Secondary syphilis occurs approximately four to ten weeks after the primary infection. While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes. There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles. The rash may become maculopapular or pustular. It may form flat, broad, whitish, wart-like lesions known as condyloma latum on mucous membranes. All of these lesions harbor bacteria and are infectious. Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache. Rare manifestations include liver inflammation, kidney disease, joint inflammation, periostitis, inflammation of the optic nerve, uveitis, and interstitial keratitis. The acute symptoms usually resolve after three to six weeks; about 25% of people may present with a recurrence of secondary symptoms. Many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classic chancre of primary syphilis.

Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person. Approximately 3 to 90 days after the initial exposure (average 21 days) a skin lesion, called a chancre, appears at the point of contact. This is classically (40% of the time) a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders 0.3–3.0 cm in size. The lesion may take on almost any form. In the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer. Occasionally, multiple lesions may be present (~40%), with multiple lesions more common when coinfected with HIV. Lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%). The most common location in women is the cervix (44%), the penis in heterosexual men (99%), and anally and rectally relatively commonly in men who have sex with men (34%). Lymph node enlargement frequently (80%) occurs around the area of infection, occurring seven to 10 days after chancre formation. The lesion may persist for three to six weeks without treatment.

Late congenital syphilis is a subset of cases of congenital syphilis. By definition, it occurs in children at or greater than 2 years of age who acquired the infection trans-placentally.

Symptoms include

- blunted upper incisor teeth known as Hutchinson's teeth

- inflammation of the cornea known as interstitial keratitis

- deafness from auditory nerve disease

- frontal bossing (prominence of the brow ridge)

- saddle nose (collapse of the bony part of nose)

- hard palate defect

- swollen knees

- saber shins

- short maxillae

- protruding mandible

A frequently-found group of symptoms is Hutchinson's triad, which consists of Hutchinson's teeth (notched incisors), keratitis and deafness and occurs in 63% of cases.

Treatment (with penicillin) before the development of late symptoms is essential.

Death from congenital syphilis is usually due to bleeding into the lungs.

The types of neurosyphilis include asymptomatic, acute syphilitic meningitis, meningovascular syphilis, parenchymatous syphilis (which includes general paresis and tabes dorsalis), and optic atrophy.

The secondary stages of syphilis persists to be more dangerous to the systems of the human body. The disseminated disease can cause constitutional symptoms and condylomata lata. Many treponemes are present in chancres in the primary stage; however, condylomata lata is usually present in the secondary stage. The pathogen can spread through blood, which can infect the vessels in the body. The infection of the heart, muscles, and vessels in the body can lead to meningovascular syphilis. Generally, rashes may start developing on the hands and soles of the feet, and it can spread to various parts of skin on the body. Other symptoms may include sore throat, headache, joint pain, fever, and patches of hair loss. As in stage one, lesions may start to form on the body, but in this stage in particular, lesions are found in mucous membranes of the mouth, throat, bones, and internal organs. Also common with stage one, the symptoms and signs of secondary syphilis will go away with or without treatment and medication. The diagnosis includes serology nonspecific and specific, both positive. The secondary stage is however highly infectious because the bacteria is spreading drastically throughout the body.

The signs and symptoms of a vertically transmitted infection depend on the individual pathogen. It may cause subtle signs such as a influenza-like illness and may not even be noticed by the mother during the pregnancy. In such cases, the effects may be seen first at birth.

Symptoms of a vertically transmitted infection may include fever and flu like symptoms. The newborn is often small for gestational age. A petechial rash on the skin may be present, with small reddish or purplish spots due to bleeding from capillaries under the skin. An enlarged liver and spleen (hepatosplenomegaly) is common, as is jaundice. However, jaundice is less common in hepatitis B because a newborn's immune system is not developed well enough to mount a response against liver cells, as would normally be the cause of jaundice in an older child or adult. Hearing impairment, eye problems, mental retardation, autism, and death can be caused by vertically transmitted infections. The mother often has a mild infection with few or no symptoms.

The genetic conditions of Aicardi-Goutieres syndrome are possibly present in a similar manner.

Not all STIs are symptomatic, and symptoms may not appear immediately after infection. In some instances a disease can be carried with no symptoms, which leaves a greater risk of passing the disease on to others. Depending on the disease, some untreated STIs can lead to infertility, chronic pain or even death.

The presence of an STI in prepubescent children may indicate sexual abuse.

Sexually transmitted infections (STI), also referred to as sexually transmitted diseases (STD) and venereal diseases (VD), are infections that are commonly spread by sex, especially vaginal intercourse, anal sex or oral sex. Many times STIs initially do not cause symptoms. This results in a greater risk of passing the disease on to others. Symptoms and signs of disease may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. STIs can be transmitted to an infant before or during childbirth and may result in poor outcomes for the baby. Some STIs may cause problems with the ability to get pregnant.

More than 30 different bacteria, viruses, and parasites can be transmitted through sexual activity. Bacterial STIs include chlamydia, gonorrhea, and syphilis among others. Viral STIs include genital herpes, HIV/AIDS, and genital warts among others. Parasitic STIs include trichomoniasis among others. While usually spread by sex, some STIs can be spread by non-sexual contact with donor tissue, blood, breastfeeding, or during childbirth. STI diagnostic tests are usually easily available in the developed world, but this is often not the case in the developing world.

The most effective way of preventing STIs is by not having sex. Some vaccinations may also decrease the risk of certain infections including hepatitis B and some types of HPV. Safer sex practices such as use of condoms, having a smaller number of sexual partners, and being in a relationship where each person only has sex with the other also decreases the risk. Circumcision in males may be effective to prevent some infections. Most STIs are treatable or curable. Of the most common infections, syphilis, gonorrhea, chlamydia, trichomoniasis are curable, while herpes, hepatitis B, HIV/AIDS, and HPV are treatable but not curable. Resistance to certain antibiotics is developing among some organisms such as gonorrhea.

In 2015, about 1.1 billion people had STIs other than HIV/AIDS. About 500 million were infected with either syphilis, gonorrhea, chlamydia or trichomoniasis. At least an additional 530 million people have genital herpes and 290 million women have human papillomavirus. STIs other than HIV resulted in 108,000 deaths in 2015. In the United States there were 19 million new cases of sexually transmitted infections in 2010. Historical documentation of STIs date back to at least the Ebers papyrus around 1550 BC and the Old Testament. There is often shame and stigma associated with these infections. The term "sexually transmitted infection" is generally preferred over "sexually transmitted disease" or "venereal disease", as it includes those who do not have symptomatic disease.

Differences between the conditions chancre and chancroid:

- Chancre is a lesion typical of infection with the bacterium that causes syphilis, Treponema pallidum

- Chancroid is a lesion typical of infection with the bacterium Haemophilus ducreyi

- Chancres are typically painless, whereas chancroid are typically painful

- Chancres are typically single, whereas chancroid are typically multiple

- Chancres cause regional bilateral lymph node enlargement, whereas chancroid cause regional unilateral lymph node enlargement

- Chancres typically exude serum, whereas chancroid typically have a grey or yellow purulent exudate

- Chancres have a hard (indurated) base with sloping edges, whereas chancroid have a soft base with undermined edges

- Chancres heal spontaneously within three to six weeks, even in the absence of treatment

- Chancres can occur in the pharynx as well as on the genitals. Not to be confused with condyloma lata, which is seen in secondary syphilis

Bejel usually begins in childhood as a small mucous patch, often on the interior of the mouth, followed by the appearance of raised, eroding lesions on the limbs and trunk. Periostitis (inflammation) of the leg bones is commonly seen, and gummas of the nose and soft palate develop in later stages.

Though caused by different infections, the signs and symptoms of TORCH syndrome are consistent. They include hepatosplenomegaly (enlargement of the liver and spleen), fever, lethargy, difficulty feeding, anemia, petechiae, purpurae, jaundice, and chorioretinitis. The specific infection may cause additional symptoms.

TORCH syndrome may develop before birth, causing stillbirth, in the neonatal period, or later in life.

These are only local and no systemic manifestations are present.

The ulcer characteristically:

- Ranges in size dramatically from 3 to 50 mm (1/8 inch to two inches) across

- Is painful

- Has sharply defined, undermined borders

- Has irregular or ragged borders

- Has a base that is covered with a gray or yellowish-gray material

- Has a base that bleeds easily if traumatized or scraped

- painful swollen lymph nodes occurs in 30 to 60% of patients.

- dysuria (pain with urination) and dyspareunia (pain with intercourse) in females

About half of infected men have only a single ulcer. Women frequently have four or more ulcers, with fewer symptoms.

The initial ulcer may be mistaken as a "hard" chancre, the typical sore of primary syphilis, as opposed to the "soft chancre" of chancroid.

Approximately one-third of the infected individuals will develop enlargements of the inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen.

Half of those who develop swelling of the inguinal lymph nodes will progress to a point where the nodes rupture through the skin, producing draining abscesses. The swollen lymph nodes and abscesses are often referred to as buboes.

A vertically transmitted infection can be called a perinatal infection if it is transmitted in the perinatal period, which is the period starting at a gestational age of between 22 and 28 weeks (with regional variations in the definition) and ending seven completed days after birth.

The term congenital infection can be used if the vertically transmitted infection persists after childbirth.

Similarities between the conditions chancre and chancroid:

- Both originate as pustules at the site of inoculation, and progress to ulcerated lesions

- Both lesions are typically 1–2 cm in diameter

- Both lesions are caused by sexually transmissible organisms

- Both lesions typically appear on the genitals of infected individuals

Although the organism that causes bejel, "Treponema pallidum endemicum", is morphologically and serologically indistinguishable from "Treponema pallidum pallidum", which causes venereal syphilis, transmission of bejel is not venereal in nature, generally resulting from mouth-to-mouth contact or sharing of domestic utensils, and the courses of the two diseases are somewhat different.

TORCH syndrome is caused by in utero infection with one of the TORCH agents, disrupting fetal development.

Pinta, the least severe of treponemal infections being limited to the skin, is thought to be transmitted by skin-to-skin contact (similar to bejel and yaws), and after an incubation period of two to three weeks, produces a raised papule, which enlarges and becomes hyperkeratotic (scaly/flaky). Lesions are usually present in the exposed surface of arms and legs. Local lymph nodes might be enlarged. Three to 9 months later, further thickened and flat lesions (pintids) appear all over the body. These generally resolve, but a proportion of people with pinta will go on to develop late-stage disease, characterised by widespread pigmentary change with a mixture of hyperpigmentation and depigmentation which can be disfiguring.

Pinta (also known as Azul, Carate, Empeines, Lota, Mal del Pinto and Tina) is a human skin disease endemic to Mexico, Central America, and South America caused by infection with a spirochete, "Treponema pallidum carateum", which is morphologically and serologically indistinguishable from the bacterium that causes syphilis.

Despite many distinguishing features, the clinical spectrums of following diseases may overlap with chancroid:

- Primary syphilis

- Genital herpes

Practical clinical approach for this STI as Genital Ulcer Disease is to rule out top differential diagnosis of Syphilis and Herpes and consider empirical treatment for Chancroid as testing is not commonly done for the latter.

Neurosyphilis has four different forms: asymptomatic, meningovascular, tabes dorsalis, and general paresis. In rare instances, active neurosyphilis can mimic Alzheimer's disease.

Symptoms of neurosyphilis include, but are not limited to the following:

- Abnormal gait

- Blindness

- Confusion, disorientation

- Sudden personality changes

- Changes in mental stability

- Dementia

- Depression

- Headache

- Fecal and urinary incontinence

- Irritability

- Memory problems

- Mood disturbances

- Numbness in the toes, feet, or legs

- Poor concentration

- Psychosis

- Seizures

- Neck stiffness

- Tremors

- Visual disturbances. There may be the sign of Argyll Robertson pupils, which are bilateral small pupils that constrict when the patient focuses on a near object but do not constrict when exposed to bright light.

- Muscle weakness

Upon further diagnostic workup, the following signs may be present:

- Abnormal reflexes

- Muscle atrophy

- Muscle contractions

In addition to evaluation of any symptoms and signs, various blood tests can be done:

- Venereal Disease Research Laboratory test (VDRL)

- Fluorescent treponemal antibody absorption (FTA-ABS)

- Rapid plasma reagin (RPR)

- Treponema pallidum particle agglutination assay (TPPA)

Also, it is important to test the cerebrospinal fluid for signs of syphilis.

Additional tests to look for problems with the nervous system may include the following:

- Cerebral angiogram

- Head CT scan

- Lumbar puncture ("spinal tap") to acquire a sample for cerebrospinal fluid analysis

- MRI scan of the brain, brainstem, or spinal cord

A syphilid is any of the cutaneous and mucous membrane lesions characteristic of secondary and tertiary syphilis.

It appears about 10 weeks after infection. Patient may present with prodromal symptoms such as fever, acratia, myalgia athralgia, headache, anorexia. Its eruption pattern is macular, papular, follicular papules, or pustule, symmetrical, generalized and dense, round or oval in shape, and is red copper in color.

Gummas have a firm, necrotic center surrounded by inflamed tissue, which forms an amorphous proteinaceous mass. The center may become partly hyalinized.

These central regions begin to die through coagulative necrosis, though they also retain some of the structural characteristics of previously normal tissues, enabling a distinction from the granulomas of tuberculosis where caseous necrosis obliterates preexisting structures. Other histological features of gummas include an "intervening zone" containing epithelioid cells with indistinct borders and multinucleated giant cells, and a "peripheral zone" of fibroblasts and capillaries. Infiltration of lymphocytes and plasma cells can be seen in the peripheral zone as well. With time, gummas eventually undergo fibrous degeneration, leaving behind an irregular scar or a round fibrous nodule.

It is restricted to necrosis involving spirochaetal infections that cause syphilis. Growths that have the appearance of gummas are described as gummatous.

Treponematosis is a term used to collectively or individually describe any of the diseases caused by the bacterial species "Treponema". There are four subspecies described which cause the following diseases:

- Syphilis ("Treponema pallidum pallidum")

- Yaws ("Treponema pallidum pertenue")

- Bejel ("Treponema pallidum endemicum")

- Pinta ("Treponema carateum")