CLINICAL PRESENTATIONS OF PRIMARY • Lesion appears 10-90 days after contact at site of exposure; may persist Evaluating Patients For Primary Syphilis for 2-3 weeks then resolves • Usually genitorectal but may be extragenital, depending on exposure site SEXUAL HISTORY, RISK ASSESSMENT, & PHYSICAL EXAM Patient with new genital lesion or suspicious genital • Clinical presentation, typical or atypical L • Typical: single painless, indurated, clean-based ulcer with rolled edges Sexual History, Risk Assessment (past year) Physical Exam & bilateral painless adenopathy • Gender of partners, number of partners • Oral cavity • Atypical: can mimic herpes & other genital ulcers (new, anonymous, serodiscordant HIV status, • Lymph nodes SEXUAL HISTORY, RISK ASSESSMENT, & PHYSICAL EXAM • ~25% present with multiple lesions exchange of sex for drugs or money) • Skin • Lesions of primary and secondary syphilis can be present at the same • Types of sexual exposure • Palms & soles time, especially in HIV positive individuals • Recent STDs; HIV serostatus DIAGNOSTIC WORK-UP • Neurologic Differential Diagnosis • Substance abuse 1 • Eyes • Darkfield (if available) • Treponemal test (TP-PA/FTA-ABS/EIA/CIA) • Herpes (most common), primary HIV ulcers, , granuloma • use • Genitalia/pelvic • Stat RPR (if available) • Herpes culture or PCR2 inguinale, trauma, and many non-STD infectious and non-infectious History of Syphilis • Perianal • RPR or VDRL serology • HIV Test causes of genital ulcers • Prior syphilis (last serologic test & last treatment) (quantitative) • More than one etiology can be present at the same time DIAGNOSTIC ISSUES IN PRIMARY SYPHILIS NEGATIVE OR • Darkfield ~ 80% sensitive, varies with skill of examiner; Presumptive Primary 3 POSITIVE UNAVAILABLE decreased sensitivity as lesion ages Primary Syphilis REACTIVE Syphilis3 • A negative RPR/VDRL does not exclude syphilis diagnosis; Darkfield Stat RPR ~75-85% sensitive in primary syphilis Treat, obtain Treat, obtain quantitative RPR and treponemal • Use same test (RPR or VDRL) in sequential testing; quantitative RPR and NON-REACTIVE OR titers are not interchangeable tests on treatment date, treponemal tests on UNAVAILABLE D W • Need both non-treponemal (RPR or VDRL) and treponemal test treatment date, report to health department, Syphilitic Ulcer, Shaft Syphilitic Ulcer, Shaft (TP-PA, FTA-ABS, EIA, CIA) to make syphilis diagnosis report to health Risk factors or high partner management, & • Treponemal tests can remain positive for life; utility limited in patients YES department, partner clinical suspicion follow-up. (If stat RPR with history of prior syphilis, comparison of non-treponemal titers needed 4 management, (e.g., MSM) non-reactive, repeat RPR 2 For more details on Treponemal Immunoassays: & follow-up. weeks after treatment.) www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/Useof NO TreponemalImmunoassays_Syphilis.pdf Obtain treponemal and non- Note: Evaluate for neurosyphilis (assess if neurologic, ophthalmic or otic treponemal tests at the same time. symptoms present, as neurosyphilis can occur at any stage of syphilis) S S TREATMENT & FOLLOW-UP Multiple Syphilitic Ulcers, Shaft Multiple Syphilitic Ulcers Resembling Herpes Treatment of Primary Syphilis •Repeat EIA/CIA test Recommended Regimen RPR+/RPR – RPR + RPR – EIA/ NON-REACTIVE 2 - 4 weeks after initial visit. 5 • Benzathine Penicillin G 2.4 million units IM x 1 TP-PA + TP-PA – TP-PA – CIA • Consider other etiologies. Alternative Regimens for Penicillin Allergic Non-Pregnant Patients: Efficacy not well established & not studied in HIV+ patients; close follow-up REACTIVE Primary Syphilis3 essential: 3 Primary Syphilis or Presumptive •Repeat RPR/VDRL C S • Doxycycline 100 mg po bid x 2 weeks or Quantitative REACTIVE Primary Syphilis3,5 with RPR – 2 - 4 weeks after Treat, obtain quantitative RPR on Syphilitic Ulcer, Multiple Syphilitic Ulcers, Vulva RPR/VDRL • 500 mg po qid x 2 weeks initial visit. If reactive, treatment date, report to health *Pregnant patients with penicillin should be desensitized and Treat, obtain quantitative RPR on repeat TP-PA or department, partner management, treated with penicillin treatment date, report to health FTA-ABS. NON-REACTIVE & follow-up. See CDC STD Treatment Guidelines: www.cdc.gov/std/treatment department, partner mangement, • Consider other California STD Treatment Guidelines Grid: & follow-up. etiologies. REACTIVE Presumptive Primary www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Document%20Library/ If RPR non-reactive, repeat RPR TP-PA Syphilis with RPR – 3,5 STD-Treatment-Guidelines-Color.pdf 1-2 weeks after treatment. S C **Additional Testing and Follow-up Treat, obtain quantitative RPR on NON-REACTIVE Syphilitic Ulcer, Perianal Note: Also test for HIV, GC/CT, and pregnancy (if female of reproductive age) treatment date, report to health Crusted Syphilitic Ulcer, Urethra • 1-2 weeks: clinical follow-up •Repeat RPR/VDRL 2 - 4 weeks after Reassess patient. If alternate diagnosis favored or department, partner management, Photo Credits • 3, 6, 9, 12, 24 months: serologic follow-up for HIV+ patients initial visit. If reactive, then repeat TP- confirmed by laboratory testing, no further action. & follow-up. Repeat RPR 2-4 weeks C - Centers for Disease Control and Prevention; D - With permission from the Denver Metro Health Clinic; S - With permission from San Francisco City Clinic; • 6, 12 months: serologic follow-up for HIV- patients PA or FTA-ABS. after treatment. If clinical suspicion for syphilis persists then treat, obtain W - With permission from University of Washington STD Prevention Training • Failure of titer to decline fourfold (e.g. 1:64 to ≤ 1:16) within 6-12 months •If repeat TP-PA/FTA-ABS is negative, from titer at time of treatment may indicate treatment failure. Titer decline quantitative RPR on treatment date, report to health Center Washington (photos from UW HSCER Slide Bank) then RPR/VDRL is likely biologic false may be slower in HIV+ patients. department, partner management, & follow-up. If To Order Additional Copies positive. • Consider retreatment and CSF evaluation if titer fails to decline treatment date RPR negative, repeat RPR 2-4 weeks See the online version of the Primary Syphilis Algorithm on the clinical •Consider other etiologies. appropriately after treatment. resources page of the CA PTC website: www.californiaptc.com Acknowledgements 1 Treponemal tests may be more sensitive than non-treponemal tests during primary syphilis. REPORTING & PARTNER MANAGEMENT 2 Also consider culture for (chancroid) if exposure in endemic areas or if lesion does not respond to syphilis treatment. Medical Directors from the National Network of STD Clinical Prevention 3 Training Centers, California STD Controllers Association, Division of STD • All syphilis cases and presumptive cases must be reported to the local All patients with suspected syphilis should be tested for HIV infection and screened for other STDs. Repeat HIV testing of patients with primary Prevention of the Centers for Disease Control and Prevention health department within one working day of diagnosis syphilis 3 months after the first HIV test, if the first test is negative. 4 If the patient is a man who has sex with men (MSM) or has high risk sexual behavior or clinical exam with classic features of a syphilitic ulcer, then Revised 7/2018 • Local health departments will assist in partner notification & management standard of care includes presumptive treatment at the time of the inital visit before diagnostic test results are available. Presumptive treatment • Contact Number at Local Health Department: 5505505-467-361105-476-3611 505-476- is also recomended if patient follow-up is a concern. 5 If the patient does not respond to treatment, repeat RPR/VDRL after treatment and consider other etiologies. CLINICAL PRESENTATIONS OF SECONDARY SYPHILIS • Symptoms typically occur 3-6 weeks after primary stage (can overlap with primary); Evaluating Patients For Secondary Syphilis resolve in 2-10 weeks • 25% may have relapse of signs & -symptoms in first year SEXUAL HISTORY, RISK ASSESSMENT & PHYSICAL EXAM Patient with new onset ras'h, atypical warty lesion, or Signs & Symptoms of Secondary Syphilis -I History, Risi< Aa111r•11t (pastyear) PhplcalExam other signs & symptoms of secondary syphilis • : most common feature (75-90%); can be macular, papular, squamous (-scale), pustular • Gender of partners • Oral cavity (rare), vesicular (very rare) or combination; usually nonpruritic; may involve palms & • Number of partners (new, anonymous, serods· • Lymph nodes soles(6o%) cordant HIV status, exchar-.ie of sex for drugs or • Skin SEXUAL HISTORY, RISK ASSESSMENT, & PHYSICAL EXAM • Lymphadenopathy: (70-90%); inguinal, epitrochlear, axillary & cesvical sites most commonly money) • Palms & soles affected • Types of sexual expoSlR • Ntu01ogic DIAGNOSTIC WORK-UP • Constitutional Symptoms: (50-80%); malaise, fever • - STDs; HIV serostatus • Eyes • Mucous Patches: (5-30%); flat gray-white patches in oral cavity & genital area • substance abuse • G-.lia/pelvic • Stat RPR (if available) • Trej>onemal test(TP-PA/FTA·ABS/EIA/CIA) • Condyloma Lata: (5-25%); moist, heaped, -like lesions in genital, peri-rectal & rectal areas, • Perlanal • RPR or VDRL serology • HIV Test & oral cavity (quantitative) • Alopecia: (10-15%); patchy hair loss, loss of lateral eyebrows History of Syphllls • Condom use • Neurosyphilis: (<2%); visual loss, hearing loss, cranial nerve palsies among other • Prior syphlis (last serologic test & last treatment) Presumptive Secondary Possible Secondary DIAGNOSTIC ISSUES IN SECONDARY SYPHILIS Syphilis REACTIVE UNAVAILABLE Syphilis "' • RPR/VDRL -100% sensitive in secondary syphilis Treat, obtain quantitative Consider o Rare caveat: pro zone reaction, false negative RPRNDRL from excess antibody RPR and treponemal presumptive interfering with antibody/antigen reaction tests on treatment date, treatment if o Prozone occ..-s <1% of secondary syphilis cases; if suspected ask lab to dilute serum to at report to health high clinical C department, partner suspicion. least 1/16 Macul opapu lar Rash Subtle Macular Rash Condyloma Lata • Use same test (RPR or VDRL) in sequential testing; titers are not interchangeable management, & follow-up. • Need both non-treponemal (RPR or VDRL) and treponemal test to make syphilis diagnosis Obtain serologic tests. • Treponemal tests (TP·PA, FTA·ABS, EIA, CIA) can remain positive for life; utility limited in patients with history of prior syphilis, comparison of non-treponemal titers needed For more c1etans on rr.ponemal lmrnunoassays: www.cdph.ca.gov/Programs/CID/ Syphilis unlikely. DCDC/CDPH%20Documen1X20Ubrary/UseofTreponemallmmunoassays_Syphilis.pdf Consider other etiologies. Note: Evaluate for neurosyphilis (assess if neurologic, ophthalmic, or otic symptoms present, s w as neurosyphilis can occur at any stage of syphilis} Secondary Condyloma Lala Condyloma Lata REACTIVE NO PROZONE' TREATMENT & FOLLOW-UP Syphilis' Treat, obtain Not Syphilis. Treatment of Secondary SyphUls quantitative RPR on Consider other etiologies. Rocommendrd R•gfmen treatment date, report • Benzathine Penicillin G 2.4 million units IM x 1 l to health department, Secondary Syphilis' Aftematlw Rogrmens for Pfflfcflffn Alfttgfc Non-Prognant Patl•nts: partner management, & follow-up. w w Efficacy not well established & not studied in HIV+ patients; close follow-up essential: Treat, obtain quantitative RPR on NON· treatment date, report to health Macula-Rash Mucous Patches • Doxycycline 100 mg po bid x 2weeks or REACTIVE department, partner management, & Possible • Tetracycline 500 mg po qid x 2 weeks follow-up. *Pregnant patients with penicillin allergy should be desensitized and treated with penicillin Secondary Syphilis of the rash of secondary syphilis includes: , , multiforme, , scabies, drug reaction, primary HIV infection Could be prior syphilis See CDC STD Treatment Gufdeflnes: www.cdc.gov/std/treatment Interpretation: possible syphilis, prior (treated or untreated). California STD Treatment Guldelfnes Grid: syphilis or false positive EIA. Rule out prozone. Treat https://www.cdph.ca.gov/Programs/CID/DCDC/CDPH%20Documen1X20Ubrary/ Rule out prozone. Reassess patient. If STO-Treatment-Guidelines<.olor.pdf if high risk or high alternate diagnosis favored or clinical suspicion. **Addltfonal Testing and Follow-up confirmed by laboratory Repeat RPR 2-4 weeks. Note: Also test for HIV, GC/CT, and pregnancy (if female of reproductive age) testing, no further action. • 1·2 weeks: clinical follow-up If at risk for syphilis repeat RPR testing < s • 3, 6, 9, 12, 24 months: serologfc follow-up for HIV+ patients z-4 weeks. Drug Reaction Guttate Psoriasis • 6, 12 months: serologic follow-up for HIV· patients • Failure of titer to decline fourfold (e.g.1:64 to s1:16) within 6-12 months from titer at time Photo Credits of treatment may indicate treatment failure. Titer decline may be slower in HIV+ patients. 1 If the patient isa man who has sex with men (MSM) ordinical exam with dassic features of secondary WWtt:h pe.rmission from University of Washington STD Prevention Training Center Washington (photos from • Consider retreatment and CSF evaluation if titer fails to decline appropriately syphilis, consider presumptive treatment at the time of initial visit before the diagnostic tests results are UW HSCER SI.de Sank); S Wtt:h permission from San Francisco City Clink; C Centers for Disease Control and Refer to CDC Treatment Guidelines for management of treatment failure & consult the STD available. Presumptive treatment is also recomended if patient follow-up is a concern. Prevention Clinical Consultation Network at www.STDCCN.org , All patients with secondary syphilis should be tested for HIV infection and screened for other STDs. To Order Additional Copies: See the online version of the Secondary Syphilis Algorithm on the clinical Rep-eat HIV testing of patients with secondary syphilis 3 months after the first HIV test, if the first test is resources page of the CAPTC website: www.californiaptc.com REPORTING & PARTNER MANAGEMENT negative. Acknowledgements: Medical Directors from the National Network of STD dinical Prevention Training 'Pro zone reaction is a false negative RPR or VDRL from excess antibody interfering with the Centers, California STD Conb'ollers Association, Division of STD Prevention of the Centers for Disease Control • • All syphilis cases and presumptive cases must be reported to the local health antigen-antibody reaction. and Prevention department within one working day of diagnosis 4 FT A-ABS is no longer considered the gold standard trep-onemal test given concerns regarding Revised 7/2018 • Loe.al health departments will assist in partner notification & management specificity. TP·PA should be used for a second treponemal test when EIA/CIA is reactive and RPR is • Contact Number at Loe.al Health Department: non-reactive.

505-476-3611