Syphilis differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2] Aysha Anwar, M.B.B.S[3]

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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.

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