Syphilis
P.K.Ghatak, MD
Syphilis is a relatively new disease. Before 1490, no one had heard of syphilis. Syphilis is caused by a Spirochete – Treponema pallidum. Yaws, Pinta, and endemic syphilis are also caused by Treponema, but they differ significantly from syphilis in their mode of transmission, clinical manifestation, and are different strains of the same bacterium.
The first publication of syphilis came from Paris in the 15th century by Jean Fernelius. He championed mercury for treatment and he called the disease Lues Venera. The name syphilis was introduced by a well known poet and physician, Girolamo Fracastoro Gallicus of Verona, in 1530. The hero in his poem was a shepherd named Syphilus, who blamed the god Apollo for causing drought and dissemination to his flock of sheep. In return, Apollo cursed him with a devastating disease, syphilis.
No one wants to admit that syphilis originated in their country; in fact, one would like to put the blame on their rival neighboring country. Syphilis spread rapidly in Europe during the Napoleonic Wars and France got the most blame for the spread. Syphilis was called the French disease at that time.
In the 15th century, Yaws and Pinta were already present in the Old World among the poor population living in unhygienic conditions. Christopher Columbus brought spirochetal diseases with his crew and introduced them to the New World. A rapid spread of the spirochete became widely scattered among the unprotected population. The rapid growth of the spirochete produced new gene mutations, just as we have witnessed in the COVID-19 epidemic. One of the gene mutations resulted in a more virulent and rapidly multiplying spirochete, transmitted sexually, called Treponema pallidum. Columbus, in his return voyage, introduced this newly evolved, mutated spirochete, which resulted in the introduction of syphilis in Europe.
A spirochetal disease in cattle, known as Pinta, was known as far back as 20,000 years. Pinta jumped to humans. A new disease emerged as Yews 10,000 years ago. Further gene mutation caused Endemic syphilis. From the endemic syphilis, sexually transmitted Syphilis emerged.
Treponema pallidum, a gram-negative, long helically coiled, tubular, flagellated motile organism, is a microaerophilic and difficult to culture organism. The outer wall of the Treponema lacks lipopolysaccharide and membrane proteins.
In 1905, Schaudinn and Hoffmann identified Spirochaeta pallidum in Berlin, Germany. Landsteiner in 1906 used “ dark field microscopy” to observe the organism in a smear. In the same year, in August, Wassermann developed a new serology test by using complement fixing, which is now called the Wassermann test for syphilis. In 1907, Paul Ehrlich introduced organic arsenic, Arsphenamine, for the treatment of syphilis, and in 1910, Ehrlich, working with Schachira Hata, refined Arsphenamine to a less toxic compound, Salvarsan, which continued to be the only effective therapy for syphilis till Penicillin replaced it in 1947.
Syphilis in earlier days was much more invasive and rapidly progressive than the clinical spectrum we see today. At one point, syphilis was about to be eliminated by Penicillin therapy and preventive measures, but a new disease, HIV/AIDS, dashed that hope.
Clinical features of Syphilis:
Syphilis is transmitted primarily by sexual contact with a person suffering from syphilis. Syphilis is also transmitted by transfusion of contaminated blood and acquired congenitally from an infected mother to a child. The incubation period of syphilis is 10 to 90 days.
The incidence of syphilis is on the rise in the USA. Higher incidence is seen in people with homosexual practice, addiction to IV drugs, having deviated sexual practice, and being HIV positive.
Syphilis is described under 3 stages: Primary syphilis, Secondary syphilis and followed by a long latent period, and then the 3rd phase, Tertiary syphilis.
Primary Syphilis.
The initial lesion is a painless Papule (pimple), called a Chancre, which develops in the genital area and around other body orifices, fingers, and any other parts of the body with a breach of the skin, that come in contact with the sex organ of an infected person during sex. The papule is generally single, hard, red, raised, and usually 0.5 to 1 mm in diameter. The papule becomes umbilicated in the center, may ulcerate, and then heals with a scar in 3 -4 days. The lesions may be multiple and occur in identical positions on both sides in the mucocutaneous membrane. Because the primary lesions are painless and hidden from sight, the patient may not be aware of the disease. Painless enlargement of the regional lymph nodes develops. With or without treatment, the chancre disappears in 3 weeks.
The pathological feature of chancre:
An intense mononuclear cell infiltration of lymphocytes, plasma cells, and macrophages is present. The endothelial cells swell and proliferate, and a perivascular cellular infiltrate occurs. Neutrophils and other inflammatory cells are seen only in the ulcerated lesions.
The treponema can be seen under dark field examination of the fluid obtained from the base of a chancre. Serological conversion generally takes place in 2-3 weeks, so a repeat test is needed if the initial test is negative. The detection of antibodies can be bypassed in favor of the detection of Treponema DNA antigen by PCR and DNA probe tests, which are more sensitive.
Secondary Syphilis.
Between 2 to 8 weeks after the appearance of a chancre, skin lesions of the secondary syphilis appear. The cutaneous lesions are non-itchy and painless, symmetrical in distribution on both sides of the body. The skin lesions are of various forms; the following types of lesions may appear: urticaria, macular, papular, maculopapular, pustular, nodular and necrotic, and mixed lesions. The lesions resemble measles, psoriasis, bullous pemphigus, pseudolymphoma, erythema multiforme, granuloma annulare, histiocytoma, leprosy, lupus erythematosus, lichen planus, mycosis fungoides, pemphigus vulgaris, psoriasis, sarcoidosis, etc.. The lesions inside the mouth, throat, and upper airways resemble superficial erosions. These lesions are very infectious.
Meningovasculitis: Symptoms of meningovasculitis are headaches, fever, irritability, neck pain, and neck stiffness, cranial nerve palsy, including movements of eye muscles and the accommodation reflex. Confusion, lethargy, sleepiness, photophobia, and seizures are usually seen.
Lesions on palms and soles are the striking features of the secondary stage; these lesions are 5 to 10 mm in diameter and may undergo necrosis.
On the mucocutaneous surface around the genital area, a characteristic lesion appears called Condyloma latum, which are 2 to 3 cm in diameter, white or grey color flat top papules with raised margins, arising due to vegetative proliferation of epidermis with dilated vessels and intense cell infiltration at the dermal and epidermal junction. These lesions are very infectious.
Loss of hair from the scalp, eyebrows, and body hair can occur.
The skin lesions of the secondary syphilis may be recurrent and may last up to 2 years and then disappear.
In many cases, the skin rashes are very subtle and not noticed by the patient. Diffuse lymph tissue enlargement of the area of skin lesions develops.
The serology is 100 % positive in the second stage.
Pathology of skin lesions is basically similar to the primary lesions with regional variation in degrees of ulceration, perivascular infiltrate, epithelial hyperplasia, vasculitis, and histocytic and plasmacytic infiltration.
The 3rd stage is Tertiary syphilis.
The hiatus between the 2nd and 3rd stages varies from a few years to several years.
Symptoms of tertiary syphilis are multiple, involving nearly all organ systems. Dominant among them are nervous, cardiovascular, cutaneous, and ophthalmic.
CNS.
General paresis.
Initially, patients show impairment of intellect and judgment, irritability, and loss of memory. Then, progressively develop a lack of interest in self-grooming, dressing, and personal hygiene. Dementia of various degrees develops and is often associated with grandiose ideas, euphoria, and delusion. Patients may be depressed or agitated. Loss of speech and loss of other mental faculties are gradual. Focal and generalized seizures develop. Muscle tremors and loss of all tendon reflexes and extensor plantar reflex, along with optic atrophy and Argyll Robertson pupils, are present.
Tabes dorsalis.
Symptoms are due to the posterior column of spinal cord lesions, associated with loss of dorsal root ganglia. Loss of pain from limbs starts initially and then develops in the rest of the body. Vibratory and position senses are lost next, which results in ataxia. Paraesthesia specially Electric shock-like pain felt often. Loss of control of the muscles results in slapping of the foot on attempted walking. Loss of bladder and bowel control develops.
Middle cerebral artery stroke.
This develops as a result of endovasculitis of the middle cerebral artery. Complete paralysis of one side with the loss of sensations and the same-sided visual field loss are present.
Cardiovascular:
Large and medium-sized muscular arteries show aneurysmal dilatation and aortic valvular insufficiency, and coronary artery stenosis. Abdominal aorta aneurysm can be large and extend to the iliac vessels. Pressure from the enlarging aneurysm produces various symptoms either in the chest or abdomen. The rupture of an aneurysm produces a catastrophic hemorrhage.
Cutaneous.
Gamma. It is a solitary, painless granulomatous mass or nodule on the skin or in the mouth or throat, which often ulcerates.
Tubero-sarpenginous skin lesions are reddish-brown ulcerated plaques. Tubero-nodular skin lesions are red violaceous nodules, partly infiltrated by inflammatory cells, usually solitary or multiple, present on the skin of the upper extremity.
Ophthalmic:
Eyes: Interstitial keratitis, Anterior and posterior granulomatous or non-granulomatous uveitis, chorioretinitis, retinal vasculitis are seen in the tertiary stage. Pain in the eyes, red eyes and blurred vision, and visual acuity changes occur.
Histopathology of Tertiary syphilis.
Gamma. A mass of soft mass formed by granuloma, chiefly made up of plasma cells, epithelioid histiocytes, lymphocytes, and giant cells, with central caseous necrotic tissue made of dead cells and fragmented collagen fibers, blood vessels show obliterative endarteritis. Gammas are the hallmark of the tertiary syphilis.
At this stage of the disease, the patients become non-infectious.
Small artery. The proliferation of the endothelium and fibrosis produces obliteration of the arterial lumen
Medium-sized artery of the legs. Violaceous nodules and plaques develop along the artery, producing vascular insufficiency.
Large artery. The muscles of the middle wall become fragmented, the intima turns wrinkled, and the adventitia becomes fibrotic; these changes produce an aneurysm.
Tree bark appearance. Arteries show skip lesions of areas of fibrosis and unaffected areas and appear as tree bark.
Immunological reaction in syphilis.
Interaction between humoral antibodies and delayed type cellular immunity determines the outcome of the primary infection. A strong delayed reaction clears the treponema from chancres, whereas if cytotoxic T-cell response or humoral reaction dominates, the organism rapidly multiplies and spreads widely in the body and is associated with prolonged infection and progression to tertiary syphilis. Delayed cellular immunity against Treponema pallidum is expressed by CD83, CD80, CD86 lymphocytes, and HLA-DR and IL-12.
Congenital Syphilis.
Women infected with syphilis as far back as 2 years and not treated, and pregnant women infected for the first time, are liable to pass the treponema to the developing child in utero through the infected placenta.
The infected fetus may be aborted or have a stillbirth. A child born alive will exhibit signs and symptoms of congenital syphilis. For convenience, symptoms are grouped as early, up to 2 years, beyond 2 years, and late, 6 years and beyond.
Early below 2 years. Hemorrhagic rhinitis, extensive sloughing of skin particularly of palms, soles, around mouth and anus. Bullous or vesicular skin lesions are common.
2 years and older. Learning and language difficulty, deafness, and impaired vision.
Late - 6 years and beyond. Frontal bossing, depressed nasal bridge, perforated nasal septum and palate, anterior tibial bowing, arthritis of both knees, interstitial keratitis, corneal opacity, and deafness. Hutchinson teeth (notched incisor teeth) and mulberry molars.
Pathology.
Placenta- Villi are enlarged and hypercellular, proliferative arteritis, necrotizing umbilical cord, and immunological staining identifies Treponema pallidum in the placental tissue.
Skin- perivascular infiltration of mononuclear cells, endothelial swelling, acanthosis, thickening of epithelium, elongation of rete ridges, and disruption of dermal-epidermal junction.
Bones and cartilages- formation of gamma and perforation, and periostitis.
Tests for Syphilis.
RPR Test ( rapid plasma reagin)- It is a blood test that measures the presence of antibodies against Treponema pallidum. [Reagin antibodies are an IgE class of antibody]
VDRL Test (venereal disease research laboratory) – The test can be done on blood and CSF(cerebrospinal fluid), and the test detects antibodies generated within 2 weeks of infection.
Confirmatory test.
TR-PA Test - Treponema pallidum particulate agglutination test must follow the VDRL test to confirm syphilis.
Treatment:
Benzathine penicillin is highly effective in the elimination of syphilis in any stage of the disease, including in latent cases. The dose is 2.4 million units given IM, only one dose.
People who are said to be allergic to penicillin must be desensitized and then receive Benzathine penicillin. In true penicillin allergy, Doxycycline, Ceftriaxone, and Azithromycin can be used.
edited: June 2025.
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