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In 1865 Mercury was the principal systemic remedy for early constitutional syphilis, while potassium iodide was especially associated with later destructive lesions; neither is an acceptable substitute for modern penicillin therapy. Historical classifications depended chiefly on clinical appearance, before identification of Treponema pallidum and modern serology.

For a primary indurated chancre, period treatment combined cleanliness, protection from friction and irritant discharges, and, in mercurial practice, a prolonged course of a Mercury preparation. Administration could be by mouth or by rubbing an ointment into the skin; some practitioners used fumigation. Local cauterisation of a sore could not be assumed to remove infection already spread beyond it. Painful soft sores and suppurating groin swellings were often discussed among venereal diseases, but modern chancroid is distinct from syphilis; an 1865 “variety” cannot automatically be assigned the same cause or treatment.^[ref]

In secondary disease, with generalised eruptions and mucosal lesions, Mercury was used in carefully watched courses, with food, hygiene and local care. Blue pill, grey powder and other mercurial compounds were alternative forms, not interchangeable quantities. Stomatitis, excessive salivation, bowel disturbance and constitutional deterioration were reasons to interrupt treatment, not desirable signs of cure. Relapse after apparent healing was recognised. For later gummatous syphilis, painful periosteal swellings, ulceration and some nervous manifestations, potassium iodide, sometimes combined with a mercurial, was a characteristic period choice. Apparent symptomatic improvement did not demonstrate eradication of the infection.^[ref][ref]

Congenital disease also received mercurial treatment in the period, together with attention to feeding and the mother. That history must be separated from present management: congenital syphilis results from maternal infection, not an inherited constitutional taint. Maternal treatment, infant examination and laboratory evaluation determine modern management; an affected infant can require a full course of parenteral penicillin even without obvious external lesions.^[ref]

Modern early acquired syphilis, including primary, secondary and early latent disease, is ordinarily treated with benzathine penicillin G, 2.4 million units intramuscularly once in adults. Late latent disease or disease of unknown duration ordinarily requires three weekly 2.4-million-unit injections. Neurosyphilis, ocular disease and otic disease require a regimen with appropriate tissue penetration, ordinarily aqueous crystalline penicillin G, 18–24 million units per day intravenously for 10–14 days, rather than the single early-disease injection. Pregnancy, allergy, congenital disease and other special circumstances need the corresponding specialist pathway. Clinical and quantitative serological follow-up, partner management and assessment for coexisting infections are part of treatment. The stage labels guide management, but nervous, ocular or auditory involvement can occur at more than one stage.^{[ref][ref][ref]}