Jarisch-Herxheimer reaction

One of the potential side effects of treatment is the Jarisch-Herxheimer reaction. It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscles pains, headache, and tachycardia.^[4] It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.^[29]

Syphilis

Treponema pallidum ►Syphilis is caused by the spirochete Treponema pallidum. ►It dies rapidly in the external environment, at drying, high temperature, acidic and alkaline media and with antiseptics but resistant to low temperatures and moist medium ►Nonpathogenic treponemes can be found in the oral cavity.

Basics on epidemiology:

►Most cases of syphilis are transmitted by sexual intercourse. ►Syphilis also can be spread by:  kissing, touching a person who has lesions on the lips, oral cavity, or any body area  transfusion of fresh human blood  during pregnancy (through the placenta) → congenital syphilis  occupational way (medical workers)

►The patient is most infectious in the early stages of the disease. Moist lesions that are present in the primary and secondary stages are the most infectious.

►Some infected individuals have no evidence of active disease

Immune response for Syphilis is an example of “non-sterile infectious immunity” as shows fight against bacteria but the response is not able to eliminate them completely.

The response exists as long as Treponema pallidum remains in the body and disappears when the bacteria were removed completely. Due to that any person may be infected repeatedly (reinfection) but detection of specific antibodies helps to detect the disease and effectiveness of treatment.

Syphilis is divided to:

►Incubating syphilis ►Primary syphilis ►Secondary syphilis ►Late (tertiary) syphilis

►Congenital syphilis (early and late)

time

Incubating Syphilis Period from moment of penetration by Treponema the skin/mucosa till appearance of first clinical findings.

The median incubation period is 3 weeks, but it varies from 3 to 90 days.

Shortened due to: • Depressed immunity/resistance (HIV, alcholol and drug - abuse etc.) • Many sites of penetration of bacteria Prolonged due to: • Intake of antibiotics for concomitant diseases Incubating Syphilis may be

Primary syphilis

►Period from the appearance of first clinical finding (chancre) till appearance of numerous syphilitic eruptions on the skin and mucosa. ►Lasts 6-8 weeks. ►Starts from seronegative period (serologic reactions are negative within first 3-4 weeks) and followed by seropositive period.

Secondary syphilis

►results from dissemination of the spirochete to all organs. ►begins from numerous syphilitic eruptions on the skin and mucosa and ends when the patient mounts a successful immune response. ►begins approximately 6 to 8 weeks after the appearance of a chancre (primary syphilis).

By clinical findings background secondary syphilis is divided to: • Secondary early syphilis (numerous syphilitic eruptions on the skin and mucosa and chancre may persist) • Secondary recurrent syphilis (period of recurrent eruptions) • Secondary latent syphilis (period without eruptions, the diagnosis can then only be established with a positive serologic test)

Latency

►The secondary stage subsides and the patient enters a latent period. The diagnosis can then only be established with a positive serologic test for syphilis during the latent period.

 Relapses of secondary syphilis can occur up to 4 years after contact.

Late (Tertiary) syphilis

►The term late syphilis refers to the clinically apparent or inapparent tertiary disease that develops in up to one third of untreated patients.

►Most of these lesions involve the vaso vasorum of the aorta or the arteries of the CNS, or both; the rest consist principally of gummas, a unique granulomatous lesion with a coagulated or amorphous center and small vessel endarteritis. ►The skin, liver, bones, and spleen are the most common sites for development of gummas

Early congenital syphilis

►is defined as syphilis acquired in utero that becomes symptomatic during the first 2 years of life ►The findings can be viewed as an exaggeration of those of acquired secondary syphilis

Late congenital syphilis ►Symptoms and signs of late congenital syphilis become evident after age 5 years. The average age at first diagnosis is 30 years. ►Hutchinson’s triad is Hutchinson’s teeth, interstitial keratitis, and VIIIth nerve deafness and is considered pathognomonic of late congenital syphilis

The diagnosis of syphilis in its infectious (primary and secondary) stages can be confirmed using dark field microscopy to show up spirochetes in smears from chancres, oral lesions, or moist areas in a secondary eruption. Serological tests for syphilis become positive only some 5–6 weeks after infection (usually a week or two after the appearance of the chancre). Diagnosis

Stages of examination of a patient with syphilis  History;  Examination of visual eruptions;  If moist lesions present - detection of Treponema pallidum in the serous discharge from eruption on the skin and mucous membranes;  Serological tests for syphilis to detect antibodies to Treponema antigens.

Non-specific antigens used in non-specific reactions: 1. Sonicated Treponema antigen obtained from nonpathogenic Treponema strain. It allows to reveal group-specific antibodies. 2. Cardiolipin antigen is received synthetically. It allows to detect antibodies to lipid antigens..

Serological tests for syphilis are subdivided into specific and non-specific

Specific reactions imply the use of antigens extracted from pathogenic Treponema strains, which allows detecting of species-specific antigens (to Treponema pallidum).

Nonspecific reactions include precipitation microreactions, Bordet-Gengou test (Reiters complement fixation test — (R)CFT), specific reactions include — IFT, TPI, IEA, IHAR.

According to the function, serological tests are subdivided into:  Screening;  Diagnostic;  Confirmatory.

Screening (selective) reactions are used for big group of selected population to suspect syphilis. They are fast in performance, cheap but not very correct.

Selective reactions include: 1. Precipitation microreaction with cardiolipin antigen; 2. VDRL-test -an analogue of microreaction; 3. RPR-test.

Diagnostic reactions are used for confirmation of diagnosis, efficiency of treatment control, and on examination of donors and pregnant women. The main diagnostic reactions are: (R)CTF — Reiter's complement fixation test, which is called Wassermann reaction (WR). It is made with sonicated Treponema and cardiolipin antigens. It is estimated as "+" and by quantitative method. CTF with two antigens together with microreaction is designated as STC serological tests complex which becomes positive in 2 weeks after beginning of the primary period.

Confirmatory reactions are used for differential diagnosis of latent syphilis, for examination of persons who have been in sexual and everyday contact with syphilitic patient, and with the purpose of control of the treatment effectiveness. Confirmatory reactions include: 1. Immunofluorescence test (IFT) and its modifications; 2. Treponema pallidum immobilization test (TPI) 3. Immune-enzyme analysis (IEA); 4. Indirect hemoagglutination reaction (IHAR); 5. Confrontation method — detection of syphilis in sexual partners; 6. Experimental treatment is used extremely rare only in visceral syphilis.

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