Tertiary syphilis - Symptoms.

Tertiary syphilis develops in patients who have received inadequate treatment or no treatment at the previous stages of syphilis. This stage appears in the 3rd-4th year of the disease and continues indefinitely. Unlike the secondary period, in the tertiary stage, internal organs, the central nervous system and the musculoskeletal system are much more often involved in the process. Tertiary syphilides are characterized by a long existence (months and years), an extremely small number of pale treponemas are found in them (due to which studies for the presence of the pathogen are not carried out at all), low infectivity, a tendency to develop specific lesions in places of non-specific irritations (primarily in places of mechanical injuries). Classical serological reactions are negative in 1/3 of patients with tertiary syphilis. During this period, the intensity of specific immunity gradually decreases (this is due to a decrease in the number of pale treponemas in the patient’s body), as a result of which true re-superinfection becomes possible with the development of a hard chancre at the site of new introduction of pale treponemas.

Syphilides of the tertiary period are represented by tuberculous and gummatous elements.

The main element of tubercular syphilid is a small, dense, hemispherical tubercle, the size of a cherry pit, with a smooth or shiny surface, dark red or bluish-red in color. The tubercle softens rather quickly, within a week or a month, and ulcerates, forming a round, rather deep ulcer with ridge-like, steeply cut edges. Gradually, the bottom of the ulcer is cleared of decay, covered with granulations and turns into an atrophic scar pigmented at the periphery, on which new rashes never appear. The group of scars has a mosaic appearance.

Gumma occurs in the subcutaneous tissue and is a limited mobile ball about the size of a walnut, bluish-red in color, of a dense elastic consistency, with sharp borders. Subjective sensations are absent or insignificant. Over time, softening and decay of the gumma with the formation of a necrotic core ("gummatous core") are noted. As a result, a deep ulcer appears, the bottom of which is covered with the remains of the decaying infiltrate. The ulcer has rounded outlines, a deep bottom and very characteristic ridge-shaped, thick, dense elastic bluish-red edges. Then the ulcer scars, leaving a discolored star-shaped scar with a zone of hyperpigmentation along the periphery. Gummas are often located on the mucous membranes of the nasal cavity and pharynx. When gumma is located on the tongue, hard and soft palate, nose, pharynx, larynx, severe and often irreparable consequences are observed (speech disorders, swallowing, breathing, "saddle" nose, complete destruction of the nose, perforation of the hard palate). A single gumma is often observed, multiple gummas are rare.

Tertiary syphilis

Tertiary syphilis is characterized by the appearance of gummas or cardiovascular involvement, but not by signs of neurosyphilis. Patients who are not allergic to penicillin and who do not have symptoms of neurosyphilis should be treated according to the following regimen.

Recommended scheme

Benzathine penicillin G, total 7.2 million units, 3 doses of 2.4 million units intramuscularly at intervals of 1 week.

Other considerations for patient management

Patients with symptoms of late syphilis should have their CSF examined before treatment. Some experts recommend treating all patients with cardiovascular syphilis with the same treatment regimen as for neurosyphilis. A full discussion of the management of patients with cardiovascular or gummatous syphilis is beyond the scope of these guidelines. Management of such patients should be guided by expert consultation.

Follow-up observation

There are very few data on long-term follow-up of patients with late syphilis. The response to treatment depends, in part, on the nature of the lesions.

Special Notes

• Allergy to penicillin

Patients with penicillin allergy should be treated with regimens recommended for the treatment of late latent syphilis.

• Pregnancy

Pregnant patients with penicillin allergy should be treated with penicillin, after desensitization if necessary (see Management of Patients with Penicillin Allergy and Syphilis in Pregnancy).

Neurosyphilis

Treatment

Central nervous system involvement may be observed at any stage of syphilis. If patients with syphilis have clinical signs of nervous system involvement (e.g., visual and auditory symptoms, cranial nerve paresis, signs of meningitis), CSF should be examined.

Syphilitic uveitis or other ocular lesions are often associated with neurosyphilis, and such patients should be treated according to the guidelines for the treatment of neurosyphilis. CSF examination should be performed in all such patients. If abnormalities in the CSF are detected, it should be re-examined during follow-up to monitor the effectiveness of treatment.

Patients with neurosyphilis or syphilitic eye disease (eg, uveitis, neuroretinitis, or optic neuritis) without penicillin allergy should be treated as follows.

Recommended scheme

Water-soluble crystalline penicillin G 18-24 million IU daily, 2-4 million IU intravenously every 4 hours for 10-14 days.

Patients may be treated with the following alternative regimen if tolerated.

Alternative scheme

Procaine penicillin 2.4 million units intramuscularly daily plus probenecid 500 mg orally 4 times daily, both for 10-14 days.

The duration of this regimen is shorter than those used to treat late syphilis in the absence of neurosyphilis. Therefore, some experts suggest using 2.4 million benzathine penicillin IM after completion of this course of treatment for neurosyphilis to provide a comparable overall treatment duration.

Other considerations for patient management

Other considerations for the management of patients with neurosyphilis include:

• All patients with syphilis should be tested for HIV.
• Many experts recommend treating patients with auditory impairment due to syphilis as neurosyphilis, regardless of CSF examination results. Although systemic steroids are often used as adjunctive therapy for syphilitic ear lesions, the benefit of this approach has not been proven.

Follow-up observation

If CSF pleocytosis is detected on initial examination, CSF should be re-examined in these patients every 6 months until cell counts return to normal. Follow-up can also be used to determine changes in CSF VDRL and CSF protein to assess the effectiveness of treatment, although these two parameters change more slowly and detection of abnormalities is less important. If CSF cell counts do not decrease within 6 months or if CSF values are not completely normalized within 2 years, retreatment should be considered.

Special Notes

• Allergy to penicillin

There are no systematic data evaluating the efficacy of alternative regimens for the treatment of neurosyphilis. Therefore, patients with penicillin allergy should be treated with penicillin, if necessary after desensitization or expert advice. In some situations, skin testing to confirm penicillin allergy may be useful (see Management of patients with penicillin allergy).

• Pregnancy

Pregnant patients with penicillin allergy should be desensitized if necessary and then treated with penicillin (see Management of Patients with Penicillin Allergy and Syphilis in Pregnancy).