What is mistaken for syphilis?

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. It has often been called “the great imitator” because it has a wide variety of symptoms and signs that are similar to those of many other diseases. Here are some conditions that are sometimes mistaken for syphilis:

Herpes

Genital herpes can cause painful blisters or ulcers on the genitals, rectum or mouth. These sores often resemble the painless syphilitic chancres that develop during primary syphilis. However, there are some differences between herpes and syphilis sores:

Herpes sores tend to come and go, while syphilis chancres will remain until treated.
Herpes sores are usually clustered together, syphilis chancres are solitary.
Herpes lesions are often preceded by tingling or burning sensations, syphilis chancres are not.

Herpes is diagnosed with viral culture of the lesions. Syphilis requires a blood test.

Chancroid

Chancroid is another sexually transmitted bacterial infection. It causes painful genital ulcers that are very similar to syphilis chancres. However, there are a few characteristic features of chancroid:

Chancroid ulcers are typically soft with ragged, undermined borders.

There is usually a painful swelling of the lymph nodes in the groin.
The ulcers may be accompanied by purulent or bloody discharge.

Chancroid testing involves culture of the ulcer discharge. Syphilis is diagnosed with a blood test.

Granuloma Inguinale

Granuloma inguinale is a bacterial STD that causes painless genital ulcers. These slowly-enlarging ulcers have raised borders and are often mistaken for painless syphilis ulcers. However, granuloma inguinale can be distinguished by:

The ulcers are more likely to be found on the anus or groin folds.
There may be enlarged inguinal lymph nodes.

The ulcers may develop into hypertrophic masses.

Granuloma inguinale is diagnosed by microscopic examination and culture of ulcer samples. Syphilis requires a blood test.

Lymphogranuloma Venereum

Lymphogranuloma venereum (LGV) is caused by certain strains of chlamydia. It can produce a small, painless genital ulcer that might be mistaken for a syphilis chancre. However, LGV has some other characteristic findings:

There is swelling of the lymph nodes in the groin and genital region.
The swollen lymph nodes may drain pus through fistulas in the skin.
There may be inflammatory destruction of rectal or genital tissues.

LGV is diagnosed by lab tests detecting chlamydia in ulcer discharge or affected tissue. Syphilis requires a blood test.

Genital Warts

Some types of human papilloma virus (HPV) can cause fleshy wart-like growths in the genital region. These may be mistaken for syphilis condylomata lata lesions which also resemble warts. However, condylomata lata can be distinguished by:

They tend to be flatter, broader and more grayish in color.

They occur in moist areas like the vulva, under the foreskin, and around the anus.
They may have an offensive odor.

HPV testing can help differentiate genital warts from syphilis lesions. Syphilis also requires a blood test.

Molluscum Contagiosum

This common viral skin infection produces small, firm, painless bumps that might resemble early syphilis lesions. However, molluscum lesions have some typical features that differ from syphilis:

They often have a dimpled or pitted center.
They are more likely to occur on the lower abdomen, inner thighs and genital region.

There are often 20 or more lesions clustered together.

Molluscum contagiosum is diagnosed by its appearance and can be confirmed by biopsy. Syphilis requires a blood test.

Scabies

Scabies is an itchy infestation of the skin caused by the human itch mite Sarcoptes scabiei. The mite burrows into the skin and lays eggs, creating an itchy rash that may resemble syphilis rashes. However, scabies can be differentiated by:

Intense itching, especially at night.
Thin, squiggly burrow tracks where the mites have tunneled.
Common locations include finger webs, wrists, elbows and genital area.

Scabies is diagnosed by microscopic identification of mites, eggs or feces obtained by skin scraping. Syphilis requires a blood test.

Leukoplakia

Leukoplakia appears as thick, white patches or plaques in the mouth. When it occurs on the mucous membranes of the cheeks or tongue, it may resemble the mucous patches that can occur with oral hairy leukoplakia. However, oral hairy leukoplakia has some distinct features:

Caused by Epstein-Barr virus, it occurs almost exclusively in people with HIV/AIDS.

Lesions have a hairy or corrugated surface.
Most commonly affects the lateral borders of the tongue.

Oral hairy leukoplakia is usually diagnosed clinically based on its appearance. Biopsy may be done to rule out other causes. Syphilis requires a blood test.

Candidiasis

Oral thrush is a yeast infection that can cause creamy white patches in the mouth that resemble oral mucous patches of syphilis. However, thrush has some typical characteristics:

Caused by the fungus Candida.
Most common in newborns, the elderly and immunocompromised.

Lesions can often be scraped off, revealing red inflamed areas underneath.

Oral thrush is diagnosed by examination and culture of the lesions. Syphilis requires a blood test.

Lichen Planus

Lichen planus is an inflammatory condition that can affect the skin, nails, hair and mucous membranes in the mouth. When it occurs in the mouth, the lace-like white lesions may mimic syphilitic mucous patches. However lichen planus lesions have some distinct features:

The lesions have a lacelike network of grayish-white lines.
They cannot be scraped off like thrush lesions.
They typically occur bilaterally on the buccal mucosa.

The clinical appearance and distribution help differentiate lichen planus from syphilis. Biopsy can also confirm lichen planus. Syphilis requires a blood test.

Leprosy

Leprosy is an infection caused by the bacterium Mycobacterium leprae. It can sometimes produce skin lesions on the face and extremities that may resemble the rash seen in secondary syphilis. However, leprosy lesions typically have these distinguishing features:

Lesions are often numb or anesthetic.

They usually occur bilaterally and asymmetrically.
There is thickening of peripheral nerves.

Leprosy is diagnosed by biopsy of skin lesions and possibly nerve testing. Syphilis requires a blood test.

Systemic Lupus Erythematosus

Lupus is an autoimmune disease that can cause a butterfly rash across the cheeks and bridge of the nose similar to that seen in congenital syphilis. However, lupus rashes have some distinguishing characteristics:

The rash worsens or improves with sun exposure.
It does not affect mucous membranes like the mouth and eyes.

The rash may be scaly and cause hair loss.

The diagnosis of lupus depends on clinical findings, autoantibody testing and ruling out other conditions like syphilis with a blood test.

Sarcoidosis

Sarcoidosis is an inflammatory condition that most often affects the lungs but can also involve the skin. It may produce red-brown skin lesions overlying the shins that mimic syphilitic rashes. However, the sarcoidosis lesions have unique features:

They tend to be symmetrical in shape and distribution.
They can form scars when healing.
There may be nodules under the skin.

Sarcoidosis is diagnosed by biopsy of involved tissue like skin lesions or lymph nodes, aided by chest imaging tests. Syphilis requires a blood test.

Vasculitis

Vasculitis refers to inflammation of blood vessels. Certain types can produce skin lesions resembling the rashes of secondary syphilis. However, vasculitis rashes have some typical features:

They often occur on the lower legs.

Individual lesions persist for days or weeks.
There are few or no systemic symptoms.

The diagnosis of vasculitis is made by biopsy of affected tissue. Blood tests help rule out syphilis and other causes.

Behcet’s Disease

Behcet’s disease is a rare autoimmune condition characterized by oral and genital ulcers. The mouth and genital sores can resemble those seen in primary and secondary syphilis stages. However, Behcet’s differs because:

Ulcers are typically more painful.
There are recurring episodes of sores.

Other symptoms like eye inflammation and arthritis occur.

Behcet’s disease is diagnosed clinically based on typical findings and ruling out other causes like syphilis with blood tests.

HIV Rash

An early HIV rash occurs in about 80% of patients within 2-3 weeks after infection. It resembles the rash of secondary syphilis because it is maculopapular, involving the trunk and extremities. However, key differences include:

HIV rash tends to be more widespread and last longer.
It is typically not on palms and soles like syphilis rash.
HIV causes systemic symptoms like fever, sore throat and muscle aches.

HIV infection is diagnosed with blood tests detecting HIV antibodies or the virus. Syphilis blood tests can help rule it out.

Chickenpox

Chickenpox causes an itchy, blister-like rash that passes through stages like syphilis does. However, chickenpox rashes have some classic features:

Lesions are very itchy.

They occur in crops with different stages visible.
They often appear first on the scalp and trunk before spreading.

Chickenpox is usually diagnosed clinically. Tests can detect VZV virus or antibodies. Syphilis requires specific blood tests.

Hand, Foot and Mouth Disease

Coxsackie virus can cause this illness with fever and painful sores in the mouth and a rash on the hands and feet. The mouth ulcers resemble oral syphilis lesions but have some distinguishing features:

Oral ulcers are preceded by fever.
They are located on the tongue, gums and inner cheeks.

A rash on palms and soles occurs at the same time.

Hand, foot and mouth disease is diagnosed clinically based on the presentation. Tests can confirm Coxsackie virus. Syphilis requires specific blood tests.

Yaws

Yaws is a tropical infection caused by the spirochete bacterium Treponema pallidum pertenue. It produces skin lesions and bone involvement very similar to venereal syphilis, but with some distinguishing features:

It is not sexually transmitted, mostly affecting children.
Bone lesions often involve the long bones of the legs or arms.
It is limited to warm, moist environments.

Yaws is diagnosed by identification of T. pallidum in lesion exudate. Syphilis requires detection of the T. pallidum pallidum strain.

Pinta

Pinta is caused by another spirochete, Treponema carateum, which is related to the syphilis bacterium. It causes skin lesions that may resemble syphilitic rashes. However, pinta can be distinguished by a few characteristics:

The skin lesions change color, starting blue then turning red.

It does not affect the palms, soles or face.
There is no systemic involvement or congenital transmission.

Pinta is diagnosed by biopsy and special stains to identify the organisms. Syphilis requires detection of T. pallidum pallidum.

Leukemia

Leukemia can sometimes cause skin findings like brownish plaques and nodules that may resemble the rash of secondary syphilis. However, leukemia cutis has some typical features:

Lesions do not follow any specific distribution pattern.
They often ulcerate and bleed.

There are other systemic symptoms of leukemia.

Leukemia cutis is diagnosed by biopsy. Routine blood work can help detect leukemia and rule out syphilis.

Conclusion

In summary, many conditions can mimic certain signs of syphilis, leading to misdiagnosis. Some of the most common to be mistaken for syphilis include herpes, chancroid, granuloma inguinale, scabies, oral thrush, HIV, vasculitis, leukemia, and other treponemal infections like yaws and pinta. However, each condition has unique characteristics that, when considered together, can help differentiate it from syphilis. Appropriate diagnostic testing like microscopy, viral/bacterial culture, biopsy, and syphilis-specific blood tests, can confirm the diagnosis.