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.

Tertiary syphilis may occur approximately 3 to 15 years after the initial infection, and may be divided into three different forms: gummatous syphilis (15%), late neurosyphilis (6.5%), and cardiovascular syphilis (10%). Without treatment, a third of infected people develop tertiary disease. People with tertiary syphilis are not infectious.

Gummatous syphilis or late benign syphilis usually occurs 1 to 46 years after the initial infection, with an average of 15 years. This stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. They typically affect the skin, bone, and liver, but can occur anywhere.

Neurosyphilis refers to an infection involving the central nervous system. It may occur early, being either asymptomatic or in the form of syphilitic meningitis, or late as meningovascular syphilis, general paresis, or tabes dorsalis, which is associated with poor balance and lightning pains in the lower extremities. Late neurosyphilis typically occurs 4 to 25 years after the initial infection. Meningovascular syphilis typically presents with apathy and seizure, and general paresis with dementia and tabes dorsalis. Also, there may be Argyll Robertson pupils, which are bilateral small pupils that constrict when the person focuses on near objects but do not constrict when exposed to bright light.

Cardiovascular syphilis usually occurs 10–30 years after the initial infection. The most common complication is syphilitic aortitis, which may result in aneurysm formation.

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.

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.

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

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.

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.

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

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

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.

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

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

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")

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.

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.

In males, the lesions occur on the glans penis, shaft of the penis or other parts of the genital region, on the inner thigh, buttocks, or anus. In females, lesions appear on or near the pubis, clitoris or other parts of the vulva, buttocks or anus.

Other common symptoms include pain, itching, and burning. Less frequent, yet still common, symptoms include discharge from the penis or vagina, fever, headache, muscle pain (myalgia), swollen and enlarged lymph nodes and malaise. Women often experience additional symptoms that include painful urination (dysuria) and cervicitis. Herpetic proctitis (inflammation of the anus and rectum) is common for individuals participating in anal intercourse.

After 2–3 weeks, existing lesions progress into ulcers and then crust and heal, although lesions on mucosal surfaces may never form crusts. In rare cases, involvement of the sacral region of the spinal cord can cause acute urinary retention and one-sided symptoms and signs of myeloradiculitis (a combination of myelitis and radiculitis): pain, sensory loss, abnormal sensations (paresthesia) and rash. Historically, this has been termed Elsberg syndrome, although this entity is not clearly defined.

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.

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.

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.

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.

Genital herpes is an infection by herpes simplex virus (HSV) of the genitals. Most people either have no or mild symptoms and thus do not know they are infected. When symptoms do occur, they typically include small blisters that break open to form painful ulcers. Flu-like symptoms may also occur. Onset is typically around 4 days after exposure with symptoms lasting up to 4 weeks. Once infected further outbreaks may occur but are generally milder.

The disease is typically spread by direct genital contact with the skin surface or secretions of someone who is infected. This may occur during sex including oral sex. Active sores are not required for transmission to occur. HSV is classified into two types, HSV-1 and HSV-2. While historically mostly cause by HSV-2, genital HSV-1 has become more common in the developed world. Diagnosis may occur by testing lesions using either PCR or viral culture or blood tests for specific antibodies.

Efforts to prevent infection include not having sex, using condoms, and only having sex with someone who is not infected. Once infected their is no cure. Antiviral medications may, however, prevent outbreaks or shorten outbreaks if they occur. The long term use of antivirals may also decrease the risk of further spread.

In 2015 about 846 million people (12%) had genital herpes. Women are more commonly infected than men. Rates of disease caused by HSV-2 have decreased in the United States between 1990 and 2010. Complications may rarely include aseptic meningitis, an increased risk of HIV/AIDS if exposed, and spread to the baby during childbirth resulting in neonatal herpes.

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.

A vertically transmitted infection is an infection caused by pathogens (such as bacteria and viruses) that uses mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother gets an infection as an intercurrent disease in pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infection.