Targeted investigations like PCR for herpesviruses and syphilis, bacterial/fungal cultures, serologies (EBV, CMV, ANA, HLA-B51), inflammatory markers, and, when indicated, biopsy may help distinguish common non-sexually acquired infections (e.g., HSV, impetigo), recurrent aphthous or Behçet’s-related ulcers, Crohn’s fissures, and drug eruptions. The gene discussed is BTG3; the disease is syphilis.