Syphilis

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Introduction:

• Syphilis is Sexually Transmissible Infection (STI), bacterial, due to a spirochete, Treponema pallidum
• It appeared at the end of the 15th century and continues to generate great interest after more than five centuries
• It is currently on the rise (HIV…)
• The natural history of the disease is stereotyped with evolution in three phases: primary (chancre), secondary (treponemic septicaemia) and tertiary (neurological and cardiovascular complications)
• Serologies allow an indirect approach, their interpretation is not always easy
• Therapeutic management is generally well codified (Penicillin G delay)

Historical:

• In Barcelona of 1494 there appeared an epidemic characterized by the occurrence of sexually transmitted genital lesions
• During the Italian Wars (1494-1559), the epidemic spread to Italy, France, Switzerland and Germany
• During the expansion in Europe, syphilis took successively the name of "Spanish evil", "evil French", "evil Neapolitan" …
• In 1530, the publication of a poem by the Italian humanist Giroloma Fracastoro, describing the evil of the shepherd Syphilus, definitively endorsed the name of the disease
• 16th-century authors cited an American origin of syphilis, imported by Christopher Columbus' crews, without any formal evidence being established

Microbiology:

• This is Treponema pallidum (TP), a spiral, mobile, spiral cosmopolitan bacterium belonging to the Order of Spirochaetals
• Identified in 1905 by Schaudinn and Hoffman, the T. pallidum is a helical bacile with regular spires and tapered ends. It belongs to the genus Treponema which contains other species: pathogens (responsible for endemic treponetoses: pian, bejel, pinta) or commensales
• Measuring 5-15 m long, T. pallidum is animated by a double movement: on the one hand, a rotation around its longitudinal axis, on the other hand, a ripple spreading from one end to the other
• Treponema pallidum division time is long, from 33 hours in early syphilis to several days in late syphilis
• Under a standard microscope, it can only be seen on a black background, the colours being difficult
• The black-bottomed microscope examination shows a moving germ (it moves majestically in the microscope field) and rigid (it does not fold over itself)
• Treponema pallidum is not cultivable in vitro, so its metabolism is little known and it is impossible to establish an antibiotic and, unlike other bacteria, to evaluate the sensitivity to antibiotics in vitro
• No resistance to Penicillin has yet been reported, Treponema pallidum is sensitive to all lactamines, cyclines and, to a lesser extent, macrolides
• Its morphological characteristics make it possible to identify the genus Treponema by direct examination under a black-bottomed microscope or after film coloring, however, this examination does not distinguish between the different species (pathogenic or commensal) Treponema
• Finally, it should be noted the existence of Commensales species of Treponema in the oral cavity, making it uninterpretable to direct examination of this location

Transmission mode:

• Sexual transmission: most common, TP is transmitted after contact with contagious lesions, it enters through a genital epithelium seat of microlesions during minor traumas that occurred during the sexual act, practices explain that a canker can be located elsewhere than on the external genitalia
• Maternal-fetal transmission: occurs during pregnancy by transplacental passage of The Treponeme from the 4th month of pregnancy, this justifies the systematic screening and treatment of any active syphilis in the first trimester of pregnancy. The possibility of infant contamination during delivery from a maternal genital canker is possible
• Blood transmission: is exceptionally involved since routine treponemic screening of blood donations. Sharing needles among intravenous drug users remains a hypothetical mode of transmission
• Professional transmission: is only possible if the examination of the syphilitic subject is done with bare hands, mucous and genital lesions are the most contagious, as they are most often eroded, bringing to the surface the treponemes contained in the Dermis. On the other hand, skin lesions are usually very little contagious because they are covered with a more or less intact skin that is not eroded
• The incubation period varies, depending on the size of the inoculum, from 10 to 90 days, on average 3 weeks

Classification:

There are several classifications that overlap in part:

• Clinical classification: distinguishes different stages: primary, secondary, asymptomatic latent, tertiary
• Therapeutic classification: due to a similarity of management, degree of contagiousness and neurological risk, it is customary to group the different phases of syphilis into two categories:

Recent (early) syphilis: groups primary, secondary and latent forms of less than one year (discovery of positive syphilitic serology without clinical injury, less than one year old), characterized by high contagiousness and low risk of s neurological

Late Syphilis: groups late latent syphilis forms of more than one year (non-datable or more than one year old) and tertiary syphilis, with a common low contagiousness but a high risk of neurological sequelae

Clinical:

• Primary Syphilis: is associated with lymphatic locoregional bacterial spread, incubation is of varying duration (average: 3 weeks). Primary syphilis is characterized by:

Syphilitic canker (inoculation point): canker is typically an exulceration (or erosion) or more rarely a well-defined mucous ulceration, 5-15 mm in diameter on average, unique, more rarely multiple, clean bottom, rosé, based on undulating with protected palpation (this is the only truly evocative semiological character, it results in the impossibility of folding, between two fingers, the surface of the ulceration that is only a block with the underlying induration), painless. Dwarf, giant, painful and inflammatory cankers (overinfection), mixed…

• Seat:

In humans: is quite electively in the balano-preputial furrow, more rarely on the acorn or on the sheath

In women: is most often on the outer part of the vulva (small lips, large lips, fork), more rarely vaginal and as it is painless, it then gladly goes unnoticed

In both sexes: canker can sit on the oral or pharyngeal mucosa (fellation), anorectal mucosa

Satellite adenopathy: appears 4-7 days after the canker, the canker is accompanied by a non-inflammatory satellite adenopathy, usually unilateral, they are multiple, small and hard ganglia, sometimes centered by a larger node ( the "prefect" of the groin in the inguinal hollow), mobile, painless, without peri-adenite, which does not fistulize to the skin. In some locations (cervix, rectum) adenopathy is not clinically visible

Evolution:

• Canker heals in 10-14 days on treatment, in 3-6 weeks without treatment, without sequelae (sometimes, residual pigmentation)
• If left untreated, adenopathy persists for several months, treated, disappears after canker
• If the patient is not treated, he will apparently be cured but his condition may progress to the later stages of syphilis

• Secondary syphilis: sepsis-inspemic spread phase of TP, appears about 6 weeks after canker (about 2 months after contage), it can coexist with inoculation canker (then called "primary-secondary syphilis"), it is marked e by several silent skin rashes, interspersed with asymptomatic phases of a few weeks or months. These "blooms" are associated with general and sometimes visceral signs of varying intensity. It is marked by a polymorphic rash "the great simulator"

Skin manifestations: The rash progresses in two more or less intertwined phases:

• Syphilitic Roseole (first flowering): marks the beginning of the secondary phase, it occurs between the 7th and 10th week, thus being able to associate with canker, it disappears in 7-10 days or lasts 1-2 months.  The rash is made of pink erythematous macules, 5-15 mm in diameter, without relief or infiltration, scattered on the trunk and root of the limbs, non-confluent, non-pruriginous, non-scaly. The pale pink colour (peach blossom), the absence of functional signs and spontaneous regression explain why the rash often goes unnoticed. Spontaneous regression without peeling except at the base of the neck (Venus necklace)
• Syphilid papulous (second flowering): Syphilids occur from the 2nd to 4th month, thus coexisting with the roseola and last from 1 to 6 months, recurrences are possible.  The papulous syphilids are polymorphic, but the elemental lesion is almost always a coppery red papule, non-pruriginous, painless, a few millimeters in diameter, non-confluent, arranged symmetrically (on the trunk, limbs and face), sometimes covered with a thin dander or surrounded by a peri-lestal circular peeling (neither constant nor specific): Biett's collar. The palmoplant location, the most characteristic, is inconsistent

Palmoplantal syphilids: are not papulous but infiltrated, they straddle the palm or plantar folds, which makes it possible to distinguish them from the physiological hyper-pigmented spots in black women

On the face: the papules can regroup, drawing circumations, S, especially on the cheeks and chin (elegant syphilids of Brocq), the reaching of the nasogenian furrows evokes seborrheic dermatitis and that of the chin acne acne

Perineal and genital syphilids: multiple, painless, non-pruriginous, papulo-erosive soft, often macerated, giving rise to a highly contagious vegetative appearance (condyloma lata). Reaching the folds is readily erosive

Clinical polymorphism is important and the lesion can be in the form of dander, scabs, ulcerations or necrosis, but the papule and never blisters are found underneath.

Mucous manifestations: the damage to the mucous membranes makes the mucous plaques, they are maculo-papulous lesions, rounded, with clear limits, painless, which can become erosive or vegetative depending on the location, they are contemporary roseolas and papulant syphilids, they are highly contagious and can last for several months, they touch the tongue ("forked plates" because the taste buds are abraded as broke), the pharynx and the larynx (the raucousness of the voice), the commissure labiale (false pearl with para-commissural papule split in two and not simple crack without relief of the bottom of the crease), external genitalia

Dandrian protests: the attainment of dphaners is classic but rare

• Alocacia in clearing: occurs in the 3rd-6th month, she achieves a hair loss in patches, incompletely peeled, circumscribed by 2-4 cm, temporo-occipital on an intact scalp. Diffuse alopecia is very rare, eyebrows, eyelashes and beard can also be affected
• Peri-onyxis: with reaching the ungueal edge, is possible

General signs: they reflect the spread of infection, they are mostly discrete but can be severe: fever (most 38-38.5 degrees Celsius up to 39-39.5 degrees Celsius), headaches (which are not synonymous with neuro-brain damage), meningeal syndrome, poly-adenopathies, hepato-spleenomegaly (with cytolytic or cholestatic biological hepatitis), poly-arthralgias, nagging "bone" pain, variable alteration of the general state, ophthalmic manifestations (papillite,  ucite, optic neuritis, justifying a systematic ophthalmological examination during secondary syphilis, their presence would modify treatment in the same way as a neurological impairment and would require treatment with Penicillin G in IV)

• Latent syphilis: a long-lasting asymptomatic latent phase follows the secondary phase. The Center for Disease Control (CDC) defines early latent (contagious) syphilis as evolving for less than a year and late latent syphilis has been evolving for more than a year, but WHO is at 2 years. The CDC classifies latent syphilis as "early latent" if one of the following events is observed in the previous 12 months: seroconversion or 4x ascent the title of VDRL, history of untreated primary or secondary syphilis, sexual contact with a confirmed or suspected early syphilis. If none of these criteria is met, latent syphilis is classified as "late latent" or indeterminate
• Tertiary Syphilis: combines, to varying degrees, skin, bone, cardiovascular and neurological lesions; the latter two, making the full severity of the disease. These lesions, combining destruction and sclerosis, are more of a delayed hypersensitivity reaction and are non-contagious, most of which are granulomatous lesions destruction and fibrosis. The transition from early secondary syphilis to late secondary syphilis and then to tertiary syphilis is characterized by a decrease in the number of lesions (which become annular), the onset of granulomatous infiltrate, and the decrease in the number of TPs and an increasingly low contagiousness

Skin manifestations:

• Skin tubers: are painless, non-pruriginous, copper-red dermal nodules, 5-30 mm in diameter, arranged on the back, face, arms. They progress to subsidence or ulceration and then central atrophy. Skin lesions can regroup and take an arciform, circumformed or serpiginating configuration
• Syphilitic gums: from multiple locations, genital gum can cause an ulceration called "redux canker", they evolve in 4 stages:

Nodular stage: are hypodermic, firm, mobile, painless, non-pruriginous nodules, 2-10 cm in diameter, unique or few

Softening stage: within a few weeks, the nodule softens and becomes fluctuating, it adheres to the skin which becomes inflammatory

The ulceration stage: the skin opens in the form of a fistula rhythm that will enlarge to achieve a perfectly rounded ulceration (as traced to the compass), a few centimeters in diameter and regular edges, the bottom of this ulceration becomes quickly clean after evacuation of cellular debris

Healing stage: within a few months, the skin closes, creating a rounded scar, at the whitish atrophic center, depressed at the periphery, pigmented

– Damage to the oral mucosa: in particular the palate vault and the uvutter, which will make a voice and can lead, in combination with the lesions of nasal osteochondrite, to a collapse of the nasal structures with nose in "pot foot"

Visceral manifestations:

• Gum and fibrosis can be seen in many organs: liver, pancreas, stomach, intestine, heart, lung, parotid glands, testicles…
• Cardiovascular syphilis: it affects the aorta and is complicated, in descending order, by aortic insufficiency, calcified aneurysm of the thoracic aorta and coronary artery. Histologically, it is a panarterite with fibrous weed and seat of miliary gums, calcification in "egg shell" of the intima
• Bone lesions: achieving long bone osteochondrite (saber blade tibia, clavicular disease), gummy osteitis of flat bones (cranial arch), sclerous osteoticitis (ivory bone), arthritis, bursitis, synovitis, nodules fibrous juxta-articulars
• Neurosyphilis: The fact that central nervous system contamination is, in fact, present at all stages of the disease justifies the treatment of neurosyphilis outside of tertiary syphilis, to which it is classically attached, can be divided into several tables:

Asymptomatic neurosyphilis: the presence of cerebrospinal fluid abnormalities is a risk factor for the subsequent onset of symptomatic neurosyphilis

Symptomatic neurosyphilis: classically, one distinguishes:

• Acute meningitis
• Cerebral vascular syphilis: occurs, on average, between 1 and 5 years after primary syphilis, it is an enarerite of the brain vessels, it manifests itself in ischemic strokes: hemiplegia, aphasia, convulsions, alteration of pupil reflexes
• Parenchymatous neurosyphilis:

General paralysis: dominated by disorders of higher functions, the abolition of reflexes, psychiatric manifestations (dementia)

Tabès (progressive locomotor ataxia): occurs on average between 15 and 20 years after syphilis, it is the result of sclerosis of the posterior cords of the bone marrow, it manifests itself by: pupil abnormalities, loss of achilléan and rotulian reflexes, rapid pain, Romberg sign, Argyll-Robertson sign, deep sensitivity disorders, ataxia, vesic disorders, paresthesia, optic atrophy, fecal incontinence, superficial sensitivity disorders (pain, touch), aches and pains plantar perforatants

CNS gums: are rare and manifest in tumor syndrome

• Congenital Syphilis: is the consequence of the transplacental passage of TP, which becomes possible during the last two trimesters (from the 4th month) of pregnancy, the risk of contamination is all the higher since maternal syphilis is  recent and close to childbirth, there are many tables:

Early congenital syphilis: reveals itself from birth to 2 years, it is the congenital equivalent of secondary syphilis, it similarly associates skin signs, bone, meningeal and various visceral

Late Congenital Syphilis: Reveals after the age of 2 years, it is the congenital equivalent of tertiary syphilis

Stigmates: are the after-effects of lesions observed during congenital syphilis, the most characteristic are rhagades and dental abnormalities

Biological diagnosis:

Treponeme is not cultivated in vitro, the diagnosis of syphilis can only be made by highlighting treponeme itself under a black-bottomed microscope or indirectly by highlighting the specific antibody response

• Examination under a black-bottomed microscope: must be performed on erosive lesions (primary syphilis canker, mucous erosive syphilids), sensitivity at the canker is 50%, it has no value at the oral level due to the possibility of false positive (saprophyte spirochetes)
• Direct immunofluorescence: This test, performed on tissue or exudate, requires heavier equipment and is used less
• Serodiagnostic: is well standardized, inexpensive and reliable. In the majority of cases, the combination of a specific treponematosis test (TPHA) and a non-specific test (VDRL) is sufficient to confirm or disprove a diagnosis of syphilis. There is no serological test to differentiate syphilis antibodies from those of non-venetian endemic treponetoses

Non-treponemic tests (non-specific or anti-cardiolipidic): use a ubiquitous cardio-lipid antigen

• Venereal Disease Research Laboratory (VDRL):

Goal:

It highlights, in the patient's serum, anti-cardiolipidic antibodies, the cardiolipidic antigen used as a target is present in all pathogenic treponemes but also in many animal or plant cells

VDRL is not a specific reaction of treponetoses, a falsely positive syphilitic serology (positive VDRL and negative TPHA) observed during dysimmunitarian diseases, especially during lupus and antibody syndrome anti-phospholipids

VDRL presents the patient's serum with a commercialized cardio lipid antigen previously attached to its cholesterol crystals. In the presence of antibodies, complexes form that clump together cholesterol crystals, which form more or less large aggregates, it is the size of these aggregates that defines positivity, which ranges from

Kinetics:

VDRL is positive, on average, 15 days after the onset of canker

The title then increases rapidly to reach a plateau during the secondary phase, which varies according to the patients, usually between 256 and 1024 U

The VDRL remains very positive throughout the secondary phase

Biological monitoring of the efficacy of the treatment is done on quantitative VDRL () and is considered to be effective in terms of the title of VDRL being divided by 4 (two dilutions) 6 months after treatment.

In the absence of such a decrease, treatment should be resumed, conversely, syphilitic recontamination (the disease is not immune) can be diagnosed not only on the clinic but also on the significant upwelling of the Quantitative VDRL (title multiplied at least by 4)

False syphilis serologies (non-treponemic causes of RSV positivity)
Infectious causes	Non-infectious causes
Bacterials: leprosy, tuberculosis, pneumococcal disease, leptospirosis, borreliosis, scarlet fever Viral: chickenpox, mumps, infectious mononucleosis, viral hepatitis, measles, HIV Parasites: malaria	Pregnancy, intravenous drug addiction, chronic hepatopathy, monoclonal gammapathy, systemic lupus erythematosus, anti-phospholipid syndrome, cancers

• Rapid Plasma Reagin (RPR): also non-specific, less used than VDRL

Treponemic (specific) tests: use a treponemic antigen, they are more sensitive and specific than reactic tests. TPHA is not expensive and is used routinely, however, the FTA is expensive. They are a little positive before the reaction tests

• Treponema Pallidum Hemagglutination Assay (TPHA): it is an agglutination reaction obtained by putting, in the presence of the patient's serum, an ultrasound of pale treponemes previously attached to animal hematias, the presence of antibodies anti-treponemics forms a complex that clumps together the hematias. The advantages of this technique are its simplicity, its sensitivity and its very good specificity. It does not differentiate syphilitic antibodies from antibodies directed against endemic treponetoses

Kinetics:

The TPHA is positive around the 8th-10th days of the canker, the intensity of the reaction is rated in cross, it reaches quickly and, in the absence of treatment, will remain – until the end of life, it is therefore at ' during secondary syphilis and after the 8th-10th day of the Canker

TPHA is only very inconsevil if the treatment has been well conducted and if it has been instituted early. Beyond this period, the TPHA will remain positive

Quantitative TPHA is not a good marker of disease scalability or response to treatment, as it varies significantly from one examination to another for the same patient

• Fluorescent Treponemal Antibody (FTA) and absorbed FTA: is, like TPHA, a specific reaction of treponetoses.  It is an indirect immunofluorescence test, it puts, in the presence of the diluted serum of the patient, a suspension of pale treponemes killed, Strain Nichols, the reaction being revealed by the addition of an animal serum anti-immunoglobulins human marked with fluores ceine. The reading is done under a UV microscope and requires a well-equipped laboratory

Kinetics:

The FTA is positive towards the 5th day of the canker, so this is the first test to be positive, a few days before the VDRL and TPHA

In the absence of treatment, the FTA remains positive in a high capacity throughout the first-secondary phase

Interest is limited to serological diagnosis in newborns in cases of suspected transmission during pregnancy (FTA IgM) and in primary syphilis at the very beginning of the canker if the 2 TPHA and VDRL tests are negative

To increase the sensitivity of the test, it is possible at first to absorb the patient's serum on an ultrasound of Reiter saprophyte treponemes which neutralizes the parasitic antibodies: it is the absorbed FTA

• Treponeme Immobilization Test (TPI or Nelson Test): it is abandoned, requires the manipulation of live treponemes, positivizing only at the end of the primary phase, and does not allow to judge the failure or effectiveness of the treatment

Other tests:

• Enzyme Linked Immuno-Sorbent Assay (ELISA): immuno-enzymatic test, purified or recombinant treponemic antigens, its place in the serodiagnostic of syphilis is not yet definitively established
• Immuno-transfer test (Western-blot): TP proteins, separated by electrophoresis, are transferred to a nitrocellulose membrane that is incubated with serum: specific bands (15.5, 17 and 47 KDa), Western blot could be a good test of diagnosis of congenital syphilis, even more sensitive and specific than the FTA absorbed
• Genomic amplification reaction: As the TP genome is known, amplification targets can be used to highlight the bacterium

	TPHA	TPHA (-)
VDRL	Non-venereal treponematosis (endemic zone) or venereal, treated or not, cured or not	False positive
VDRL (-)	– Serological sequelae of non-venereal treponemat osis- Syphilis, a priori, cured – Primary syphilis within 10-15 days of canker	– Absence of treponema tosis- Syphilis in in cubation- Primary syphilis within 10 days of canker

Histology:

The histology of syphilis is not very specific, the image characteristic of secondary syphilis associates a more or less dense inflammatory infiltrate of the dem where lymphocytes and plasma cells predominate with vessel damage. The most common epidermal disease is exocytosis

Differential diagnosis:

• Primary Syphilis: At the canker stage, the differential diagnosis is that of other causes of genital ulceration, syphilis should be systematically evoked in the face of any mucous, genital, or oral ulceration
• Secondary syphilis: secondary syphilis is the "great simulator" and should be evoked in the face of any maculo-papulous, fleeting or persistent rash: roseola can cause a certainness, a toxidermy (maculeous exanthema), in the face, it can seborrheic dermatitis, acne, psoriasis. Papulant lesions can simulate psoriasis (erythemato-squamele), lichen plan, eczema

Treatment:

• Purpose: to prevent transmission and avoid the appearance of late complications of syphilis, break the chain of contamination this justifies the detection and treatment of multiple partners
• General recommendations: these are those of the World Health Organization: in the face of any genital ulceration, we should not wait for the result of the TPHA-VDRL to treat, similarly, examination under a black-bottomed microscope should not delay the start-up treatment

If the diagnosis of early syphilis is mentioned: do a careful clinical examination (looking for neurological signs), look for another STI (gonococcus, C. trachomatis, HIV, hepatitis B…), make a prescription for TPHA-VDRL:

• Either treat right away (probabilistic approach): which is often the case before a mucous ulceration and see the patient with the TPHA-VDRL result
• Either review the patient with the TPHA-VDRL result (especially if secondary syphilis)

Do not hesitate to contact a specialist in certain difficult situations: pregnant woman, HIV-positive subject, Penicillin allergy

Routine eye examination for secondary syphilis: a possible eye-to-eye injury would alter treatment as well as neurological impairment

• Early Syphilis (primary, secondary and early latent): The diagnosis of early latent syphilis is only acceptable if the patient can provide negative syphilitic serology less than one year old, prior to the discovery of positive serology while he's asymptomatic

Recommended treatment regimen: is the same for all 3 situations (primary, secondary, early latent), in the absence of Penicillin allergy and contraindications to intramuscular injections: a single intramuscular injection of 2.4 M Benzathine Benzyl-Penicillin G IU (Extencillin®)

• In the case of penicillin allergy in a patient with early syphilis, injection (s) can be replaced with 14 days of Doxycycline (100 mg, per bone, morning and evening) or Tetracycline hydrochloride (2 g/d for 15 days) except in pregnant women and HIV-positive patients (indication of tolerance induction) or Erythromycin (2 g/d for 15 days)

Follow-up treatment: the efficacy of the treatment must be controlled clinically and biologically at 6, 12 and 24 months, biological follow-up is done on quantitative VDRL (title divided by 4 (2 dilutions) at 6 months), if not the case, the opinion of a specialist e is justified. VDRL should be negative one year after treatment for primary syphilis and within 2 years of treatment for secondary syphilis

• Late syphilis: 3 intramuscular injections of 2.4 MUI of Extencillin® one week apart, in case of allergy to Penicillin and a tolerance induction. An alternative is Doxycycline (200 mg/d) or Tetracycline (2 g/d) for 4 weeks or Erythromycin (2 g/d) for 30 days. Clinical and serological surveillance needs to be very close
• Neurosyphilis: Penicillin G (12-24 MUI/d) intravenously for 10-14 days or intramuscular penicillin-procain (2-4 MUI) associated with oral probénécidedation (2 g/d), if not èdensensitization
• Syphilis in pregnant women: the risk is that of congenital syphilis, the treatment of syphilis is the same, for the same stage of the disease as recommended in non-pregnant women, some authors recommend a second injection to J8, follow-up clinical and biological is monthly, ultrasound monitoring is essential for the search for signs of very evocative fetal disease. In case of penicillin allergy, most often a tolerance induction will be necessary, cyclines are contraindicated, macrolides can be used as they misadprescise the placental barrier and there are documented resistances on the clinical and microbiological plan
• Congenital Syphilis: A child is at risk of congenital syphilis if he or she was born to a mother whose syphilitic serology (treponemic and non-treponemic tests) is positive and if the child has presented one of the following situations: no treatment, no treatment, treatment less than one month prior to delivery, treatment that does not include Penicillin, lack of significant decrease in the title of non-treponemic tests after treatment, treatment whose exact terms are unknown, serological follow-up after treatment. Treatment is based on water-standardized Benzyl-Penicillin (100,000-150,000 IU/kg/d divided into 2-3 daily infusions 50,000 IU) or procain-Penicillin (50,000 IU/kg/d in an intramuscular injection) for 10-14 days. The interruption of a single day of treatment requires that the treatment be repeated
• Syphilis of the HIV-positive subject: The standard treatment with Penicillin is the same for primary or secondary syphilis of the HIV-positive person. A pre-treatment CSF study is not warranted except for obvious neurological or ophthalmological manifestations (as in HIV-negative subjects), which would require treatment with Penicillin G in IV: 20 MUI/d for 10-15 days
• Topics of sexual contact: the ideal is to be able to clinically examine and perform serology in all subjects sexual contact by remembering that if contact is recent (up to a month), serology can still be negative, this is not always Possible. A systematic treatment of contact subjects may be offered with an injection of 2.4 MUI of Extencillin®

Prevention of Jarisch-Herxheimer's reaction:

• This reaction consists of a worsening of clinical manifestations with headache, myalgia, high fever and is dose-independent and occurs after injection with Penicillin
• Her pathophysiology is still unknown (massive lysis of TP?), she is common in case of early syphilis, she is benign except in pregnant women
• It can be prevented, in part, by the joint administration of Prednisolone (0.5 mg/kg/d) the day before and the first 3 days of treatment

Conclusion:

Although the diagnosis and treatment of syphilis has become much simpler and more reliable in recent decades, it continues to generate great interest after more than five centuries.