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The New England Journal of MedicineCase 19-2024: A 46-Year-Old Man with Arthritis and Rash

Evaluation and Diagnosis of Secondary Syphilis in a Middle-Aged Man with Polyarticular Inflammatory Arthritis and Rash

A 46-year-old man presented with arthritis and rash, experiencing episodes of lightheadedness and diaphoresis. His clinical evaluation revealed an elevated erythrocyte sedimentation rate and a rash, eventually leading to a diagnosis of secondary syphilis. This case highlights the importance of considering infectious etiologies in patients with polyarticular inflammatory arthritis and rash, particularly when accompanied by systemic symptoms and a relevant sexual history.

Key Points:

  • Patient Presentation: A 46-year-old man presented with arthritis, rash, lightheadedness, and diaphoresis.
  • Initial Symptoms: Lightheadedness episodes associated with diaphoresis and mild nausea.
  • Emergency Department Evaluation: Normal glucose, electrolytes, kidney-function tests, liver enzymes, complete blood count, and urinalysis. Elevated alkaline phosphatase (157 U/L), erythrocyte sedimentation rate (104 mm/hr), C-reactive protein (6.3 mg/L), and d-dimer (990 ng/mL). Sinus tachycardia observed on ECG. Chest CT showed no pulmonary embolus.
  • Rheumatology Clinic Follow-up: History of mild COVID-19, arthritis onset, rash development, alopecia, weight loss, and nasal crusting post-COVID-19. Rash involving chest, back, and legs but sparing palms and soles.
  • Medical History and Lifestyle: History of asthma, eczema, cigarette smoking, and alcohol use. Sexually active with men, with the latest sexual activity occurring 5 months prior.
  • Physical Examination Findings: Patchy alopecia, nasal crusting, ulcerative lesion at the mouth commissure, swelling, warmth, and mild tenderness of wrists and ankles. Hyperpigmented, macular rash with scaling.
  • Differential Diagnosis Considerations:
    • Autoimmune and Autoinflammatory Diseases: Psoriatic arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE), dermatomyositis, systemic vasculitis, VEXAS syndrome.
    • Nonrheumatic Diseases: Drug reactions, cancer, infections (tuberculosis, arthritogenic alphaviruses, parvovirus B19, syphilis).
  • Diagnosis of Secondary Syphilis:
    • Treponemal antibody test and rapid plasma reagin (RPR) test confirmed the diagnosis.
    • Secondary syphilis explained polyarthritis, rash, alopecia, nasal, and oral ulceration.
  • Management:
    • Intramuscular benzathine penicillin G administered.
    • Repeat RPR test recommended on the day of treatment to establish a baseline.
    • HIV, gonorrhea, and chlamydia testing, followed by HIV preexposure prophylaxis (PrEP) initiated.
    • Partner notification and empirical treatment for recent sexual contacts.
  • Outcome: Resolution of symptoms post-treatment, with significant improvement in RPR titer.

According to the Centers for Disease Control and Prevention (CDC), there were more than 76,000 reported cases of syphilis in the US in 2021, marking a 74% increase since 2017. The CDC also reports that men who have sex with men are disproportionately affected, accounting for 36% of all primary and secondary syphilis cases and nearly 47% of all male primary and secondary syphilis cases in 2021. (Yale Medicine)

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