Syphilis is a sexually transmitted disease caused by the bacterium *Treponema pallidum* that progresses in four stages: primary, secondary, latent and tertiary.¹

During the primary stage, there is always a painless ulcer where the infection enters the body, which usually occurs ten days to three months after sexual intercourse. Untreated, it will progress to the secondary stage where one might notice a skin rash on any part of his/her body, sores around the mouth, anus or genital organs as well as an accompanying fever.¹

A hidden stage follows this, during which there are no symptoms although the illness may still persist. This phase is called the latent phase and can last for years. It is also very possible for one to develop tertiary syphilis many years later after acquiring it; a condition characterised by severe health problems such as gummas (inflammatory nodules), cardiovascular damage or even neurosyphilis (paresis).¹

For the prevention of complications during the course of infection, early recognition must be made with the administration of antibiotics according to test results. Prevention also involves avoiding unprotected forms of sexual activity for secondary syphilis and general STIs.¹

The primary stage of syphilis

Identification and symptoms 

Primary syphilis typically appears as a single painless ulcer known as a chancre at the site of infection. This lesion can result in three weeks after initial contact but may also be multiple, atypical or painful.³ Being painless, the chancre is usually inconspicuous so may sometimes go unnoticed. Typically, it will heal without treatment within 3-6 weeks.⁴

Diagnostic procedures

The diagnosis of primary syphilis implies using direct and indirect techniques. Thus, direct methods consist of differentiation with dark field examinations and employing molecular tests such as PCR to detect the Treponema pallidum bacteria from a lesion exudate.⁹ Moreover, the diagnosis is confirmed by employing two types of diagnostic methods that include nontreponemal tests such as VDRL or RPR as well as treponemal tests including TP-PA assays or EIAs.⁹

Treatment options

The first-line therapy for primary syphilis is a single intramuscular/intravenous injection of Penicillin G that has been found to be most effective across all stages of this condition. It is important to note that its doses and preparations can vary by stage and clinical manifestation profile.³ Desensitisation procedures through the use of antibiotic substitutes e.g., doxycycline or ceftriaxone are recommended to patients with penicillin allergies.³

The secondary stage of syphilis

Identification and symptoms

Patients have condyloma lata in the perianal area (the area surrounding the anus) and a rash with both flat and raised parts on the back, arms, shoulders, or chest during the second stage of syphilis. Consequently, the nickname “the great imitator” was assigned to it due to various symptoms that can closely resemble those of other diseases.² Besides, this stage may include mucocutaneous lesions frequently seen on the palms and soles.⁶ Moreover, fever, muscle aches, and swollen lymph nodes are common systemic symptoms which may complicate the clinical presentation.²

Diagnostic challenges 

As there are many diverse manifestations of secondary syphilis, it poses a challenge when trying to diagnose it. The standard diagnostic procedures involve darkfield microscopy in which the causative agent, Treponema pallidum, can be visualised directly and serological tests can be conducted to determine the presence of antibodies linked with it.⁷ In instances where serological tests show negative results despite the disease being highly suspected,  Immunohistochemistry can aid with better sensitivity and specificity.⁷ Given the wide array of symptoms and mimicry with other diseases, it is vital that a comprehensive analysis is conducted, including a detailed history and physical examination.⁸

Treatment and management strategies

Timely and correct recognition, followed by proper medication, is necessary for effective treatment of secondary syphilis. It is suggested that the first treatment to be administered should be a single shot of benzathine penicillin G.⁷ In case of allergic reactions to penicillin in patients, doxycycline or ceftriaxone can be prescribed as substitutes.⁷ Treatment is important because it helps soothe symptoms while preventing development into worse stages of the ailment. This is why it is essential for medical care to commence before the condition worsens.⁸

The latent stage of syphilis

Understanding asymptomatic nature

Patients often have no signs of latent syphilis, leading to unnoticed progress of the condition.10 This stage is identified by the reactivity of blood serum without clinical manifestation of the primary, secondary or tertiary syphilis phases.9 Untreated syphilis might be easily missed due to the absence of its specific symptoms, hence enhancing transmission and causing complications within the infected person's body.¹⁰ 

Diagnosis 

During the latent stage, diagnosis heavily depends on serological testing because it is the only way in which the infection can be detected when it has no symptoms at all.¹¹ The earliest latent form of syphilis defined by infection occurring during the first year necessitates precision in diagnostic technique in order to inhibit progression.¹¹ The difference between early and late latent syphilis is very important in that the treatment modalities and likelihood of relapse to more infectious stages differ.¹¹

Long-term health implications

In case it is not treated, latent syphilis may deteriorate into tertiary syphilis and result in severe health problems like neurosyphilis and cardiovascular complications.¹⁰ Consequently, the risk of these severe cases highlights the significance of timely diagnosis and treatment to minimise the protracted health risks.⁹ Additionally, latent syphilis can be vertically transmitted and poses a risk for foetal health, necessitating meticulous management in pregnant women in order to prevent congenital syphilis.⁹

The tertiary stage of syphilis 

Tertiary syphilis, or third-stage syphilis, manifests decades after the initial infection. This form of the disease often presents itself with severe complications that contain more than one bodily system. It may include gummas, cardiovascular problems, general paresis and tabes dorsalis.³ Since symptoms occur in such variety, doctors need to be able to detect them by examining their patients’ conditions as well as using special tests on body fluids from which they might suspect there is organ involvement.⁹

Diagnostic requirements

It’s very important to test patients suspected of having neurosyphilis, especially those diagnosed with tertiary syphilis, due to the high risk or likelihood of this condition developing in these patients. Furthermore, clinicians should also check whether the patient is infected with HIV because this co-infection can lead to changes in the therapeutic approach as well as patient outcomes.⁹

Treatment regimens

The treatment involves large dosage penicillin regimens, which are adapted to suit the specific disease manifestations. For cardiovascular syphilis, some healthcare providers recommend following the treatment regimen for neurosyphilis, as advised by an infectious disease expert.⁹ If penicillin is contraindicated, substitutes such as doxycycline or ceftriaxone can be considered. Erythromycin is also another choice among penicillin-allergic cases.¹¹ Consistent monitoring must be done to oversee if the treatment is working and to manage any long-term problems.¹¹

FAQs

What are the stages of syphilis, and in what order do they occur?

If not treated, syphilis progresses through four separate stages – primary, secondary, latent (hidden) and tertiary (late) stages. Each stage comes with different symptoms and health challenges.

What happens in the tertiary stage of syphilis?

The final stage of infection in syphilis, also known as the tertiary or late stage, can cause severe health problems. This may include serious complications in the heart and blood vessels, mental disorders, blindness or other complications involving the nervous system.

How do primary and secondary syphilis lesions differ?

The primary stage of syphilis is usually marked by a single, painless sore known as a chancre. In contrast, the secondary stage can manifest through a variety of symptoms, including fever, swollen lymph nodes, a rash, and condyloma latum(wart-like lesions around the genital or anal regions).

How is the latent stage of syphilis detected?

The latent stage of syphilis, characterised by the absence of visible clinical symptoms, is identified through serological (blood) tests. This stage is classified based on the duration since infection: early latent syphilis is defined as an infection acquired within the past year. All other cases are considered late latent syphilis or latent syphilis of unknown duration.

Conclusion

Understanding syphilis and its progression is critical not only for individual health but also for public health initiatives aimed at controlling the spread of this infection. The strategies for prevention, including regular screening and education on safe sexual practices, are essential components in the battle against syphilis.