Clinical progression of ocular syphilis and neurosyphilis despite treatment with massive doses of penicillin. Failure to demonstrate treponemes in affected tissues.

The progression of an infectious disease despite 'adequate therapy' may be an enigma to the clinician in the present antibiotic era. In certain diseases, such as tuberculosis, the resistance of the causative organism to the antibiotics used may explain the progression. There are certain other diseases in which such resistance can only partly explain the failure of treatment. With syphilis it would appear that more than one factor may be involved in the progression of disease. The worsening of the signs and symptoms of the original lesion or the development of new lesions elsewhere despite 'adequate treatment' can be called 'clinical progression'. It is particularly liable to occur in cases of ocular syphilis and of neurosyphilis, and may appear at any time after treatment, either at the site originally affected or at an entirely different site. Organisms resembling treponemes may or may not be present in the tissues. Serological tests for syphilis may or may not give positive results; hence, diagnosis largely depends on historical, epidemiological, and clinical evidence. In the management of ocular syphilis and of neurosyphilis, the clinicim has to consider the possibility of early or of long-standing syphilis and the possibility of reinfection or of superinfection with the disease; in some cases there may be an association with chronic infections such as tuberculosis, leprosy, and filariasis; or with other disorders such as diabetes mellitus, hypertension, atherosclerosis, and malnutrition. In a small but significant group of cases the disease progresses. This group is important because it suggests that penicillin has not entirely eliminated the development of late syphilis; because its pathogenesis is not clearly understood, this matter requires further study. Accurate diagnosis in such cases is not easy and, in view of our lack of knowledge regarding the exact pathogenesis, specific trcatment cannot always be based on sound principles.