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Tertiary Syphilis

Tertiary syphilis represents the end stage of progression of syphilis which is a sexually transmitted disease caused by treponema pallidum, a spirochete.


The presentation of tertiary syphilis typically reflects three major pathophysiologic mechanisms comprising the CNS and cardiovascular involvements, and gummata.

Neurologic manifestations of tertiary syphilis may just be limited to abnormal CSF changes with no neurologic signs or symptoms. In other cases, it presents most commonly with demetia (general paralysis of the insane), tabes dorsalis, and meningovascular disease. Tabes dorsalis presents with ataxia, foot slap, wide-step gait, loss of balance, and dysaesthesias comprising of loss of senations of pain and temperature. Cerebrovascular accidents are long term effects of syphilitic CNS involvement. The typical symptoms of meningitis include: headache, neck stiffness, and focal neurologic deficits which occur in syphilitic meningitis.

Cardiovascular manifestation is centered on aortitis which typiaclly involves the aortic root. Aortitis may subsequently result in aortic valve incompetence, aortic aneurysm, and angina pectoris.

Gummata are inflammatory plaques of fibrous tissue which may affect any organ, but are most commonly seen in the skin and bones. These nodules cause pressure symptoms. Gummata typically present with severe bone pain.

  • Summarized by the mnemonic PARESIS: P Personality changes A Affect R Reflexes (hyperreflexia) E Eye (Argyll Robertson Pupil – reacts to accommodation, not light – aka “Prostitute’s Pupil”) S Sensorium – hallucinations, delusions I Intellect decreased[errolozdalga.com]
  • Several contemporary rumours held that Hitler contracted syphilis from a prostitute in Vienna in 1908 or 1910. Some accounts suggested that the prostitute was Jewish.[fpp.co.uk]
  • ‘He never married, and it is possible that as a young man he contracted syphilis during a single sexual encounter with a prostitute.’[oxforddictionaries.com]
  • Drug usage, active male homosexuality, unprotected sex, and prostitution are all contributing to the rise in early syphilis and thus the increased incidence of neurosyphilis.[priory.com]
  • APrevention of new cases should have a strategy of information on the disease and its prevention for the general population and specifically for the more vulnerable populations (prostitutes, intravenous drug users, etc.).[scielo.br]
  • Secondary corneal amyloidosis is a rare finding and only 17 cases have been reported in the literature.[ncbi.nlm.nih.gov]
  • […] virus-positive man: a case report. ( 8419580 ) Kearns G....Honda G. 1993 47 Tertiary syphilis of the face. ( 2050849 ) Chung G....Whipple S. 1991 48 Vertebral involvement in tertiary syphilis. ( 2224422 ) Magaro M....Romani M. 1990 49 Secondary localized amyloidosis[malacards.org]
  • […] presence of coronary artery disease with no known atherosclerotic risk factors should include preoperative testing for connective tissue disorders, chronic inflammatory disease, and cold hemagglutinins, because of the possible use of obligatory deep hypothermia[ncbi.nlm.nih.gov]
Soft Tissue Mass
  • Cervical spine computed tomography scan showing calcification in the soft tissue mass posterior to the cord and in the ligamentum flavum. Images further detail the C4–5 ankylosis.[ncbi.nlm.nih.gov]
Saddle Nose
  • Ulcers in these areas may cause destruction of the bony and cartilaginous structures (saddle nose) or perforations that sometimes persist despite treatment.[clinicaladvisor.com]
  • The deformity resulting from the destruction of the bony frame work of the nose and the shrinking of fibroid tissue produces typical saddle nose which is characteristic of syphilis.[peertechz.com]
  • Later symptoms may include deafness, teeth deformities and saddle nose — where the bridge of the nose collapses.[mayoclinic.org]
  • Later manifestations of congenital syphilis include bone and teeth deformities, such as “saddle nose” (due to destruction of the nasal septum), “saber shins” (due to inflammation and bowing of the tibia), “Clutton’s joints” (due to inflammation of the[emedicine.medscape.com]
  • In the case of lower tabes at the beginning, constipation and urinary retention prevail, followed by urinary and fecal incontinence. The characteristic moment for the tabes is the irregularity of the pupils.[en.medicine-worlds.com]
Vomiting without Nausea
  • A person feels a headache of diffuse and arching nature, fever and vomiting without nausea and not bringing relief. Lymphocytic pleocytosis is detected in the cerebrospinal fluid.[en.medicine-worlds.com]
  • Damage to the oculomotor nerve is manifested by squint and ptosis, facial - by asymmetry of the face, pre-vernulitkovogo - hearing loss, and so on.[en.medicine-worlds.com]
  • Pressure ulcers are common among elderly patients. Here, we describe a case of tertiary syphilis with ulcerated gummata, appearing as a possible pressure ulcer.[ncbi.nlm.nih.gov]
  • For several weeks in the tertiary syphilitic tubercle necrotic processes are observed with transformation into an ulcer or phenomena of dry necrosis. The ulcer has a regular round shape and smooth edges.[en.medicine-worlds.com]
  • Systemic signs of tertiary disease include a heart murmur, cranial nerve palsies, pupillary abnormalities (Argyll Robertson pupil), signs of tabes dorsalis, foot ulcers, and iritis.[visualdx.com]
  • Definition of tertiary syphilis : the third stage of syphilis that develops after disappearance of the symptoms of secondary syphilis and is marked by ulcers in and gummas under the skin and commonly by involvement of the skeletal, cardiovascular, and[merriam-webster.com]
Annular Skin Lesion
  • The clinician should maintain a high index of suspicion for syphilis in the differential diagnosis of unusual annular skin lesions in a patient with noncaseating granulomas seen on skin biopsy.[ncbi.nlm.nih.gov]
Neuropathic Arthropathy
  • Treatment options for neuropathic arthropathy of the hip are limited. Arthrodesis has had poor success and treatment with THA has had high complication rates. Syphilis is not merely a historic cause of neuropathic arthropathy.[ncbi.nlm.nih.gov]
  • […] serous carcinoma. ( 21161022 ) Shim H.J. 2010 27 Progressive painless lower limbs weakness in a dialyzed patient: undiagnosed tertiary syphilis: a case report. ( 20180955 ) Dahmani O....Djellid J. 2010 28 Case report: Neuropathic arthropathy of the hip[malacards.org]
Low Back Pain
  • The low back pain and numbness abated after operation. But the follow-up radiographs showed absorption of the bone grafts and failure of instrumentation. A Charcot's arthropathy was formed between L4 and L5.[ncbi.nlm.nih.gov]
  • Case presentation A 44-year-old man who suffered with low back pain for 6 months and progressive radiating pain at lower extremity for 1 week.[bmcinfectdis.biomedcentral.com]
  • Partial ankylosis of the C4–5 disc space was also noted ( Figs. 1A, 1B ).[ncbi.nlm.nih.gov]
  • […] theories have been proposed: a neurotraumatic theory, suggesting the destructive joint process is the result of repeated trauma to the insensate joint, and a neurovascular theory, which proposes that hyperemia, secondary to autonomic neuropathy, leads to osteopenia[ncbi.nlm.nih.gov]
  • The clinical picture is diverse: from depressive disorders to agitation, from hearing loss to paralysis of the limbs. In severe cases, there is a combination of progressive paralysis and tabes (tabo-paralysis).[en.medicine-worlds.com]
  • In the setting of agitated behavior with resistant psychotic symptoms related to neurosyphilis, olanzapine, the atypical antipsychotic alternative, has demonstrated efficacy. [85] Presently, however, there are no specific guidelines to address psychiatric[emedicine.medscape.com]
  • Defects in judgment, emotional lability, grandiose delusions, megalomania, depression, catatonia, amnesia, and hyperreflexia have been described.[aibolita.com]
Long Tract Signs
  • In this article, we present what we think to be the first reported case of gummatous syphilis in the cervical spine, presenting as a mass lesion with long tract signs. The relevant literature to date is also reviewed.[ncbi.nlm.nih.gov]


Screening tests for syphilis includes the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) test. If these tests are positive , a further confirmatory test is recommended. The confirmatory tests for syphilis include fluorescent treponemal antibody-absorption (FTA-ABS) and microhemagluttination assay T pallidum (MTA-TP). Cerebrospial fluid analysis may be necessary in cases of meningeal involvement.

Elevated Sedimentation Rate
  • Our patient suffered from a troubled sight, pain in the right hypochondrium, one enlarged submandibular lymph node, an elevated sedimentation rate, disturbed liver tests and two hepatic lesions upon abdominal computed tomography.[ncbi.nlm.nih.gov]
Elevated Sedimentation Rate
  • Our patient suffered from a troubled sight, pain in the right hypochondrium, one enlarged submandibular lymph node, an elevated sedimentation rate, disturbed liver tests and two hepatic lesions upon abdominal computed tomography.[ncbi.nlm.nih.gov]


Antibiotic therapy with penicillin is the mainstay of treatment of all stages of syphilis. Ocular and neurosyphilis is treated with acqueous penicillin, 3 to 4 million units given intravenously every 4 hours, or procaine penicillin G, 2.4 million units IM once a day plus 500mg probenecid given orally, both drugs are administered for 10-14 days, subsequently with benzathine penicillin 2.4 million units IM once every week for three weeks. In cases of penicillin hypersensitivity or allergy, a cephalosporin is considered; ceftriaxone IM or IV 2g once a day for 14 days.

Asymptomatic neurosyphilis is treated also to prevent neurologic sequalae. Oral or intramuscular antipsychotics may be necessary to manage the paresis. Analgesics are indicated for tabes dorsalis and paresthesias. Neuropathic pains may respond to carbamazepine.


Most cases of tertiary syphilis are treatable, especially in the face of prompt diagnosis and treatment. If diagnosis and treatment are delayed, organ damage and complications of tertiary syphilis may be irreversible.

Poor prognostic factors also include the severity of the disease and the presence of comorbid diseases including opportunistic infections, and sexually transmitted diseases. Mortality may result from respiratory, liver, neurologic, or cardiovascular complications.


Syphilis is caused by the spirochete, treponema pallidum. T pallidum is a motile bacterium which, although described as coiled or spiral, has been shown to posses a flat-wave structure by high-resolution time-lapse microscopy [3].

T pallidum is exclusively a human pathogen with no other known host. Furthermore, in-vitro culture of T pallidum is not possible.

T pallidum gains entry into the body via unprotected sexual intercourse, via breaks or sites of abrasions in the genitals and mucous membranes [4]. Therefore, oral sex is another route of transmission of the infection [5]. Other routes of transmission of syphilis is blood transfusion and vertical (mother-to-fetal) transmission via the placenta.


Approximately 12 million new cases of syphilis were recorded in 1999. Over 90% of those cases occurred in developing countries [6]. Syphilis is estimated to occur in 700,000 to 2.6 million pregnancies yearly. The complications of syphilis in pregnancy include spontaneous abortions, intrauterine fetal demise, and congemital syphilis [7]. In sub Saharan Africa, syphiis accounts for approximately 20% of perinatal deaths [7]. However, death rates have reduced from 202,000 in 1990 to 113,000 in 2010 [8].

The incidence of syphilis is higher among those with a preexisting sexually transmitted infection, particularly HIV, homosexual men, and intravenous drug users [9] [10] [11].

In the united states, by 2007, the incidence rate of syphilis was six times higher in men than women. This was opposed to the equal incidence rates recorded in 1997. Syphilis was observed to be most common among African Americans in the US in 2010. Furthermore, the incidence rate of syphilis in the US has been increasing steadily every year [12].

Tertiary syphilis usually presents after at least 3 years of the primary infection. Tertiary syphilis occurs in 30-40% of all infected persons. At this phase, T pallidum multiplies and spreads throughout the organs of the body but the patient is not contagious anymore. The national Institute of Health (NIH) through its Office of Rare Diseases (ORD) has tagged tertiary syphilis as a "rare disease". This means that it occurs in less than 200,000 of US population.

Sex distribution
Age distribution


After the secondary stage of the infection, serological studies reveal negative nontreponemal antibody test results in 25% of patients. These findings are as a result of spontaneous remission of the infection. However, in another 45% of the patients, antibody tests remain positive, but the patient presents with no further symptoms or signs. Tertiary syphilis occurs in the remaining cases. It usually occurs in untreated cases of syphilis. Typically tertiary syphilis occurs after 5 - 20 years of the primary infection.

In tertiary syphilis, T pallidum invades and replicates in various organs in the body, particularly the central nervous system. CNS involvement could manifest as meningovascular syphilis which involves pathologic changes in the meningeal vessels. Meningovascular syphilis may present with focal neurologic deficits and CSF findings of increased cellularity and high protein levels. Syphilitic meningitis is another common CNS manifestation of the infection. The endarteritis caused by syphilis may also predispose to acute stroke syndromes.

CNS involvements could also manifest as tabes dorsalis which is characterized by demyelination of the dorsal root and posterior columns and destruction of the dorsal root ganglia.

Cardiovascular involvement is typically manifested as an aneurysm of the ascending and transverse parts of the aortic arch. This results from the typical syphilitic gummatous changes in the tunics media of the aorta. Consequent to the aneurysm, aortic valve incompetence, aortic rupture, and pressure necrosis of adjacent structures may occur. 

An isolated gumma is a typical granulomatous reaction to T pallidum and is commonly observed in the skin and bones, however, it may occur in any organ. Gummas produce pressure symptoms.

Often, microscopic examination of samples of the affected organs in tertiary syphilis reveals a small amount of the spirochetes. Characteristically, tertiary syphilis is not contagious.


Practicing safe sexual intercourse is the main preventive measure against syphilis. Syphilis screening is recommended for all pregnant women to foster early diagnosis and treatment to prevent congenital syphilis.


Syphilis is a sexually transmitted infection caused by treponema pallidum, a spirochete. T pallidum is found exclusively in humans and is transmitted via sexual intercourse, vertical transmission from mother to fetus, and blood transfusion. However, it may rarely result from contact of a break in skin with the lesion. The main etiological classifications of syphilis are congenital and acquired syphilis.

Congenital syphilis may be classified as early or late based on the onset of presentation. Early congenital syphilis becomes symptomatic within the first 2 years of life, while late syphilis presents after the age of 2 years.

Syphilis acquired through sexual intercourse, if untreated, progresses through four stages with characteristic symptoms and progressive disease severity. The stages of syphilis include: primary, secondary, latent, and tertiary stages. Generally, syphilis may be indistinguishable from other sexually transmitted diseases by its symptomatology alone [1].

Primary syphilis manifests as a local infection of the genitals presenting with a macule which progresses into a painless ulcer and a chancre after 14-21 days of exposure. However, the incubation period could be as long as 90 days.

Secondary syphilis develops after 4 - 8 weeks of onset of primary infection and is often asymptomatic. Secondary syphilis is a laboratory diagnosis made with positive serological findings after less than 1 year ( CDC criteria) or less than 2 years (WHO criteria) after the primary infection [2] [3]. Latent syphilis is somewhat similar to secondary syphilis diagnosed as an asymptomatic infection acquired more than a year (CDC criteria) or more than two years (WHO criteria) after the primary infection [2].

Tertiary syphilis is the end-stage of the disease and manifests after several years of the primary infection presenting with neurosyphilis, cardiovascular pathologic changes, and gummata which may appear in any organ of the body.

Treatment of all stages of syphilis is with penicillin. However, cephalosporins may be used in cases of penicillin allergy.

Patient Information


Syphilis is a sexually transmitted infection caused by a bacterium called treponema pallidum. There are four stages of syphilis; primary, secondary, latent, and tertiary, and these stages represent the different levels of progression of the disease. The secondary stage usually occurs between one to two months after the primary stage, while the tertiary stage occurs many years after the primary one and is characterized by spread of the infection to vital organs of the body including the brain, eyes, and heart.


Syphilis is caused by a bacterial agent called treponema pallidum and the infection can be contracted via unprotected genital sex and oral sex. It could also be transmitted via blood transfusion and from a pregnant woman to her unborn child through the placenta.

The key features of tertiary syphilis are the involvement of the brain, eye, heart, and skin. At this stage of the infection, the bacteria enter into the brain damaging the lining of the brain and spinal cord, called the meninges, and the blood vessels in the brain. The bacteria may also cause damage to the nervous network in the spinal cord.

In the heart, the bacterium damages the lining of the aorta which is the great blood vessel that carries blood away from the heart to all parts of the body. There are some large nodules called gummata (singular: gumma) which are products of inflammation caused by syphilis. The gummata are characteristically seen in the skin and bones at this stage of the infection.


Syphilis is most commonly seen among those with other sexually transmitted infections such as HIV, homosexual men, and those who abuse intravenous drugs.


Early diagnosis and prompt treatment are the factors which make for a cure of this infection. If diagnosis or treatment is delayed, complications of this infection may be irreversible.

Death often results from damages for the brain, liver, lungs, and the heart.

In pregnant women with syphilis who are untested, spontaneous abortions, stillbirth, and malformations and abnormal appearance may be seen in the baby.


The effect of this infection on the brain may result in loss of balance, inability to coordinate one's movement, numbness of the skin, inability to feel hot or cold, disorientation, confusion, and impaired concentration.

The effect on the heart manifests as angina, abnormal enlargement (aneurysm) of the aorta, and poor heart valve function. 

The gummata appear as large lumps in the skin, bones, and in a few cases may affect other organs of the body. These lumps press on adjacent organs or structures causing compressive symptoms.


The initial step in investigating syphilis is to screen for its presence. A common screening test is called Veneral disease research Laboratory (VDRL). If the screening is positive, further tests are done to confirm the infection.

In cases where syphilis causes meningitis, which is the inflammation of the lining of the brain and spinal cord, a procedure called lumbar puncture may be necessary. This procedure involves collecting fluid which is present within the lining of the brain and spinal cord and analyzing it for typical findings of the infection.


The main stay of treatment of all stages of syphilis is penicillin. In cases where a patient is allergic to penicillin, cephalosporins such as ceftriaxone may be used.


Safe sex is the key preventive measure against syphilis. Furthermore, pregnant women should be screened for syphilis to prevent complications in the baby.



  1. Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005; 18:205-216.
  2. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010; 59:1-110.
  3. Izard J, Renken C, Hsieh CE, et al. Cryo-electron tomography elucidates the molecular architecture of Treponema pallidum, the syphilis spirochete. J Bacteriol. 2009; 191:7566-7580.
  4. Goh BT. Syphilis in adults. Sex Transm Infect. 2005; 81:448-452.
  5. Edwards S, Carne C. Oral sex and transmission of non-viral STIs. Sex Transm Infect. 1998; 74:95-100.
  6. Stamm LV. Global challenge of antibiotic-resistant Treponema pallidum. Antimicrob Agents Chemother. Feb 2010;54(2):583-9.
  7. Woods CR. Congenital syphilis-persisting pestilence. Pediatr. Infect. Dis. J. June 2009; 28 (6): 536–7.
  8. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15; 380(9859): 2095–128.
  9. Coffin LS, Newberry A, Hagan, H, Cleland CM, Des Jarlais DC, Perlman DC. Syphilis in drug users in low and middle income countries. Int J Drug Policy. 2010 Jan;21(1):20-7. 
  10. Gao L, Zhan L, Jin Q . "Meta-analysis: prevalence of HIV infection and syphilis among MSM in China". Sex Transm Infect. 2009 Sep;85(5):354-8.
  11. Karp G, Schlaeffer F, Jotkowitz A, Riesenberg, K. Syphilis and HIV co-infection. Eur J Intern Med. 2009 Jan;20(1):9-13.
  12. Clement ME, Okeke NL, Hicks CB. Treatment of Syphilis. JAMA. 2014 Nov 12;312(18):1905-17.

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Last updated: 2019-07-11 21:31