Pathophysiology of syphilis

The pathophysiology of Syphilis is worth knowing, and a great concern for many in this present world.


It remains a contemporary plague that continues to afflict millions of people worldwide.

Spirochete Treponema pallidum is the pathogen that causes this bacterial infection. Due to its many protean clinical manifestations, it has been named the “great imitator.”


Treponema genus is a spiral-shaped bacteria with a rich outer phospholipid membrane that belongs to the spirochetal order. It has a slow metabolizing rate as it takes an average of 30 hours to multiply.

Introduction to the pathophysiology of syphilis

pallidum is the only agent that causes venereal disease. The other T. pallidumsubspecies cause non-venereal disease that is transmitted via nonsexual contact: Treponema pertenuecauses yaws, Treponema pallidum endemicum causes endemic syphilis, and Treponema carateum causes pinta. All the treponematoses have similar DNA but differ in their geographical distribution and pathogenesis.

The origin of syphilis has been controversial and under great debate, and many theories have been postulated regarding this.

The pre-Columbian theory looked at findings on skeletal markers of syphilis before 1490. However, there is insufficient proof, as evidenced by the DNA and paleopathology findings, to support the existence of syphilis before 1492.


Risk Factors on the pathophysiology of syphilis

You’re at higher risk of getting syphilis if you:

  • Have unprotected sex
  • You have numerous sex partners
  • Have HIV
  • You are gay

The infection progresses through 3 stages and can affect many organ systems.

Pathophysiology of syphilis and stages

Treponema pallidum is a very tiny organism that is invisible on light microscopy. Thus, it is identified by its distinct spiral movements on darkfield microscopy.

The primary syphilis presentation is a solitary non-tender genital chancre in response to invasion by the T. pallidum.

pathophysiology of syphilis

However, patients can have multiple non-genital chancres, such as digits, nipples, tonsils, oral mucosa. These lesions can occur at any site of direct contact with the infected lesion.

Even without treatment, these primary lesions will go away without scarring. If left untreated, primary syphilis can progress to secondary syphilis.

Secondary syphilis results from hematogenous {blood} dissemination of the infection and is protean which gives it the name “great imitator” {mimics the symptoms of numerous diseases}

Both primary and secondary lesions resolve without treatment, and the patient enters either an early or latent phase in which no clinical manifestations are present. The infection can only be detected at this stage with serological testing.

Some patients in this stage will progress to the tertiary stage, characterized by cardiovascular syphilis, neurosyphilis, and late benign syphilis.

The incubation period is about 20 to 90 days. The organism does invade the CNS early, but symptoms appear late.

Below is the summary of the pathophysiology of syphilis with the 3 stages involved

Primary syphilis

In the pathophysiology of syphilis, the primary stage can also be regarded as the early stage.

Here, an infected person gets one or more sores called chancres, which are small painless ulcers.

It occurs on the genitals, rectum, anus, or around your mouth between 10 and 90 days (3 weeks on average) after you’re exposed to the disease.

If left untreated, they heal without a scar within 6 weeks.

Secondary syphilis

In this stage of the pathophysiology of syphilis, infected persons get a rosy “copper penny” rash on the palms of their hands and the soles of their feet.

Pathophysiology of syphilis

They may also have different rashes on other parts of their body.

These may look like rashes caused by other diseases and will resolve on their own without treatment.

Tertiary syphilis

In this stage of the pathophysiology of syphilis, the infection if left untreated, will progress to the stage marked by severe problems relating to the cardiovascular system, nervous system, and other systems. The impairment caused by syphilis to these systems could be fatal.

From the tertiary stage of syphilis, it progresses to other stages which may also be regarded as the types of syphilis.

Neurosyphilis where it affects the nervous system

Congenital syphilis where it can be transmitted from mother to child

As tuberculosis cannot be discussed without mentioning HIV syphilis cannot be discussed without mentioning HIV.

Both are clinically related in the sense that a person with sexually transmitted syphilis has an estimated two- to fivefold increased risk of contracting HIV.

This is because a syphilis sore can bleed easily, providing an easy way for HIV to enter your bloodstream during sexual activity.

The pathophysiology of syphilis made easy

Stage of syphilis Clinical manifestations
Primary Chancre, regional lymphadenopathy
Secondary Maculopapular rash on the flank, shoulder, arm, chest, back, hands, and soles of feet; malaise, headache, generalized lymphadenopathy; less common: fever, anorexia, weight loss, mucous patches; condyloma lata; alopecia, meningitis; myalgia; ocular complaints; hepatic, pulmonary, and neurological involvement
Latent Asymptomatic
Cardiovascular syphilis Aortic aneurysm, aortic valvular insufficiency, coronary artery ostial stenosis
Acute syphilitic meningitis Headache, meningeal irritation, ocular involvement, cranial nerve palsies
Meningovascular Focal neurological deficits, cranial nerve palsies
General paresis Prodrome: headache, vertigo, personality disturbances, followed by an acute vascular event with focal findings
Tabes dorsalis Insidious onset of dementia associated with the delusional state, fatigue, intention tremors, loss of facial muscle tone
  Lightning pains (lower extremities and abdomen most commonly), ataxia, Argyll Robertson pupil, areflexia, loss of proprioception
Gumma Monocytic infiltrates with tissue destruction of any organ
Congenital syphilis
Early Fulminant disseminated infection, mucocutaneous lesions, osteochondritis, anaemia, hepatosplenomegaly, neurosyphilis
Late Interstitial keratitis, lymphadenopathy, hepatosplenomegaly, bone involvement, condylomata, anaemia, Hutchinsonian teeth, eight‐nerve deafness, recurrent arthropathy, neurosyphilis
HIV co‐infection Multiple persistent chancres; ocular involvement and neurosyphilis more common; rapid progression to gummatous disease characterized by lesions of skin, bone, and viscera










Syphilis Diagnosis and Tests

Blood tests

A quick test at your doctor’s office or a public health clinic can diagnose syphilis.

Cerebrospinal fluid tests

If your doctor thinks you might have neurosyphilis, they’ll test fluid taken from around your spinal cord.

Darkfield microscopy

Syphilis bacteria are visible through a microscope in fluid taken from a skin sore or lymph node.

Can syphilis be prevented?

There is no vaccine available to prevent syphilis.

The use of safe sex practices, including condom use, can only prevent syphilis if the infectious chancre is located in a body area protected by a condom.

Washing or douching after sexual activity cannot prevent the infection. It is not always possible to know whether a sex partner is infected with syphilis because the chancre (ulcer) may be located inside the vagina or rectum.

Neonatal syphilis is preventable by treating the mother early in her pregnancy.


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