Secondary syphilis can present with a very broad range of symptoms. However, the hallmark of this stage of infection is the appearance of a maculopapular rash. The diameter of lesions, which are red-to-brown in color, ranges from 3-10 mm and initially appear on the trunk, followed by their dissemination to the extremities, including the palms and soles, which is one of the main distinguishing features [9]. Condylomata lata is a term that describes the development of raised grayish or white papillary skin lesions in intertriginous areas, which are also specific features for secondary syphilis. Macules and papules may progress into pustules. Mucous patches, grayish oval-shaped erosions or ulcerations are also commonly observed in patients during this stage.

Apart from skin lesions, patients may exhibit symptoms related to virtually any organ. Constitutional symptoms, such as fever, malaise, weight loss, myalgia, and arthralgia may precede the rash. Generalized lymphadenopathy, involving cervical, axillary and inguinal regions, is frequently present. Gastrointestinal involvement may result in symptoms such as vomiting, abdominal pain. Ocular involvement, including the development of keratitis, uveitis, retinitis, optic neuritis may occur [10]. Periostitis, meningitis, hepatitis and pharyngitis may also be encountered in variable percentages.

Lues maligna is a rare, but severe presentation of secondary syphilis, which presents with generalized progressive polymorphic ulcers accompanied with the poor systemic condition [4].

• Generalized Lymphadenopathy

  Generalized lymphadenopathy could be an indication of various diseases including malignancies or infections. [ncbi.nlm.nih.gov]

  Signs Highly infectious lesions can occur on mucus membrane Generalized Lymphadenopathy Papulosquamous Dermatosis Characteristics Pale, pink to red discrete round Macula r to papular lesions Scaling over surface Size: "Nickels and Dimes" Papule s Plaque [fpnotebook.com]

  Generalized lymphadenopathy, involving cervical, axillary and inguinal regions, is frequently present. Gastrointestinal involvement may result in symptoms such as vomiting, abdominal pain. [symptoma.com]

• Splenomegaly

  A 56-year-old man developed disseminate lymphadenopathies, associated with hepato-splenomegaly, fever, nocturnal sweating and weight loss. Imaging studies in particular FDG-PET/CT raised the suspicion of a malignant disease. [ncbi.nlm.nih.gov]

  […] leukoderma ( ICD-10-CM Diagnosis Code A52.79 Other symptomatic late syphilis 2016 2017 2018 2019 Billable/Specific Code Applicable To Late syphilitic leukoderma Syphilis of adrenal gland Syphilis of pituitary gland Syphilis of thyroid gland Syphilitic splenomegaly [icd10data.com]

  Less common symptoms of secondary syphilis include: Weight loss Patchy alopecia (hair loss) Kidney problems (such as glomerulonephritis) Meningitis Hepatitis Splenomegaly (an enlarged spleen) Cranial nerve palsies (weakness or paralysis of nerves in the [ada.com]

  A compilation of early clinical presentations of congenital syphilis in 9 studies involving a total of 212 infants included abnormal bone radiographs (61%); hepatomegaly (51%); splenomegaly (49%); petechiae (41%); other skin rashes (35%); anemia (34%) [emedicine.medscape.com]

• Fever

  Abstract A 34-year-old, HIV-positive man living in Texas presented with a 2-week history of fever, malaise, myalgias, oral ulcers, and papules on his chest, back, face, and extremities, including the palms. [ncbi.nlm.nih.gov]

  Fever, headache, hypotension and tachycardia usually appear and resolve within 24 hours, but patients in later stages of syphilis may develop life-threatening complications. [symptoma.com]

• Malaise

  We report a case in which an HIV-positive man developed general malaise, skin rash and biochemical hepatitis within days of starting a nevirapine-based antiretroviral treatment regimen. At the same time, his syphilis serology proved positive. [ncbi.nlm.nih.gov]

  Secondary syphilis is characterized by systemic symptoms, such as malaise and fever as well as a maculopapular rash involving the trunk and extremities including the palms and soles. [link.springer.com]

  This response is characterized by low-grade fever, myalgias, headache and malaise that begin within a few hours after initiation of therapy and last for 12–24 h. [cmaj.ca]

• Fatigue

  A 21-year-old Brazilian man presented with a two-month history of asymptomatic cutaneous lesions accompanied by fever and fatigue. [ncbi.nlm.nih.gov]

  Secondary Rough red or reddish brown rash on palms of hands and soles of feet Swollen lymph nodes Fever Sore throat Patchy hair loss Headaches and body aches Extreme tiredness ( fatigue ) These symptoms will go away, even if you don’t get treated. [webmd.com]

  Other symptoms of secondary stage syphilis include: fever swollen lymph glands sore throat patchy hair loss headaches weight loss muscle aches fatigue Latent syphilis: Latent syphilis causes no symptoms. [southernnevadahealthdistrict.org]

  In addition to the rash, other symptoms of secondary syphilis include: Fever Sore throat Headache Swollen lymph glands and nodes Fatigue Muscle aches and joint pain Weight loss and loss of appetite Hair loss Patches near genitals or skin folds that resemble [medguidance.com]

• Chills

  Photo Credit Dolly Faibyshev for The New York Times Work Out and Chill? Cool temperature workouts may be the answer for those who want to exercise without becoming a hot mess. [nytimes.com]

  After you have received the treatment, you may suffer from a reaction known as Garish-Herxheimer, during which you may have nausea, aches and pains, headache, fever and chills. Usually, these symptoms only last one day. [medguidance.com]

  Symptoms of Jarisch-Herxheimer include: chills rash fever of up to 104 degrees Fahrenheit tachycardia ( rapid heart rate ) hyperventilation headache muscle aches joint pain nausea The Jarisch-Herxheimer reaction is common and potentially serious. [healthline.com]

  Symptoms and signs of this reaction include: Chills Fever General ill feeling ( malaise ) Headache Muscle and joint pain Nausea Rash These symptoms usually disappear within 24 hours. [nlm.nih.gov]

• Constitutional Symptom

  Apart from skin lesions, patients may exhibit symptoms related to virtually any organ. Constitutional symptoms, such as fever, malaise, weight loss, myalgia, and arthralgia may precede the rash. [symptoma.com]

  Systemic findings Constitutional symptoms - Fever/malaise/sore throat Lymphadenopathy - Firm, rubbery. Often symmetric and wide spread (approximately 50%). [clinicaladvisor.com]

  symptoms such as fever, malaise, generalized lymphadenopathy, arthralgias, and weight loss. [aafp.org]

  Constitutional symptoms including fever, headache, arthralgias, malaise, pharyngitis, and generalized lymphadeno-pathy are common. The dominant feature of secondary syphilis is a mucocutaneous rash, which appears in 90% of patients. [vertigoexercises.us]

• Aphthous Stomatitis

  These were wrongly diagnosed as 'aphthous stomatitis' and treated with betamethasone gargling. Perforation of the palate occurs following development fo gumma in late stage of syphilis. [ijdvl.com]

• Hepatosplenomegaly

  Hepatosplenomegaly may be present. In some cases lesions of secondary syphilis appear before the chancre heals. [dartmouth.edu]

  There was no hepatosplenomegaly. Fig. 1: Papulosquamous lesions on the patient's trunk. Fig. 2: Mucous patches involving the lips. Fig. 3: Involvement of the palm. Blood samples were taken for HIV antibody and VDRL testing. [cmaj.ca]

  Diagnosis: Early (first two years): rash including condylomata lata, vesiculobullous lesions, snuffles, haemorrhagic rhinitis, osteochondritis, periostitis, pseudoparalysis, mucous patches, perioral fissures, hepatosplenomegaly, generalised lymphadenopathy [patient.info]

  Hepatosplenomegaly can be often found. Diversity of skin lesions with a combination of signs and symptoms are often confused with many other diseases. All the skin lesions in secondary syphilis are infectious as they harbor bacteria. [clinicaladvisor.com]

  Secondary syphilis can affect many other organs: About half of patients have lymphadenopathy, usually generalized, with nontender, firm, discrete nodes, and often hepatosplenomegaly. [msdmanuals.com]

• Hepatomegaly

  Physical examination was remarkable only for hepatomegaly. His hematocrit was 36%, ESR 122mm/hr, iron 18, TIBC 204, alkaline phosphatase 199; other liver function studies were normal. CEA, AFP, SPEP and B-HCG levels were normal. [med.harvard.edu]

  Computed tomography (CT) cervico-thoraco-abdominal-pelvic showed hepatomegaly and multiple cervical, thoracic, abdominal, pelvic and inguinal adenopathy suggestive of a lymphoproliferative disorder. [reumatologiaclinica.org]

  A compilation of early clinical presentations of congenital syphilis in 9 studies involving a total of 212 infants included abnormal bone radiographs (61%); hepatomegaly (51%); splenomegaly (49%); petechiae (41%); other skin rashes (35%); anemia (34%) [emedicine.medscape.com]

• Arthritis

  After excluding the aetiologies of cancer metastasis and tuberculosis, we confirmed the diagnosis of syphilitic arthritis. The patient received the medical treatment of antibiotics and the surgical treatment of total hip arthroplasty. [ncbi.nlm.nih.gov]

  […] semilunar valve 半月弁 seminal vesicle 精嚢 seminiferous tubule 精細管 seminoma セミノーマ/精上皮腫 sensitization 感作/増感 sensory dissociation 知覚解離/感覚解離 sensory-motor period 感覚運動期 separation anxiety disorder 分離不安障害 separation-individuation 分離・個体化 sepsis/septicemia 敗血症 septic arthritis [jpeds.or.jp]

  Syphilis was once a major public health threat, commonly causing serious long-term health problems such as arthritis, brain damage, and blindness. [webmd.com]

  Maurer Synovitis in secondary syphilis Arthritis Rheumat, 22 (1979), pp. 170-176 [7] C.J. Mullick, A.P. Liappis, D.A. Benator, A.D. Roberts, D.M. Parenti, G.L. [reumatologiaclinica.org]

  Osteomyelitis, septic arthritis and soft tissue infection: the organisms. In: Diagnosis of bone and joint disorders. Philadelphia, Saunders. 1981; Ch. 62. 3) Tight R and Warner J. Skeletal involvement in secondary syphilis detected by bone scanning. [med.harvard.edu]

• Skin Rash

  Although the skin biopsy was compatible with secondary syphilis, there was no change in the skin rash 3 weeks after the first penicillin administration. Another 2 doses of penicillin were given but 4 weeks later the rash persisted. [ncbi.nlm.nih.gov]

  […] symmetric bilateral & asymptomatic usually 24 1 Reply Other cutaneous LESIONS in secondary syphilis are * A skin rash on the arms, legs, and trunk — The rash can take a variety of forms, such as small blotches or indented circles; small blisters filled [dailyrounds.org]

• Eruptions

  The most commonly observed cutaneous presentation is a generalized, non-pruritic, papulosquamous eruption varying from pink to violaceous to brown, with mucous membrane involvement. [ncbi.nlm.nih.gov]

• Alopecia

  Alopecia syphilitic, Syphilitic alopecia, Syphilitic alopecia (disorder) Czech Syfilitická alopecie Hungarian alopecia syphilitica, syphilises alopecia Spanish alopecia sifilítica (trastorno), alopecia sifilítica, Alopecia sifilítica Portuguese Alopecia [fpnotebook.com]

  BACKGROUND: Syphilitic alopecia (SA) is mainly described in single case reports, and there are only a few epidemiological studies. [ncbi.nlm.nih.gov]

  Alopecia, anogenital condylomata lata and pitted hyperkeratotic palmoplantar papules (syphilis cornee) may also be seen. In severe cases, ulcerative lesions termed lues maligna may develop. [dermpedia.org]

  Patchy alopecia of the scalp and loss of the lateral eyebrows occur in some patients. Lymphadenopathy, fever, and malaise may also be present. A history of an ulcerating primary lesion (chancre) mayor may not be obtainable. [streetdirectory.com]

• Cutaneous Manifestation

  Abstract Syphilis is a well-known sexually transmitted infection infamous for its protean cutaneous manifestations. [ncbi.nlm.nih.gov]

• Eczema

  The recent resurgence of syphilis mandates that clinicians maintain a heightened suspicion for Treponema infection, and that they be aware of the variety of cutaneous presentations that may mimic eczema, psoriasis, drug eruption, erythema multiforme, [ncbi.nlm.nih.gov]

  The clinical hypothesis was dyshidrotic eczema and Bowen's disease for the finger lesion and nummular eczema for the leg lesion. An incisional biopsy was performed in both lesions. [karger.com]

  […] less commonly, tuberculosis, chancroid Anal ulcers : genital herpes, anal fissure, bacterial infections, trauma, inflammatory bowel disease Mouth ulcers : herpes simplex (cold sore), aphthous ulcers, trauma Rash Drug eruption Pityriasis rosea Psoriasis Eczema [dermnetnz.org]

• Syphilitic Chancre

  Discussion In the primary form of the disease, the specific lesion is the syphilitic chancre, which may be associated with a regional, painless, nonsuppurative lymphadenomegaly [ 2, 8 ]. [karger.com]

  Perforation of the syphilitic chancre on the shaft of penis following topical triamcinolone has been reported. [4] Steroids whether topical or systemic are detrimental in infectious diseases such as leprosy and syphilis in the absence of specific antibacterial [ijdvl.com]

  chancre NOS secondary A51.39 atrophoderma maculatum A51.39 Ulcer, ulcerated, ulcerating, ulceration, ulcerative syphilitic (any site) (early) (secondary) A51.39 ICD-10-CM Codes Adjacent To A51.39 A50.6 Late congenital syphilis, latent A50.7 Late congenital [icd10data.com]

  If untreated, syphilitic chancres heal spontaneously within 3 to 8 weeks and disappear. [ncbi.nlm.nih.gov]

• Headache

  Patients present with bone pain, which may manifest as headaches or shin splits, depending on the affected bone. [ncbi.nlm.nih.gov]

  After you have received the treatment, you may suffer from a reaction known as Garish-Herxheimer, during which you may have nausea, aches and pains, headache, fever and chills. Usually, these symptoms only last one day. [medguidance.com]

  Some people never develop symptoms, however others experience the following symptoms: Seizures Headache, stiff neck, and fever brought on from an inflammation of the lining of the brain. [southernnevadahealthdistrict.org]

  This response is characterized by low-grade fever, myalgias, headache and malaise that begin within a few hours after initiation of therapy and last for 12–24 h. [cmaj.ca]

  Cutaneous lesions are preceded by a flulike syndrome (sore throat, headache, muscle aches, meningismus, and loss of appetite) and generalized, painless lymphadenopathy. Hepatosplenomegaly may be present. [dartmouth.edu]

• Personality Change

  changes and impotence due to nerve or brain damage Diagnosis If your doctor suspects that you have syphilis, he or she will look for any of the typical symptoms of the disease, especially for a chancre in the genital area. [drugs.com]

  Impairment of memory and speech, personality changes, irritability, and psychotic symptoms develop and may advance to progressive dementia. [emedicine.medscape.com]

  […] and cognitive changes, visual changes, hearing loss, neuropathy, and loss of bowel and bladder functions. [aafp.org]

• Tremor

  Tumors may develop on skin, bone, testes, and other tissues; cardiovascular symptoms such as aortic aneurysm and aortic valve insufficiency may develop; degenerative central nervous system disease can produce dementia, tremors, loss of muscle coordination [healthcommunities.com]

  Complications of tertiary syphilis include: brain damage: Depending on which part is damaged, symptoms could range from motor effects (such as tremors) to mood disorders (such as having delusions of grandeur). [medbroadcast.com]

  Tremors of the mouth, tongue, outstretched hands, and whole body may occur; other signs include pupillary abnormalities, dysarthria, hyperreflexia, and, in some patients, extensor plantar responses. Handwriting is usually shaky and illegible. [msdmanuals.com]

The initial diagnosis of syphilis in the secondary stage can be made based on properly obtained patient history and thorough physical examination. Recent sexual behavior that may have posed a risk for contracting an STD, together with typical features such as disseminated rash including the palms and soles, condylomata lata, and the recent development of chancres (the hallmark of primary syphilis) can provide key elements in establishing the diagnosis. A confirmation of T. pallidum as the causative agent can be done using various tests [11]:

• Microscopical evaluation - Because T. pallidum cannot be visualized by classical light microscopy, special methods must be used. Darkfield microscopy is a method which includes an immediate examination of material scraped from skin lesions, which can detect viable spirochetes. However, because T. pallidum cannot survive laboratory transport, the direct fluorescent antibody (DFA) test is more commonly used, which comprises introduction of fluorescent anti-treponemal antibodies into the sampled material. Antibodies bind to spirochetes that are both motile and nonmotile, but more importantly, oral and rectal swabs can be examined by this method since darkfield microscopy may identify commensal spirochetes from these regions and make a falsely positive diagnosis [5].
• Serology - There are various tests that can be used for confirming syphilis. The serologic evaluation includes non-treponemal tests that confirm the presence of antibodies reacting with certain cellular components that bind to T. pallidum. Treponemal tests, on the other hand, detect T. pallidum-specific antibodies. Non-treponemal tests include Venereal Disease research Laboratory (VDRL) test and the Rapid Plasma Reagin (RPR) test, which are shown to be 100% sensitive in secondary stages of syphilis [5], but certain diseases, such as systemic lupus erythematosus (SLE) or antiphospholipid syndrome may present with positive VDRL and RPR levels. Fluorescent treponemal antibody-absorption (FTA-ABS) and Treponema pallidum particle agglutination (TP-PA) are two treponemal tests which are used in making a definite diagnosis [12]. The first include binding of fluorescent antibodies to T. pallidum, while TP-PA is a test in which agglutination of particles occurs if the inspected material contains T. pallidum antigens.

All patients with suspected syphilis should be tested for HIV infection, as well as hepatitis B and C and other STDs, including Chlamydia trachomatis and Neisseria gonorrhea because their coinfection is not uncommon.

The mainstay of treating patients in secondary syphilis, but in other stages as well, is the administration of penicillin. Administration of 2.4 million units as a single dose IM is the recommended regimen [13]. Alternative regimens include administration of ceftriaxone 1g either IM or IV q24h for 10-14 days, azithromycin 2g as a single dose PO, doxycycline 100 mg PO q12h for 14 days, or tetracycline 500 mg PO q6h for 14 days, depending on history of allergies or other factors which limit the use of penicillin, but virtually all regimens except azithromycin has shown inferior results to penicillin [14].

In rare cases, a systemic reaction that occurs 6-8 hours after administration of therapy, known as Jarisch-Herxheimer reaction, may occur and is most commonly observed in patients who are treated in the secondary stage of syphilis [4]. The cause involves the release of various components of treponemes that are being killed by antibiotics and are recognized by cells of the immune system. As a result, massive activation of pro-inflammatory cells and release of cytokines lead to development to either mild or severe and life-threatening symptoms. Fever, headache, hypotension and tachycardia usually appear and resolve within 24 hours, but patients in later stages of syphilis may develop life-threatening complications.

The prognosis of patients with secondary syphilis is very good if treatment is initiated, as complete recovery and cure may occur with timely treatment. However, without treatment, patients may progress into a latent stage and eventually develop tertiary syphilis, with cardiovascular and neurologic complications that can pose a significant risk to the patient. In very rare cases, severe variants of secondary syphilis (known as Lues maligna) may develop [4].

Treponema pallidum is a bacterial pathogen belonging to the group of spirochetes because of their coiled and helical shape. It is very thin (0.1-0.5 µm x 5-20 µm), which makes it undetectable under light microscopy. This bacteria thrives under anaerobic or microaerophilic (very low O2 concentrations) conditions, as it is extremely sensitive to oxygen. T. pallidum readily crosses the blood-brain barrier and the placental barrier, because of its potent virulence. It is able to move through tissues by using flagellar ligaments located in the periplasmic space, which extend virtually throughout the entire spirochete [4]. Its unique characteristics include the ability to maximally reduce expression of lipoproteins and other molecules on its outer membrane, which enables it to evade immune defenses and recognition by dendritic cells and macrophages.

Syphilis is diagnosed in all parts of the world with variable prevalence and incidence rates. Overall, it is estimated that 10.6 million new cases occurred annually in the year 2008, while more than 36.4 million individuals had active syphilis [2]. Incidence rates were highest in Africa, where it is established that syphilis occurred in approximately 8-9 per 1000 individuals, while the European regions reported incidence rates of less than 1 per 1000 [2]. In the United states, Syphilis is established to be the third most common STD, after Chlamydia trachomatis and Neisseria gonorrhea [5]. The main mode of transmission includes any form of sexual contact, but vertical transmission can also occur. More than 1.3 million pregnant women were estimated to have active syphilis worldwide [6], which presents a significant risk for fetal invasion of T. pallidum. A significant predilection toward male gender is established, with a 2-4:1 ratio, perhaps because the highest incidence rates of this STD is noted among men who are having sex with men (MSM population) [7].

The pathogenesis of syphilis invariably starts with the transmission of T. pallidum via direct contact from the infected host, primarily during sexual intercourse and its inoculation to the skin or mucosa. Once the bacteria reaches the new host, it is able to penetrate through the initial layers of the skin through breaks or abrasions, but it may penetrate through intact skin as well. As it reaches the subepithelial layers, it begins to rapidly multiply and disseminate through the blood vessels and the lymphatic system [4], which is the hallmark of secondary stage of syphilis, in which generalized dissemination leads to the development of a generalized rash. In order to achieve the process of multiplication, the bacteria uses several flagella located in its periplasmic space for movement and its tip serves for attachment to host structures. Several substances have been discovered to be key pieces in this process, including several hemolysins, fibronectin, and laminin, which are used for adherence and cleavage of various host components. Normally, the immune system should recognize foreign pathogens through recognition of pathogen-associated molecular patterns (PAMPs), but because of practically absent expression of components on the outer membrane of the bacteria, cells, and receptors of the immune system are unable to detect them. As a result, it is free to replicate and disseminate into all tissues and organs, including the central nervous system and at some point, for unknown reasons, dendritic cells are able to recognize the antigen and induce a proper immune response, including stimulation of Th1 CD4+ T-Helper cells and interferon gamma (IFN-γ) [8]. Why the infection then reaches latent stages and how it is able to survive in hosts and cause tertiary infections with life-threatening complications in some cases remains unknown.

Significant steps in terms of prevention can be made. Firstly, protection during sexual intercourse is shown to significantly reduce the possibility of transmission of syphilis, but other STDs as well [15]. Because syphilis can be transmitted by oral sex as well, reducing sexual contact that may be of risk is also an effective treatment strategy.

Syphilis is among the most common sexually transmitted diseases (STDs) diagnosed worldwide. It is caused by Treponema pallidum, which belongs to the group of spirochete bacteria [1]. Epidemiological data suggest that more than 30 million adults have this infection worldwide and more than 10 million new cases occur annually [2]. Humans are the only natural hosts and sexual contact is the primary mode of transmission of T. pallidum, while vertical transmission from mother to child is also possible. T. pallidum reaches the host through either intact or damaged skin and mucosa and is able to evade immune defenses through several mechanisms. The most important one, however, is the ability of bacteria to express very few molecules on their outer membrane, which limits the capacity of the innate immune system to recognize this pathogen and its antigens. As a result, the bacteria is able to roam freely in the extracellular space, make direct contact with host tissues and disseminate throughout the human organism. The clinical presentation of syphilis can be challenging due to the presence of many symptoms at various stages of the disease, but in general, this infection is classified into four stages. Primary syphilis includes development of a skin lesion (chancre) over the course of 10-14 days at the site where bacteria penetrated the tissues; Secondary syphilis reflects the dissemination of bacteria throughout the human body and is characterized by a maculopapular rash that initially develops on the trunk and extends to the extremities, including the palms and soles. The rash develops approximately 2-6 months after infection by T. pallidum and in addition to its maculopapular forms, several other skin lesions may be encountered. The development of pustules may be seen as the maculopapular rash further progress. In intertriginous areas, the maculopapular rash can progress into gray or white papillary formations known as condylomata lata [3]. Skin lesions may regress and then appear again within a few weeks, which is not uncommon. In addition to skin manifestations, various other symptoms may be present during this stage. Constitutional symptoms, such as nausea, vomiting, abdominal pain, weight loss, fever, myalgia, and arthralgia may be present, while cervical, axillary or inguinal lymphadenopathy may be encountered as well. The secondary stage is known to be the time when the patient is most infectious. In some patients, secondary syphilis can progress into a latent stage (third stage), and in rare cases, tertiary syphilis (fourth stage) may develop, which may cause severe, life-threatening cardiovascular and neurological manifestations. The diagnosis of patients with secondary syphilis can be made during the physical examination, aided by a thorough patient history, including recent sexual contact and previous exposure to carriers of syphilis. A definite diagnosis can be made by dark-field microscopy and through various serological tests. Human immunodeficiency virus (HIV) infection, but other STDs should be tested for as well in all individuals presenting with syphilis, as coinfection of these pathogens is frequent. Treatment of patients during the secondary stage of syphilis includes administration of benzathine penicillin G as a single dose of 2.4 million units intramuscularly, while alternative regimens exist for penicillin-allergic patients.

Syphilis is one of the most common sexually transmitted diseases worldwide and it is caused by a bacteria, Treponema pallidum. Global estimates suggest that more than 30 million people suffer from this infection and that every year, 10 million people contract this infection. It is almost exclusively transmitted by sexual intercourse, including oral, genital and anal, but transmission of syphilis from mother to child during pregnancy is also possible because the bacteria can breach the placental barrier and infect the fetus. However, syphilis is much more common among males, with most frequent rates observed among men who are having sex with men (MSM population). The course of this infection is divided into four stages: primary, secondary, latent stage and tertiary. The secondary stage of syphilis represents dissemination of bacteria throughout the body after their initial entry through the skin and subsequent spreading through blood vessels and the lymphatic system. It is the time period in which the infected individual is most prone to spreading the infection. The hallmark of secondary syphilis is the development of a rash over the entire body, which occurs between 2-6 months after contracting the spirochete. The rash firstly develops on the trunk and then spreads to the extremities. One of the main distinguishing features of this rash is that it spreads to the palms and soles as well. This rash is reddish-to-brown in color and consists of red-to-brown spots several millimeters in diameter. In intertriginous areas, such as the armpit, the area under the breasts, or the gluteal region, grayish-to-white elevations of the skin, known as condylomata lata, may develop. Flu-like symptoms, such as malaise, muscle and joint pain, fever and weight loss may appear a few days before the rash develops. Enlarged lymph nodes in the neck, armpits, and groins are frequently observed. In addition to the skin, secondary syphilis may cause symptoms related to hearing, vision, but also bone pain and gastrointestinal symptoms such as vomiting and diarrhea may develop. The diagnosis of syphilis in the secondary stage can be made through physical examination and observation of the rash that involves the palms and soles, but a definite diagnosis can be made by obtaining material from the rash for a specific microscopic evaluation called dark-field microscopy. This method implies investigation of bacteria through binding of fluorescent antibodies and their visualization in a dark field, as these bacteria cannot be seen in regular light microscopy. Other methods include detection of antibodies against Treponema pallidum in blood, as well as other tests that confirm their presence. Treatment includes administration of penicillin as a single dose intramuscularly, while patients who are allergic to penicillin may receive azithromycin, doxycycline or tetracycline. In very rare cases, a reaction to therapy, known as Jarisch-Herxheimer reaction, may develop and includes symptoms such as fever, flushing, headaches and blood pressure disturbances, which occurs as a result of interaction between the degrading bacteria and the host immune system. Significant steps in prevention can be made, through the use of protection during intercourse, but more importantly, avoiding sexual contact that may be of risk, since secondary syphilis may eventually cause life-threatening complications if it reaches the tertiary stage of the disease.

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