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.

• Weakness

  The patient then developed unilateral limb weakness. Computed tomography showed lung lesions and hilar lymphadenopathy, while magnetic resonance imaging showed an increased signal in the cervical cord. [ncbi.nlm.nih.gov]

  This type of syphilis infects the brain and spinal cord and can cause dizziness, personality changes, headaches, muscle weakness, and even paralysis. [sharecare.com]

  He started complaining of a symmetrical painful proximal lower limbs weakness attributed initially to lumbar root compression according to lumbar CT scan and EMG/NCS findings. [casesjournal.biomedcentral.com]

  A person feels persistent weakness, a feeling of lack of air and shortness of breath even with a slight load, heartbeat and arrhythmia. During the examination revealed the deafness of the tones and the pulse of a weak filling. [en.medicine-worlds.com]

  […] unable to walk Numbness in the toes, feet, or legs Problems with thinking, such as confusion or poor concentration Mental problems, such as depression or irritability Headache, seizures, or stiff neck Loss of bladder control ( incontinence ) Tremors, or weakness [nlm.nih.gov]

• Saddle Nose

  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]

  Ulcers in these areas may cause destruction of the bony and cartilaginous structures (saddle nose) or perforations that sometimes persist despite treatment. [clinicaladvisor.com]

  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]

  Later symptoms may include deafness, teeth deformities and saddle nose — where the bridge of the nose collapses. [mayoclinic.org]

• Ulcer

  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]

  Snapshot A 35-year-old man presents to the clinic after noticing an ulcer on his penis. He is unsure how long the ulcer has been present, as he has not felt pain in the area. He denies any symptoms of discharge, rash, or dysuria. [step1.medbullets.com]

  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]

• Macula

  Gass, MD, acute syphilitic posterior placoid chorioretinopathy (ASPPC) results from syphilitic infection of the retinal pigment epithelium in the macula or peripapillary region. 13,19 As the name suggests, lesions are typically large and placoid (See [reviewofophthalmology.com]

• Acne Vulgaris

  More severe rashes may resemble acne vulgaris, scabies, psoriasis, seborrhea, fungal infections or even human papilloma virus-induced warts. [nmihi.com]

• 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

  A 44-year-old man who suffered with low back pain for 6 months and progressive radiating pain at lower extremity for 1 week. Radiologic findings showed osteolytic lesion and new bone formation in the parts of the bodies of 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]

• Ankylosis

  Partial ankylosis of the C4–5 disc space was also noted ( Figs. 1A, 1B ). [ncbi.nlm.nih.gov]

• Meningism

  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. [symptoma.com]

  Syphilitic meningitis is unique among bacterial meningitis in that the CSF Pleocytosis is composed of lymphocytes rather than neutrophils. [pathwaymedicine.org]

  The clinical options for early neurosyphilis are as follows: latent meningitis; clinically acute meningitis; basal meningitis; hydrocephalus (chronic and acute); meningomyelitis; meningovascular syphilis; lesion of individual cranial nerves. [en.medicine-worlds.com]

  Thus, initial early manifestations of neurosyphilis include asymptomatic CSF infection before progressing to acute syphilitic meningitis that may have accompanying ocular disease (ocular syphilis) or inner ear disease (otosyphilis) 1,4. [radiopaedia.org]

• Dizziness

  This type of syphilis infects the brain and spinal cord and can cause dizziness, personality changes, headaches, muscle weakness, and even paralysis. [sharecare.com]

  Symptoms of neurosyphilis may include headache, dizziness, paresis, behavior change, dementia, pain, ataxia, blindness, deafness, incontinence, and impotence. [visualdx.com]

  These included encephalitis, dizziness, neck pustules, chest pain and an "accentuated heartbeat". Ms Hayden also points to signals which suggests a mental decline in his last years, including "paranoid rages". [news.bbc.co.uk]

  He had lesions on his shins so painful that they sometimes prevented him from wearing boots, and suffered intermittently from encephalitis, dizziness, flatulence, neck pustules, chest pain, gastric pain and restrictive palsies - all are associated with [fpp.co.uk]

  Otosyphilis is a rare but very serious cause of hearing loss and dizziness 2. It is diagnosed with a lumbar puncture as it is a form of neurosyphilis 3. It is treated with daily penicillin 4. [dizziness-and-balance.com]

• Hyperreflexia

  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 [errolozdalga.com]

  Defects in judgment, emotional lability, grandiose delusions, megalomania, depression, catatonia, amnesia, and hyperreflexia have been described. [aibolita.com]

  […] intracranial mass (especially if they invade into the brain parenchyma) or spinal cord compression 1,2,4 may be associated with myelitis (acute syphilitic meningomyelitis) resulting in upper motor neuron lesion signs on examination such as spastic paresis and hyperreflexia [radiopaedia.org]

  […] daily for 4 weeks Tertiary (late) syphilis Gummatous disease, cardiovascular disease Nontreponemal tests (71% to 73%) Treponemal-specific tests (94% to 96%) Same treatment as for late latent syphilis Neurosyphilis Seizures, ataxia, aphasia, paresis, hyperreflexia [aafp.org]

• Areflexia

  Disruption of the dorsal roots leads to loss of pain and temperature sensation and areflexia. [emedicine.medscape.com]

• Babinski Sign

  The neurological signs and symptoms presented herein might evoke a picture similar to that of chronic myelopathy in which the pyramidal pathway is involved, characterized by active reflexes and positive Babinski's sign. [casesjournal.biomedcentral.com]

  Common symptoms include decreased tendon reflexes (76% with reflex change, 67% with absent ankle jerk, 5% with Babinski sign), seizures, and neuro-opthalmologic findings (45% with pupillary abnormality, 12% with chorioretinitis/retinary pigmentosa, and [priory.com]

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.

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.

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.

Overview.

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.

Etiology/pathophysiology.

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.

Epidemiology.

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

Prognosis.

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.

Presentation.

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.

Workup.

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.

Treatment.

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.

Prevention.

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

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