Syphilis Synonym: Lues. Definition: Chronic infectious disease caused by Treponema pallidum that may infect any organ, causing an infinite number of
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1 Syphilis Synonym: Lues. Definition: Chronic infectious disease caused by Treponema pallidum that may infect any organ, causing an infinite number of clinical presentations. Treponemal diseases: Syphilis is one of the treponemal diseases which include: 1-Ordinary Syphilis, caused by T pallidum subspecies pallidum 2-Endemic Syphilis (Bejel), caused by T. pallidum subspecies endemicum 3-Yaws, caused by T. pallidum, ssp pertenue 4-Pinta, caused by T. carateum Treponema are motile bacteria of the family Spirochaetaceae, which also includes the genera Borrelia and Leptospira. The endemic treponematoses (Bejel, Yaws, Pinta) are important both because they infect large numbers of people and because they cause false-positive reactions for syphilis; even the Treponema pallidum specific tests cannot help separate the diseases. The diseases go through stages parallel to syphilis, but with significant differences in organ involvement. Pathogenesis: Treponema pallidum is a very small, spiral bacterium (spirochete) whose form and corkscrew rotation motility can be observed only by dark-field microscopy). The generation time is long, 30 hours; this plays an important role in therapy. Serum levels of antibiotics must therefore persist for at least 7 to 10 days to kill all replicating organisms. The organism is very fragile and rapidly destroyed by heat and antiseptics. Transmission: The transmission rate is between 10% and 60%. T. pallidum can be transmitted by: 1-Inoculation through skin or mucous membranes (sexual contact). 2-Transplacentally (congenital syphilis). 3-Intravenous transmission (blood transfusion) Incubation period: ranges from 9-90 days (average 2-4 weeks). Immunity: may be both humeral, cell-mediated, but neither protect the individual, and there is no relative immunity against a second infection. Classification: Syphilis is divided into ordinary and endemic. Ordinary syphilis is divided into acquired and congenital. 1
2 Acquired syphilis Stages: Untreated syphilis may pass through four stages. Syphilis begins with the infectious cutaneous primary and secondary stages that may terminate without further sequelae or may evolve into a latent stage that lasts for months or years before the now-rare tertiary stage( marked by the appearance of cardiovascular, neurological and deep cutaneous complications. WHO use 2-year period to distinct the early (infectious) phase from the late (noninfectious) phase of the infection. Primary syphilis Is defined by a skin lesion, or hard chancre plus lymphadenopathy. Chancre is a single ulcer, oval in shape, ham-colored, indurated (button-like). It is painless, exudates a clear serum and does not bleed easily. This is the typical or classical type. Chancre is atypical in 50% of cases, being multiple, painful (secondarily infected), soft (non-indurated), or bleed easily. Any location is possible. Men: Prepuce, glans, sulcus, shaft. In homosexuals, perianal region or rectum. Women: Vagina or cervix (often overlooked), labia majora or minora, clitoris, posterior commissure, perianal region, rectum. Extragenital lesions (10%): Lips, tongue, palate, finger. Regional lymphadenopathy: Appears 1 2 weeks after chancre; usually unilateral; 1 2 cm, discrete, firm, non tender lymph nodes without inflammation of overlying skin. Note: Males present more than females with the stage of primary chancre, while females present more than males with the secondary stage. Differential diagnosis: 1-Herpes genitalis: commonest cause of genital ulcer. recurrent, painful, multiple grouped vesicles that easily rupture into erosions. 2-Traumatic ulcers: zip-fastener injury, painful and not firm or button-like. 3-Fixed drug eruption: Erosion, no ulcer; no lymphadenopathy; usually helpful drug history. 4-Chancroid: Painful, soft, undermined ulcer. 5-Lymphogranuloma venereum: Little or no ulceration, but fluctuant lymphadenopathy. 6-Behcet disease: multiple recurrent painful ulcers, oral ulcerations and eye manifestations. 2
3 7-Tertiary syphilitic gumma or secondary syphilis may simulate a primary chancre. 8-Erosive balanitis, Plasma cell balanitis of Zoon, Erythroplasia of Queyrat (mucosal squamous cell carcinoma in situ), carcinoma. Course: The primary chancre heals spontaneously within 2-6 weeks, even without treatment. The majority of patients then pass into a short period of latency (2 weeks 6 months), after which they pass into secondary stage of syphilis. In 25% of patients, the secondary stage starts while the primary chancre is still present. Secondary syphilis Characterized by constitutional symptoms, cutaneous rash, and other systemic changes: Constitutional symptoms: patient is toxic, febrile, anorexic, loses weight, and has a hoarse or husky voice. This is followed by characteristic rash. Cutaneous rash: depending on time of presentation, this may be: 1-Macular rash (roseolar rash): generalized or truncal, non itchy, dull red macules that need a natural light to be seen. 2-Papular rash: generalized scaly dull red rash, typically on the palms and soles. 3-Papulosquamous rash: large fleshy rash of whitish scales, may be psoriasiform, lichenoid or annular. 4-Pustuloulcerative rash: massive rapid reaction with ulcers and pustules, known as malignant syphilis. 5-Follicular syphilis: irregular patchy (moth-eaten) hair loss, rare. 6-Syphilitic leukoderma: Any of the secondary lesions can heal with postinflammatory hypopigmentation. usually resolves. 7-Mucous memberane involvement: no common in our countery, appearing as erythematosus whitish patches (zig-zag pattern) or ulcerations (snail-track ulcers). 8-Condylomata lata: pale, smooth flat-topped, papules occurring mainly on wrm moist areas (genitalia or perianal area). Other systemic changes: 1-Generalized lymphadenopathy: Most regular feature, painless firm lymphadenopathy involving antecubital, axillary, nuchal, preauricular, and other nodes. 2-Liver: Acute hepatitis. 3-Kidneys: Acute glomerulonephritis. 4-Spleen: Enlarged in almost 100% of cases. 5-CNS: Meningitis or meningoencephalitis; 25% have CSF abnormalities. Perhaps more common in HIV/AIDS. 3
4 6-Musculoskeletal: Periostitis, polyarthritis, tenosynovitis. Differential diagnosis: 1-Eruption (trunk): drug eruptions, pityriasis rosea, pityriasis versicolor, acne, psoriasis, lichen planus, leprosy, measles rubella, chicken pox, rose spots of typhoid 2-Hands and feet: erythema multiforme. 3-Condyloma lata: agenital warts, haemorrhoids; 4-Oral lesions: aphthous ulcers, candidiasis. Relapseing syphilis Due to inadequate treatment or to reduced immunity: 1-Clinical relapse: reappearance of cutaneous or mucocutaneous lesions, ocular, or neurological signs. 2-Serological relapse: negative VDRL test become positive, or titre is increasing. 3-Transplacental relapse: supposedly cures female give birth to affected child, infect her partner, or when blood is transmitted. Latent syphilis Secondary syphilis is followed by a latency, which is seldom less than 5 years, during which the patient is asymptomatic but is serologically positive. Tertiary syphilis Comprises gummatous skin and mucosal lesions (benign tertiary syphilis), cardiovascular manifestations, and neurologic manifestations. Cutanous lesions: are destructive and ulcerative, ending with scar formation, but contain sparse organisms and are not associated with lymphadenopathy. 1-Superficial nodular type: Grouped red-brown papules and nodules (1 2 cm) that clear centrally and expand peripherally over years leaving a serpiginous outline.. 2-Deep gummatous types: Firm 1 3 cm subcutaneous nodules that are painless and usually solitary, but frequently ulcerate to punched-out ulcers that heal poorly, leaving papery white scars. Typical sites include palate (perforation), nose (collapse causing saddle nose), scalp, and face. Musculoskeletal: Periosteitis, Osteolysis, Gumma involving bone. Cardiovascular: aortic aneurysm and aortic insufficiency. Neurosyphilis: Meningovascular, Tabes dorsalis 4
5 Congenital Syphilis Syphilis in utero from mother to fetus. The degree of fetal damage depends on the time of infection in the mother and, more importantly, on whether or not she is treated promptly and appropriately. Early congenital syphilis Lesions occur during the first 2 years of life. The fetus s immature immune response allows syphilis to run a rapid and damaging course. Prognosis is especially poor if signs and symptoms are present at birth. Clinical findings include: 1- Present at birth: Low birth weight, abnormally large placenta, hepatosplenomegaly, blisters and erosions mainly on palms and soles (pemphigus syphiliticus), osteomyelitis mortality rate 50%. 2-Developing in first months in untreated infants: Snuffles (chronic runny nose, often bloody), periorificial rhagades, pemphigus syphiliticus may also appear here in delayed fashion, periosteitis and osteochondritis involving mainly long bones with so much pain that infants do not move limbs (Parrot pseudoparalysis), CNS disease (50%), glomerulonephritis with nephritic syndrome. Late congenital syphilis Lesions occur after 2 years of life. Resembles late syphilis, but cardiac involvement is uncommon. Clinical findings include: 1-Cutaneous findings: Analogous to late syphilis 2-Neurosyphilis: Late onset but affects 30 50%. 3-Interstitial keratitis ending in opacity and blindness. 4-Sensory deafness 5-Teeth involvement and abnormalities. The last 3 findings are called Hutchinson's triad 5
6 Stigmata Clinical lesions that develop secondary to congenital syphilis and are permanent, even after treatment. One or more is almost always present. Findings include: 1-Frontal bossing 2-Saddle nose 3-Periorificial furrowed scars 4-Hutchison incisors (screwdriver tip shaped, often notched). 5-high arched palate 6-Corneal opacity and blindness 7-VIII nerve palsy and deafness 8-Saber shins due to thickened tibia. 9-Positive serology of syphilis for all life Diagnosis 1-History 2-Clinical picture 3-Darkfield examination: Treponema pallidum cannot be seen with usual stains such as Gramstain; darkfield microscopy is the most convenient way to identify the organism. Lesions that are usually positive include chancres, early congenital syphilis, condylomata lata, and other secondary lesions where secretions can be extracted. Darkfield of limited utility for mucosal lesions as there are many normal spirochetes in the mouth. 4-Biopsy of skin lesion: abundance of plasma cells is suggestive. 5-Lymph none puncture 6- Serology 7-Therapeutic trial Serologic Diagnosis of Syphilis. There are a number of serologic tests for syphilis. They are used to make the diagnosis, to confirm the effectiveness of therapy, and to monitor patients for recurrence. Serological tests for syphilis become positive only some 5 6 weeks after infection (usually a week or two after the appearance of the chancre). There are two basic categories of tests: 1-Nontreponemal tests: Identify antibodies against phospholipids such as lecithin or cardiolipin. Wasswemann reaction (WR) and Venereal Disease Research Laboratory (VDRL) 2-Treponemal tests: Identify antibodies against Treponema pallidum. e.g. Treponema pallidum Hemagglutination Test (TPHA Test) and fluorescent treponemal antibody/absorption (FTA/ABS) test. 6
7 Venereal Disease Research Laboratory Test (VDRL Test) Basis: Flocculation test. Nonspecific antibodies that react with both Treponema pallidum cell wall phospholipids and cardiolipin are identified. The patient s serum is mixed in a colloidal solution of cholesterol, lecithin, and cardiolipin. If antibodies are present, a precipitate occurs. The serum is diluted and the level at which a reaction still occurs (for example 1:64) is noted. After treatment, the titer will drop over months. Indications: Screening and monitoring of therapy. Evaluation: Highly sensitive nontreponemal test, 100% positive in secondary syphilis. Advantages: Cheap, reproducible, worldwide usage, ability to titrate makes it quantitative. Disadvantages: 10 20% false-positive results; a positive VDRL test must always be confirmed. VDRL is positive 2 weeks after the development of primary chancre, return negative in early syphilis after successful treatment but remain positive for life in late syphilis even with treatment. False-positive reactions: 1-Technical or lab errors: most common cause. 2-Biological patient have positive reaction but no syphilis A-Acute (not more than 6 months, low titre, disappearing spontaneously): viral diseases (measles, mumps, chicken pox, herpes genitalis even common cold) and pregnancy. B-Chronic (last more than 6 months): Diabetes mellitus, cirrhosis, autoimmune diseases (lupus erythematosus, systemic sclerosis, rheumatoid arthritis), advanced systemic malignancies, multiple blood transfusions, advanced age, i.v. drug abuse. Treponema pallidum Hemagglutination Test (TPHA Test) Basis: Sheep erythrocytes coated with Treponema pallidum antigens are incubated with patient serum; if antibodies are present, the red cells agglutinate. Indications: Screening. Evaluation: Highly specific; false positive under 0.1%; becomes positive in third week and remains positive for life of patient. Advantages: Easy to do. Disadvantages: Standardized reagents not available so reproducibility varies; expensive. Fluorescent Treponema pallidum Antibody Absorption Test (FTA ABS Test) Basis: A slide is coated with Treponema pallidum. Patient s serum is absorbed with nonpathogenic treponemes and then applied to slide. Antibodies bound to Treponema pallidum are identified with immunofluorescence. Indications: Confirmatory. Evaluation: Becomes positive in fourth week and remains so forever. Advantages: Very sensitive and specific. Disadvantages: Standardized reagents not available so reproducibility varies. 7
8 Treatment This should follow the current recommendations of the World Health Organization (WHO). Penicillin is still the treatment of choice (e.g. for early syphilis benzathine penicillin 1.2 million units given intramuscularly into each buttock at a single session, or procaine penicillin units intramuscularly daily for 14 days), with long-term high-dose oral erythromycin and tetracycline being effective alternatives for those with penicillin allergy. The use of long-acting penicillin injections overcomes the everpresent danger of poor compliance with oral treatment. Every effort must be made to trace and treat infected contacts. Jarisch-Herxheimer reaction: A complex allergic response to antigens released from dead microorganisms can complicate the treatment of syphilis. A transient acute febrile reaction with headache and myalgia may develop within 24 hours of therapy. It is more prevalent with treatment of early syphilis. Follow-up All patients treated for syphilis must be followed to assess the effectiveness of initial treatment. Patient is checked for any rash, other physical signs, and quantitative VDRL tests are obtained monthly for 3 months, then every 3 months for next 9 months, and every 6 months for 1 year. If antibody titers do not decrease fourfold within 6 months for patients with primary or secondary syphilis, treatment failure or reinfection should be considered, and evaluation for possible HIV infection should be initiated. 8
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