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==Differentiating Syphilis from other Diseases==
==Differentiating Syphilis from other Diseases==
Syphilis is named as "Great Imitator" because symptomatology of syphilis in different stages mimicks large variety of other diseases.<ref name="pmid21694502">{{cite journal| author=Carlson JA, Dabiri G, Cribier B, Sell S| title=The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity. | journal=Am J Dermatopathol | year= 2011 | volume= 33 | issue= 5 | pages= 433-60 | pmid=21694502 | doi=10.1097/DAD.0b013e3181e8b587 | pmc=3690623 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21694502  }} </ref>


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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="9;" | Primary
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="9;" | Primary
| style="padding: 5px 5px; background: #F5F5F5;" | [[Herpes simplex]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Herpes simplex]]
| style="padding: 5px 5px; background: #F5F5F5;" | Presents as multiple, round, superficial oral and genital [[ulcers]] which are painful.
| style="padding: 5px 5px; background: #F5F5F5;" | Presents as multiple, round, superficial oral and genital [[ulcers]] which are painful.<ref name="pmid17939933">{{cite journal |author=Fatahzadeh M, Schwartz RA |title=Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management |journal=J. Am. Acad. Dermatol. |volume=57 |issue=5 |pages=737–63; quiz 764–6 |year=2007 |pmid=17939933 |doi=10.1016/j.jaad.2007.06.027}}</ref> 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 [[allergy|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.<ref name="pmid17939933"/>
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Granuloma inguinale]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Granuloma inguinale]]
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|-
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| style="padding: 5px 5px; background: #F5F5F5;" | [[Lymphogranuloma venereum]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Lymphogranuloma venereum]]
| style="padding: 5px 5px; background: #F5F5F5;" | Self-limited [[genital ulcer]] or [[papule]] with tender inguinal or femoral [[lymphadenopathy]].<ref name="pmid12081191">{{cite journal |vauthors=Mabey D, Peeling RW |title=Lymphogranuloma venereum |journal=Sexually Transmitted Infections |volume=78 |issue=2 |pages=90–2 |year=2002 |pmid=12081191 |pmc=1744436 |doi= |url=}}</ref>  
| style="padding: 5px 5px; background: #F5F5F5;" | Self-limited [[genital ulcer]] or [[papule]] with tender inguinal or femoral [[lymphadenopathy]].<ref name="pmid12081191">{{cite journal |vauthors=Mabey D, Peeling RW |title=Lymphogranuloma venereum |journal=Sexually Transmitted Infections |volume=78 |issue=2 |pages=90–2 |year=2002 |pmid=12081191 |pmc=1744436 |doi= |url=}}</ref><ref name="Workowski-2010">{{Cite journal  | last1 = Workowski | first1 = KA. | last2 = Berman | first2 = S. | last3 = Workowski | first3 = KA. | last4 = Bauer | first4 = H. | last5 = Bachman | first5 = L. | last6 = Burstein | first6 = G. | last7 = Eckert | first7 = L. | last8 = Geisler | first8 = WM. | last9 = Ghanem | first9 = K. | title = Sexually transmitted diseases treatment guidelines, 2010. | journal = MMWR Recomm Rep | volume = 59 | issue = RR-12 | pages = 1-110 | month = Dec | year = 2010 | doi =  | PMID = 21160459 }}</ref>  
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Condyloma acuminatum]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Condyloma acuminatum]]
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| style="padding: 5px 5px; background: #F5F5F5;" | [[Candidiasis]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Candidiasis]]
| style="padding: 5px 5px; background: #F5F5F5;" | Presents as redness, itching and discomfort of affected area
| style="padding: 5px 5px; background: #F5F5F5;" | Presents as redness, itching and discomfort of affected area.<ref>{{cite book | last = Baron | first = Samuel | title = Medical microbiology | publisher = University of Texas Medical Branch at Galveston | location = Galveston, Tex | year = 1996 | isbn = 0-9631172-1-1 }}</ref><ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 978-0-443-06839-3 }}</ref>
|-
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| style="padding: 5px 5px; background: #F5F5F5;" | Other STIs
| style="padding: 5px 5px; background: #F5F5F5;" | Other STIs
| style="padding: 5px 5px; background: #F5F5F5;" | Such as [[chlamydia]], [[gonnorhea]], and [[trichomonas vaginalis]]
| style="padding: 5px 5px; background: #F5F5F5;" | Such as [[chlamydia]], [[gonnorhea]], and [[trichomonas vaginalis]]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="8;" | Secondary
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold;" rowspan="11;" | Secondary
| style="padding: 5px 5px; background: #F5F5F5;" | [[HIV]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[HIV]]
| style="padding: 5px 5px; background: #F5F5F5;" | 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.  
| style="padding: 5px 5px; background: #F5F5F5;" | 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.  
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| style="padding: 5px 5px; background: #F5F5F5;" | Viral exanthem
| style="padding: 5px 5px; background: #F5F5F5;" | Viral exanthem
| style="padding: 5px 5px; background: #F5F5F5;" | such as [[measles]], [[mumps]], [[chicken pox]], [[cytomegalovirus]], [[coxsackie virus]], [[rubella]]. Presenting findings may include fever, rash, and constitutional symptoms.<ref name=rash>Kang, Jin Han. "Febrile Illness with Skin Rashes." Infection & chemotherapy 47.3 (2015): 155-166.</ref>
| style="padding: 5px 5px; background: #F5F5F5;" | such as [[measles]], [[mumps]], [[chicken pox]], [[cytomegalovirus]], [[coxsackie virus]], [[rubella]]. Presenting findings may include fever, rash, and constitutional symptoms.<ref name=rash>Kang, Jin Han. "Febrile Illness with Skin Rashes." Infection & chemotherapy 47.3 (2015): 155-166.</ref>
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Scarlet fever]]
| style="padding: 5px 5px; background: #F5F5F5;" | 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]].
|-
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| style="padding: 5px 5px; background: #F5F5F5;" | [[Insect bite]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Insect bite]]
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| style="padding: 5px 5px; background: #F5F5F5;" | [[Rocky mountain spotted fever]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Rocky mountain spotted fever]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Symptoms]] may include [[maculopapular rash]], [[petechial rash]], [[abdominal pain]] and [[joint pain]].
| style="padding: 5px 5px; background: #F5F5F5;" | [[Symptoms]] may include [[maculopapular rash]], [[petechial rash]], [[abdominal pain]] and [[joint pain]].
 
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Rickettsialpox]]
| style="padding: 5px 5px; background: #F5F5F5;" | 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.
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Kawasaki disease]]
| style="padding: 5px 5px; background: #F5F5F5;" | 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]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" | [[Yaws]]
| style="padding: 5px 5px; background: #F5F5F5;" | [[Yaws]]
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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 [[STD|sexually transmitted diseases]] such as [[chlamydia]], [[gonorrhea]], [[trichomoniasis]], [[bacterial vaginosis]] and [[HIV|HIV infection]].
Different [[rash]]-like conditions may be misdiagnosed with [[syphilis]], including:<ref name="MooreSeward2006">{{cite journal|last1=Moore|first1=Zack S|last2=Seward|first2=Jane F|last3=Lane|first3=J Michael|title=Smallpox|journal=The Lancet|volume=367|issue=9508|year=2006|pages=425–435|issn=01406736|doi=10.1016/S0140-6736(06)68143-9}}</ref>
*[[Insect bite]]s - In an [[insect bite]], the insect injects [[formic acid]], which can cause an immediate [[skin]] reaction often resulting in a [[rash]] and swelling in the injured area, often with formation of [[vesicles]].
*[[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]].
*[[Measles]] - commonly presents with high [[fever]], [[coryza]] and [[conjunctivitis]], with observation of [[oral mucosa|oral mucosal]] lesions ([[Koplik's spots]]), followed by widespread [[skin rash]].
*[[Monkeypox]] - presentation is similar to [[smallpox]], although it is often a milder form, with [[fever]], [[headache]], [[myalgia]], [[back pain]], [[swollen lymph nodes]], a general feeling of discomfort, and exhaustion. Within 1 to 3 days (sometimes longer) after the appearance of [[fever]], the patient develops a papular [[rash]], often first on the face. The lesions usually develop through several stages before crusting and falling off.
*[[Rubella]] - commonly presents with a facial [[rash]] which then spreads to the [[trunk]] and [[limbs]], fading after 3 days, low grade [[fever]], swollen [[glands]], [[joint pain]]s, [[headache]] and [[conjunctivitis]]. The [[rash]] disappears after a few days with no staining or peeling of the [[skin]]. ''[[Forchheimer's sign]]'' occurs in 20% of cases, and is characterized by small, red [[papules]] on the area of the [[soft palate]].
*Atypical [[measles]] - symptoms commonly begin about 7-14 days after infection and present as [[fever]], [[cough]], [[coryza]] and [[conjunctivitis]]. Observation of [[Koplik's spots]] is also a characteristic finding in measles.
*[[Coxsackievirus]] - the most commonly caused disease is the [[Coxsackie A]] disease, presenting as ''hand, foot and mouth disease''. It may be [[asymptomatic]] or cause mild [[symptoms]], or it may produce [[fever]] and painful [[blisters]] in the mouth ([[herpangina]]), on the palms and fingers of the hand, or on the soles of the feet. There can also be [[blisters]] in the [[throat]]  or above the [[tonsils]]. Adults can also be affected. The [[rash]], which can appear several days after high temperature and painful sore throat, can be itchy and painful, especially on the hands/fingers and bottom of feet.
*[[Acne]] - typical of teenagers, usually appears on the [[face]] and upper neck, but the [[chest]], [[human back|back]] and [[shoulder]]s may have [[acne]] as well. The upper [[arm]]s can also have [[acne]], but lesions found there are often [[keratosis pilaris]], not [[acne]]. The typical [[acne]] lesions are [[comedones]] and [[inflammatory]] [[papules]], [[pustules]], and [[nodules]]. Some of the large [[nodules]] were previously called "[[cyst]]s"
*[[Molluscum contagiosum]] -  lesions are commonly flesh-colored, dome-shaped, and pearly in appearance. They are often 1-5 millimeters in diameter, with a dimpled center. Generally not painful, but they may itch or become irritated. Picking or scratching the lesions may lead to further [[infection]] or scarring. In about 10% of the cases, [[eczema]] develops around the lesions. They may occasionally be complicated by secondary [[bacterial infections]].
*[[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]].
*Toxic [[erythema]] - common [[rash]] in infants, with clustered and [[vesicular]] appearance.
*[[Rat-bite fever]] - commonly presents with [[fever]], [[chills]], open sore at the site of the bite and [[rash]], which may show red or purple plaques.
*[[Parvovirus B19]] - the [[rash]] of fifth disease is typically described as "slapped cheeks," with [[erythema]] across the cheeks and sparing the nasolabial folds, forehead, and mouth.
*[[Cytomegalovirus]] - common [[symptoms]] include [[sore throat]], swollen [[lymph nodes]], [[fever]], [[headache]], [[fatigue]], [[weakness]], [[muscle pain]]  and [[loss of appetite]].
*[[Scarlet fever]] - commonly includes [[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]].
*[[Rocky Mountain spotted fever]] - [[symptoms]] may include [[maculopapular rash]], [[petechial rash]], [[abdominal pain]] and [[joint pain]].
*[[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. Those in the mouth are usually extremely painful and reduce the patient's ability to eat or drink. [[Conjunctivitis]] of the eyes occurs in about 30% of children. A [[rash]] of round lesions about an inch across, may arise on the face, trunk, arms and legs, and soles of the feet, but usually not on the scalp.
*[[Varicella-zoster virus]] - commonly starts as a painful [[rash]] on one side of the face or body. The [[rash]] forms blisters that typically scab over in 7-10 days and clears up within 2-4 weeks.
*[[Chickenpox]] - commonly starts with [[conjunctival]] and catarrhal [[symptoms]] and then characteristic spots appearing in two or three waves, mainly on the body and head, rather than the hands, becoming itchy raw pox (small open sores which heal mostly without scarring). Touching the fluid from a [[chickenpox]] blister can also spread the disease.
*[[Meningococcemia]] - commonly presents with [[rash]], [[petechiae]], [[headache]], [[confusion]], and [[stiff neck]], high [[fever]], mental status changes, [[nausea]] and [[vomiting]].
*[[Rickettsialpox]] - first [[symptom]] is commonly a bump formed by a mite-bite, eventually resulting in a black, crusty scab. Many of the [[symptoms]] are [[flu]]-like including [[fever]], [[chills]], [[weakness]] and [[muscle pain]] but the most distinctive [[symptom]] is the [[rash]] that breaks out, spanning the person's entire body.
*[[Meningitis]] - commonly presents with [[headache]], [[nuchal rigidity]], [[fever]], [[petechiae]] and [[altered mental status]].
*[[Impetigo]] - commonly presents with pimple-like lesions surrounded by [[erythematous]] [[skin]]. Lesions are [[pustules]], filled with [[pus]], which then break down over 4-6 days and form a thick crust. It's often associated with insect bites, cuts, and other forms of [[trauma]] to the [[skin]].
*[[Candidiasis]] - [[Symptoms]] of [[candidiasis]] vary depending on the area affected. Most candidial [[infections]] result in minimal complications such as redness, itching and discomfort, though complications may be severe or even fatal if left untreated in certain populations. In [[immunocompetent]] persons, [[candidiasis]] is usually a very localized [[infection]] of the [[skin]] or [[mucosal]] membranes, including the [[oral cavity]] ([[thrush]]), the [[pharynx]] or [[esophagus]], the [[gastrointestinal tract]], the [[urinary bladder]], the fingernails or toenails (onychomycosis), and the genitalia (vagina, penis).<ref>{{cite book | last = Baron | first = Samuel | title = Medical microbiology | publisher = University of Texas Medical Branch at Galveston | location = Galveston, Tex | year = 1996 | isbn = 0-9631172-1-1 }}</ref><ref>{{cite book | last = Mandell | first = Gerald | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Churchill Livingstone/Elsevier | location = Philadelphia, PA | year = 2010 | isbn = 978-0-443-06839-3 }}</ref>
*[[Chancroid]] - [[sexually transmitted infection]] characterized by painful sores on the genitalia. Chancroid is known to be spread from one to another individual through sexual contact.
*[[Condyloma acuminata]] - often occur in clusters and can be very tiny or can spread into large masses in the [[genital]] or [[penis]] area. In women they occur on the outside and inside of the [[vagina]] on the opening ([[cervix]]) of the [[uterus]], or around the [[anus]]. They are approximately as prevalent in men, but the [[symptoms]] may be less obvious. When present, they usually are seen on the tip of the [[penis]]. They also may be found on the shaft of the [[penis]], on the [[scrotum]]  or around the [[anus]]. Rarely, [[genital warts]] also can develop in the mouth or throat of a person who has had oral sex with an [[infected]] person.
*Drug eruptions - cutaneous [[drug eruption]]s are the most frequent type of adverse drug reactions and the overwhelming majority of these reactions are thought to be [[allergic]] in origin. Common eruptions include: [[morbilliform rash]], [[urticaria]], [[erythema multiforme]] and toxic epidermal necrolysis.
*[[Genital warts]] - often occur in clusters and can be very tiny or can spread into large masses in the [[genital]] or [[penis]] area. In women they occur on the outside and inside of the [[vagina]] on the opening ([[cervix]]) of the [[uterus]], or around the [[anus]]. They are approximately as prevalent in men, but the [[symptoms]] may be less obvious. When present, they usually are seen on the tip of the [[penis]]. They also may be found on the shaft of the [[penis]], on the [[scrotum]]  or around the [[anus]]. Rarely, [[genital warts]] also can develop in the mouth or throat of a person who has had oral sex with an [[infected]] person.
*[[Granuloma inguinale]] - clinically, the disease is commonly characterized as painless, progressive ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular and bleed easily on contact. However, the clinical presentation also can include hypertrophic, necrotic, or sclerotic variants.
*[[Herpes simplex]] - Primary orofacial herpes / Herpes simplex type 1 presents itself as multiple, round, superficial [[oral ulcer]]s <ref name="pmid17939933">{{cite journal |author=Fatahzadeh M, Schwartz RA |title=Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management |journal=J. Am. Acad. Dermatol. |volume=57 |issue=5 |pages=737–63; quiz 764–6 |year=2007 |pmid=17939933 |doi=10.1016/j.jaad.2007.06.027}}</ref> 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 [[allergy|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.<ref name="pmid17939933"/>. They present with [[blister]]s and [[ulcer]]s in genital area that are similar to orofacial herpes. [[Herpes simplex|Herpes infection]] can recur even after successful initial treatment. The first episode is usually longer (two to four weeks) more painful and severe than the subsequent/recurrent episodes.
*[[Herpes zoster]] - or shingles usually starts as a painful rash on one side of the face or body. The rash forms blisters that typically scab over in 7–10 days and clears up within 2–4 weeks. Before the rash develops, there is often pain, itching, or tingling in the area where the rash will develop. This may happen anywhere from 1 to 5 days before the rash appears. The pain may be extreme in the affected nerve, where the rash will later develop, and can be characterized as stinging, tingling, aching, numbing, or throbbing, and can be pronounced with quick stabs of intensity. During this phase, herpes zoster is frequently misdiagnosed as other diseases with similar symptoms, including [[myocardial infarction|heart attacks]] and [[renal colic]]. Most commonly, the rash occurs in a single stripe around either the left or the right side of the body. In other cases, the rash occurs on one side of the face. In rare cases (usually among people with weakened immune systems), the rash may be more widespread and look similar to a chickenpox rash. Shingles can affect the eye and cause loss of vision.
*[[Lymphogranuloma venereum]] - The most common clinical manifestation of LGV among heterosexuals is tender inguinal and/or femoral [[lymphadenopathy]] that is typically unilateral. A self-limited [[genital ulcer]] or [[papule]] sometimes occurs at the site of [[inoculation]]. However, by the time patients seek care, the lesions have often disappeared. [[Rectal]] exposure in women or MSM can result in [[proctocolitis]], including mucoid and/or hemorrhagic rectal discharge, [[anal pain]], [[constipation]], [[fever]], and/or [[tenesmus]]<ref name="Workowski-2010">{{Cite journal  | last1 = Workowski | first1 = KA. | last2 = Berman | first2 = S. | last3 = Workowski | first3 = KA. | last4 = Bauer | first4 = H. | last5 = Bachman | first5 = L. | last6 = Burstein | first6 = G. | last7 = Eckert | first7 = L. | last8 = Geisler | first8 = WM. | last9 = Ghanem | first9 = K. | title = Sexually transmitted diseases treatment guidelines, 2010. | journal = MMWR Recomm Rep | volume = 59 | issue = RR-12 | pages = 1-110 | month = Dec | year = 2010 | doi =  | PMID = 21160459 }}</ref>
*[[Urethritis]] - [[Discharge]] (milky or pus-like) from the penis, stinging or burning during urination, [[itching]], tingling, burning or irritation inside the penis.
*[[Yaws]] -  tropical [[infection]] of the [[skin]], [[bones]] and [[joints]] caused by the [[spirochete]] bacterium ''Treponema pertenue''. Other treponematosis diseases are bejel (''Treponema endemicum''), pinta (''Treponema carateum''), [[syphilis]] (''Treponema pallidum''), and [[Lyme Disease]] (''Borrelia burgdorferi'').


==References==
==References==

Revision as of 19:25, 26 September 2016

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 must be differentiated from other common diseases that cause rash such as measles, rubella, Kawasaki disease , and mononucleosis. Syphilis must also be differentiated from other genital infections such as chancroid, Condyloma acuminata, genital warts, Herpes simplex, and Herpes zoster.

Differentiating Syphilis from other Diseases

Syphilis is named as "Great Imitator" because symptomatology of syphilis in different stages mimicks large variety of other diseases.[1]

Stage of Syphilis Differential diagnosis Findings
Primary Herpes simplex Presents as multiple, round, superficial oral and genital ulcers which are painful.[2] 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.[2]
Granuloma inguinale Commonly characterized as painless, progressive ulcerative lesions without regional lymphadenopathy. The lesions are highly vascular and bleed easily on contact.[3]
Chancroid Characterized by painful sores on the genitalia.[4]
Lymphogranuloma venereum Self-limited genital ulcer or papule with tender inguinal or femoral lymphadenopathy.[5][6]
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.[7]
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.[8][9]
Other STIs Such as chlamydia, gonnorhea, 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. Presenting findings may include fever, rash, and constitutional symptoms.[10]
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.
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.[11][12][13]
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 seizures Neurosyphilitic disease can present with seizures.
Other causes of stroke[14] Presents as weakness, sensory loss, gait abnormality and cranial nerve damage.
Other causes of meningitis][15] Such as bacterial, fungal and viral meningitis. It commonly presents with headache, nuchal rigidity, fever, petechiae and altered mental status.
Meningococcemia Rash, petechiae, headache, confusion, and stiff neck, high fever, mental status changes, nausea and vomiting.
Psychosis Presents as hallucinations, delusions, auditory hallucinations, and flat or blunted affect and emotion, poverty of speech (alogia), anhedonia, and lack of motivation.[16]
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).[17]
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 stiffnes.
Other causes of lymphadenitis May present as fever, myalgias, weight loss, and lymph node enlargement.[18]
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.[19]
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.[18][20]


References

  1. ↑ Carlson JA, Dabiri G, Cribier B, Sell S (2011). "The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity". Am J Dermatopathol. 33 (5): 433–60. doi:10.1097/DAD.0b013e3181e8b587. PMC 3690623. PMID 21694502.
  2. ↑ 2.0 2.1 Fatahzadeh M, Schwartz RA (2007). "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J. Am. Acad. Dermatol. 57 (5): 737–63, quiz 764–6. doi:10.1016/j.jaad.2007.06.027. PMID 17939933.
  3. ↑ O'Farrell N (2002). "Donovanosis". Sexually Transmitted Infections. 78 (6): 452–7. PMC 1758360. PMID 12473810.
  4. ↑ Coovadia YM, Kharsany A, Hoosen A (1985). "The microbial aetiology of genital ulcers in black men in Durban, South Africa". Genitourin Med. 61 (4): 266–9. PMC 1011828. PMID 2991120.
  5. ↑ Mabey D, Peeling RW (2002). "Lymphogranuloma venereum". Sexually Transmitted Infections. 78 (2): 90–2. PMC 1744436. PMID 12081191.
  6. ↑ Workowski, KA.; Berman, S.; Workowski, KA.; Bauer, H.; Bachman, L.; Burstein, G.; Eckert, L.; Geisler, WM.; Ghanem, K. (2010). "Sexually transmitted diseases treatment guidelines, 2010". MMWR Recomm Rep. 59 (RR-12): 1–110. PMID 21160459. Unknown parameter |month= ignored (help)
  7. ↑ F. G. Bruins, F. J. A. van Deudekom & H. J. C. de Vries (2015). "Syphilitic condylomata lata mimicking anogenital warts". BMJ (Clinical research ed.). 350: h1259. PMID 25784708.
  8. ↑ Baron, Samuel (1996). Medical microbiology. Galveston, Tex: University of Texas Medical Branch at Galveston. ISBN 0-9631172-1-1.
  9. ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 978-0-443-06839-3.
  10. ↑ Kang, Jin Han. "Febrile Illness with Skin Rashes." Infection & chemotherapy 47.3 (2015): 155-166.
  11. ↑ K. Doi, T. Kasaba & Y. Kosaka (1989). "[A comparative study of the depressive effects of halothane and isoflurane on medullary respiratory neurons in cats]". Masui. The Japanese journal of anesthesiology. 38 (11): 1427–1437. PMID 2585712. Unknown parameter |month= ignored (help)
  12. ↑ Sapira JD (1981 Apr). ""Quincke, de Musset, Duroziez, and Hill: some aortic regurgitations"". South Med J. 74 (4): 459–67. Check date values in: |date= (help)
  13. ↑ Pugh PJ, Grech ED (2002). "Images in clinical medicine. Syphilitic aortitis". N Engl J Med. 346 (9): 676. doi:10.1056/NEJMicm010343. PMID 11870245.
  14. ↑ Hotson JR (1981). "Modern neurosyphilis: a partially treated chronic meningitis". West J Med. 135 (3): 191–200. PMC 1273113. PMID 7340118.
  15. ↑ Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  16. ↑ Friedrich F, Geusau A, Greisenegger S, Ossege M, Aigner M (2009). "Manifest psychosis in neurosyphilis". General Hospital Psychiatry. 31 (4): 379–81. doi:10.1016/j.genhosppsych.2008.09.010. PMID 19555800.
  17. ↑ Scolding N (2001). "The differential diagnosis of multiple sclerosis". Journal of Neurology, Neurosurgery, and Psychiatry. 71 Suppl 2: ii9–15. PMC 1765571. PMID 11701778.
  18. ↑ 18.0 18.1 J. Deschenes, C. D. Seamone & M. G. Baines (1992). "Acquired ocular syphilis: diagnosis and treatment". Annals of ophthalmology. 24 (4): 134–138. PMID 1590633. Unknown parameter |month= ignored (help)
  19. ↑ Young MF, Sanowski RA, Manne RA (1992). "Syphilitic hepatitis". Journal of Clinical Gastroenterology. 15 (2): 174–6. PMID 1401840.
  20. ↑ T. F. Jr Schlaegel & S. F. Kao (1982). "A review (1970-1980) of 28 presumptive cases of syphilitic uveitis". American journal of ophthalmology. 93 (4): 412–414. PMID 7072806. Unknown parameter |month= ignored (help)


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