1. TREPONEMAL DISEASES
DR. FERDA ÖZKAN

2. Spirochetes are Gram-negative, slender corkscrew-shaped bacteria with axial periplasmic flagella wound around a helical protoplasm.
The bacteria are covered in a membrane called an outer shell, which may mask bacterial antigens from the host response.

3. The treponemes are bacteria which produce chronic, generally non-fatal infections.
They produce no injurious substances themselves, and the pathology is due to the body's reaction to their presence.
They cannot be grown in vitro by present techniques.
They are too slender to be seen in conventional stains such as Gram stain, but can be visualized by silver stains, dark field examination, and immunofluorescence techniques.

4. Treponema organisms stained by fluorescent-tagged antibodies

5. Treponema pallidum (dark-field microscopy) showing several spirochetes in scrapings from the base of a chancre

6. SYPHILIS (lues)
A sexually transmitted disease caused by Treponema pallidum, a spirochete.
Syphilis probably came from the New World with Columbus, and the present endemic began soon afterwards.
Spirochetes are extremely vulnerable to the environment (soap, drying, etc.), and are transmitted only by intimate personal contact.
Syphilis is one of the infections in which downward modulation of host lymphocyte responsiveness by a serum factor occurs, and this early weakening of host immune reactivity may contribute to the latency and chronicity of ongoing infection.

7. The natural course of acquired syphilis evolves in three stages.
CONGENITEL SYPHILIS
The natural course of acquired syphilis evolves in three stages.
Primary syphilis
Secondary syphilis
Tertiary syphilis:
Only the primary and secondary stages are considered contagious.

11. Primary syphilis
One week to three months after meeting the spirochete, the patient develops
a solitary, slightly elevated (papule),
punched-out,
painless, indurated ulcer (hard chancre) at the site of inoculation (glans penis in males and on the vulva or cervix in females) ,
followed by painless swelling of the regional lymph nodes.
In approximately 10% of cases the canchre may be extragenital: lips, fingers, oropharynx, anorectum.
Treponemes spread throughout the body by hematologic and lymphatic dissemination even before the appearence of the chancre.
This lesion heals in a few weeks, and often goes unnoticed. The serous exudate of the chancre contains plenty of infectious spirochetes.

12. Hard chancre (syphilis)

13. Syphilitic chancre in the scrotum

14. Microscopically, the lesion is
obliterative endarteritis ("onionskinning", etc., i.e., the endothelium of the vessels proliferates and swells, causing infarction),
and a dense perivascular infiltrate composed mostly of plasma cells.

15. Tissue infected with the spirochete Treponema pallidum, the causative agent of syphilis. On the left, cell infiltration in the tissue; on the right spirochetes visualized by silver staining.

16. Secondary syphilis
The secondary stage follows in approximately two to ten weeks after the primary chancre and is due to spread and proliferation of the spirochetes within the skin and mucocutaneous tissues.
It is characterized by a generalized or, less often, localized skin eruptions. The patient usually develops:
a fleeting, variable rash over the skin and mucosal surfaces
rashes often affect the palms and soles (others are Rocky Mountain spotted fever, toxic shock syndrome, and Kawasaki disease)
most often the rash is macular, with discrete red-brown lesions, rarely over 5 mm in diameter.
reddened mucous rashes may appear in the mouth or vagina.
the mucous patches and skin lesions harbor organisms, but the most contagious are the wet ones.

17. Biopsy shows similar changes to a chancre.
These manifestations too, disappear spontaneously in about 1 to 3 months.
Occasionally, secondary syphilitic lesions are better localized.
Thus, papular lesions in the region of the penis or vulva may become large, elevated, broad plaques.
They sometimes occur on the lips and perianal region. These flat, red-brown elevations (up to 2-3 cm in diameter) are designed Condylomata lata. A syphilitic condyloma is extremely infectious.
Histologically, there are plenty of plasma cells, as well as the characteristic obliterative endarteritis, under a hyperplastic epithelial cover.
All patients are seropositive.

18. Secondary syphilis

19. Perivascular dermal infiltrate containing mononuclear and plasma cells in secondary syphilis.

20. Secondary syphilis in the dermis with perivascular lymphoplasmacytic infiltrate and endothelial proliferation

21. Tertiary syphilis Tertiary syphilis has become very rare.
The cardiovascular system is most commonly affected (80-85%).
Involvement of the proximal (thoracic) aorta (mesaortitis syphilitica) causes aortic insufficiency and weakness of the aortic wall, which will form an aneurysm, and eventually rupture.

22. CNS involvement accounts for about 5-10%.
Neurosyphilis takes four major forms:
1. General paresis a dementing disease with hypomanic behavior and psychosis.
2. Meningovascular syphilis, fibrosis of the meninges, leading perhaps to headache or even hydrocephalus .
3. Tabes dorsalis, a sensory syndrome involving the dorsal columns of the spinal cord.
4. Gummas, which mimic brain tumors clinically and radiologically.

23. This gross photo shows the findings typical of meningovascular-parenchymatous syphilis - thickening of the meninges at the dorsum of the brain and generalized cerebral atrophy.

24. Tabes dorsalis involves the dorsal roots and posterior columns of the spinal cord. Staining the cord specifically for myelin demonstrates the localization of demyelination to the posterior columns as shown on this slide.

25. With the same myelin stain, it also is possible to appreciate the demyelination which occurs in the dorsal spinal roots. The junction of the dorsal root and spinal cord is shown in the center of this slide. Note the pallor in this region

26. Tertiary syphilis (saddle nose)

27. Gumma

28. Gummas are syphilitic granulomas with gummatous (coagulative) necrosis
Gummas are syphilitic granulomas with gummatous (coagulative) necrosis Histologically, an active gumma consists of a central coagulation necrosis rimmed by macrophages and plenty of plasma cells.
Gummas are common in the liver and testes and the bones (subperiosteum).
In the liver, scarring due to gummas may cause a distinctive lesion known as hepar lobatum.
Destruction of the bridge of the nose (saddle nose) is also common.

29. Trichrome stain of liver shows liver gumma (scar), stained blue, which is caused by tertiary syphilis (also known as hepar lobatum

30. CONGENITAL SYPHILIS
The treponemes do not invade the placental tissue or the fetus until the fifth month of gestation, and therefore syphilis is an uncommon cause of early abortion.
It causes late abortion, stillbirth, or death soon after delivery, or it may persist in latent form to become apparent only during childhood or adult life.

31. The first stage (primary syphilis) is not present in congenital syphilis.
The most striking lesions affect the mucocutaneous tissues and bones.
There are extensive rashes particularly on the palms and soles and about the mouth and anus.
These lesions teem with spirochetes, and, at birth, the child's skin and secretions are highly infectious.

32. The most striking features of the congenital syphilis are:
generalized osteochondritis and periostitis causes saber shins in tibia (sabre tibia) and other bony deformities,
dental deformities (mulberry molars, Hutchinson's teeth, screwdriver incisors),
gummas destroying the bridge of the nose (vomer) cause the characteristic saddle nose deformity,
gummas destroying the hard palate cause perforation,
pulmonary consolidation (pneumonia alba; white pneumonia)
hepar lobatum, enlargement and severe distortion of liver architecture due to gummas, and related splenomegaly
mental retardation, nerve deafness (eighth nerve atrophy), blindness (optic atrophy, interstitial keratitis, choroiditis).

33. Among these many possible findings, most characteristic of delayed or tardive congenital syphilis is the triad of;
Interstitial keratitis,
Hutchinson's teeth,
Eight nerve deafness.
Fluorescence tests are more expensive but more specific, and are useful for confirmation of a positive screening test.
Syphilis is still easily treated with penicillin or other antibiotics.
CNS syphilis requires more intensive therapy. The spirochete invades the brain, so some physicians recommend higher doses of antibiotics even for the early disease.

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