Syphillis

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Last updated: August 8, 2026Bookmark

Syphilis is a sexually transmitted disease that is transmitted through breaks in the skin or mucous membranes after contact with individuals with early (primary and secondary) syphilis. It is caused by the spirochete Treponema pallidum – the “great imitator” since it mimics other diseases*.*

It peaks between 30 and 40 years and affects men more than women.

Stages of syphilis

Stage	Characteristics
Primary syphilis	Generalised lymphadenopathy and a chancre
Secondary syphilis	Occurs weeks after the chancre has healed due to haematogenous spread. It is a highly infectious stage.
Early latent syphilis	Serologically confirmed infection in the absence of any clinical features
Tertiary latent syphilis	Serologically confirmed infection in the absence of any clinical features > 2 years of infection
Tertiary (late) syphilis	Gummatous syphilis, cardiovascular syphilis, or neurosyphilis

Transmission
- Sexual contact
- Vertical (transplacental)
- Blood exposure or direct skin contact with infectious lesions (rare)
Risk factors
- Unprotected sex
- Multiple sexual partners
- Co-infection with HIV
- Men who have sex with men (MSM)
- Pregnancy
Pathophysiology
- Microscopic abrasions → Treponema pallidum enters subcutaneous tissue → formation of a primary chancre → hematogenous spread → immune complex deposition in arterial walls → endarteritis obliterans
- Untreated syphilis progresses to late syphilis which is characterised by:
  - Neurosyphilis
  - Gummatous syphilis
  - Cardiovascular syphilis
Signs and symptoms
- Hard anogenital ulcer (painless chancre)
- Maculopapular rash
  - Symmetrical
  - Affects the trunk, face, palms or soles
- Fever
- Malaise
- Myalgia
- Fatigue
- Arthralgia
- Lymphadenopathy
- Tonsilitis
- Flat papules around the genitals (condylomata lata)
- Oral snail-track ulcers
- Alopecia
- Hepatitis
- Hepatosplenomegaly
- Rhinitis
- Uveitis
- Optic neuritis
- Meningism
- Glomerulonephritis
- Periosteitis
Differentials
- Chancroid
- Genital herpes
- Primary HIV infection
- Psoriasis
- Alopecia areata
- Oral cancer
- Lymphogranuloma venereum
- Granuloma inguinale
- Candidiasis
- Trauma
- Reiter’s syndrome
- Behcet’s syndrome
- Fixed-drug eruption
- Scabies
Investigations
- Direct detection
  - Dark field microscopy to visualize Treponema pallidum
  - PCR where available
- Non-treponemal serological tests: These are screening tests that measure the response to cellular damage. A fourfold titer change is clinically significant.
  - RPR
  - VDR
- Treponemal serological tests: These are confirmatory tests that are specific for Treponema pallidum.
  - T. pallidum particle agglutination assay (TPPA)
  - Treponema pallidum hemagglutination assay (TPHA)
  - Fluorescent treponemal antibody absorption test (FTA-ABS)
  - Enzyme immunoassay (EIA)
- Lumbar puncture for CSF VDRL or FTA-ABS to diagnose neurosyphillis
- HIV serology
Treatment
- Contact tracing
- Avoidance of sexual contact
- Full sexual health screening
- IV/IM penicillin
- Doxycyline or ceftriaxine in case of penicillin allergy
Complications
- Gummas – granulomas in the skin, mucosa, bone, joints, and viscera (lungs and testes)
- Ascending aortic aneurysm
- Aortic regurgitation
- Neurosyphilis

Treatment of syphilis by stage

Stage	Treatment
Primary, secondary or early latent	IM Benzathine penicillin G once
Late latent or tertiary without neurosyphilis	IM Benzathine penicillin G weekly for 3 doses
Neurosyphillis/Ocular/Otic	IV crystalline penicillin G for 10 – 14 days
Penicillin allergy	Doxycycline or ceftriaxone
Penicillin allergy in pregnancy	Penicillin desensitization followed by penicillin

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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