Syphilis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]{{#meta: itemprop="medicalWebPageAudiences" content="patient"}}{{#meta: itemprop="medicalWebPageSpecialities" content="cardiology"}}{{#meta: itemprop="medicalWebPageInfoTypes" content="symptoms,diagnosis,treatment,causes,prognosis,complications"}} Classification Classic::Classification Atypical::

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[4]

Sexually transmitted diseases Main Page
Syphilis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Syphilis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy Primary and Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis HIV-Infected Patients Pregnancy Management of Sexual Partners
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Syphilis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Syphilis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Syphilis
CDC on Syphilis
Syphilis in the news
Blogs on Syphilis
Directions to Hospitals Treating Syphilis
Risk calculators and risk factors for Syphilis

Overview

Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. The signs and symptoms of syphilis are numerous; before the advent of serological testing, precise diagnosis was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless antibiotic-resistant) can be easily treated with antibiotics including penicillin. The oldest and still most effective method is an intramuscular injection of benzathine penicillin. If not treated, syphilis can cause serious effects such as damage to the heart, aorta, brain, eyes, and bones. In some cases these effects can be fatal. In 1998, the complete genetic sequence of T. pallidum was published which may aid understanding of the pathogenesis of syphilis.

Historical Perspective

The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his epic noted poem, written in Latin, entitled Syphilis sive morbus gallicus (Latin for "Syphilis or The French Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagionibus ("On Contagious Diseases"). Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank disease" (frengi) and the Tahitians called it the "British disease". These 'national' names are due to the disease often being present among invading armies or sea crews, due to their high amount of unprotected sexual contacts with prostitutes. It's interesting to notice how the invaders named it after the invaded country and vice versa. It was also called "Great pox" in the 16th century to distinguish it from smallpox. In its early stages, the Great pox produced a rash similar to smallpox (also known as variola). However, the name is misleading, as smallpox was a far more deadly disease. The terms "Lues" (or Lues venerea, Latin for "venereal plague") and "Cupid's disease" have also been used to refer to syphilis. In Scotland, Syphilis was referred to as the Grandgore. It was also called The Black Lion.

Classification

Syphilis may be classified according to the development of disease into 2 groups: congenital and acquired. Acquired syphilis may be classified further into 4 subtypes: primary, secondary, latent and tertiary syphilis.

Pathophysiology

Syphilis is caused by the spirochete, Treponema pallidum. It has an incubation period of 3 - 12 weeks. The 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 meninges and blood vessels are initially involved with the brain parenchyma and spinal cord being involved in the later stages of the disease. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity to the spirochete.

Causes

Syphilis is caused by a spirochete, Treponema pallidum. The spirochete rapidly penetrates via intact mucosal membranes or microscopic dermal abrasions. It is spread through intimate sexual contact, blood transfusion or vertical transmission from infected mother to fetus.

Differentiating Syphilis from other Diseases

Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Hence, patients with tertiary syphilis should also be tested for other sexually transmitted diseases such as chlamydia, gonorrhea, trichomoniasis, bacterial vaginosis and HIV infection.

Epidemiology and Demographics

In 2012, the incidence of syphilis was estimated to be 6 million cases worldwide. From year 2005 to 2014, the incidence of syphilis in the United States increased from 2.9 to 6.3 cases/100,000/year. The rate of reported cases increased by 15.1% between 2013 and 2014 in the United States. Syphilis incidence increased in every region of the Untied States in 2014, with the highest rate in the West and lowest rate in the Midwest. In 2012, the prevalence of syphilis was estimated to be approximately 18 million cases in men and women aged 15-29 worldwide. The incidence and prevalence of syphilis may be affected by age, gender, race, sexual behavior and geographical distribution.

Risk Factors

The risk factors of syphilis include unprotected sex, IV drug abuse and occupational risk for health care professionals.

Screening

Screening guidelines for syphilis include all high risk non pregnant individuals aged 15-65, all pregnant females, men who have sex with men, women who have sex with women, HIV positive individuals. Routine screening of adolescents who are asymptomatic for syphilis is not recommended

Natural History, Complications and Prognosis

Initial presentation of syphilis is appearance of painless chancre after 3-4 weeks of exposure. If left untreated, chancre self resolves and may progress to develop constitutional symptoms and generalized symmetric rash in four to eight weeks. In less than 10% of individuals, complications such as hepatitis, iritis, nephritis, and neurological problems may develop at this stage. However, it resolves in four to eight weeks without treatment and patient enters into asymptomatic latent phase. About a quarter of patients may develop recurrence of similar symptoms in one year. If left untreated, 35% of patients may develop tertiary syphilis which include complications such as cardiovascular involvement, neurologic infection and gummatous lesions involving skin, bone and joints which is associated with significant morbidity and mortality. The prognosis of syphilis varies by stage of disease.Prognosis of primary and secondary syphilis is good with treatment. For tertiary syphilis, prognosis varies by site of involvememnt and duration of disease. 90% of patients with neurosyphilis respond to treatment. However, mortality rates are high with cardiovascular complications.

Treatment

Medical Therapy

Penicillin G, administered parenterally, is the preferred drug for treating all stages of syphilis. If allergic, then tetracycline or doxycycline may also be used. During pregnancy, parenteral penicillin G is the only therapy with documented efficacy for syphilis.

Management of Primary and Secondary Stages

Parenteral penicillin G has been used effectively for more than 50 years to achieve clinical resolution (i.e., the healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for non-penicillin regimens.

Tertiary Syphilis

Tertiary syphilis refers to gumma and cardiovascular syphilis but not to all neurosyphilis. Patients who are not allergic to penicillin and have no evidence of neurosyphilis should be treated with the following regimen.

Neurosyphilis

CNS involvement can occur during any stage of syphilis. However, CSF laboratory abnormalities are common in persons with early syphilis, even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities. If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of meningitis), a CSF examination should be performed. Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., uveitis, neuroretinitis, and optic neuritis) should be treated with the recommended regimen for neurosyphilis; those with eye disease should be managed in collaboration with an ophthalmologist. A CSF examination should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal CSF test results should be provided follow-up CSF examinations to assess treatment response.

Primary Prevention

As of 2010, there is no vaccine effective for prevention.

Secondary Prevention

While abstinence from intimate physical contact with an infected person is very effective at reducing the transmission of syphilis, it should be noted that T. pallidum readily crosses intact mucosa and cut skin, including areas not covered by a condom. Proper and consistent use of a latex condom can reduce, but not eliminate, the spread of syphilis.[5]

References

Template:WikiDoc Sources

Pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [6] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[7]; Nate Michalak, B.A.

Sexually transmitted diseases Main Page
Syphilis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Syphilis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy Primary and Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis HIV-Infected Patients Pregnancy Management of Sexual Partners
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Syphilis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Syphilis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Syphilis
CDC on Syphilis
Syphilis in the news
Blogs on Syphilis
Directions to Hospitals Treating Syphilis
Risk calculators and risk factors for Syphilis

Overview

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.

Pathogenesis

The pathogenesis of syphilis may be described in the following steps:

Transmission

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

Incubation

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

Dissemination

• 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

• 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

Different stages of syphilis results from the interaction between the antigen and the host immune response.

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

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.

Associated conditions

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.

Microscopic pathology

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

Template:WikiDoc Sources

Epidemiology and Demographics

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [8] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[9]; Nate Michalak, B.A.

Sexually transmitted diseases Main Page
Syphilis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Syphilis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy Primary and Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis HIV-Infected Patients Pregnancy Management of Sexual Partners
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Syphilis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Syphilis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Syphilis
CDC on Syphilis
Syphilis in the news
Blogs on Syphilis
Directions to Hospitals Treating Syphilis
Risk calculators and risk factors for Syphilis

Overview

In 2012, the incidence of syphilis was estimated to be 6 million cases worldwide. From year 2005 to 2014, the incidence of syphilis in the United States increased from 2.9 to 6.3 cases/100,000/year. The rate of reported cases increased by 15.1% between 2013 and 2014 in the United States. Syphilis incidence increased in every region of the Untied States in 2014, with the highest rate in the West and lowest rate in the Midwest. In 2012, the prevalence of syphilis was estimated to be approximately 18 million cases in men and women aged 15-29 worldwide. The incidence and prevalence of syphilis may be affected by age, gender, race, sexual behavior and geographical distribution.

Epidemiology

Incidence

• Worldwide incidence of syphilis:
  • 2004: approximately 12 million cases
  • 2008: approximately 10.9 million cases
  • 2012: approximately 6 million cases
• Incidence of syphilis in the United States:
  • From 2005 to 2014, the incidence of primary and secondary syphilis increased from 2.9 to 6.3 cases/100,000/year.
  • From 2009 to 2014, the incidence of late and latent syphilis increased from 5.6 to 7.4 cases/100,000/year.
  • The rate of reported cases increased by 15.1% between 2013 and 2014.
  • Syphilis incidence increased in every region of the Untied States in 2014, with the highest rate in the West and lowest rate in the Midwest.

Source: https://www.cdc.gov/

Prevalence

• In 2008, the prevalence of syphilis was estimated to be 36.4 million cases worldwide.
• In 2012, the prevalence of syphilis is estimated to be 18 million cases in men and women aged 15-29 worldwide.
• In 2014, the prevalence of syphilis in the United States was estimated to be 20 cases/100,000 individuals.

Demographics

The incidence and prevalence of syphilis may be affected by the following demographic factors:

Age

In 2014, the highest rate of primary and secondary syphilis in the United States was seen in age groups 20-24 years and 25-29 years.

Source: https://www.cdc.gov/

Gender

• There is increased incidence of primary and secondary syphilis in men who have sex with men (MSM).
  • In 2014, 61% of 19,999 total reported cases of primary and secondary syphilis were estimated to be among MSM.

Primary and Secondary Syphilis — Reported Cases by Stage, Sex, and Sexual Behavior, 2014

Source: https://www.cdc.gov/

Race

• Syphilis is more prevalent in the African American population as compared to other racial groups.
• In 2014, the highest incidence of primary and secondary syphilis in the United States was reported to be in the African American population and the lowest incidence was observed in Caucasisans, Asians and multiracial groups.

Primary and Secondary Syphilis — Reported Cases by Sex, Sexual Behavior, and Race/Ethnicity, United States, 2014

Source: https://www.cdc.gov/

Geographical distribution

Worldwide, the highest incidence and prevalence of syphilis was seen in Africa and South East Asia, while the lowest was seen in Europe and the Eastern Mediterranean region in 2012.

United States

• Rates of reported cases of primary and secondary syphilis by state for 2014 is shown in the map below:

Source: https://www.cdc.gov/

• Rates of reported cases of primary and secondary syphilis by region for 2014 is shown in the map below:

Source: https://www.cdc.gov/

References

Template:WikiDoc Sources

Risk Factors

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [10]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[11]

Sexually transmitted diseases Main Page
Syphilis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Syphilis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy Primary and Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis HIV-Infected Patients Pregnancy Management of Sexual Partners
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Syphilis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Syphilis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Syphilis
CDC on Syphilis
Syphilis in the news
Blogs on Syphilis
Directions to Hospitals Treating Syphilis
Risk calculators and risk factors for Syphilis

Overview

Common risk factors in the development of syphilis include unprotected sexual intercourse, intravenous drug abuse, men who have sex with men and healthcare occupations.

Risk Factors

Risk factors include:

• Multiple sexual partners
• Prostitution
• Illicit drug use
• Unprotected sex
• Men who have sex with men
• Residence in highly prevalent areas
• HIV infection
• Presence of other STIs
• Previous history of STIs
• Intravenous drug use
• Health care professionals who are predisposed to occupational risk
• Low socioeconomic status

References

Template:WikiDoc Sources

Screening

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [12] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[13]

Sexually transmitted diseases Main Page
Syphilis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Syphilis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy Primary and Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis HIV-Infected Patients Pregnancy Management of Sexual Partners
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Syphilis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Syphilis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Syphilis
CDC on Syphilis
Syphilis in the news
Blogs on Syphilis
Directions to Hospitals Treating Syphilis
Risk calculators and risk factors for Syphilis

Overview

Screening guidelines for syphilis include all high risk non-pregnant individuals aged 15-65, all pregnant females, men who have sex with men, women who have sex with women, and HIV positive individuals. Routine screening of adolescents who are asymptomatic for syphilis is not recommended.

Screening

Screening guidelines for syphilis are:

Non-pregnant adults and adolescents (age 15-65)

• All individuals who are at increased risk for syphilis should be screened for syphilis Grade A recommendation.
• Routine screening of adolescents who are asymptomatic for syphilis is not recommended.

Pregnant women

• At first prenatal visit
• Retest at early third trimester and delivery if high risk
• High risk populations which require frequent screening include:

• Uninsured women
• Women living in poverty
• Sex workers
• Illicit drug users
• Presence of other sexually transmitted diseases (STDs)
• Other women living in communities with high syphilis morbidity

Men who have sex with men

• Annually for sexually active men who have sex with men
• Every 3 to 6 months if increased risk

Women who have sex with women

• Routine screening is recommended

HIV positive individuals

• At first HIV evaluation for sexually active individuals
• Annually after first evaluation
• More frequent testing for individuals who are at increased risk or are residing in highly prevalent areas of syphilis

Screening tests

Screening tests recommended for syphilis include the following:

Screening non-treponemal tests

• Venereal Disease Research Laboratory (VDRL)
• Rapid Plasma Reagin(RPR)

Confirmatory treponemal tests

• Fluorescent treponemal antibody absorbed (FTA-ABS)
• Treponema pallidum particle agglutination (TPPA)

References

Template:WikiDoc Sources

Causes

Syphilis causes

Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [14]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [15] Aysha Anwar, M.B.B.S[16]

Sexually transmitted diseases Main Page
Syphilis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Syphilis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
X Ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy Primary and Secondary Syphilis Latent Syphilis Tertiary Syphilis Neurosyphilis HIV-Infected Patients Pregnancy Management of Sexual Partners
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Syphilis On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Syphilis All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Syphilis
CDC on Syphilis
Syphilis in the news
Blogs on Syphilis
Directions to Hospitals Treating Syphilis
Risk calculators and risk factors for Syphilis

Overview

Syphilis is named as the "Great Imitator" because the symptomatology and physical exam findings of syphilis in different stages mimicks large variety of other diseases. Syphilis must be differentiated from other common diseases that cause rash such as measles, rubella, Kawasaki disease , and mononucleosis. Syphilis also has overlapping symptoms with the other genital infections such as chancroid, condyloma acuminata, genital warts, herpes simplex, and herpes zoster.

Differentiating Syphilis from other Diseases

Syphilis is named as a "great imitator" because symptomatology and physical exam findings of syphilis in different stages mimicks large variety of other diseases.

Stage of Syphilis	Differential diagnosis	Findings
Primary	Herpes simplex(1,2)	Presents as multiple, round, superficial oral and genital ulcers which are painful. Adults with non-typical presentation are more difficult to diagnose. However, prodromal symptoms that occur before the appearance of herpetic lesions helps to differentiate HSV from other conditions with similar symptoms like allergic stomatitis. Genital herpes can be more difficult to diagnose than oral herpes since most genital herpes/HSV-2-infected persons have no classical signs and symptoms.
Granuloma inguinale	Commonly characterized as painless, progressive ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular and bleed easily on contact.
Chancroid	Characterized by painful sores on the genitalia.
Lymphogranuloma venereum	Self-limited genital ulcer or papule with tender inguinal or femoral lymphadenopathy.
Condyloma acuminatum	Presents as warty lesions in the form of clusters and can be very tiny or can spread into large masses in the genital or penile area.
Urethritis	Discharge (milky or pus-like) from the penis, stinging or burning during urination, itching, tingling, burning or irritation inside the penis.
Cystitis	Presents as abnormal urine color (cloudy), blood in the urine, frequent urination or urgent need to urinate, painful or burning urination, pressure in the lower pelvis or back, flank pain, back pain, nausea, vomiting, and chills
Candidiasis	Presents as redness, itching and discomfort of affected area.
Other STIs	Such as Chlamydia, Gonorrhea, and Trichomonas vaginalis
Secondary	HIV	Acute illness present with fever, lymphadenopathy, rash, fatigue, and myalgia. AIDS classically presents with weight loss, night sweats, fatigue, diarrhea, mucosal sores, cough, and cognitive and neurological deficits.
Pityriasis rosea	Pink and flaky oval-shaped rash followed by clusters of smaller, more numerous patches of rash. May be accompanied by headache, fever, nausea and fatigue.
Viral exanthem	Such as measles, mumps, chicken pox, cytomegalovirus, coxsackie virus, rubella. Findings may include fever, rash, and constitutional symptoms.
Scarlet fever	Presenting symptoms include fever, punctate red macules on the hard and soft palate and uvula (Forchheimer's spots), bright red tongue with a "strawberry" appearance, sore throat and headache and lymphadenopathy.
Insect bite	Immediate skin reaction often resulting in a rash and swelling in the injured area, often with formation of vesicles.
Mononucleosis	Common symptoms include low-grade fever without chills, sore throat, white patches on tonsils and back of the throat, muscle weakness and sometime extreme fatigue, tender lymphadenopathy, petechial hemorrhage and skin rash.
Rocky mountain spotted fever	Symptoms may include maculopapular rash, petechial rash, abdominal pain and joint pain.
Rickettsialpox	Overlapping symptoms with secondary syphilis may include flu-like illness including fever, chills, weakness and muscle pain but the most distinctive symptom is the rash that breaks out, spanning the person's entire body.
Kawasaki disease	Commonly presents with high and persistent fever, red mucous membranes in mouth, "strawberry tongue", swollen lymph nodes and skin rash in early disease, with peeling off of the skin of the hands, feet and genital area
Yaws	Tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pertenue
Stevens-Johnson syndrome	Symptoms may include fever, sore throat and fatigue. Commonly presents ulcers and other lesions in the mucous membranes, almost always in the mouth and lips but also in the genital and anal regions.
Tertiary	Brain tumour	Findings which may overlap with neurosyphilis include headache,seizures, visual changes and personality changes.
Other causes of seizures	Neurosyphilitic disease can present with seizures and must be differentiated from other causes of seizures.
Other causes of stroke	Presents as weakness, sensory loss, gait abnormality and cranial nerve damage.
Meningococcemia	Rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.
Multiple sclerosis	May presents as changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty in moving, difficulties with coordination and balance (ataxia), problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptomatology (mainly depression).
Other causes of meningitis]	Such as bacterial, fungal and viral meningitis. It commonly presents with headache, nuchal rigidity, fever, petechiae and altered mental status.
Psychosis	Presents as hallucinations, delusions, auditory hallucinations, and flat or blunted affect and emotion, poverty of speech (alogia), anhedonia, and lack of motivation.
Vasculitides	Cardiovasular syphilis may present as aortitis and aortic aneurysm. Overlapping symptoms with other vasculitis may include back pain, fever, abdominal pain, chest pain, shortness of breath, fatigue, arm and leg weakness, lightheadedness, dizziness, fainting, and headaches.
Other causes of congestive heart failure	Presenting symptoms include dizziness, dyspnea on ordinary exertion or greater shortness of breath with usual activities, fainting, fatigue, hemoptysis or frothy sputum, nocturia or urination during the night, nocturnal cough, orthopnea or sleeping on pillows, palpitations or extra heart beats, paroxysmal nocturnal dyspnea or awakening at night with shortness of breath, shortness of breath, syncope or passing out and weakness.
Other causes of glomerulonephritis	May presents as blood in the urine (dark, rust-colored, or brown urine), foamy urine (due to excess protein in the urine), swelling (edema) of the face, eyes, ankles, feet, legs, or abdomen.
Other causes of arthritis	Gummatous lesions of syphilis in joints may present as joint pains and stiffness.
Other causes of lymphadenitis	May present as fever, myalgia, weight loss, and lymph node enlargement.
Other causes of hepatitis	Common presenting symptoms may include dark urine, fatigue, weight loss, fever usually low-grade, itching, jaundice (yellowing of the skin or eyes), loss of appetite, nausea and vomiting.
Other causes of nephrotic syndrome	Presents as proteinuria, edema, weight gain, fatigue and dyspnea.
Other causes of uveitis	Symptoms of uveitis include eye pain, eye redness, and photophobia. Intermediate, posterior, and panuveitis commonly present with floaters, blurry vision, and impaired vision.

Differentiating secondary syphilis from other diseases

• Secondary siphilis should be differentiated from other diseases causing erythamosquamous rash. the differentials include the following:

Disease	Rash Characteristics	Signs and Symptoms	Associated Conditions	Images
Cutaneous T cell lymphoma/Mycosis fungoides	Premycotic phase: A scaly, red rash in areas of the body that usually are not exposed to the sun. This rash does not cause symptoms and may last for months or years. Patch phase: Thin, erythematous, eczema-like rash. Plaque phase: Small raised bumps (papules) or hardened lesions on the skin, which may be erythematous. Tumor phase: Tumors form on the skin. Infection secondary to ulcers.	Epidermal atrophy or poikiloderma Generalized itching (pruritus) Pain in the affected area of the skin Insomnia Red (erythematous) patches scattered over the skin of the trunk and the extremities Tumor-like lobulated outgrowths form on the skin in the latter phase of the disease Weight loss Lymphadenopathy Malaise and fatigue Anemia May progress to Sezary syndrome (skin involvement plus hematogenous dissemination)	Sezary syndrome	courtesy of wikipedia.org - By Bobjgalindo - Own work, GFDL, https://commons.wikimedia.org/w/index.php?curid=7139812
Pityriasis rosea	Pink or salmon in color, which may be scaly; referred to as "herald patch" Oval shape Long axis oriented along the cleavage lines Distributed on the trunk and proximal extremities Squamous marginal collarette and a “fir-tree” or “Christmas tree” distribution on posterior trunk Secondary to viral infections Resolves spontaneously after 6-8 weeks	Preceded by a prodrome of: Sore throat Gastrointestinal disturbance Fever Arthralgia	Infection by any of the following: HHV-6 HHV-7 HHV-8	By James Heilman,MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=16305230
Pityriasis lichenoides chronica	Recurrent lesions are usually less evenly scattered than in cases of psoriasis Brownish red or orange-brown in color Lesions are capped by a single detachable, opaque, mica-like scale Often leave hypopigmented macules	High fever Malaise Myalgias Paraesthesia Pruritus	Infection by any of the following: Epstein-Barr virus (EBV) Toxoplasma gondii Human immunodeficiency virus (HIV)	courtesy of http://www.regionalderm.com
Nummular dermatitis	Multiple coin-shaped eczematous lesions Commonly affecting the extremities (lower>upper) and trunk May ooze fluid and become dry and crusty	Often appears after a skin injury, such as a burn, abrasion (from friction), or insect bite Lesions commonly relapse after occasional remission or may persist for long periods Pruritus	Associated with: Dry skin Emotional stress Allergens (rubber chemicals, formaldehyde, neomycin, chrome, mercury, and nickel) Staphylococcus infection Seasonal variation Alcohol Drugs Atopy	courtesy of your-doctor.net dermatology atlas
Secondary syphilis	Round, coppery, red colored lesions on palms and soles Papules with collarette of scales	Fever Generalized lymphadenopathy Sore throat Patchy hair loss Headache Weight loss Myalgia Fatigue	Associated with: Condylomata lata Corona verinata Positive VDRL test	Source: https://www.cdc.gov/
Bowen’s disease	Erythematous, small, scaly plaque, which enlarges erratically over time Scale is usually yellow or white and it is easily detachable without any bleeding Well-defined margins	Pruritus Pain Bleeding lesions	Associated with: Erythroplasia of Queyrat (Bowen's disease of the penis) Squamous cell carcinoma Solar radiation and ultraviolet (UV) exposure Radiotherapy Immunosuppression Arsenic exposure Human papilloma virus (HPV) type 16 Merkel cell polyomavirus Sjögren’s syndrome	By James Heilman, MD - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11509003
Exanthematous pustulosis	Numerous small, primarily non-follicular, sterile pustules, arising within large areas of edematous erythema	Fever Leukocytosis Intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophils and eosinophils	Associated with: Antibiotics (penicillins, sulfonamides, tetracyclines) Carbamazepine Calcium channel blockers (Diltiazem) Hydroxychloroquine	Acute generalized exanthematous pustulosis: an unusual side effect of meropenem". Indian J Dermatol 55 (2): 176–7. DOI:10.4103/0019-5154.62759. PMID 20606889. PMC: 2887524., CC BY 1.0, https://commons.wikimedia.org/w/index.php?curid=52979729
Hypertrophic lichen planus	Classically involves shin and ankles and is characterized by hyperkeratotic plaques and nodules covered by a scale Lesions may transform into hyperkeratotic thickened, elevated, purplish or reddish plaques and nodules	Chronic pruritus Scaling May be asymptomatic	Associated with Hepatitis C virus infection
Sneddon–Wilkinson disease	Flaccid pustules that are often generalized and have a tendency to involve the flexural areas Annular configuration	Pruritus May be asymptomatic	Associated with: Monoclonal gammopathy, usually an IgA paraproteinemia Crohn's disease Osteomyelitis Adalimumab	courtesy http://www.atlasdermatologico.com.br/disease.jsf?diseaseId=427
Small plaque parapsoriasis	Erythematous plaques with fine scaly surface May present with elongated, finger-like patches Symmetrical distribution on the flanks Known as digitate dermatosis	Lesions may be asymptomatic May be mildly pruritic May fade or disappear after sun exposure during the summer season, but typically recur during the winter	May progress to mycosis fungoides	courtesy http://www.regionalderm.com
Intertrigo	Red and fleshy looking lesion in skin folds Itching Oozing May be sore	Pruritus Musty odor	Associated with: Infections (Fungal, bacterial, viral) Allergies Diabetes Obesity	courtesy of cdc.gov
Langerhans cell histiocytosis	Scaling and crusting of scalp	Pathological fractures Visceromegaly (hepatomegaly, spleenomegaly) Chronic cough Dyspnea Lymphadenopathy	Associated with: Diabetes insipidus Pancytopenia	courtesy http://www.regionalderm.com
Tinea manuum/pedum/capitis	Scaling, flaking, and sometimes blistering of the affected areas Hair loss with a black dot on scalp in case of tinea capitis	Pruritus KOH preparation of the lesions confirms fungal infection	Associated with: Diabetes Immunosupression Intimate contact with infected person May lead to asthma exacerbation	courtesy regionalderm.com
Seborrheic dermatitis	Papulosquamous, scaly, flaky, itchy, and red rash found particularly at sebaceous gland-rich areas of the body	Pruritus	Associated with: AIDS Stress Fungal infection Fatigue Sleep deprivation Change of season Parkinson's disease Biotin deficiency	By Roymishali - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=27267929

Syphilitic oral lesions must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.

Disease	Presentation	Risk Factors	Diagnosis	Affected Organ Systems	Important features	Picture
Diseases predominantly affecting the oral cavity
Oral Candidiasis	Dysphagia or odynophagia White patches on the mouth and tongue	Newborn babies Denture users Poorly controlled diabetes As a side effect of medication, most commonly having taken antibiotics. Inhaled corticosteroids for the treatment of lung conditions (e.g, asthma or COPD) may also result in oral candidiasis which may be reduced by regularly rinsing the mouth with water after taking the medication. People with poor nutrition, specifically vitamin A, iron and folate deficiencies. People with an immune deficiency (e.g. as a result of AIDS/HIV or chemotherapy treatment). Women undergoing hormonal changes, like pregnancy or those on birth control pills. Organ transplantation patients	Clinical diagnosis Confirmatory tests rarely needed	Localized candidiasis Oral and esophageal candidasis Candida vulvovaginitis Chronic mucocutaneous candidiasis Invasive candidasis Candidaemia Candida endocarditis Candida osteoarticular disease	Oral candidiaisis is a benign self limiting disease unless accompanied by immunosuppression.	Tongue infected with oral candidiasis - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=11717223.jpg
Herpes simplex oral lesions	Fever Sore throat Painful ulcers	Stress Recent URTI Female sex	Physical examination Viral culture Tzanck smear	Orofacial Infection Anogenital Infection Ocular Infection Herpes Encephalitis Neonatal Herpes Herpetic Whitlow Herpes Gladiatorum	The symptoms of primary HSV infection generally resolve within two weeks	Oral herpes simplex infection - By James Heilman, MD - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=19051042.jpg
Aphthous ulcers	Painful, red spot or bump that develops into an open ulcer	Being a female Between the ages of 10-40 Family history of aphthous ulcers	Physical examination Diagnosis of exclusion	Oral cavity	Self-limiting , Pain decreases in 7 to 10 days, with complete healing in 1 to 3 weeks	Apthous ulcer on the lower surface of the tongue - By Ebarruda - Own work, CC BY-SA 3.0, httpscommons.wikimedia.orgwindex.phpcurid=7903358
Squamous cell carcinoma	Non healing ulcer, nodule, indurated plaque or mass May involve skin, lips, inside the mouth, throat or esophagus	Chronic sun or UV exposure Fair skin Elderly age (>45 yrs) Male sex Smoking	Physical exam Biopsy	Oral Cavity Floor of mouth Lateral tongue Throat Esophagus	Malignant Can spread to TMJ Some times associated with leukoplakia	Squamous cell carcinoma - By Luca Pastore, Maria Luisa Fiorella, Raffaele Fiorella, Lorenzo Lo Muzio - http://www.plosmedicine.org/article/showImageLarge.action?uri=info%3Adoi%2F10.1371%2Fjournal.pmed.0050212.g001, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=15252632
Leukoplakia	White leathery spots on the mucous membranes of the tongue and inside of the mouth Lateral borders of tongue	Atypical Tobacco use Chronic irritation Immunodeficiency Bloodroot (sanguinaria)	Physical exam Diagnosis of exclusion Biopsy	Vulvar lesions occur independent of oral lesions	Associated with HIV Persistant white spots Benign but can progress to carcinoma after almost 10 years Oral proliferative verrucous leukoplakia is an aggressive sub type with multiple lesions and higher conversion to warts or carcinoma	courtesy of http://www.regionalderm.com ]
Melanoma	A lesion with ABCD Asymmetry Border irregularity Color variation Diameter changes Bleeding from the lesion	UV radiations Genetic predisposition Old age Male gender Family or personal history of melanoma Multiple benign or atypical nevi	ABCD characteristics Bleeding or ulceration may show malignancy Serum LDH may be elevated in case of malignancy Biopsy	Can metastasize All UV radiation or sun exposed areas can be effected independently 1-2 to hundreds of granules	Neural crest cell derivative Development begins with disruption of nevus growth control Progression involves MAPK/ERK pathway N-RAS or BRAF oncogene also involved	Oral melanoma - By Emmanouil K Symvoulakis, Dionysios E Kyrmizakis, Emmanouil I Drivas, Anastassios V Koutsopoulos, Stylianos G Malandrakis, Charalambos E Skoulakis and John G Bizakis - Symvoulakis et al. Head & Face Medicine 2006 2:7 doi:10.1186/1746-160X-2-7 (Open Access), [1], CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=9839811
Fordyce spots	Rice-like granules or spots Small, painless, raised, pale, red or white 1 to 3 mm in diameter	Greasy skin types Some rheumatic disorders Hereditary nonpolyposis colorectal cancer Lower gingiva (gums) Vestibular mucosa	Physical exam Small keratin-filled pseudocysts May be seen on incidental mucosal biopsy Biopsy not done for them primarily	Oral cavity Vermilion border of the lips Oral mucosa of the upper lip Buccal mucosa in the commissural region often bilaterally Genitals	Benign neoplasms with sebaceous features Visible sebaceous glands No surrounding mucosal change Several adjacent glands may coalesce into a larger cauliflower-like cluster	Fordyce spots - Por Perene - Obra do próprio, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19772899
Burning mouth syndrome	Burning or tingling on the lips, tongue, or entire mouth	Nutritional deficiencies Chronic anxiety or depression Diabetes type 2 Menopause Oral thrush or dry mouth, or damaged nerves transmitting taste Female gender Menopause	Presentation Physical exam	Oral cavity	Pain typically is low in the morning and builds up over the day Low dosages of benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective
Torus palatinus	Bony growth on midline of the hard palate Nodular mass covered with normal mucosa	Genetic predisposition Autosomal dominant	Physical exam Types Flat tori Spindle tori Nodular tori Lobular tori	Hard palate	More common in Asian and Inuit populations Twice more common in females Repeated trauma can cause bleeding Surgery may be required in symptomatic	Torus palatinus - By Photo taken by dozenist, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=846591
Diseases involving oral cavity and other organ systems
Behcet's disease	Painful mouth sores Acne like skin lesions Headache, fever, poor balance, disorientation Abdominal pain, diarrhea or bleeding Uveitis Joint swelling and joint pain Genital sores wit pain and scaring Aneurysms	Over active immune system	Physical examination	Mouth Genitals GIT Eye Joints Skin Vascular system Brain	Outbreaks of exaggerated inflammation Affects smaller blood vessels	Behcet's disease - By Ahmet Altiner MD, Rajni Mandal MD - http://dermatology.cdlib.org/1611/articles/18_2009-10-20/2.jpg, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17863021
Crohn's disease	Chronic, episodic diarrhea or constipation Abdominal pain Vomiting Weight loss or weight gain	Smoking Whites and European Jews Hormonal contraception Diets high in microparticles, sweet, fatty or refined foods Industrialized country	Typical history and symptoms Skip lesions on biopsy Anti-Saccharomyces cerevisiae antibodies (ASCA) Anti-neutrophil cytoplasmic antibodies (ANCA)	Eyes Joints Skin	May lead to Obstructions Abscesses Free perforation Hemorrhage
Agranulocytosis	Fever or chills Frequent infections Unusual redness, pain, or swelling around a wound Mouth ulcers Abdominal pain Burning sensation when urinating Sore throat	Medications Cytotoxic chemotherapy Hematologic malignancies Autoimmune disorders	Neutropenia <100 cells per micro litre Eosinopenia Basopenia	Oral cavity Skin GIT Urinary system Conjunctiva	Immunocompromization Types Drug-induced Malignant Autoimmune
Syphilis	Chancre Regional lymphadenopathy	Multiple sexual partners Illicit drug use Unprotected sex Men who have sex with men Residence in highly prevalent areas HIV infection Presence of other STIs Previous history of STIs Intravenous drug use	Darkfield microscopy Non treponemal tests like VDRL and RPR test) Treponemal testsFTA-ABS tests, (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays)	Oral cavity Penis Cervix Labia Anal canal Rectum CNS CVS	Primary syphilis Chancre Secondary syphilis Condylomata lata Latent syphilis Asymptomatic Tertiary syphilis Gummas Neurosyphilis	oral syphilis - By CDC/Susan Lindsley - http://phil.cdc.gov/phil_images/20021114/34/PHIL_2385_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2134349
Coxsackie virus	Fever Sores in the mouth Rash with blisters Aches	Pregnancy immunodeficiency	History and Physical exam Throat swabs Swabs from the lesion Tzanck test	Oral cavity Skin	Symptomatic treatment	Coxsackie virus stomatitis - Adapted from Dermatology Atlas.
Chicken pox	Conjunctival symptoms Catarrhal symptoms Characteristic spots on the trunk appearing in two or three waves Itching	Pregnancy Premature infants born to susceptible mothers All infants born at less than 28 weeks gestation or who weigh =1000 grams Immunocompromised	History and physical exam PCR to detect VZV in skin lesions (vesicles, scabs, maculopapular lesions)	Oral cavity Skin	Sodium bicarbonate in baths or antihistamines for itching Paracetamol (acetaminophen) for fever Prednisolone is contraindicated	Chickenpox - By James Heilman, MD - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=52872565
Measles	Fever Rash Cough Coryza (runny nose) Conjunctivitis (pink eye) Malaise Koplick spots in mouth	Unvaccinated individuals Crowded and/or unsanitary conditions Traveling to less developed and developing countries Immunocompromized Winter and spring seasons Born after 1956 and never fully vaccinated Health care workers	History and examination PCR for Measles-specific IgM antibody PCR for Measles RNA	Oral cavity Skin Respiratory tract Eyes Throat	Caused by Morbillivirus Primary site of infection is the respiratory epithelium of the nasopharynx Transmitted in respiratory secretions, via aerosol droplets containing virus particles	Koplick spots (Measles) - By CDC - http://phil.cdc.gov/PHIL_Images/20040908/4f54ee8f0e5f49f58aaa30c1bc6413ba/6111_lores.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=824483

Secondary syphilis must be differentiated from other causes of rash and arthritis

Disease	Findings
Nongonococcal septic arthritis	Presents with an acute onset of joint swelling and pain (usually monoarticular) Culture of joint fluid reveals organisms
Acute rheumatic fever	Presents with polyarthritis and rash (rare presentation) in young adults. Microbiologic or serologic evidence of a recent streptococcal infection confirm the diagnosis. Poststreptococcal arthritis have a rapid response to salicylates or other antiinflammatory drugs.
Syphilis	Presents with acute secondary syphilis usually presents with generalized, pustular lesions at the palms and soles with generalized lymphadenopathy Rapid plasma reagin (RPR), Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) tests confirm the presence of the causative agent.
Reactive arthritis (Reiter syndrome)	Musculoskeletal manifestation include arthritis, tenosynovitis, dactylitis, and low back pain. Extraarticular manifestation include conjunctivitis, urethritis, and genital and oral lesions. Reactive arthritis is a clinical diagnosis based upon the pattern of findings and there is no definitive diagnostic test
Hepatitis B virus (HBV) infection	Presents with fever, chills, polyarthritis, tenosynovitis, and urticarial rash Synovial fluid analysis usually shows noninflammatory fluid Elevated serum aminotransaminases and evidence of acute HBV infection on serologic testing confirm the presence of the HBV.
Herpes simplex virus (HSV)	Genital and extragenital lesions can mimic the skin lesions that occur in disseminated gonococcal infection Viral culture, polymerase chain reaction (PCR), and direct fluorescence antibody confirm the presence of the causative agent.
HIV infection	Present with generalized rash with mucus membrane involvement, fever, chills, and arthralgia. Joint effusions are uncommon
Gout and other crystal-induced arthritis	Presents with acute monoarthritis with fever and chills Synovial fluid analysis confirm the diagnosis.
Lyme disease	Present with erythema chronicum migrans rash and monoarthritis as a later presentation. Clinical characteristics of the rash and and serologic testing confirm the diagnosis.

References

Natural History, Complications & Prognosis

Natural History

 complications and prognosis

Diagnosis

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Treatment

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