Syphilis is a chronic venereal infection caused by the spirochete Treponema pallidum. It has various stages including primary, secondary, latent, and tertiary syphilis. Penicillin is the treatment of choice and can cure syphilis in all stages. Common side effects of treatment include allergic reactions and Jarisch-Herxheimer reactions, which cause flu-like symptoms.

1. Drug Therapy Of
Syphilis
Labeeb
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2. Sexually Transmitted Diseases ( STD )
• Syphilis
• Gonorrhea
• Non Gonococcal
Urethritis
• Chancroid
• Lymphogranuloma
Venereum
• Granuloma Inguinale
• Vaginitis
• Genital Warts
• Genital Herpes
• AIDS
• Hepatitis B

3. Syphilis
• Chronic venereal infection caused by the spirochete
Treponema pallidum.
• Source of infection : active cutaneous or mucosal
lesion in a sexual partner in early stages of syphilis.

4. Classification
Stage Acquired Congenital
Early Primary
Secondary
Latent
Late Latent
Benign Tertiary
Cardiovascular
Neurosyphilis
• Penicillin is the drug of choice for all stages of infection.

5. Acquired syphilis :
Primary syphilis :
• IP – between 14 & 28 days.
• A dull red macule → papular → indurated ulcer – Hard
Chancre.
• Inguinal lymph nodes enlarged, mobile, discrete & rubbery.
• Chancre and lymph nodes : painless.
• Without treatment, resolves within 2-6 weeks to leave thin
atrophic scar.

6. • Extra genital chancres – fingers, tongue, tonsil, nipple, anus.
• Diagnosed by Dark field microscopy or direct Fluorescent Ab
tests of exudates.

7. Oral chancre Hard Chancre

8. Secondary syphilis :
• 6-8 weeks after development of chancre when treponemes
disseminate.
• Mucocutaneous lesions & generalised lymphadenopathy.
• Fever, malaise, headache common.
• Rashes on trunk and characteristically on palms & soles.
• Condyloma lata in warm moist areas – vulva, perianal areas.

9. • Mucosal patches – genitalia, mouth, pharynx, larynx.
• Less common : hepatitis, renal ds, eye ds & GI abnormalities.
• Diagnosed by serological tests.

11. Condyloma lata -

12. Latent syphilis :
• Asymptomatic but presence of positive syphilis serology.
1. Early Latency : within 1 year of infection, may be
transmitted sexually.
2. Late Latency : patient no longer sexually infectious.

13. Tertiary syphilis :
1. Gummatous syphilis / Benign tertiary syphilis.
2. Cardiovascular syphilis.
3. Neurosyphilis.

14. Benign tertiary syphilis :
• Skin , mucous membrane, bone, muscle and viscera involved.
• Gumma : c/c granulomatous lesion.
• Healing occurs slowly, formation of tissue paper scars.

15. Gumma -

16. Cardiovascular syphilis :
• Aortitis which may involve aortic valve / coronary ostia.
• Clinical features – aortic incompetence, angina, aortic
aneurysm.
• Proximal aorta mainly involved.
• Surgical intervention required.

17. Neurosyphilis :
• Asymptomatic infection with CSF abnormalities.
• Symptomatic forms :
Meningovascular disease, Tabes dorsalis, General paresis.

18. Congenital syphilis
• Greater chance during early stages of disease.
• Stigmata do not develop until 4th month of pregnancy.
Manifestations:
1. Still birth
 Hepatomegaly, bone abnormalities, pancreatic fibrosis &
pneumonitis.

19. 2. Infantile syphilis
 c/c rhinitis (snuffles) , mucocutaneous lesions.
 visceral & skeletal changes, ascites, hydrops.
3. Late / Tardive syphilis
I. Hutchinson triad - notched central incisors, interstitial keratitis
with blindness & deafness from 8th nerve injury.
II. Saber shin deformity
III. Mulberry molars
IV. Saddle nose deformity
V. Clutton joints

21. Congenital Syphilis

22. Serological tests
1. Non treponemal ( non specific ) tests :
I. Venereal Disease Research Laboratory ( VDRL ) test
II. Rapid Plasma Reagin ( RPR ) test
2. Treponemal ( specific ) tests :
I. Treponemal antigen based Enzyme Immunoassay (EIA) for IgG
& IgM.
II. T.pallidum Hemagglutination Assay ( TPHA )
III. T.pallidum Particle Agglutination Assay ( TPPA )
IV. Fluorescent Treponemal Antibody-Absorbed ( FTA-ABS ) test
 CSF examination

23. Management
Prophylaxis :
• Benzathine Penicillin 2.4 MU single dose before or
12 hrs within contact affords protection.
• Procaine Penicillin 2.4 MU i.m , into each buttock (
total 4.8 MU) , preceded by 1g of Probenecid helps
to prevent both Syphilis and Gonorrhea.

24. Treatment
Disease Treatment Alternatives
Early ( primary,
secondary and latent < 1
yr )
Benzathine Penicillin 2.4
MU i.m, 1-3 weekly inj.
Or
Procaine Penicillin 1.2 MU
i.m x 10 days
Doxycycline 100mg BD
oral x 15 days
Or
Ceftriaxone 1g i.m x 7 days
Or
Erythromycin 500mg QID
oral x 15 days
Or
Desensitization and
treatment with penicillin
Late Benzathine Penicillin 2.4
MU i.m weekly x 4 weeks
Or
Procaine Penicillin 1.2 MU
i.m x 20 days
Doxycycline
Or
Erythromycin for 30 days
Or
Ceftriaxone 1g i.m/i.v x
15 days
Or
Desensitization and
treatment with penicillin

25. Disease Treatment If allergy
Neurosyphilis Aqueous crystalline
Penicillin G ( 18-24 MU/d
i.v, given as 6 divided doses
or continuous infusion) for
10 -14 days
Or
Aqueous Procaine Penicillin
G ( 2-4 MU/d i.m ) +
Oral Probenecid ( 500mg
QID) , both for 10-14 days.
Desensitization and
treatment with penicillin.

26. • Azithromycin 2g single dose is an another alternative.
• Successful treatment → resolution of clinical signs, declining
titers of non treponemal tests ( four fold decline).

27. Syphilis in Pregnancy
• T.pallidum enters fetal circulation after 20th week, fetal
infection unlikely before that.
• Perinatal effects max with primary & secondary syphilis.
• Penicillin – drug of choice.
• For 1° & 2° or latent syphilis of less than 1 yr duration,
 Benzathine PenicillinG 2.4 MU i.m, as a single dose
(or)
 Crystalline Benzyl Penicillin for 10 days

28. • When duration is > 1 yr,
 Benzathine Penicillin 2.4 MU i.m, weekly for 3 doses is
given.
• Breast feeding is not contraindicated.
• Every neonate with congenital syphilis should be treated:
 Benzyl Penicillin for 10 days
 For Interstitial keratitis, local / systemic Glucocorticoids.
 Alternative - Erythromycin stearate
 500mg, once in 6 hrs x 2 weeks

29. Penicillins
• β lactum antibiotic, narrow spectrum.
• 1 MU = 0.6 g
 MOA : interfere with synthesis of cell wall by inhibiting
transpeptidases ( required for maintaining cross linking).
i.e, is bactericidal.

30. Benzathine PenicillinPenicillin

31. Pharmacokinetics :
• PnG is acid labile, destroyed by gastric acids.
• Less than 1/3 of oral dose is absorbed in active form.
• Reaches most body fluids, 60% plasma protein bound.
• T ½ = 30 min
• Rapid renal excretion –
 10% by glomerular filtration. 90% by tubular secretion.
• Tubular secretion blocked by Probenecid.

32. Repository Penicillin G injections
• Insoluble salts of PnG which must be given i.m, not i.v
• They release PnG slowly at site of injection
1. Procaine Penicillin G
 Plasma levels attained are low , but sustained for
12-24 hrs.
2. Benzathine Penicillin G
 Plasma conc very low , but effective for upto 4 weeks.

33. Adverse effects
1. Hypersensitivity
2. Local irritation
• Pain, nausea, thrombophlebitis.
• Toxicity to brain – mental confusion, muscular twitching,
convulsions, coma.
• Accidental i.v injection of Procaine Penicillin – CNS
stimulation, hallucination, convulsions, micro embolism.
3. Superinfection
4. Jarish Herxheimer reaction

34. Doxycycline
• Tetracycline, broad spectrum antibiotic.
 MOA :
▫ Primarily bacteriostatic.
▫ Inhibits protein synthesis by binding to 30S ribosomes .
• Intestinal absorption complete, no interference with food.
• ADR – irritative effects, phototoxicity.
• C/I in pregnancy – a/c hepatic necrosis, teeth & bone affected.

35. Ceftriaxone
• 3rd generation cephalosporin.
• Given parenteral.
• Bactericidal, MOA similar to penicillin.
• Longer duration of action, T ½ = 8hr
• Elimination equally in bile and urine.
• ADR – hypoprothombinemia & bleeding.

36. Erythromycin
MOA -
▫ Acts by inhibiting bacterial protein synthesis.
▫ It combines with 50S ribosome unit, interfere with translocation
• Is acid labile. Food delays absorption by delaying gastric emptying.
• Widely distributed in body. Crosses placenta, not BBB.
• 70-80% plasma protein bound.
• Primarily excreted in bile. Renal excretion minor.
• ADR- GI ds, hypersensitivity, reversible hearing impairment.

37. Treatment reactions
1. Allergy
2. Jarisch – Herxheimer Reaction :
▫ An acute febrile reaction that follows the treatment (1st
dose)
▫ Headache, malaise, myalgia, tachycardia, shivering,
exacerbations of lesions, even vascular collapse.
▫ Common in early syphilis. Rare and severe in late syphilis.
▫ May cause worsening of neurological disease, ophthalmic
disease, myocardial ischemia, laryngeal stenosis.

38. ▫ Is due to rapid destruction of large no. of spirochetes with
release of endotoxin.
▫ Lasts for 12-72 hrs, does not need interruption of therapy.
▫ Aspirin and sedation afford relief of symptoms.
▫ Cannot be prevented by giving graduated doses of penicillin.
▫ Prevent it in cardiovascular & neurosyphilis by –
Prednisolone in single daily dose of 30mg in morning, 2 days
before starting penicillin.

39. 3. Procaine Reaction
▫ After accidental intravenous injection of Procaine Penicillin.
▫ CNS stimulation, hallucination, fits, convulsions, fear of
impending death.
▫ Symptoms short lived.
▫ Verbal assurance & physical restraint necessary.
▫ Reaction prevented by aspiration before i.m injection to
ensure needle is not in blood vessel.

40. Treatment
Disease Treatment Alternatives
Early ( primary,
secondary and latent < 1
yr )
Benzathine Penicillin 2.4
MU i.m, 1-3 weekly inj.
Or
Procaine Penicillin 1.2 MU
i.m x 10 days
Doxycycline 100mg BD
oral x 15 days
Or
Ceftriaxone 1g i.m x 7 days
Or
Erythromycin 500mg QID
oral x 15 days
Or
Desensitization and
treatment with penicillin
Late Benzathine Penicillin 2.4
MU i.m weekly x 4 weeks
Or
Procaine Penicillin 1.2 MU
i.m x 20 days
Doxycycline
Or
Erythromycin for 30 days
Or
Ceftriaxone 1g i.m/i.v x
15 days
Or
Desensitization and
treatment with penicillin

41. Disease Treatment If allergy
Neurosyphilis Aqueous crystalline
Penicillin G ( 18-24 MU/d
i.v, given as 6 divided doses
or continuous infusion) for
10 -14 days
Or
Aqueous Procaine Penicillin
G ( 2-4 MU/d i.m ) +
Oral Probenecid ( 500mg
QID) , both for 10-14 days.
Desensitization and
treatment with penicillin.