Syphilis: Clinical Aspects


Syphilis is a common sexually transmitted disease which, if left untreated, can result in a multiorgan infection. The causative organism is the spirochaete (from the Greek ‘spiral hairs’) Treponema pallidum. Other subspecies cause similar diseases such as yaws and pinta but these tend to be less severe and do not cause multisystem morbidity. Syphilis is a classic biphasic illness characterised by an initial skin infection which may be followed years later by involvement of the central nervous system (CNS), skeletal and cardiovascular systems with the great vessel the aorta at particular risk. Congenital transmission can occur and a range of clinical features can afflict the baby. Severe deformities, and even intrauterine death, are associated with transmission late in the pregnancy. Early and appropriate antimicrobial treatment of syphilis in all its guises is therefore of critical importance. Newer imaging techniques have become a useful adjunct in aiding diagnosis, which still relies heavily on serological assays and clinical acumen.

Key Concepts:

  • Enhancement of infectivity of syphilis and of early syphilitic lesions, in patients with concomitant HIV.

  • The relapsing nature of syphilis, both in early stages and in the late congenital disease, as in interstitial keratitis and Clutton's joints.

  • Primary form of syphilis is an early localised primary lesion. The secondary phase is manifested by a systemic disease, whereas the later stages are again localised.

  • Similarly, early congenital lesions tend to be disseminated, whereas late lesions are localised.

  • Newer imaging techniques are useful both in diagnosis and for monitoring treatment, especially in those patients with brain and cardiovascular syphilis.

Keywords: clinical syphilis; HIV; rash; syphilis of heart; syphilis of nervous system; treatment

Figure 1.

Bone scan of syphilitic periostitis using a 99mTc radioisotope. Reproduced from Teng‐Teng et al. with permission from BMJ Publishing Group Ltd.

Figure 2.

Experimental T. pallidum infection in rabbits. Ulcerative rash on the shaved surface of a rabbit inoculated intravenously with T. pallidum showing diffuse symmetrical distribution of the lesions.

Figure 3.

Right eye of patient at presentation: (a) colour fundus photograph showing the raised creamy yellow choroidal lesion and retinal haemorrhages; (b) early and (c) late phase of the FFA showing early hyper‐ and hypofluorescence and late leak; (d) ICG of the right eye showing hyperfluorescent spots nasal to the disc; and (e) Optical Coherence Imaging (OCT) demonstrating the presence of subretinal fluid. Reproduced from Joseph et al. with permission from Nature Publishing Group.

Figure 4.

Charcot knee showing subluxation of the joint with shortening. Patient presented with swelling and mild nocturnal joint pain.

Figure 5.

(a and b) Angiography showed critical obstruction from both right and left main coronary ostia. (c) Biopsy revealed nonspecific aortitis characterised by lymphocyte and plasma cell infiltrate adjacent to small vessels in the adventitia. (d) Contrast‐enhanced multidetector computed tomography confirmed the ostial coronary obstructions. (e) Three‐dimensional surface reconstruction showing clearly near‐obstruction of both right and left coronary ostia, as well as the three surgical bypass grafts (arrowheads, from left to right: saphenous vein to right coronary; left internal thoracic to left anterior descending; saphenous vein to marginal branch of the circumflex coronary arteries, respectively). Aortitis (the basic lesion of cardiovascular syphilis), aortic aneurysms and aortic regurgitation may all be detected by angiography, although such conditions may be primarily identified on echocardiography in the first instance. However an interesting case report published in 2009, shows the full role angiography and imaging can play in syphilitic aortitis. Reproduced from Vianna et al. with permission from Oxford University Press.

Figure 6.

Congenital syphilitic liver showing massive infiltrate of T. pallidum. The architecture of the liver is well preserved (Warthin and Starrey stain; original magnification ×900).



Blencowe H, Cousens S, Kamb M, Berman S and Lawn JE (2011) Lives saved tool supplemental and treatment of syphilis in pregnancy to reduce stillbirths and neonatal mortality. BMC Public Health 11(Suppl. 3): S9.

Brisset M, Chadeni ML, Cordioliani Y et al. (2011) MRI features of neurosyphilis. Review of Neurology (Paris) 167: 337–342.

CDC (2010)‐ulcers:htm±syphilis

Cha JY, Ishiwata A and Mobashery S (2004) A novel beta‐lactamase activity from a penicillin‐binding protein of Treponema pallidum and why syphilis is still treatable with penicillin. Journal of Biological Chemistry 15: 14197–14121.

Donders GG, Desmyter J, Hooft P and Dewet GH (1997) Apparent failure of one injection of benzathine penicillin G for syphilis during pregnancy in human immunodeficiency virus‐seronegative African women. Sexually Transmitted Diseases 24: 94–101.

Ghanem KG, Moore RD, Rompalo AM et al. (2008) Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV infected patients. Clinical Infectious Diseases 47: 258–265.

Hook EW and Marra CM (1992) Acquired syphilis in adults. New England Journal of Medicine 326: 1060–1069.

Hook EW 3rd, Behets F, Van Damme K et al. (2010) A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. Journal of Infectious Diseases 20: 1729–1737.

Houston S, Hof R, Francescuti T et al. (2011) Bifunctional role of Treponema pallidum extracellular matrix binding adhesion TP0751. Infection and Immunity 79: 1386–1398.

Joseph A, Rogers S, Browning A et al. (2006) Syphilitic acute placoid chorio‐retinitisin non‐immuno‐compromised patients. Eye (London)2007 21: 1114–1119 (e‐pub 2006).

Kinghorn GR (2004) Syphilis. In: Cohen J and Powderly WG (eds) Infectious Diseases, 2nd edn, pp. 807–816. London: Mosby.

Kumar B and Muralidhar S (1998) Malignant syphilis: a review. AIDS Patient Care and STD 12: 921–925.

Lynn WA and Lightman S (2004) Syphilis and HIV: a dangerous combination. Lancet Infectious Diseases 4: 456–466.

Mora P, Borruat F‐X and Guex‐Crosier P (2005) Indocyanine green anomalies in ocular syphilis. Retina 25: 171–181.

Peeling RW, Mabey D, Fitzgerald DW et al. (2004) Avoiding HIV and dying of syphilis. Lancet 364: 1562–1563.

Rompalo AM, Cannon RO, Quinn TC and Hook EW 3rd (1992) Association of biologic false‐positive reactions for syphilis with human immunodeficiency virus infection. Lancet Infectious Diseases 165: 1124–1126.

Rolfs RT, Joesoef MR, Hendershot EF et al. (1997) A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. New England Journal of Medicine 337: 307–314.

Sellati TJ, Wilkinson DA, Sheffield JS et al. (2000) Virulent Treponema lipoprotein and synthetic polypeptides induce CCR5 on human monocytes and enhance the susceptibility to infection of human immunodeficiency virus type 1. Journal of Infectious Diseases 181: 288–293.

Sheffield JS, Sanchez PJ, Wendel GD Jr et al. (2002) Placental histopathology of congenital syphilis. Obstetrics & Gynecology 100: 126–133.

Skorkovska K and Wilhelm H (2009) Afferent papillary disorders in postchiasmal lesions of the visual pathways. Klinische Monatsblätter für Augenheilkunde 226: 886–890.

Stamm LV (2010) Global challenge of antibiotic‐resistant Treponema pallidum. Antimicrobial Agents and Chemotherapy 54: 583–589.

Teng‐Teng Chung, Avril N and Chew LS (2009) Minerva. British Medical Journal 339: 870.

Thomson HS and Kardon RH (2006) The Argyll Robertson pupil. Journal of Neuropathology 26: 134–138.

Tipple C, Hanna MOF, Hill S et al. (2011) Getting the measure of syphilis: q. PCR to better understand early infection. Sexually Transmitted Infections 87: 479–485.

Tucker JD, Li JZ, Robbins GK et al. (2011) Ocular syphilis among HIV‐infected patients: a systematic analysis of the literature. Sexually Transmitted Infections 87: 4–8.

Vianna CB, Shiozaki AA and Cesar LA (2009) Syphililitic aortitis causing critical obstruction to coronary ostia. European Heart Journal 2: 191 (e‐pub 2008).

Further Reading

Baughn RE and Musher D (2005) Secondary syphilitic lesions. Clinical Microbiology Reviews 18: 205–216.

Hira SK, Bhat GJ, Patel JB et al. (1985) Early congenital syphilis: clinico‐radiologic features in 202 patients. Sexually Transmitted Diseases 12: 177–183.

Stokes JH, Beerman H and Ingraham NR Jr (1944) Modern Clinical Syphilology, 3rd edn. Philadelphia: WB Saunders.

Tramont EC (2010) Treponema pallidum (Syphilis). In: Mandel GL, Bennett JE and Dolin R (eds) Principles and Practice of Infectious Disease, 7th edn, vol. 2, chap. 238, pp. 3035–3053. New York: Elsevier Churchill Livingstone.

Wiedmann A (Ed.) (1962) Syphilis and Ulcus Molle. Heidelberg: Springer (German).

Worster‐Drought C (1940) Neurosyphilis (Syphilis of the Nervous System). London: John Bale.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Wright, David J, Norris, Steven J, Dhillon, Rishi H‐P, and Edmondson, Diane G(Jan 2012) Syphilis: Clinical Aspects. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002245.pub3]