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Home , Syphilis

3/11/2013

Syphilis: A Case-based Review

Thomas Cherneskie, MD, MPH NYC Department of Health and Mental Bureau of STD Control

Serologic Interpretation

RPR NonReactive / RPR NonReactive / FTA-ABS NonReactive FTA-ABS Reactive No Diagnosis Very Early Primary Syphilis Incubating syphilis Secondary Syphilis w/ Prozone Very Early Primary Syphilis Late untreated syphilis w/ sero-reversal of RPR History of Treated Syphilis Syphilis Rxed inadvertently in past False-negative Non-Treponemal test False-positive Treponemal Test (rare)

RPR Reactive / RPR Reactive / FTA-ABS NonReactive FTA-ABS Reactive Biologic False Positive Positive Syphilis Diagnosis False-negative Treponemal Test (rare) Endemic (non-sexual) treponemal ds

BIOLOGIC FALSE POSITIVE REACTIONS CAUSES Genital Disease ACUTE (< 6 months) . CHRONIC > 6 months . The Usual Suspects Physiologic Physiologic Older age - type 1 & 2 Vaccinations Chronic Infection (e.g.) Primary Syphilis- pallidum Typhoid - Yellow Lymphogranuloma Venereum (LGV)- C. trachomatis Acute (e.g.) HIV/AIDS Herpes varicella-zoster Autoimmune Disorders (e.g.) Donovanosis- Herpes simplex Infectious mononucleosis Rheumatoid /Balanitis Autoimmune thyroiditis (Erosive) Mumps Other Conditions (e.g.) Aphthosis major Multiforme Viral Malnutrition Behcet’s disease Reiter’s Syndrome HIV sero-conversion illness Malignancy Fixed Trauma Pneumonia (incl. ) Hepatic cirrhosis Stevens Johnson Syndrome Lyme disease Intravenous drug use Cancer- Squamous Cell

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Diagnosis of Chancroid Chancroid (Haemophilus ducreyi) • Clinical Diagnosis: Bubo c/ painful ulcers • Gram negative coccobacillus with short incubation (3-10 days, average ~5) • Important to rule out Syphilis and HSV • Endemic in regions of sub-Saharan Africa, SE Asia, India, South America, Caribbean • Men typically present with genital ulceration • Women usually present w/ non-ulcerative symptoms (Vaginal discharge or bleeding; pain with defecation/urination/sex; ulcers are usually sub-clinical) • Painful Adenitis in 40-50% cases (80% of Syphilis) • Systemic symptoms generally absent

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LGV: Clinical Presentation • Primary – small non-painful genital at site of after an incubation period of 3 – 30 days, can ulcerate – May remain undetected in , vagina • Secondary clinical manifestations – 2-6 weeks after primary lesion – Tender inguinal, femoral adenopathy, Uni- or bilateral, may progress to fluctuance (buboes) – or proctocolitis associated with receptive anal intercourse, often times hemorrhagic • Tertiary complications – Lymphoedema, , granulomas, strictures

LGV: Treatment

• Consider Presumptive Treatment for LGV – Anal receptive sex and signs/symptoms of proctitis especially among MSM – + anorectal specimen: S/Sx proctitis or HIV+ status – with extensive

• 100mg PO BID x 21 days (preferred) • Azithromycin 1g PO q week x 3 weeks (lacking clinical data, but probably effective)

Characteristics of Ulcerating Genital Infections Syphilis Staging Syphilis HSV Chancroid Primary Number Single (60%) Multiple Multiple • Muco-cutaneous Ulceration Edges Well demarcated Erythematous Irregular Secondary Round/Oval Cratered Undermined • Localized or Diffuse Cutaneous Eruption Depth Variable Superficial Deep/ Excavated

Base Clean Serous • Mucous Patches PURULENT Min. Vascular Non-vascular Vascular/Friable • Condyloma Lata Induration + - - • Patchy Alopecia - +/- + + + Painful Latent

Nodes Firm Firm Fluctuant • Asymptomatic at Treatment

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MANY OF THESE CLINICAL PHOTOS HAVE BEEN MADE AVAILABLE FROM NYU DEPARTMENT OF DERMATOLOGY

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CDC NYU DEPARTMENT OF DERMATOLOGY

Differential Diagnosis of Secondary Syphilis

• • Drug eruption • Viral • Acute HIV • Sarcoidosis (annular )

• Any of Unknown Origin, especially with systemic complaints

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CDC

9 3/11/2013 NYU DEPARTMENT OF DERMATOLOGY NYU DEPARTMENT

Syphilis Staging: Latent Infection Relevance of Accurate Staging of Syphilis Infection Any of the following during the 12 months prior LATENT PRIMARY SECONDARY to Dx = EARLY LATENT EARLY UNKNOWN LATE Currently YESWhy? Possible No Any of the following > 12 months prior to Dx = Infectious ?

LATE LATENT Duration of Rx Bicillin LA IM x1 Bicillin LA IM x3 Doxy PO x 2 weeks Doxy PO x4 weeks • Unequivocal Signs/Symptoms • Serologic Conversion Management of Previous Previous Previous SexualContacts 3 months 6 months 12 months ? • Exposure to an infectious case Serologic RPR titer: If RPR >/= 1:32: Response to Rx 2 dilutions 2 dilutions • Four-fold (2 dilution) rise in titer in 6 - 12 months in 12 - 24 months in a previously treated patient If HIV+: ?LP YES YES

• Only possible exposure New in 2010 CDC Rx Guidelines

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Treatment Regimens

Syphilis – Issues Underscored in 2004 2010 CDC Treatment Guidelines Packaging • Must ensure use of Bicillin LA (not C-R) • Azithromycin (2g oral) not recommended • possible alternative to PCN based on limited clinical studies – risk allergic cross-reactivity Current – optimal dose not defined Packaging • Caution- Any non-PCN regimen in HIV+

Based on 2010 CDC Treatment Guidelines

Relevance of Accurate Staging of Syphilis Infection

LATENT PRIMARY SECONDARY EARLY UNKNOWN LATE 2 yrs thru 9 mo ago 5 mo ago 3 mo ago thru present Currently YESWhy? Possible No Infectious ? Matthew Jason Brian Duration of Rx Bicillin LA IM x1 Bicillin LA IM x3 Maximum Range for Exposure Rash Doxy PO x 2 weeks Doxy PO x4 weeks Treated 6 months Management of Previous Previous Previous SexualContacts 3 months 6 months 12 months ? Symptom Onset

Serologic RPR titer: If RPR >/= 1:32: Response to Rx 2 dilutions 2 dilutions in 6 -12 months in 12-24 months If HIV+: ?LP YES YES

Approach to Inadequate Response to Therapy by Syphilis Stage Serologic Response to Treatment

* Primary, Secondary Syphilis • Evaluate for possible re-infection Resolution of symptoms • Re-screen for HIV By 6-12 months- Fall in RPR titer by 2 titers • Consider suboptimal treatment * Early Latent, Late Latent Syphilis –Incorrect staging of infection If RPR titer Neurosyphilis (CSF exam) ??? HIV-infected Patients • Re-treat with Bicillin 2.4 mU IM x 3

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Latent Syphilis: Indications for CSF Exam 1:128 1: 64 • Neurologic or Ophthalmic Signs/Symptoms 1: 32 • Evidence of Active Tertiary (, ) 1: 16 • Inadequate Serologic Response to Treatment 1: 8 1: 8 • HIV+ with Late Latent or Latent Unknown Dur. 1: 4

HIV+ patients Although associated with clinical and CSF 1: 2 ● RPR >/= 1:32 abnormalities consistent with neurosyphilis- if asymptomatic, no data that 1: 1 ● CD4

1:128 1:128

1: 64 1: 64 1: 32 1: 32 1: 16 1: 16 1: 8 1: 8 1: 8 1: 8 1: 4 SEROFAST RPR 1: 4 1: 2 1: 2 1: 1 1: 1

Treatment 3 mo. 6 mo. 9 mo.12 mo. 1.5 yrs Treatment 3 mo. 6 mo. 9 mo.12 mo. 1.5 yrs

No syphilis diagnosis Initial EIA Treponemal Test 1:128 (Recent infection cannot be ruled out) 1: 64 +

1: 32 RPR + Syphilis (old or new) • No Hx: Rx 1: 16 - • Hx of Syphilis: reRx if ↑ titer 1: 8 1: 8 1: 8

1: 4 Re-Exposure ? Old Rxed Syphilis 2nd Treponemal Test If no known Hx Rx (FTA-ABS; TP-PA) 1: 2 - 1: 1 + No Rx Rx indicated or use a 3 rd treponemal test (unless Hx Rx) Treatment 3 mo. 6 mo. 9 mo.12 mo. 1.5 yrs as a ‘tie-breaker’

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Serologic Interpretation

RPR NonReactive / RPR NonReactive / FTA-ABS NonReactive FTA-ABS Reactive No Syphilis Diagnosis Very Early Primary Syphilis Incubating syphilis infection Secondary Syphilis w/ Prozone Very Early Primary Syphilis Late untreated syphilis w/ sero-reversal of RPR History of Treated Syphilis Syphilis Rxed inadvertently in past False-negative Non-Treponemal test False-positive Treponemal Test (rare)

RPR Reactive / RPR Reactive / FTA-ABS NonReactive FTA-ABS Reactive Biologic False Positive Positive Syphilis Diagnosis False-negative Lyme disease Treponemal Test (rare) Endemic (non-sexual) treponemal ds

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