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Summary Table

Category	Details
Risk Factors	Men who have sex with men (MSM), multiple sexual partners, unprotected intercourse (genital, oral, anal), intravenous drug use (shared needles), sex workers, co-infection with HIV, pregnant women (vertical transmission)
Etiology	Treponema pallidum subspecies pallidum, a spirochete bacterium; chronic and systemic infection
Patient Presentation	Primary: painless genital ulcer. Secondary: diffuse non-pruritic rash including palms and soles. Latent: asymptomatic, positive serology only. Tertiary: gummatous destruction, aortic aneurysm, tabes dorsalis
Classic Physical Exam	Primary: solitary, painless, clean-based ulcer with indurated margins (chancre), non-tender inguinal lymphadenopathy. Secondary: symmetric copper-colored maculopapular rash on trunk, palms, and soles; condylomata lata in moist areas; mucous patches on oral mucosa; moth-eaten alopecia; generalized lymphadenopathy
Key Diagnostic Results	Screening/monitoring: RPR or VDRL (non-treponemal). Confirmation: TPHA, TP-Rapid, FTA-ABS (treponemal). Direct detection: dark-field microscopy, PCR on lesion specimen
Management	Early syphilis (primary, secondary, early latent): Benzathine penicillin G 2.4 million units IM, single dose. Late syphilis (late latent, tertiary): Benzathine penicillin G 2.4 million units IM weekly for 3 weeks. Congenital: IV aqueous penicillin G for 10-15 days
Keywords	Painless chancre, ulcus durum, condylomata lata, mucous patches, moth-eaten alopecia, Hutchinson's triad, Argyll Robertson pupil, Jarisch-Herxheimer reaction, VDRL/RPR, tabes dorsalis, serofast

1. Pathophysiology

Syphilis is caused by Treponema pallidum subspecies pallidum, a thin, motile spirochete that cannot be cultured on artificial media. The organism enters the body through microscopic breaks in mucous membranes or skin during sexual contact (genital, oral, or anal), through contaminated needles, through contaminated blood products, or transplacentally from mother to fetus.

Once T. pallidum penetrates the epithelium, it multiplies locally at the site of inoculation and simultaneously disseminates hematogenously within hours. This is a critical concept: syphilis is a systemic disease from the very beginning, even though the initial lesion appears localized. The immune response at the inoculation site produces the classic chancre of primary syphilis, an ulcer formed by the inflammatory infiltrate attempting to contain the organism. This chancre is painless because T. pallidum does not produce toxins that trigger significant nociceptor activation, and the immune response is predominantly a granulomatous-type reaction rather than a neutrophilic one.

The bacterium's outer membrane lacks lipopolysaccharide (LPS), which is why the early immune response is relatively muted and why the organism can evade detection for prolonged periods. T. pallidum also has very few surface-exposed proteins, making it a so-called "stealth pathogen" that avoids antibody-mediated clearance.

If untreated, the primary chancre resolves spontaneously in 3 to 6 weeks (even without treatment), which is a classic exam trap: resolution does not mean cure. The spirochetes continue to circulate, and the disease transitions to secondary syphilis as the immune system mounts a broader, systemic response to the now-widespread organism. The diffuse rash of secondary syphilis reflects the hematogenous dissemination that occurred weeks earlier. The involvement of palms and soles is a high-yield finding because these are areas with thick keratinized skin that most rashes spare; the ability of T. pallidum to infiltrate dermal vasculature even in these areas is distinctive.

Condylomata lata arise in warm, moist intertriginous areas (perianal, vulvar folds) because T. pallidum thrives in these environments. These flat, moist, highly infectious lesions are rich in spirochetes. They should not be confused with condylomata acuminata (genital warts caused by HPV), which are pointed and verrucous rather than flat.

After secondary syphilis, the disease enters a latent phase where the patient is asymptomatic but serologically reactive. This phase is subdivided by duration: early latent (less than 1 year since transmission) and late latent (more than 1 year). The distinction matters because infectivity and treatment regimen differ.

In approximately one-third of untreated patients, tertiary syphilis develops years to decades later. This stage involves three main patterns: gummatous disease (granulomatous destruction of skin, bone, or viscera), cardiovascular syphilis (obliterative endarteritis of the vasa vasorum of the aorta, leading to aortitis, aortic aneurysm, and aortic regurgitation), and neurosyphilis (which can actually occur at any stage). The cardiovascular manifestation typically appears 10 to 30 years after the initial infection, while gummas can appear from 1 to 46 years later.

Neurosyphilis deserves special attention because it does not fit neatly into the staged progression. Treponemal invasion of the CNS can occur early (meningitis, cranial nerve palsies) or late (general paresis, tabes dorsalis). The Argyll Robertson pupil, which accommodates but does not react to light, is a classic late neurosyphilis finding tested frequently.

In congenital syphilis, T. pallidum crosses the placenta, with the risk of fetal infection increasing with maternal spirochetemia. Early congenital syphilis (manifesting before age 2) can present with rhinitis ("snuffles"), maculopapular rash, hepatosplenomegaly, and bony changes. Late congenital syphilis (manifesting after age 2) produces the classic Hutchinson's triad: interstitial keratitis, Hutchinson's teeth (peg-shaped notched incisors), and eighth cranial nerve deafness. Other findings include saddle nose, frontal bossing, saber shins, and mulberry molars.

2. Classification and Clinical Manifestation

Classification Overview

Classification	Subcategory	Defining Feature
Congenital	Early congenital	Symptoms appear within the first 2 years of life
Congenital	Late congenital	Symptoms appear after age 2
Acquired	Early (< 1 year since transmission)
	- Primary	Chancre at inoculation site
	- Secondary	Systemic rash and mucocutaneous lesions
	- Early latent	Asymptomatic, seropositive, < 1 year duration
	Late (> 1 year since transmission)
	- Late latent	Asymptomatic, seropositive, > 1 year duration
	- Tertiary (gummatous)	Granulomatous tissue destruction
	- Tertiary (cardiovascular)	Aortitis, aortic aneurysm, aortic regurgitation
	- Tertiary (neurosyphilis)	Meningitis, tabes dorsalis, general paresis

Clinical Manifestation by Stage

Stage	Timing	Key Clinical Features
Primary	3-4 weeks after infection	Papule evolving into a painless ulcer (chancre), typically 1-2 cm, solitary, round or oval, clean base, firm indurated border, located on genitalia, anus, or oral cavity. Non-tender regional lymphadenopathy, commonly inguinal, usually bilateral
Secondary	4-8 weeks after primary lesion	Non-pruritic maculopapular rash (70% of cases), copper-colored, involving trunk, palms, and soles. Condylomata lata in moist/intertriginous areas. Mucous patches (painless shallow oral ulcers). Moth-eaten (patchy) alopecia. Generalized bilateral symmetric lymphadenopathy. Flu-like symptoms (fever, malaise)
Early Latent	< 1 year after infection	Completely asymptomatic. Diagnosis made solely by positive treponemal AND non-treponemal serology
Late Latent	> 1 year after infection	Completely asymptomatic. Positive treponemal and non-treponemal serology. No longer sexually transmissible, but vertical transmission to fetus remains possible
Tertiary: Gumma	1-46 years after infection	Destructive granulomatous nodules or ulcerative lesions in skin, mucosa, bone, or viscera
Tertiary: Cardiovascular	10-30 years after infection	Aortic aneurysm (especially ascending aorta), aortic regurgitation, aortitis, coronary ostial stenosis, myocarditis
Tertiary: Neurosyphilis	Variable (can occur at any stage)	Early forms: asymptomatic meningitis, meningovascular disease, cranial nerve palsies (especially CN VII, VIII). Late forms: general paresis (personality/cognitive decline), tabes dorsalis (posterior column degeneration with ataxia, lightning pains, Argyll Robertson pupils, Charcot joints)
Early Congenital	< 2 years of age	70% asymptomatic at birth. Copper-colored maculopapular rash (hands and feet), rhinitis/snuffles, condylomata lata, rhagades (perioral fissures), periostitis, osteochondritis, pseudoparalysis of Parrot, hepatosplenomegaly, nephrotic syndrome, uveitis
Late Congenital	> 2 years of age	Hutchinson's triad (interstitial keratitis, Hutchinson's teeth, CN VIII deafness), mulberry molars, saddle nose, frontal bossing, saber shins, lymphadenopathy, hepatosplenomegaly

Complications

Complication	Clinical Clues
Neurosyphilis	Can be asymptomatic (detected only by CSF analysis). Suspect in: HIV co-infection with CD4 < 350 or non-treponemal titer >= 1:32, treatment failure, late syphilis treated with non-penicillin regimen. Symptomatic forms: meningitis, cranial nerve palsy, stroke, tabes dorsalis
Ocular syphilis	Eye pain, photophobia, red eye, decreased visual acuity. Can occur at any stage
Otosyphilis	Hearing loss, tinnitus, vertigo. Can occur at any stage
Pregnancy	Abortion, preterm birth, intrauterine fetal death (IUFD), stillbirth, congenital syphilis

3. Diagnostic Workup

Test Category	Test Name	What It Detects	When It Becomes Positive	Primary Use
Direct (from lesion)	Dark-field microscopy	Live spirochetes	At time of active lesion	Diagnosis of primary syphilis when serology is still negative
Direct (from lesion)	PCR	T. pallidum DNA	At time of active lesion	Diagnosis when dark-field is unavailable
Non-treponemal (serum)	RPR, VDRL	Anti-cardiolipin antibodies	~4 weeks after infection	Screening, monitoring treatment response
Treponemal (serum)	TPHA, TP-Rapid, TP-PA, FTA-ABS	Anti-T. pallidum antibodies	~14 days after infection	Confirmation of diagnosis

Diagnostic Approach in Detail

The diagnostic workup for syphilis relies on two separate categories of serologic testing, and understanding the logic behind each is what exam questions test.

Non-treponemal tests (RPR and VDRL) detect antibodies directed against cardiolipin-lecithin-cholesterol antigens released during cell damage. They are not directed against the spirochete itself. These tests become positive approximately 4 weeks after initial infection, meaning they can be negative during early primary syphilis when the chancre is already present. This is the classic "window period" trap on exams: a patient with a painless genital ulcer and a negative VDRL may still have syphilis.

Non-treponemal titers are quantitative and correlate with disease activity. They are therefore used to monitor treatment response. A successful treatment is defined as a four-fold or greater decline in titer (e.g., from 1:32 to 1:8). After successful treatment, titers should decline and may become non-reactive. However, some patients become serofast, meaning their titer plateaus at a low level (typically 1:8 or below) and never fully converts to non-reactive. Serofast status within 1-2 years after treating early syphilis is not considered treatment failure.

False-positive non-treponemal results are a heavily tested concept:

Duration	Causes of False Positive
Acute (< 6 months)	Malaria, varicella, hepatitis, measles (morbilli), recent vaccination, pregnancy
Chronic (> 6 months)	Advanced age, connective tissue disease (SLE, rheumatoid arthritis), malignancy, chronic liver disease, leprosy, IV drug use, other autoimmune conditions

The titer for false positives is generally low, typically 1:4 or below.

Another important pitfall is the prozone phenomenon: in secondary syphilis, antibody levels can be so high that they overwhelm the test, producing a false-negative result. If secondary syphilis is strongly suspected clinically despite a non-reactive VDRL/RPR, request dilution of the sample and retest.

Treponemal tests (TPHA, TP-Rapid, TP-PA, FTA-ABS) detect antibodies directed against T. pallidum itself. They become positive earlier, approximately 14 days after infection, and generally remain positive for life even after successful treatment. This means they cannot be used to monitor treatment response or distinguish active from prior treated infection.

Treponemal tests can also produce false positives in infections with other treponemes, including T. pallidum subspecies pertenue (the causative agent of yaws/frambusia), which is relevant in tropical endemic areas.

Interpretation of Combined Serologic Results

VDRL	TPHA	Interpretation
Reactive	Non-reactive	False-positive non-treponemal test (not syphilis)
Reactive	Reactive	Active untreated syphilis, OR previously treated syphilis with persistently low non-treponemal titer (serofast), OR yaws (frambusia)
Non-reactive	Reactive	Previously treated and cured syphilis, OR very early primary syphilis (before non-treponemal seroconversion), OR untreated late latent/tertiary syphilis, OR prozone effect, OR yaws
Non-reactive	Non-reactive	No syphilis, OR incubation period (too early for any test to be positive)

Direct Detection Methods

When a patient presents with a primary chancre and serology is still negative (within the first 4 weeks), direct visualization with dark-field microscopy of the lesion exudate can identify motile spirochetes. This is not widely available in clinical practice but remains a valid initial diagnostic method for active ulcerative lesions.

PCR is the molecular alternative, detecting T. pallidum DNA from ulcer or erosion specimens. It has high sensitivity and is particularly useful when dark-field microscopy is unavailable.

For suspected neurosyphilis, CSF analysis via lumbar puncture is required. CSF findings include elevated protein, lymphocytic pleocytosis, and a reactive CSF-VDRL (highly characteristic but not perfectly sensitive).

4. Management and Treatment

Category	First-Line Treatment	Second-Line / Alternative	Notes
Congenital syphilis (confirmed or high-risk neonate)	Aqueous benzyl penicillin 100,000-150,000 U/kg/day IV for 10-15 days	Procaine penicillin 50,000 U/kg/day IM for 10-15 days	Treat if: confirmed congenital syphilis, clinically normal but mother untreated, mother treated < 30 days before delivery, or mother received non-penicillin regimen
Congenital (low-risk, adequately treated mother)	Close monitoring; if treatment needed: Benzathine penicillin G 50,000 U/kg IM single dose	-	Mother must have received adequate penicillin therapy with no signs of reinfection
Early acquired syphilis (primary, secondary, early latent)	Benzathine penicillin G 2.4 million units IM, single dose (1.2 million units per buttock)	Doxycycline 100 mg PO twice daily for 14 days (non-pregnant only), OR Ceftriaxone 1 g IV daily for 10 days	Perform penicillin skin test before injection. Observe patient for 30 minutes after injection
Late acquired syphilis (late latent, tertiary non-neuro)	Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (interval between doses must not exceed 14 days)	Doxycycline 100 mg PO twice daily for 21-28 days (non-pregnant only), OR Procaine penicillin 600,000 U/day IM for 17-21 days	If any dose is missed beyond 14-day interval, restart the 3-dose series
Penicillin-allergic, pregnant	Penicillin desensitization, then standard penicillin therapy	If desensitization not possible: Erythromycin 500 mg PO four times daily for 14 days (early) or 30 days (late); neonate MUST still receive congenital syphilis treatment at birth	Erythromycin and azithromycin do NOT cross the placenta adequately
Neurosyphilis / Ocular / Otosyphilis	Refer to venereology subspecialist for evaluation and management	-	Aqueous crystalline penicillin G IV is the standard, but management should be subspecialty-directed

Early Acquired Syphilis (Primary, Secondary, Early Latent)

The cornerstone of treatment is Benzathine penicillin G (BPG) 2.4 million units, given as a single intramuscular injection. The dose is split between two injection sites (1.2 million units per buttock). Before administering BPG, penicillin allergy testing should be performed to rule out hypersensitivity. The patient should be observed for 30 minutes post-injection to monitor for anaphylaxis.

For patients with confirmed penicillin allergy who are not pregnant, the first alternative is doxycycline 100 mg orally twice daily for 14 days. The second alternative is ceftriaxone 1 gram intravenously once daily for 10 days. Note that doxycycline is contraindicated in pregnancy; for pregnant patients with penicillin allergy, penicillin desensitization followed by standard penicillin therapy is the recommended approach.

Late Acquired Syphilis (Late Latent, Gummatous, Cardiovascular)

The regimen is Benzathine penicillin G 2.4 million units IM once weekly for three consecutive weeks. A critical rule: the interval between each dose must not exceed 14 days. If a dose is delayed beyond this window, the full three-dose course must be restarted. This is a commonly tested point.

For non-pregnant, penicillin-allergic patients, the alternative is doxycycline 100 mg orally twice daily for 21 to 28 days. For pregnant, penicillin-allergic patients where desensitization is not feasible, erythromycin 500 mg four times daily for 30 days can be used, but this is suboptimal: since erythromycin and azithromycin do not cross the placenta reliably, the neonate must be treated for congenital syphilis at birth regardless of maternal treatment.

Pregnancy-Related Considerations

Treatment during pregnancy must be initiated within 4 weeks before delivery to be considered adequate. Each week of treatment delay increases the transmission risk by up to 125%, and for gestational ages of 28 weeks or more, the risk of transmission doubles. HIV co-infected patients receive the same syphilis treatment regimen as HIV-negative patients.

Jarisch-Herxheimer Reaction

After initiating treatment (especially in early syphilis), patients may develop the Jarisch-Herxheimer reaction within 4 to 6 hours. This is characterized by fever, chills, myalgia, arthralgia, and headache. It is caused by the sudden release of treponemal antigens from dying organisms and resolves spontaneously within 24 hours. It is not an allergic reaction to penicillin and should not prompt discontinuation of therapy. Management is supportive with aspirin or ibuprofen. This reaction is not dependent on the type or dose of antibiotic used.

If clinical signs, symptoms, or laboratory findings suggest neurosyphilis (symptomatic or asymptomatic), ocular syphilis, or otosyphilis, the patient should be referred to a venereology subspecialist for further evaluation and specialized management.

Sexual Partner Management

Scenario	Action
Sexual contact < 90 days before patient's diagnosis (primary, secondary, or early latent)	Treat presumptively as early syphilis, even if the partner's serology is negative
Sexual contact > 90 days before diagnosis, serology unavailable and follow-up not possible	Treat presumptively as early syphilis
Sexual contact > 90 days, serology negative	No treatment needed
Sexual contact > 90 days, serology positive	Treat based on clinical and serologic staging
Long-term sexual partner of patient with late latent syphilis	Perform clinical and serologic evaluation; treat according to results
Sexual partners of primary syphilis patients	Trace contacts within the past 3 months plus the duration of symptoms
Sexual partners of secondary syphilis patients	Trace contacts within the past 6 months plus the duration of symptoms
Sexual partners of early latent syphilis patients	Trace contacts within the past 1 year

Follow-Up and Treatment Response

Parameter	Details
Monitoring test	VDRL/RPR (non-treponemal, quantitative)
Monitoring schedule	Months 1, 3, 6, 9, 12, 18, and 24 after treatment
Treatment success	>= 4-fold decline in VDRL/RPR titer (e.g., 1:32 to 1:8 or lower)
Expected timeline for titer decline	Early syphilis: 6-12 months. Late syphilis: 12-24 months
Serofast	Titer stabilizes at a low level (typically <= 1:8) and does not become non-reactive; this is NOT treatment failure if the patient was treated adequately
Treatment failure in early syphilis	Titer does not decrease >= 4-fold, OR titer increases >= 4-fold (sustained > 2 weeks), OR symptoms persist or recur
Treatment failure in latent syphilis	Clinical signs/symptoms of syphilis appear, OR titer does not decrease >= 4-fold in 12-24 months, OR titer increases >= 4-fold (sustained > 2 weeks)
Action on treatment failure	Refer to venereology subspecialist to evaluate for: reinfection, non-compliance, use of non-penicillin regimen, or asymptomatic neurosyphilis

Prognosis

Prognosis Domain	Syphilis Without Complications
Quo ad vitam	Ad bonam (favorable)
Quo ad functionam	Ad bonam (favorable)
Quo ad sanationam	Dubia ad bonam (uncertain, leaning favorable)

Treponema pallidum remains sensitive to penicillin. Although treatment failure can occur and may be more common in HIV-co-infected patients, penicillin therapy is generally effective across all stages. Recurrence is more commonly due to reinfection than true relapse, and reinfection is most likely during the first year after treatment.

5. Differential Diagnosis and Distractors

Primary Syphilis

Differential	Why It Is Similar	Key Discriminator
Herpes genitalis (HSV)	Genital ulcer, sexually transmitted	HSV ulcers are painful, multiple, grouped, vesicular at onset, and often recurrent with prodromal tingling. Chancre is painless, solitary, and non-vesicular
*Chancroid (H. ducreyi)*	Genital ulcer, STI, can cause lymphadenopathy	Chancroid ulcer is painful, has ragged undermined edges, purulent base (dirty, not clean), and tender suppurative inguinal lymphadenopathy (bubo). Chancre is painless with clean base and non-tender nodes
Granuloma inguinale (Donovanosis)	Painless genital ulcer	Donovanosis produces a beefy-red, friable, progressive ulcer that bleeds easily and shows Donovan bodies on biopsy. No lymphadenopathy. Chancre is indurated with clean base and has lymphadenopathy
Lymphogranuloma venereum (LGV)	Genital ulcer followed by lymphadenopathy	LGV ulcer is small and transient (often missed). The dominant finding is painful matted inguinal lymphadenopathy with a "groove sign" (nodes above and below the inguinal ligament). In syphilis, nodes are non-tender

Secondary Syphilis

Differential	Why It Is Similar	Key Discriminator
Pityriasis rosea	Diffuse maculopapular rash on trunk	Pityriasis rosea begins with a herald patch (single oval lesion), followed by a "Christmas tree" distribution on the back. Does NOT involve palms/soles. No condylomata lata or mucous patches. RPR/VDRL negative
Psoriasis	Scaly papules/plaques on trunk and extremities	Psoriasis has silvery-white thick scales, Auspitz sign (pinpoint bleeding on scale removal), and often involves extensor surfaces, scalp, and nails. No condylomata lata. RPR/VDRL negative
Erythema multiforme	Diffuse rash involving palms	Erythema multiforme has classic target (iris) lesions with three concentric color zones. Often linked to HSV infection or drug exposure. No mucosal patches or lymphadenopathy
Drug eruption	Diffuse maculopapular rash	Temporal relationship to medication initiation. Often pruritic (secondary syphilis rash is classically non-pruritic). No condylomata lata, no mucous patches, RPR/VDRL negative
Viral exanthem	Diffuse rash with systemic symptoms	Usually in younger patients, more acute onset, self-limited, associated with upper respiratory symptoms. RPR/VDRL negative

Condylomata Lata vs. Condylomata Acuminata

Feature	Condylomata Lata (Syphilis)	Condylomata Acuminata (HPV)
Appearance	Flat, moist, gray-white plaques	Pointed, verrucous, cauliflower-like
Location	Perianal, vulvar folds, moist areas	Genital, perianal
Pain	Painless	Usually painless
Infectivity	Extremely high (teeming with spirochetes)	Moderate
Serology	RPR/VDRL positive	RPR/VDRL negative

6. Traps and High-Yield Pearls

The most common way students get syphilis questions wrong is by confusing the roles of treponemal and non-treponemal tests. Non-treponemal tests (RPR/VDRL) are used for screening and monitoring, not confirmation. Treponemal tests (TPHA, FTA-ABS) are used for confirmation, not monitoring. Using the wrong test for the wrong purpose is the core mistake. If a question asks "how do you confirm treatment success," the answer is a declining RPR/VDRL titer, never a treponemal test.

The second major trap involves the window period in primary syphilis. A patient with a painless genital ulcer and a negative VDRL may still have syphilis. The non-treponemal test does not become positive until approximately 4 weeks after infection, while the chancre can appear as early as 3 weeks. During this gap, the correct diagnostic step is dark-field microscopy or PCR of the lesion, or repeat serology in 2 to 4 weeks.

Third, students often fail to recognize that the resolution of the chancre does not mean the disease is cured. The chancre heals spontaneously in 3 to 6 weeks regardless of treatment. If a vignette describes a patient whose genital ulcer "resolved on its own" and now presents weeks later with a diffuse rash, you are looking at the progression from primary to secondary syphilis.

Fourth, understand the Jarisch-Herxheimer reaction. A patient who develops fever, chills, and worsening rash within hours of receiving penicillin for syphilis is having this reaction, not a penicillin allergy. This distinction is critical: allergic reactions involve urticaria, angioedema, or anaphylaxis; the Jarisch-Herxheimer reaction involves flu-like symptoms that resolve within 24 hours.

Fifth, the prozone phenomenon is a classic board-style question. A patient with all the classic features of secondary syphilis who has a negative RPR/VDRL should prompt you to request sample dilution and retesting. The antibody excess in florid secondary syphilis can paradoxically produce a false-negative result.

Sixth, remember that in pregnancy, doxycycline is contraindicated and macrolides (erythromycin, azithromycin) do not adequately cross the placenta. The only acceptable approach for pregnant patients with penicillin allergy is desensitization followed by penicillin therapy. Even if the mother receives erythromycin, the neonate must still be treated for congenital syphilis.

Finally, the core competency being tested in syphilis questions is pattern recognition across stages and correct sequencing of diagnostic tests. A painless chancre is primary. A rash on palms and soles with condylomata lata is secondary. An asymptomatic patient with positive serology needs staging by duration to determine the treatment regimen (single dose vs. three weekly doses). A four-fold decline in RPR/VDRL titer confirms treatment success. These are the patterns that repeat across exam questions.

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