What is the most likely diagnosis and recommended evaluation for an adult male with recurrent non‑itchy, non‑odorous penile rash, negative sexually transmitted disease testing, and new visual symptoms of eye floaters and glare when looking at headlights?

Recurrent Non-Itchy Penile Rash with Negative STD Testing and Visual Symptoms: Likely Reactive Arthritis (Reiter's Syndrome)

The combination of recurrent non-itchy, non-odorous penile rash with negative STD testing plus new-onset eye floaters and glare strongly suggests reactive arthritis (Reiter's syndrome), a post-infectious inflammatory condition that can follow urethritis even after the initial infection has cleared. 1

Diagnostic Reasoning

The clinical triad points toward reactive arthritis:

• Urethritis/balanitis component: Recurrent penile rash without typical infectious features (no itch, no odor, negative STD tests) suggests post-infectious inflammation rather than active infection 1
• Ocular involvement: Eye floaters and glare from headlights indicate uveitis or conjunctivitis, classic features of reactive arthritis 1
• Post-chlamydial syndrome: Reactive arthritis is specifically listed as a complication of Chlamydia trachomatis infection in men, even after microbiologic cure 1

Essential Diagnostic Workup

Confirm absence of active infection first:

• Repeat nucleic acid amplification test (NAAT) on first-void urine for N. gonorrhoeae and C. trachomatis to definitively exclude persistent infection 2
• Urethral Gram stain looking for >5 WBCs per oil immersion field to document whether urethritis is still present 1
• Consider testing for Mycoplasma genitalium and Ureaplasma urealyticum, which cause one-third of non-chlamydial NGU cases and may not respond to initial therapy 1

Evaluate for reactive arthritis:

• Ophthalmology referral for slit-lamp examination to assess for anterior uveitis (the eye symptoms are concerning for intraocular inflammation, not just floaters) 1
• HLA-B27 testing (positive in 60-80% of reactive arthritis cases, though not required for diagnosis)
• Assess for joint symptoms (arthritis may be subclinical or develop later)
• ESR and CRP to document systemic inflammation

Rule out dermatologic mimics:

• Skin biopsy of penile lesion if appearance is atypical, to exclude plasma cell balanitis, lichen sclerosus, or HPV-related changes 3, 4
• Potassium hydroxide (KOH) preparation to exclude candidal infection 4

Treatment Algorithm

If Objective Urethritis is Present (>5 WBCs on Gram stain):

First-line therapy:

• Doxycycline 100 mg orally twice daily for 7 days 1, 2
• Alternative: Azithromycin 1 g orally as single dose (better for M. genitalium) 1, 2

For persistent symptoms after initial treatment:

• Metronidazole 2 g orally single dose PLUS erythromycin base 500 mg orally four times daily for 7 days (covers T. vaginalis and tetracycline-resistant U. urealyticum) 1

If No Objective Urethritis but Symptoms Persist >3 Months:

This indicates chronic prostatitis/chronic pelvic pain syndrome:

• Do NOT retreat with antibiotics without objective signs of inflammation 1, 2
• Symptoms alone are insufficient basis for antimicrobial therapy 1, 5
• Consider referral to urology for chronic pelvic pain syndrome management 2, 6

For Reactive Arthritis (Post-Infectious Inflammation):

• NSAIDs for symptomatic relief of inflammation
• Ophthalmology co-management for uveitis (may require topical corticosteroids)
• Rheumatology referral if joint symptoms develop or systemic inflammation persists
• Do not give prolonged antibiotics once infection is cleared—reactive arthritis is immune-mediated, not infectious 1

Critical Management Points

Partner evaluation is mandatory:

• All sexual partners within preceding 60 days must be evaluated and treated, even if the index patient's tests are now negative 1, 2, 5
• Reinfection from untreated partners is the most common cause of recurrent symptoms 1, 5

Sexual abstinence:

• No intercourse until 7 days after therapy initiation AND symptoms resolved AND partners treated 1, 2, 5

Screen for other STIs:

• Test for syphilis and HIV in all patients with confirmed urethritis 1, 2

Common Pitfalls to Avoid

• Do not empirically retreat with antibiotics based on symptoms alone without documenting objective urethritis (>5 WBCs on Gram stain or positive leukocyte esterase) 1, 2, 5
• Do not ignore the eye symptoms—glare and floaters suggest uveitis, which can cause permanent vision loss if untreated; urgent ophthalmology referral is needed 1
• Do not assume negative STD tests mean no prior infection—reactive arthritis develops after the infection has cleared 1
• Do not overlook partner treatment—failure to treat partners leads to reinfection in the majority of "treatment failures" 1, 5
• Do not continue antibiotics beyond 3 months for persistent symptoms without objective inflammation—this represents chronic pelvic pain syndrome, not infection 1, 2, 6

Alternative Diagnoses to Consider

If reactive arthritis is excluded:

• Plasma cell balanitis (Zoon's balanitis): Benign condition presenting as smooth, shiny, red-orange plaque on glans; requires biopsy to exclude squamous cell carcinoma in situ 3
• Lichen sclerosus: Atrophic white patches on glans and foreskin; can cause phimosis and meatal stenosis 3
• HPV-associated balanoposthitis: May present with recurrent inflammation; 56% of cases show HPV DNA on biopsy 7
• Allergic or irritant contact dermatitis: From condoms, lubricants, or hygiene products; typically itchy (which this patient lacks) 3, 4

The absence of itch and odor makes infectious balanitis, candidiasis, and contact dermatitis less likely 3, 4. The eye symptoms are the key distinguishing feature pointing toward reactive arthritis rather than isolated dermatologic disease.