History

Fact Explanation
History of contact with infected person Treponema pallidum [1] is a gram negative spiral-shaped bacterium with a flagella belongs to the family Spirochaetaceae. Dermal micro abrasions or intact mucous membranes are the routes of entry into the body. [2] Direct contact with a syphilis lesion in the form of anal, vaginal, or oral sex is the main mode of transmission of syphilis. Therefore an unprotected anal, vaginal, or oral sex or direct contact with the lesions increase the risk of getting the disease. Usually they develop lesions 3 weeks after exposure. [2] Primary ,secondary and early latent periods are the most infectious periods. [1]
Painless ulcers on the penis, vagina, anus, the rectum Syphilis has main 3 stages: primary, secondary and latent. Firm, round, and painless sore(chancre) [1] is the first symptom to occur, at the first site of T. pallidum invasion, which may be healed by few weeks. There can be more than one chancres. This is painless when compared to chancroid. During the secondary stage there can be involvement of mucous membrane manifesting as sores in the labia or cervix., vagina, anus, rectum and mouth.
Mouth and lip ulcers Due to the mucous membrane involvement. [2]
Rash There can be a red or brown rash associated with syphilis occurring on the palms, soles, trunk or other parts of body which it is not itchy. Usually occurs 2-8 weeks after acquiring the infection. This occurs if the primary infection progressed to the secondary stage. [2]
Fever, muscle aches, headaches and fatigue, sore throat, weight loss During the second stage, as the systemic features of syphilis. [2] Second stage features usually occur within 3 months of initial infection.
Numbness, paralysis, loss of consciousness and seizures These are symptoms of the late stage of syphilis. There are 2 stages according to the epidemiological aspect. [1] Early latency stage (one-year period without symptoms of primary or secondary syphilis ) is known to be an infectious period, late latency period (period more than one year) is noninfectious.
Blindness, focal weakness, pain on neck retraction, nausea, vomiting Due to the neurosyphilis. [2] Neurosyphilis is where organism pass through the blood brain barrier and causes neurological symptoms. Cerebrovascular accident , meningitis, visual problems may occur.
Risk factors: Having multiple sexual partners, having sex with a partner who has many sex partners, commercial sex workers These increase the risk of contracting syphilis. [4]
History HIV or other sexually transmitted diseases Having one sexually transmitted disease increases the risk of another sexually transmitted disease. [4]
Congenital syphilis: spontaneous abortion, stillbirth, and premature delivery Infected woman can transmit the disease to the developing fetus, and this risk of fetal infection is higher during the first year of infection.[2,3]
References
  1. SINGH AE, ROMANOWSKI B. Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features Clin Microbiol Rev [online] 1999 Apr, 12(2):187-209 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88914
  2. LAFOND RE, LUKEHART SA. Biological Basis for Syphilis Clin Microbiol Rev [online] 2006 Jan, 19(1):29-49 [viewed 14 July 2014] Available from: doi:10.1128/CMR.19.1.29-49.2006
  3. GENC M, LEDGER W. Syphilis in pregnancy Sex Transm Infect [online] 2000 Apr, 76(2):73-79 [viewed 14 July 2014] Available from: doi:10.1136/sti.76.2.73
  4. TRUONG HM, KELLOGG T, KLAUSNER JD, KATZ MH, DILLEY J, KNAPPER K, CHEN S, PRABHU R, GRANT RM, LOUIE B, MCFARLAND W. Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting? Sex Transm Infect [online] 2006 Dec, 82(6):461-466 [viewed 17 September 2014] Available from: doi:10.1136/sti.2006.019950

Examination

Fact Explanation
Painless ulcer Chancre is situated at anus, vagina, cervix. The important feature is this ulcer is painless and nontender. Lues maligna is where lesions may become necrotic. [1]
Rash This may be a mucocutaneous rash. Maculopapular, papular, macular, and annular papular lesions are seen trunk and proximal extremities. [1]
Generalized nontender lymphadenopathy This occurs in the majority during the second stage of the infection. [1]
Syphilitic alopecia (loss of hair) Hair loss [2] in syphilis has a characteristic appearance, described as “moth-eaten” appearance.
Condylomata lata These are enlarged, intertriginous mucosal papules that are macerated and form flat, moist, lesions which are highly infectious. [1]
Vision abnormalities Neurosyphilis, will be manifesting as ocular disease. [1]
Neck stiffness Due to meningitis as a complication. [1]
References
  1. LAFOND RE, LUKEHART SA. Biological Basis for Syphilis Clin Microbiol Rev [online] 2006 Jan, 19(1):29-49 [viewed 14 July 2014] Available from: doi:10.1128/CMR.19.1.29-49.2006
  2. KENNEDY C. Syphilis presenting as hair loss. Br Med J [online] 1976 Oct 9, 2(6040):854 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1688965

Differential Diagnoses

Fact Explanation
Herpes Simplex There are 2 types of herpes viruses: type 1 and 2. HSV type 1 causes oral lesions "Herpes labialis", and HSV type 2 causes genital herpes with vesicular lesions on or around the genitals and rectum and even thighs and buttocks. [2] It may be skin discolouration or an open sore. The lesions may be itchy at the beginning, unlike the chancres in syphilis, these are usually painful lesions. There can be small, red blisters in or around the affected area. Sexual intercourse, skin to skin contact and delivery are the modes of transmission of herpes.
Chancroid This lesion is caused by Haemophilus ducreyi, which is a small, gram-negative, facultative anaerobic bacillus. It causes painful genital ulcers associated with inguinal lymphadenopathy. Chancres differs from chancroids where the chancroids are painless. [1]
Candidiasis Candida albicans is the predominant pathogen causing mucocutaneous candidiasis. [4] Immunocompromised states, broad-spectrum antibiotics, cytotoxic chemotherapies, and transplantation increase the risk of candidiasis. Rash initially starts with vesiculopustules later ruptures leaving erythematous area with scalloped edges. Satellite lesions are commonly found which may coalesce and extend into larger lesions. Females can have vaginal discharge with odour which may be itchy. Males will have lesions over the penis "balanitis". Oral thrush, nail infections are the other manifestations of candidiasis. Sometimes it causes invasive illnesses.
Genital Warts Genital Warts are caused by human papillomavirus (HPV). Most commonly involving types are HPV type 6 and 11which also have a malignant potential. Anogenital warts are the most common clinical manifestation of HPV infection and 20–30% of genital warts can spontaneously regress. [3] These are small bumps like lesions and occasionally advanced when they form cauliflower like growths. HPV types can cause cervical cancer in females.
References
  1. WEISS HA, THOMAS SL, MUNABI SK, HAYES RJ. Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis Sex Transm Infect [online] 2006 Apr, 82(2):101-110 [viewed 14 July 2014] Available from: doi:10.1136/sti.2005.017442
  2. WALD ANNA, ZEH JUDITH, SELKE STACY, WARREN TERRI, RYNCARZ ALEXANDER J., ASHLEY RHODA, KRIEGER JOHN N., COREY LAWRENCE. Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons. N Engl J Med [online] 2000 March, 342(12):844-850 [viewed 14 July 2014] Available from: doi:10.1056/NEJM200003233421203
  3. ANIC GM, GIULIANO AR. Genital HPV infection and related lesions in men Prev Med [online] 2011 Oct, 53(Suppl 1):S36-S41 [viewed 14 July 2014] Available from: doi:10.1016/j.ypmed.2011.08.002
  4. PFALLER MA, DIEKEMA DJ. Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem Clin Microbiol Rev [online] 2007 Jan, 20(1):133-163 [viewed 14 July 2014] Available from: doi:10.1128/CMR.00029-06

Investigations - for Diagnosis

Fact Explanation
Darkfield microscopy Treponema pallidum can not be identified with light microscopy. [3] It is therefore visualized by dark ground microscopy on a sample taken from an open sore. These are motile spiral organisms that may appear loosely coiled, thick, and coarse.
Serology nontreponemal tests: Venereal Disease Research Laboratory and rapid plasma reagin and tests Detects antibodies to lipoidal antigens present in either the host or T. pallidum and not specific to syphilis. [2] VDRL can give false negative results during the early course of disease and false positive results in infectious mononucleosis, lupus erythematosus, antiphospholipid antibody syndrome, hepatitis A, leprosy, and malaria.
Treponema pallidum particle agglutination assay (TPPA), Treponema pallidum haemagglutination assay (TPHA) and an enzyme immunoassay (EIA) If the VDRL is positive, it should be confirmed with a more specific investigation like Treponema pallidum particle agglutination assay (TPPA), Treponema pallidum haemagglutination assay (TPHA) and an enzyme immunoassay (EIA). These tests are specific to treponemal antigens and need for the disease conformation. [1,2]
References
  1. SMIT PIETER W, VAN DER VLIS THOMAS, MABEY DAVID, CHANGALUCHA JOHN, MNGARA JULIUS, CLARK BENJAMIN D, ANDREASEN AURA, TODD JIM, URASSA MARK, ZABA BASIA, PEELING ROSANNA W. The development and validation of dried blood spots for external quality assurance of syphilis serology. Array [online] 2013 December [viewed 14 July 2014] Available from: doi:10.1186/1471-2334-13-102
  2. LARSEN SA, STEINER BM, RUDOLPH AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev [online] 1995 Jan, 8(1):1-21 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172846
  3. Dark ground microscopy and treponemal serology for diagnosis of early syphilis J Clin Pathol [online] 2004 Dec, 57(12):1263 [viewed 17 September 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770499

Investigations - Fitness for Management

Fact Explanation
Screening for other sexually transmitted diseases As the person is vulnerable for contracting other diseases especially HIV,[1] it is important to screen for them. Blood should be checked for hepatitis: hepatitis B surface antigen test, hepatitis C antibody testing [2] and Human Immunodeficiency Virus (HIV) with Enzyme immunoassay (EIA) tests and rapid antibody testing.
References
  1. LAFOND RE, LUKEHART SA. Biological Basis for Syphilis Clin Microbiol Rev [online] 2006 Jan, 19(1):29-49 [viewed 14 July 2014] Available from: doi:10.1128/CMR.19.1.29-49.2006
  2. ARNOLD SR, FORD-JONES EL. Congenital syphilis: A guide to diagnosis and management Paediatr Child Health [online] 2000, 5(8):463-469 [viewed 16 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819963

Investigations - Followup

Fact Explanation
Serology Patients with early and congenital syphilis usually need serologic testing (nontreponemal and treponemal tests) 1, 3, 6, 12, and 24 months after treatment and those after late disease need the testing at 12 and 24 months after treatment. [1]
Cerebro spinal fluid analysis Cerebro spinal fluid examinations 6-monthly for the first 2 years or until the CSF becomes normal are needed in neurosyphilis. [1] Pleocytosis will be seen over initial 6 months.HIV infected persons need frequent reviews at annual intervals.
Congenital syphilis Asymptomatic infants of affected mothers are followed monthly until their nontreponemal antibody disappears. [2]
References
  1. SINGH AE, ROMANOWSKI B. Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features Clin Microbiol Rev [online] 1999 Apr, 12(2):187-209 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88914
  2. ARNOLD SR, FORD-JONES EL. Congenital syphilis: A guide to diagnosis and management Paediatr Child Health [online] 2000, 5(8):463-469 [viewed 16 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819963

Investigations - Screening/Staging

Fact Explanation
Cerebro spinal fluid analysis [1] There is increased protein and leukocyte levels in the cerebrospinal fluid in neurosyphilis. [1]
Cerebro spinal fluid -VDRL (Venereal Disease Research Laboratory) test This will be reactive in the presence of neurosyphilis. [1]
References
  1. LAFOND RE, LUKEHART SA. Biological Basis for Syphilis Clin Microbiol Rev [online] 2006 Jan, 19(1):29-49 [viewed 14 July 2014] Available from: doi:10.1128/CMR.19.1.29-49.2006

Management - General Measures

Fact Explanation
Management of pain and fever Acetaminophen or nonsteroidal anti-inflammatory medications (ibuprofen, naproxen, ketoprofen) can be used for the management of fever and pain. [5]
Steroid therapy Steroid therapy reduces the incidence of febrile reactions associated with the "Jarisch-Herxheimer reaction" reaction, [1]
Prevention ABC approach is a key strategy for the prevention of sexually transmitted diseases where it focuses on behavioural changes in individuals and programmes to implement such changes in the individual. Abstinence, Be faithful, use Condoms are the key elements of this approach. Avoiding unsafe sexual relationships [4] or restricting the sexual relationships to a faithful one partner is the best way to achieve the prevention. In cases where the person does not adhere this, using condoms is advised. Condoms have to be used in the correct way at each time person involved in the the sexual activities. It helps to prevent transmission of syphilis by preventing contact with the syphilitic ulcers. Antenatal testing using VDRL better provision of antenatal services, and appropriate treatment of pregnant women are important in preventing congenital syphilis. [2,3]
References
  1. SINGH AE, ROMANOWSKI B. Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features Clin Microbiol Rev [online] 1999 Apr, 12(2):187-209 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88914
  2. SALOOJEE H, VELAPHI S, GOGA Y, AFADAPA N, STEEN R, LINCETTO O. The prevention and management of congenital syphilis: an overview and recommendations. Bull World Health Organ [online] 2004 Jun, 82(6):424-30 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15356934
  3. GENC M, LEDGER W. Syphilis in pregnancy Sex Transm Infect [online] 2000 Apr, 76(2):73-79 [viewed 14 July 2014] Available from: doi:10.1136/sti.76.2.73
  4. TRUONG HM, KELLOGG T, KLAUSNER JD, KATZ MH, DILLEY J, KNAPPER K, CHEN S, PRABHU R, GRANT RM, LOUIE B, MCFARLAND W. Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting? Sex Transm Infect [online] 2006 Dec, 82(6):461-466 [viewed 17 September 2014] Available from: doi:10.1136/sti.2006.019950
  5. LAFOND RE, LUKEHART SA. Biological Basis for Syphilis Clin Microbiol Rev [online] 2006 Jan, 19(1):29-49 [viewed 17 September 2014] Available from: doi:10.1128/CMR.19.1.29-49.2006

Management - Specific Treatments

Fact Explanation
Penicillin Penicillin is the treatment of choice for treatment of syphilis. Primary and secondary stage is treated with a single dose of benzathine penicillin G (2.4 million units IM), whereas late stage requires more several doses. Penicillin kills susceptible bacteria by interfering with production of cell walls. [3] Dying treponemes can release some inflammatory substances causing induction of inflammation, manifesting as muscle aches, fever, headache with worsening of the lesions within 24 hours of antibiotics. This is called, "Jarisch-Herxheimer reaction" and it occurs often with the treatment with penicillin than with erythromycin or tetracycline . [1]
Other antibiotics Doxycycline, tetracycline, probenecid, erythromycin are the alternatives. The newer cephalosporins, i.e., cefmetazole, ceftizoxime, and cefetamet are the newer agents under the experimentation. [1]
Management of complications Treatment should be given to the infants, depending on the maternal serological status and clinical signs of syphilis in the infant. [2] Meningitis, visual problems need special attention.
Management of congenital syphilis Congenital syphilis can cause dangerous effects like cerebral palsy, hydrocephalus, sensorineural hearing loss and musculoskeletal deformity. In situations where diagnosis of congenital syphilis is suspected before delivery, examination of the placenta and cord should be done for typical pathological changes and spirochetes, desquamation or ulcerative skin lesions or nasal discharge (‘snuffles’), for spirochetes. If the baby is exposed to syphilis antenatally, serological testing for syphilis, should be done. Aqueous crystalline penicillin G, 50,000 units/kg/dose intravenously every 12 h in the first seven days of life,then increased up to every 8 h till 10 to 14 days. [4]
The treatment for syphilis in pregnancy The treatment for syphilis in pregnancy is same as that of non pregnant individuals. However the only agent that is appropriate in pregnancy is penicillin. Tetracyclines are contraindicated in pregnancy due to the adverse effects on fetal bone and tooth development. Erythromycin also contraindicated due to the placental transfer. Penicillin is given as 2.4 million units of benzathine penicillin G (BPG) intramuscularly in one dose. Same dose weekly for three weeks is recommended for the late latent syphilis. [4]
Vaccine Passive transfer of antibodies against T. pallidum can be done and experiments are done on a multivalent vaccine as an effective vaccine for syphilis. [3]
References
  1. SINGH AE, ROMANOWSKI B. Syphilis: Review with Emphasis on Clinical, Epidemiologic, and Some Biologic Features Clin Microbiol Rev [online] 1999 Apr, 12(2):187-209 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC88914
  2. SALOOJEE H, VELAPHI S, GOGA Y, AFADAPA N, STEEN R, LINCETTO O. The prevention and management of congenital syphilis: an overview and recommendations. Bull World Health Organ [online] 2004 Jun, 82(6):424-30 [viewed 14 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15356934
  3. LAFOND RE, LUKEHART SA. Biological Basis for Syphilis Clin Microbiol Rev [online] 2006 Jan, 19(1):29-49 [viewed 14 July 2014] Available from: doi:10.1128/CMR.19.1.29-49.2006
  4. ARNOLD SR, FORD-JONES EL. Congenital syphilis: A guide to diagnosis and management Paediatr Child Health [online] 2000, 5(8):463-469 [viewed 16 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819963