interactions with HIV

Outline

• • • • • • • • History Microbiology Epidemiology Diagnosis Pathophysiology Clinical Manifestations Treatment Syphilis and HIV

Pre-Penicillin Era

•

Highly prevalent in many countries/societies in pre-penicillin era

•

Dramatic drop in incidence/prevalence after introduction of penicillin in mid 1940s

Epidemiological Synergy

•

HIV and syphilis co-facilitate transmission of each other

 Despite CDC campaign to eradicate in 2000s total cases per year continue to increase 

EPIDEMIOLOGY

: Worldwide; primarily involving young people between 20-35 years 

HOST RANGE

: Humans

Microbiology

•

Treponema pallidum

, causative agent isolated 1905 • Family Spirochaetacaeae

Treponema

Gram-negative have an outer membrane motile microaerophilic to anaerobic found in the oral cavity, intestinal tract, genital areas of man and some animals

The primary mode of transmission is via sexual contact .

Syphilis is passed from person to person through direct contact with a syphilis sore . Sores occur mainly on the mouth.

external genitals, vagina, anus, or in the rectum. Sores also can occur on the lips and in the

blood transfusion

Syphilis is also transmitted congenitally from an infected mother to her infant.

Congenital Syphilis

•

Syphilis is transmissible from mother to infant

•

Transmission usually occurs during early stages, but may occur at any stage in an untreated mother

Clinical Stages

•

Syphilis is conventionally divided into several stages:

–

Primary

–

Secondary

–

Latent

–

Late, or tertiary

Untreated, syphilis progresses through a primary and secondary stage before becoming latent. Up to 1/3 of people with untreated syphilis develop tertiary disease late in life, primarily cardiovascular and neurologic.

Natural History of Untreated Syphilis

Pathophysiology

• Transmission, usually sexual, requires direct contact lesion, incubation period 21 days •

PRIMARY

: Initial lesion develops at site of transmission, cellular response/perivascular infiltrate.

•

SECONDARY

: Treponemes macrophages.

disseminate , cleared by •

TERTIARY

: Result of chronic inflammation, hypersensitivity reaction and end organ damage

Primary syphilis incubation period - 10-90 days(3weeks) lesion at the site of inoculation – chancre (hard chancre) lesion not infectious lesion spontaneously disappears in 2-6 weeks bacteria enter blood stream

Primary Syphilis

• • • • Chancre appears within 3 weeks of infection Single center painless papule at site of inoculation distinct indurated borders and ulcerated Spontaneously heals Discreet, firm painless lympadenopathy

Primary syphilis

Secondary Syphilis

• • Defined by disseminated symptoms and positive serology – Bilateral symmetric rash, palms/soles – Fever, sore throat, malaise – Arthalgias – Condyloma lata Usually 2-8 weeks after appearance of chancre .

• Even if untreated, eventually macrophage clearance and treponemicidal complement leads to resolution.

Rash is never vesicular except in congenital form

: rash-condyloma lata-generalized LAP pruritis : mocus patch-ulcer-erosion : chancre-rash-condyloma lata-mocus patch .: fever-malaise-pharyngitis laryngitis-anorexia –weight loss-arthralgia : asymptomatic-symptomatic(headech meningitis-meningismus)

(diplopia-decreased vision) : tinnutis-vertigo-cranial nerve involvement(2,8) : GN-nephrotic syn.

: hepatitis

• Period of asymptomatic infection, however serologic test continue to be positive.

– Early Latent : documented within one(4) year acquisition, very infectious.

of – Late Latent : greater than 1(4) year since transmission

Tertiary Syphilis

• 30% of untreated P&SS progresses to tertiary.

• Combination of treponemal invasion of end organs and delayed type hypersensitivity response in skin, CVS, CNS .

• GUMMA : late benign granulomas to skin/viscera • CVS : endarteritis obliterans to vaso vasorum

• • • • Involvement may occur as soon as 1 yr post acquisition.

Asymptomatic

: 15% of PS and 40% SS have abnormal CSF findings

Acute Meningitis

: typical meningeal findings dx via PCR, VDRL

Meningovascular

vessels.

– General paresis : diffuse inflammation/ syphilitic endarteritis eventual vascular occlusion of cerebral : chronic infection cerebral cortex/meninges – Tabes Dorsalis : demyelination of posterior columns, dorsal roots, and dorsal root ganglia.

•

Meningeal neurosyphilis

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includes acute syphilitic meningitis

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headache, fever, CSF abnormalities

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Meningovascular neurosyphilis

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“syphilitic stroke”

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hemiparesis, hemiplegia, aphasia, seizure

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Parenchymatous neurosyphilis

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general paresis

–

tabes dorsalis

Parenchymatous neurosyphilis

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General paresis (dementia paralytica)

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T. pallidum directly invades cerebrum

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memory loss, personality changes, headache, delusions, seizure

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neurologic findings include:

• • • •

Argyll Robertson pupils slurred speech expressionless face tremors

Parenchymatous neurosyphilis

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Tabes dorsalis

– –

occurs after long latent period (20-25 yrs.)

• •

early features : lightning pains, paresthesias, diminished DTRs, poor pupillary responses late features crises” : ataxia, bladder and rectal disturbances, Charcot joints, “visceral “tabetic facies” due to ptosis and flabbiness of facial muscles

Tertiary syphilis

Syphlitic Aortic Aneurysm

Aortic Aneurysm

Ruptured Aortic Aneurysm

Tree-barking Clot

Stenosis of Coronary Arteries

Charcot Joint

Gumma of Face

Gummas of the Nose

Gumma - Nose

Gmmas of Arm

Gummas - Arm

Ulcerating Gumma

•

Late complications of syphilis occurred in about 1/3 of patients in the preantibiotic era

•

Prompt penicillin therapy of early disease not only prevents infection in others , but also prevents late complications

•

Neurosyphilis may present and progress rapidly in patients co-infected with HIV

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perinatal death -premature delivery -Low birth weigth -congenital anomalies

Syphilis in newborns

Congenital syphilis : Transplacental : beginning 9 - 10 weeks analogous to secondary adquired syphilis affects bone, brain, liver, lung placenta: large and thickened, hypercellular villi, UC abscess-like necrotic foci Vertical transmission : more freq. primary and secondary.

Risk diminishes with after 4 years of infection

Clinical manifestations of early CS

• The earliest sign of CS is nasal discharge (snuffles) that occurs 1-2 weeks before the onset of the rash. Treponemes abound in the discharge, providing a definitive means of diagnosis .

• Secondary lesions on face; they first appeared during the fourth postnatal week.

• The vesiculobullous eruption, known as pemphigus syphiliticus, is highly distinctive when present. When the bullae rupture, they leave a macerated, dusky red surface that readily dries and crusts

• Other stigmata seen before the age of 2 years include maculopapular rash,

hepatosplenomegaly

and jaundice.

Congenital syphilis. Diaphysitis with abundant callus formation secondary to pathologic fractures through the metaphyseal lesions. The lesions healed, and there were no sequelae

Laboratory Examination

• Since the treponeme is too small to be visualized under light microscopy, oblique light dark field microscopy is required to identify organisms.

• Serology: – Non-Treponemal: RPR, VDRL – Treponemal Test: MHA-TP, FTA-ABS

Laboratory Diagnosis

• Blood serum for antibodies detection a. Non-specific: non-treponemal tests (lipoidal

antibody)

• R apid P lasma R eagin RPR • • V enereal D isease R eference L aboratory VDRL Autamate reagin test ART b. Specific: treponemal tests • T reponema p allidum H em A gglutination assay TPHA • • T reponema FTA abs p allidum P article A gglutination assay TPPA

•

DIAGNOSIS

Diagnostic testing involves a two-step with a nonspecific specific process, beginning test and concluding with a treponeme test for patients screening positive.

The non-treponemal s creening tests include the VDR L (Venereal Disease Research Laboratory), RPR (rapid plasma reagin), or ART (automated reagin test). Nontreponemal test antibody titers usually correlate with disease activity and should be reported with a quantitative titer . On the other hand, other disease states or physiologic states , such as pregnancy, can yield false-positive results.

Because the current incidence of syphilis is so low, the majority of positive screening tests are not due to treponemal infection.

• • • The FTA-ABS test (Fluorescent Treponemal Antibody Absorption Test) for syphilis is an example of an indirect fluorescent antibody procedure.

This is a

confirming test

for syphilis In this test, killed T. pallidum,(the known antigen), is fixed on a slide . The patient's serum is added to the slide. If the patient has syphilis, antibodies against the T. pallidum will react with the antigen on the slide.

• Other spirochetal dis:

• • • • Penicillin G , in benzathine, aqueous procaine, or aqueous crystalline form, is the drug of choice for treatment of all stages of syphilis, and is the only effective treatment for the prevention of congenital syphilis in pregnancy.

Erythromycin may be curative in the mother, but may not prevent congenital syphilis because of the variability of transplacental passage of the antibiotic. Ceftriaxone alternative regimen for patients who have penicillin allergy may prove useful in adults as an azithromycin in the penicillin-allergic pregnant woman has not been adequately evaluated.

– – PCN G Benzathine single dose IM 2.4 million units IM PCN procaine(2.4 million units IM daily +probencid for 14 days) – – – – – – Ceftriaxon 250 IV_IM for 5 days Ceftriaxon 1 gr IM for 14 days Azithromycin 2 gr stat,1 gr daily for 8 days Doxycycline 100mg bid(15 days) Tetrasyclin 500 QID (15 days) Azithromycin 2 gr single dose

PCN G benzathine 2.4 m u IM weekly for 3 weeks. PCN G IV 12-24 million units q 4hr for 14 days

(Congenital :

PCN G IV(10 days) or procain PCN).

• • • Within hours after treatment, patients can develop an acute complication called the Jarisch-Herxheimer reaction . Symptoms include fever, chills, myalgias, headache, tachycardia, hyperventilation, vasodilation, and mild hypotension.

Although the reaction occurs in 10% to 25% of patients overall, it is most common in the treatment of early syphilis.

All children born to mothers who were sero-positive during pregnancy:

•

A single intramuscular dose of benzathine benzylpenicillin 50,000 IU/kg

: Re-evaluation after treatment at 3, 6 and 12 months of age.

: or >1yrs:3-6-12-24 m until 5 yrs.

clears.

neurosyphilis should be evaluated (clinical and CSF) every 6 months until CSF

– HIV pts have higher titers in early stage.

– Late stage HIV may have delayed or absent serologic response.

– Higher incidence of false reactive nontreponemal Ab test HIV pts.

– High co-infection rate for HIV and syphilis.

– Early syphilis lesions may potentiate acquisition of HIV virus.

– More likely to present multiple or persistent chancres – Skin rash is more pronounced – More rapid progression to neurosyphilis – Gummas more common and typically involve the viscera – Recommendations the same as HIV negative, but follow-up w VDRL and RPR q 1,2,3.6,9,12 months.

T H N A K Y O U !