Gulshan Sethi Syphilis is undergoing a resurgence perhaps as a result of an increase in unsafe sex practices, but more importantly because of its association with HIV infection. Syphilis and its consequences, including congenital syphilis, are associated with significant morbidity and mortality. It is caused by infection with the spirochaete Treponema pallidum, which causes infection only in humans [1]. Other species of Treponema are also known to cause human disease. T. pertenue causes yaws, a tropical ulcer disease which has largely died out, and T. carateum causes the disfiguring condition of pinta, which is endemic in South America. The Treponema subspecies are morphologically and serologically indistinguishable from one another. Syphilis remains a common condition worldwide with nearly 20 million cases in 2016 [2]. In the years after the Second World War, rates of syphilis in the Western world declined as a result of more settled conditions and effective antibiotic treatment. Increased rates were again seen in the 1970s and 1980s, predominantly in homosexual men, but these tailed off in the early 1990s, coinciding with the safer sex campaigns against HIV. Since the late 1990s, however, rates in men and, to a lesser extent, in women have increased substantially. In England, following a gradual increase in the number of new syphilis diagnosed between 2000 and 2012, a 126% increase from 3344 diagnoses in 2013 to 7541 in 2018 has been seen, including a 5.5% increase between 2017 and 2018. Although this increase has been noted primarily among gay, bisexual, and other men who have sex with men (who account for 75% of cases in 2018), increased diagnoses have also been seen in heterosexuals. There has also been a rise in cases of congenital syphilis since 2011 [3,4]. A similar picture is seen in the United States, where a total of 30,644 new cases of syphilis were reported in 2017, which equates to a rate of 9.5 cases per 100 000 population. This represents a 10.5% increase compared with 2016 (8.6 cases per 100 000 population), and a 72.7% increase compared with 2013 (5.5 cases per 100 000 population) [5]. T. pallidum enters the tissues via small abrasions in mucous membrane or skin. The organism then attaches to local host cells and multiplies, and is then carried to the regional lymph nodes. At the site of initial entry, a primary chancre is formed which contains millions of spirochaetes and appears clinically 2–6 weeks after infection. At the same time, there is haematogenous dissemination to distant organs. The resulting treponemal bacteraemia is characterised by the systemic symptoms and signs associated with secondary syphilis. Transplacental transmission to the foetus occurs most commonly in this stage. Cell‐mediated and humoral responses destroy the majority of the organisms, but some will persist, perhaps because the treponemal cell surface presents few targets for the host immune response. Clinical disease with T. pallidum is divided into five stages: primary, secondary, early latent, late latent, and tertiary. The primary, secondary, and early latent stages are associated with high rates of sexual and vertical transmission, while the late latent stage is less infectious although sexual and vertical transmission may still occur. In the tertiary stage, sexual transmission does not occur but vertical transmission is a rare possibility. The primary and secondary stages are characterised by the development of antibody responses that can be used to assess the progress of disease and response to treatment. Serological responses to syphilis are of two types. There are those which are specific to T. pallidum and serological tests detect antibodies to the organism and remain positive for life regardless of whether the infection is treated or not. Current tests include the treponemal enzyme immunosorbent assay (EIA), T. pallidum particle agglutination (TPPA) test, T. pallidum haemagglutination (TPHA) test, and fluorescent treponemal antigen (FTA) test, which may measure immunoglobulin (Ig)G or IgM. Non‐specific immunological responses are those that are mounted to lipid antigens on the treponemal cell surface and are measured using tests such as the Venereal Disease Reference Laboratory (VDRL) test or the rapid plasma reagin (RPR) test. Both tests increase in titre from the primary to the secondary stages of disease, fall in latent or treated disease, and can be positive in other treponemal and non‐treponemal diseases. The secondary stage can last for several weeks and may be associated with intermittent relapses and remissions, but is eventually stopped by the host immune response. This stage is followed by complete resolution of clinical symptoms, although specific serological tests remain positive. A period of latency follows the secondary stage where organisms are still present in many organs but are no longer in the bloodstream. The first two years after infection are described as the early latent stage (in the United States, this refers to the first year only), during which there is a significant risk of secondary relapse. However, subsequent to this, in the late latent phase, secondary relapse does not occur. The tertiary stage occurs in about a third of individuals with untreated disease and is characterised by invasion of the tissues of the central nervous system, cardiovascular system, skin, eyes, and other organs. It is thought that this is because of declining immune responses [1]. This stage usually occurs 3–12 years after infection [6] and is associated with the formation of destructive granulomatous lesions called gummata, which may be found in skin, bones, or internal organs. Treponemal organisms are sparse or absent in these. The primary chancre is characterised by a perivascular infiltrate of plasma cells, lymphocytes, and macrophages together with an obliterative endarteritis. Similar histological changes are seen in the lymph nodes and other organs. A syphilitic gumma is composed of a granuloma with monocytic and lymphocytic infiltrates and features of an endarteritis.
11
Syphilis
Epidemiology
Pathophysiology
Stages of syphilis
Histological features
Clinical features
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
