Syphilis pathophysiology On the Web
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Syphilis is caused by a spirochete, Treponema pallidum. It has an average incubation period of 3 - 12 weeks. However, it may vary according to the size of innoculum. Spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the central nervous system being invaded during the early phase of infection. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity reaction to the spirochete.
Treponema pallidum is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare).
The incubation period varies with the size of innoculum (9-90 days).
- Following transmission, Treponema pallidum uses the intact or abraded mucous membrane to enter the body.
- It then disseminates to the lymphatics and blood stream to gain access to any organ of the body.
- Syphilis uses fibronectin molecules to attach to the endothelial surface of the vessels in organs resulting in inflammation and obliteration of the small blood vessels causing vasculitis (endarteritis obliterans).
- Organism has slow replication rate (30-33 hrs) and evades the initial host immune response.
- It may seed to different organs of the body especially the cardiovascular system and central nervous system resulting in tertiary syphilis.
- The initial infection in primary syphilis is limited due to Th1 response and lack of the antibody response.
- It is speculated that there is a shift from Th1 to Th2 response during secondary syphilis.
- Cytotoxic T cells and an incomplete humoral response is mainly responsible for persistence of infection and tissue damage in tertiary syphilis.
- Ineffective type 4 delayed hypersensitivity reaction containing macrophages and sensitized T cells is mainly responsible for the gumma formation in various organs.
There is no known genetic association of syphilis. However, neurosyphilis may be associated with the gene polymorphism for IL-10 production with increased levels seen in the patients with neurosyphilis.
Syphilis is associated with increased transmission of HIV. The underlying mechanism may be related to the accumulation of dendritic cells containing CCR5 co-receptors at the site of infection, the same receptor entity binding the HIV.
On microscopic histopathological analysis, characteristic findings of syphilis depends on the stage of the disease:
- Mononuclear leukocytic infiltration, macrophages, and lymphocytes
- Swelling and proliferation of small blood vessels
- Swelling and dilatation of blood vessels in the dermis
- Epidermal hyperplasia and neutrophilic infiltration
- Inflammatory cell infiltrate, predominantly plasma cell
- Small vessel inflammation (endarteritis obliterans)
- Granulomatous lesions (gumma) containing central necrosis, inflammatory cells, such as lymphocytes, macrophages, plasma cells and fibroblasts.
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