Syphilis
P.K.Ghatak, MD
Syphilis is a relatively new disease. Before 1490 no one heard of syphilis, Syphilis is caused by a Spirochete – Treponema pallidum. Yews, Pinta and endemic syphilis are also caused by Treponema but they differ significantly from syphilis in their mode of transmission, clinical manifestation and having different strains of the same bacterium in each case.
The first publication about 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. The syphilis spread rapidly in Europe during the Napoleonic war and France got the most blame for the spread and 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 in the new world. A rapid spread of the spirochete became widely scattered among the unprotected population. The rapid growth of the spirochete, produced several gene mutations, just like we have witnessed 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 introducing syphilis in Europe.
A spirochetal disease in the cattle, known as Pinta was known as far back 20,000 years. Pinta jumped to humans and a new disease emerged as Yews 10,000 years ago. Further mutation, introduced Endemic syphilis. From the endemic syphilis, sexually transmitted present day Syphilis emerged.
Treponema pallidum, a gram negative, long helical coiled, tubular, flagellated motile organism, microaerophilic and difficult to culture in the laboratory. The outer wall of the Treponema lacks lipopolysaccharide and membrane proteins.
There were flurries of activities in all the major nations of Europe in order to detect, diagnose and effectively treat syphilis when ordinary citizens, celebrities and royals were infected and dying of syphilis.
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 fixating 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 lesser 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 from the world by Penicillin therapy and preventive measures, but a new disease, HIV/AIDS put this off indefinitely.
Clinical features of Syphilis:
Syphilis is transmitted primarily by sexual contact with a person who is harboring 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 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, 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 may occur in identical positions on opposite sides on the mucocutaneous membrane. Because the primary lesions are painless and may be hidden from sight, the patient may not be aware of a lesion. 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. The endothelial cells swell and proliferate and 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 and if available.
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 all known variety of well known skin conditions like measles, psoriasis, bullous pemphigus, pseudolymphoma, erythema multiforme, granuloma annulare, histiocytoma, leprosy, lupus erythematosus, lichen planus, mycosis fungoides, pemphigus vulgaris, psoriasis, sarcoidosis etc. In additional to skin lesions, lesions inside the mouth, throat and upper airways may be present in the form of superficial erosions. These lesions are very infectious.
Meningovaculitis. Symptoms include headaches, fever, irritability, neck pain and neck stiffness. Cranial nerve palsy including movements of eye muscles and accommodation reflex. Confusion, lethargy, sleepiness, photophobia and seizures.
In others, iritis to retinitis and other lesions develop in both eyes.
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, these are 2 to 3 cm in diameter, white or grey color fat top papules with raised margins, arise 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.
Systemic symptoms may be totally absent, Symptoms when present are malaise, weakness, anorexia, nausea, headaches, blurred vision and hearing difficulties.
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.
There is a hiatus of a few years to several years when patients exhibit no symptoms.
Symptoms of tertiary syphilis involve all systems and all tissues. Dominant among them are nervous , cardiovascular, cutaneous and eyes. These features are many and only some well known features will be mentioned here.
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. Others are depressed and agitated. Gradually loss of speech and progressive loss of all mental faculties. Focal and generalized seizures develop. Muscle tremors and flat facial affects, loss of all tendon reflexes and extensor planter reflex along with optic atrophy and Argyl Robertson pupils demonstrated.
Tabes dordalis. This is primarily of the posterior column of spinal cord lesions associated with loss of dorsal root ganglions. 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 for muscles of movement 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 corresponds with the same sided loss of sensations and same sided visual field loss. In the left middle cerebral artery lesion the speech is lost.
Cardiovascular. Large and middle sized muscular arteries show aneurysmal dilatation and aortic valvular insufficiency and coronary artery stenosis. Abdominal aorta aneurysm can be large and extend to iliac vessels. Pressure from the enlarging aneurysm produces various symptoms either in the chest or abdomen. The rupture of aneurysm produces catastrophic hemorrhage.
Cutaneous. Gamma, Tubero-sarpenginous and Tubero- nodular syphilitic skin lesions.
Gamma. It is a solitary, painless granulomatous mass or nodule on the skin or in the mouth or throat, 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.
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, epitheliod histiocytes, lymphocytes and giant cells with central caseous necrotic tissue made of dead cells and fragmented collagen fibers, blood vessels show obliterative endartreritis. Gammas are the hallmark of the tertiary syphilis.
At this stage of the diseases the patients become non- infectious.
Blood vessels undergo these changes in the tertiary stage-
Small artery. The proliferation of 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 of cellular immunity determine 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 lost, aborted prematurely and may have a stillbirth. A child born alive will exhibit signs and symptoms of congenital syphilis. For convenience, they 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 incisors teeth) and mulberry molars.
Pathology.
Placenta- Villi are enlarged and hypercellular, proliferative arteritis, necrotizing umbilical cord, immuno 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 IgE class of antibody]
VDRL Test (venereal disease research laboratory) – test can be done on blood and CSF(cerebrospinal fluid), 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 so called allergy to penicillin must be desensitized and then receive Benzathine penicillin. In true penicillin allergy Doxycycline, Ceftriaxone and Azithromycin can be used.
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