Syphilis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]; Nate Michalak, B.A.

Overview[edit | edit source]

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.^{[1][2][3][4][5][6][7]}

Pathogenesis[edit | edit source]

The pathogenesis of syphilis may be described in the following steps:^{[1][2][3][4][5][6][7][8][9][10][11]}

Transmission[edit | edit source]

Treponema pallidum is usually transmitted via direct contact with the infected lesion (sexual contact) or blood transfusion (rare).

Incubation[edit | edit source]

The incubation period varies with the size of innoculum (9-90 days).

Dissemination[edit | edit source]

• 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.

Seeding[edit | edit source]

• 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.

Immune response[edit | edit source]

Different stages of syphilis results from the interaction between the antigen and the host immune response.^[1][2]

Acute response

• 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.

Chronic

• 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.

Genetics[edit | edit source]

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.^[11]

Associated conditions[edit | edit source]

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.^[9]

Microscopic pathology[edit | edit source]

On microscopic histopathological analysis, characteristic findings of syphilis depends on the stage of the disease:

Primary syphilis

• Mononuclear leukocytic infiltration, macrophages, and lymphocytes
• Swelling and proliferation of small blood vessels

Secondary syphilis

• Swelling and dilatation of blood vessels in the dermis
• Epidermal hyperplasia and neutrophilic infiltration
• Inflammatory cell infiltrate, predominantly plasma cell

Tertiary syphilis

• Small vessel inflammation (endarteritis obliterans)
• Granulomatous lesions (gumma) containing central necrosis, inflammatory cells, such as lymphocytes, macrophages, plasma cells and fibroblasts.

References[edit | edit source]

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