What is the most appropriate management for a patient with a sudden onset of a red rash, erythematous macules and papules, swollen lymph nodes, and ulcers, who had a genital sore 6 weeks ago, and is about to travel?

Secondary Syphilis Requiring Immediate Intramuscular Benzathine Penicillin G

This patient has secondary syphilis based on the classic presentation of diffuse rash with erythematous macules and papules on trunk, hands, and feet, oral ulcers (mucous patches), lymphadenopathy, and a preceding genital ulcer (primary chancre 6 weeks ago), and requires immediate treatment with intramuscular benzathine penicillin G 2.4 million units as a single dose before she travels. 1, 2

Why This Diagnosis is Critical

The clinical presentation is pathognomonic for secondary syphilis:

• Diffuse rash involving palms and soles is the hallmark of secondary syphilis, occurring in 90% of cases 3, 4
• Oral ulcers (mucous patches) combined with genital history confirms mucocutaneous involvement characteristic of disseminated treponematosis 1, 4
• Generalized lymphadenopathy in neck and groin indicates systemic spread of Treponema pallidum 3, 4
• Timeline of 6 weeks after primary chancre fits perfectly with secondary syphilis development, which typically occurs 4-10 weeks after the initial infection 2, 4

Why Immediate Treatment is Non-Negotiable

Empiric treatment must be administered immediately before she travels, as waiting for confirmatory test results risks progression to devastating tertiary complications including neurosyphilis, cardiovascular syphilis, and irreversible organ damage. 1, 2

• The CDC explicitly recommends empiric treatment for syphilis when clinical presentation is highly suggestive, particularly in high-risk patients who cannot return for follow-up 1
• Secondary syphilis has a 90% serologic positivity rate, making false negatives unlikely, but treatment should never be delayed for test results in this clinical scenario 1
• Untreated secondary syphilis progresses to late latent and tertiary stages with irreversible CNS and cardiovascular damage 2, 4

The Correct Treatment Regimen

Benzathine penicillin G 2.4 million units intramuscularly as a single dose is the only recommended first-line treatment for early syphilis (primary, secondary, or early latent). 3, 1, 2

• This single injection provides sustained treponemicidal levels for 2-4 weeks, ensuring complete treatment even if the patient doesn't return 5
• Penicillin remains the only proven therapy with decades of clinical experience showing >95% cure rates for early syphilis 4, 5
• Alternative oral regimens like doxycycline require 14 days of twice-daily dosing with strict adherence, making them inappropriate for a traveling patient who cannot be monitored 4, 5

Why the Other Options Are Wrong

Oral acyclovir for 7 days would only treat HSV and completely miss the syphilis diagnosis, allowing progression to tertiary disease with catastrophic consequences 3, 6

• While HSV can cause genital ulcers, it does not cause the diffuse palmoplantar rash, generalized lymphadenopathy, or oral mucous patches seen here 3
• The 6-week timeline from genital ulcer to systemic symptoms is inconsistent with HSV recurrence 3

Oral diphenhydramine, prednisone, topical hydrocortisone, PRN acetaminophen, and fluids treats this as an allergic reaction or viral syndrome, which is dangerously incorrect 1

• This symptomatic approach ignores the underlying bacterial infection and allows T. pallidum to continue disseminating
• Corticosteroids may actually suppress the immune response and worsen outcomes in untreated syphilis

Essential Concurrent Actions

HIV testing must be performed immediately, as genital ulcers facilitate HIV transmission and syphilis-HIV coinfection occurs in up to 30% of MSM with syphilis. 1, 2

• HIV-positive patients may have atypical presentations, slower healing, and higher treatment failure rates 1, 5
• Repeat HIV and syphilis testing at 3 months is mandatory if initial results are negative 1, 7

All sexual contacts within 90 days before symptom onset must be treated empirically with benzathine penicillin G, regardless of symptoms or test results. 1, 8

• Partner notification is mandatory to prevent reinfection and contain transmission 8
• Secondary syphilis patients are highly infectious through mucocutaneous lesions 2, 4

Critical Follow-Up Requirements

Quantitative nontreponemal titers (RPR or VDRL) must be obtained before treatment and repeated at 6,12, and 24 months to document treatment response. 3, 4

• A fourfold decline in titers (e.g., 1:64 to 1:16) within 6 months indicates successful treatment 3, 4
• Failure to achieve fourfold decline by 6 months suggests treatment failure or reinfection and requires CSF examination 4, 5

If she develops neurologic symptoms, visual changes, or hearing loss at any point, immediate CSF examination is required to rule out neurosyphilis. 4, 5

Common Pitfalls to Avoid

• Never delay treatment waiting for serologic confirmation when clinical presentation is classic for secondary syphilis in a patient who cannot return for follow-up 1
• Never assume the genital ulcer was "just herpes" without considering syphilis in the differential, as primary chancres are often painless and mistaken for other conditions 1, 4
• Never use oral alternatives like doxycycline in patients who cannot be monitored for adherence or who are traveling 4, 5
• Never forget that 10% of patients have coinfections (HSV with syphilis), but treating syphilis takes priority given its life-threatening complications 1, 7