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Syphilis

Causative organism is Treponema pallidum –

  1. Incubation Period
    It varies from 9 to 90 days (usually 2-4 weeks).
    Incubation period of 3 weeks, with a range from 9 to 90 days. risk of transmission ranges -  one third of sexual partners with a single exposure to early syphilis become infected. Late disease is generally associated with minimal risk of transmission.
Fig: Stage of Syphilis

  1. Clinical Features
     
    Acquired Syphilis
    1. Primary
      1. The primary lesion is a painless chancre at the site of inoculation.
        1. Lesion begins as an erythematous macule that ulcerates within days.
        2. This ulcer is normally solitary and indurated, with a nonpurulent, clean base and yellow-gray exudates. Several days later, a painless, bilateral, regional lymphadenopathy often results.
        3. The majority of primary chancres heal within 6 weeks of presentation. 50% of untreated syphilis infections progress to the second stage, whereas the other 50% enter latency.
    2. Secondary
      1. The secondary stage of syphilis typically begins 6 to 8 weeks after the onset of the primary lesion. Although the primary lesion is localized to the site of inoculation, secondary syphilis results from hematogenous dissemination and thus presents with widespread manifestations.
      2. Constitutional symptoms, such as fever, malaise, or generalized lymphadenopathy, are common. The skin is most frequently affected, 80% of patients demonstrating cutaneous involvement.
      3. The second stage is the most contagious period of syphilis.
      4. A generalized macular, maculopapular, or papulosquamous rash often appears.  pink macules to (the more common) dusky red, non pruritic scaling papules present. Lesions have a predilection for palms and soles. Papular involvement of the scalp may lead to patchy syphilitic alopecia.
    3. Condylomata lata often occur when the papular eruption is located in moist intertriginous areas, such as the buttocks, groin, labia, or inner thighs.
    4. Opposition of the moist surfaces causes maceration of the papule, forming broad flat-topped lesions. these lesions are the most infectious variety of secondary syphilis.
    5. Thirty percent to 50% of all patients with secondary syphilis also develop mucous membrane involvement.  The most common manifestation is the syphilitic sore throat, and the second most common is the mucous patch.
  2. Latent
    1. Without treatment, secondary syphilis spontaneously resolves and enters latency.
    2. Latent syphilis may occur between the first and second stages or the second and third stages.
    3. This period is characterized by positive serologies without signs or symptoms of disease. 
    4. Although the causative organism continues to multiply in this stage, patients may remain asymptomatic for life.
    5. Only one third of untreated cases progress to tertiary syphilis. The latent stage is divided into early and late periods.  infection of less than 1 year as early latent disease, which is considered infectious. Meanwhile, that which is greater than 1 year is described as late latent disease, which is considered noninfectious.
    6. The World Health Organization has established a dividing line of 2 years between these stages.
  3. Tertiary
    1. Cardiovascular syphilis (3A) - It usually occurs after a latent period of 10-20 or more years.
      1. Angina pectoris due to coronal ostial stenosis
      2. Aortic incompetence
      3. Aortic aneurysm (ascending aorta is the commonest site)
    2. Neurosyphilis
      1. Asymptomatic neurosyphilis
        There is no clinical abnormality but abnormal CSF.
      2. Meningovascular neurosyphilis
        It usually occurs 3-7 years after infection, affecting cerebral and/or spinal meninges.
      3. General paralysis of insane (GPI)
        This usually occurs 10-20 years or more after infection. The clinical features include dementia with recent memory loss, loss of insight, euphoria with delusion of grandeur, tremor, spastic paraparesis, convulsions, incontinence and finally bedridden.
      4. Tabes dorsalis
        Similarly this occurs 10-20 years or more after infection. The clinical features include lightning pain in legs, paraesthesia, sensory ataxia (positive rombergism and ataxic gait), sensory loss in proprioception and vibration, deep pain in Achilles tendon, absent reflexes, overflow incontinence, Argyll Robertson pupils, optic atrophy, Charcot's joints and visceral crises.
      5. Ocular syphilis
        The typical features are ocular atrophy, optic neuritis, chorioretinitis with pepper and salt fundus
  4. Skin
    Two different types of cutaneous lesions may arise.
    1. Nodular or noduloulcerative lesions are small, firm, non pruritic, and painless and predominantly affect the back, face, and arms. These lesions have the potential for ulceration, with resultant scarring.
    2. Gummas are painless, deep granulomatous lesions, normally originating from subcutaneous tissue. Predominant locations include the face, scalp, calf, sternum, and sternoclavicular area typically heal with retractile scarring
    3. Congenital Syphilis
      Congenital syphilis is transmitted in utero after the first 16 weeks of pregnancy, therefore it is usually not a cause of abortion during the first trimester.
       
      The infected child born later in a family usually has less severe syphilis. Again, it has been divided according to the arbitrary dividing line of two years into early and late types.
    4. Early Congenital
      The features are similar to secondary syphilis. Usually it occurs 2-8 weeks after birth, presenting with failure to thrive, muco-cutaneous lesions (condylomata lata), generalized lymphadenopathy, nasal snuffles and skin rash.
    5. Late Congenital
    6. The onset usually occurs at or near puberty. Well-known stigmata include nerve deafness, interstitial keratitis, Hutchison's teeth (Hutchison's triad), rhagades around mouth, Clutton’s joint, osteitis & chondritis (saddle nose, frontal bossing, sabre tibia) and perforated palate.
    7. Malignant syphilis:
      1. Widespread papulopustules become necrotic & break down into ulcers covered by layers of thick, dirty-looking crust resembling an oyster shell (“rupioid”).
      2. It involves predominantly the face and scalp.
      3. Oral ulcers and mucous patches may develop.
      4. Most patients have abnormal immune systems or poor health, more common in HIV-infected persons.
      5. D.D.-pyoderma, ecthyma, acne necrotica, papulonecrotic tuberculids, acne varioliformis,
  5. Investigations
    1. Dark Ground Examination (DGE)
      1. Genital sore x DGE for three consecutive days.
      2. Normal saline could be used for rinse of the sore.
      3. All the other antiseptic solution or systemic antibiotics should be avoided during this investigation.
      4. If antibiotic is really indicated, cotrimoxazole is permitted as it does not interfere with identification of spirochaete.
      5. Treponema pallidum should be distinguished from other nonpathogenic spirochaete by their morphology and movement. Typically they have 5-20 regular spirals and far greater activity than the other spirochaete. Their characteristic movement include angulation, rotation, undulation, compression and expansion.
  6. Serological Tests
    VDRL (Venereal Disease Research Laboratory) Test
    Quantitative titre is measured for the latter purpose. However it is a nonspecific test and biological false positive may occur Confirmation with specific tests is therefore necessary.

Table : Biological False-positive VDRL

Acute (< 6 months)

Pregnancy, other spirochaetal infections (leptospirosis, relapsing fever), viral infections (infectious mononucleosis, measles, chickenpox) or vaccinations (yellow fever, typhoid)

Chronic (> 6 months)

Old age, chronic infection (leprosy, tuberculosis, malaria), autoimmune diseases (esp. SLE), intravenous abuser, malignancy

 
  1. Fta-Absorption Test (Fluorescent Treponemal Antibody)
    1. This is a specific confirmatory test in syphilis.
    2. It becomes positive earlier than VDRL and is the first serological test to become positive.
    3. However it is not suitable for large scale screening and the titre does not reflect the disease activity.
    4. In borderline case (for example, those with weakly reactive or 1+ titre), it would be difficult for the technician to interpret and laboratory error with false positive might occur.
    5. In such a case, it is advisable to repeat the test together with TPHA. If there is still doubt, follow up the patient and repeat the tests at regular interval before label the patient with the diagnosis of syphilis.
  2. Tpha Test (Treponema Pallidum Hemagglutination)
    1. This is technically more simple as compared with other confirmatory tests and it is as specific as FTA. It is not routinely done is performed when the result of FTA is equivocal.
    2. The main disadvantages of this test are the relatively expensive cost and relatively late positivity in primary syphilis.

Interpretation of Different Serological Tests in Syphilis
 

VDRL

FTA

TPHA

Interpretation

-

-

-

 No syphilis incubation period very early stage

+

+

+

 Untreated or recently treated

+

+

-

 Primary syphilis false positive VDRL & FTA

+

-

+

 False positive VDRL & TPHA false negative FTA

-

+

+

 Treated syphilis untreated late syphilis

+

-

-

 Biological false positive

-

+

-

 Early primary syphilis untreated or recently treated false positive FTA

-

-

+

 Treated syphilis false positive TPHA


Fig. Percentage of Positivity of Different Serological Tests

 

Test/Stage

Primary

Secondary

Latent

Late

VDRL
(after Px.)

75%+
(-)

100%+
(-)

75%+
(-/+)

75%+
(+)

FTA
(after Px.)

90%+
(+)

100%+
(+)

97%+
 (+)

100%+
(+)

TPHA
(after Px.)

60%+
(+)

100%+
(+)

97%+
 (+)

100%+
(+)

  1. Lumbar Puncture
    1. Clinically suspicious of neurosyphilis or other tertiary syphilis
    2. Late latent cases from Medical Examination Board or cases involved in medicolegal aspect Cerebrospinal fluid findings in neurosyphilis:
       
      Microscopy: lymphocytes > 5/mm3
       
      Biochemistry: protein > 0.4 gm/l
       
      Serology: VDRL (negative in > 1/4 neurosyphilis)
       
      FTA or TPHA (negative test virtually excludes neurosyphilis)

Others (depends on clinical suspicion)

 

Chest X-Ray, Electrocardiography, Echocardiography, Cardiac catheterization, biopsy of gumma

  1. The Diagnosis Of Syphilis Is Usually Based On Serology. The primary chancre of syphilis, however, may be present for 1 to 3 weeks before serologies become positive. Therefore it is imperative to perform a dark-field examination or fluorescent microscopy of lesional exudate to visualize the spirochete directly in primary syphilis. screening is first performed with the nontreponemal tests, Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR).
  2. With Late Syphilis, The Nontreponemal Antibody Titers Do Not Always Decrease As Expected. False-positive results may occur for multiple reasons, including collagen vascular disease, advancing age, chronic liver disease, narcotic drug use, various acute infections such as herpes, and numerous chronic infections such as tuberculosis or HIV. Because of the lower specificity of these tests, positive results should be confirmed with the more precise treponemal tests, fluorescent treponemal antibody absorption test (FTA-ABS) and microhemagglutination assay for T. pallidum (MTA-TP). Treponemal tests do not correspond to disease activity, and they normally remain reactive indefinitely despite effective treatment.




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