Syphilis (Clinical)

Overview

Epidemiology^[3,11,12]

• Worldwide annual new cases: approximately 6.3 million
• Worldwide case rate: 17‒18 per 100,000 
• Geographic distribution:
  • Highest prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in the WHO Western Pacific region: 93 cases per 100,000
  • Second highest prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in WHO African region: 47 cases per 100,000
  • WHO Americas region: 34 cases per 100,000 population
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in the United States is rising.
• Men > women, particularly in men who have sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria with men (MSM)
• Most common age group: 20–29 years old
• Increased prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in minorities
• Note: Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis increases the rate of HIV HIV Anti-HIV Drugs acquisition by 2‒5 times.

Etiology

• Causative organism:^[6,11]
  • Treponema pallidum Treponema pallidum The causative agent of venereal and non-venereal syphilis as well as yaws. Treponema subsp. pallidum (T. pallidum)
  • Gram-negative spirochete Spirochete Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema (spiral-shaped)
• Transmission:^[6,11,15] 
  • Human to human: T. pallidum has very limited ability to survive outside the body.
  • Sexual contact:
    • Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology may enter through genital, anorectal, or oral sites.
    • Transmission rate: Approximately ⅓ of sexual contacts develop the disease.
  • Direct contact with infected tissues:
    • Via direct contact during primary or secondary syphilis Secondary Syphilis Syphilis with a syphilitic sore, mucous patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes, condyloma Condyloma Sexually transmitted form of anogenital warty growth caused by the human papillomaviruses. Male Genitourinary Examination latum, or rash Rash Rocky Mountain Spotted Fever 
    • Sharing needles with an infected person
  • Vertical ( congenital Congenital Chorioretinitis syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis):
    • Bacterial entry into the fetus through the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity
    • Transmission rate: 60%‒80% from an infected mother to a fetus
• Risk factors:^[7]
  • Acquired syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis:
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria partner with primary, secondary, or early latent syphilis Latent syphilis The stage of syphilis that occurs following the primary (chancre) and secondary stages. The patient is asymptomatic at the latent stage but remains seropositive for the spirochete. Syphilis
    • Sexually active MSM
    • People living with HIV HIV Anti-HIV Drugs
    • Unprotected sexual contact
    • Multiple sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria partners
    • Work in the sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria trade
    • History of incarceration Incarceration Inguinal Canal: Anatomy and Hernias
    • Men < 29 years of age
  • Congenital Congenital Chorioretinitis syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis:
    • Late or no prenatal care Prenatal care Prenatal care is a systematic and periodic assessment of pregnant women during gestation to assure the best health outcome for the mother and her fetus. Prenatal care prevents and identifies maternal and fetal problems that adversely affect the pregnancy outcome. Prenatal Care
    • Maternal drug use
    • Inadequate treatment of syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Pathophysiology^[11‒13]

• Virulence factors Virulence factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: toxins, biological and surface adhesion molecules that affect the ability of the microorganism to invade and colonize a host. Haemophilus:
  • Hyaluronidase Hyaluronidase Bacteroides:
    • Allows tissue invasion
    • Facilitates dissemination
  • Corkscrew motility Corkscrew motility Treponema:
    • Able to move in thick substances (e.g., connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology)
    • Assists with dissemination
  • Fibronectin Fibronectin Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Connective Tissue: Histology:
    • Protective coating
    • Comes from the host
    • Prevents phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation and immune recognition Immune Recognition Yaws, Bejel, and Pinta
• Pathogenesis:
  • Primary syphilis Primary Syphilis Syphilis:
    • T. pallidum adheres to skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions or mucosal membranes → hyaluronidase Hyaluronidase Bacteroides production → tissue invasion
    • The organism coats itself in the host’s fibronectin Fibronectin Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Connective Tissue: Histology → prevents recognition and phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation by the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs → development of the chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis (initial ulcerative lesion)
    • Eventual local immune control → resolution of chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis
    • During the primary period, some spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema move into local lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy.
  • Later stages:
    • Spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema multiply and disseminate through the bloodstream → invade other organs and tissues
    • Host immune-inflammatory response → systemic clinical manifestations

Clinical Presentation

Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis is a multistage disease. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can present at any stage, and infected individuals may not exhibit symptoms for years.

Primary syphilis Primary Syphilis Syphilis^{[1,3,5,11‒13,15]}

• Initial: localized infection
• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is approximately 10–90 days (average, 3 weeks).
• Symptoms may go unnoticed.
• Characterized by a chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis (primary lesion), which occurs at the site of inoculation:
  • Painless
  • Begins as a firm, red papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes
  • Becomes a firm ulcer (typically 1‒2 cm in diameter) with raised, indurated borders
  • Common locations:
    • Genitalia
    • Anus
    • Posterior pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy
    • Lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy
  • Heals spontaneously in 3–6 weeks (regardless of treatment)
  • Note: Because these lesions are painless, and often occur in areas that are hard to see, the patient may not notice them.
• Regional lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy:
  • Palpable, rubbery lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy
  • Usually inguinal
  • Bilateral
  • Nontender

Secondary syphilis Secondary Syphilis Syphilis^{[1,3,5,11‒13,15]}

• Systemic disease that develops 2–12 weeks after the primary infection Primary infection Herpes Simplex Virus 1 and 2 
• Lasts 4–8 weeks
• Constitutional symptoms Constitutional Symptoms Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis:
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Malaise Malaise Tick-borne Encephalitis Virus
  • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
  • Headaches
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
• Generalized lymphadenopathy Generalized Lymphadenopathy Lymphadenopathy:
  • Firm
  • Tender (may be very mild)
  • Rubbery
  • Affected nodes usually are in the axillary, cervical, inguinal, and femoral regions.
• Mucocutaneous features (all are highly contagious):
  • Generalized rash Rash Rocky Mountain Spotted Fever
    • Nonpruritic
    • Macular, papular, or nodular
    • Scaly or smooth
    • Red, reddish-brown, or copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements color
    • Involves the trunk, extremities, palms, and soles
  • Mucosal patches Patches Vitiligo:
    • White erosions Erosions Corneal Abrasions, Erosion, and Ulcers 
    • May be seen in the mouth (buccal or lingual mucosa) or genital regions
  • Condylomata lata Condylomata Lata Syphilis:
    • Grayish-white color
    • Wart-like lesions
    • Mostly seen around the anus and vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor: Anatomy (near the location of the primary chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis, in warm, moist areas)
  • Lues maligna Lues Maligna Syphilis:
    • More severe, ulcerating skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions
    • Seen in immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (e.g., HIV HIV Anti-HIV Drugs)
  • Alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia (hair loss): can be in a diffuse or a “moth-eaten” pattern
• Systemic manifestations (possible):
  • GI involvement:
    • Hepatitis
    • GI infiltration and/or ulcerations
    • Proctitis Proctitis Inflammation of the mucous membrane of the rectum, the distal end of the large intestine. Chronic Granulomatous Disease
  • Musculoskeletal involvement:
    • Periostitis Periostitis Inflammation of the periosteum. The condition is generally chronic, and is marked by tenderness and swelling of the bone and an aching pain. Acute periostitis is due to infection, is characterized by diffuse suppuration, severe pain, and constitutional symptoms, and usually results in necrosis. Reactive Arthritis
    • Synovitis Synovitis Inflammation of the synovial membrane. Rheumatoid Arthritis
    • Osteitis
  • Renal involvement:
    • Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome
    • Acute nephritis
    • Renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
  • Ocular involvement (ocular syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis):
    • Keratitis Keratitis Inflammation of the cornea. Herpes Simplex Virus 1 and 2
    • Anterior uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
    • Posterior uveitis Posterior Uveitis Diseases of the Uvea
    • Optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies
  • Ear involvement (otic or auricular syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis):
    • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies
    • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo

Latent syphilis Latent syphilis The stage of syphilis that occurs following the primary (chancre) and secondary stages. The patient is asymptomatic at the latent stage but remains seropositive for the spirochete. Syphilis^{[1,3,5,11‒13,15]}

• Period between secondary and tertiary syphilis Tertiary Syphilis Syphilis during which the disease lays dormant 
• Positive serologic test with no visible signs or symptoms
• Classified based on the duration since initial infection:
  • Early: < 1‒2 years after initial infection
  • Late: > 1‒2 years after initial infection
• May last months to years (often decades)
• The disease can resolve, relapse Relapse Relapsing Fever with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions/mucosal lesions (i.e., recurrent secondary disease), or progress to tertiary syphilis Tertiary Syphilis Syphilis.

Tertiary syphilis Tertiary Syphilis Syphilis^{[1,3,5,10‒15]}

• Seen in 33% of untreated cases
• Occurs 1–30 years after the initial infection
• Neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis:
  • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis (occurs most commonly within the 1st year after infection):
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Neck stiffness Neck Stiffness Meningitis
    • Photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache
    • Focal neurologic deficits Neurologic Deficits High-Risk Headaches
    • Cranial nerve deficits
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Meningovascular disease (average timing is 2‒7 years after infection, though it may occur at any time):
    • Endarteritis → stroke
    • Meningomyelitis → spastic weakness, paresthesia, muscular atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
  • Paretic neurosyphilis Paretic Neurosyphilis Syphilis (typically, 10‒20 years after infection):
    • Chronic progressive meningoencephalitis Meningoencephalitis Encephalitis → cerebral atrophy Cerebral Atrophy Subdural Hemorrhage
    • Mood disturbances
    • Psychiatric disease (e.g., depression, mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder, psychosis)
    • Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment impairment
    • Tremors
    • Dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease
    • Seizure
    • Pupillary abnormalities can occur but are rare.
  • Tabes dorsalis Tabes dorsalis Parenchymatous neurosyphilis marked by slowly progressive degeneration of the posterior columns, posterior roots, and ganglia of the spinal cord. The condition tends to present 15 to 20 years after the initial infection and is characterized by lightning-like pains in the lower extremities, urinary incontinence; ataxia; severely impaired position and vibratory sense, abnormal gait, optic atrophy; Argyll-Robertson pupils, hypotonia, hyperreflexia, and trophic joint degeneration. Syphilis (locomotor ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia; typically, 15‒25 years after infection):
    • Demyelination Demyelination Multiple Sclerosis of the dorsal columns Dorsal Columns Posterior Cord Syndrome and the dorsal roots
    • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
    • Stabbing (“lightning-like”) pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the back and legs
    • Loss of vibratory sense and proprioception Proprioception Sensory functions that transduce stimuli received by proprioceptive receptors in joints, tendons, muscles, and the inner ear into neural impulses to be transmitted to the central nervous system. Proprioception provides sense of stationary positions and movements of one’s body parts, and is important in maintaining kinesthesia and postural balance. Neurological Examination
    • Loss of reflexes
    • Paresthesia
    • Charcot joints
    • Urine retention and incontinence
    • Argyll Robertson pupils (pupils accommodate but do not react to light)
• Cardiovascular syphilis Cardiovascular syphilis Cardiovascular manifestations of syphilis, an infection of treponema pallidum. In the late stage of syphilis, sometimes 20-30 years after the initial infection, damages are often seen in the blood vessels including the aorta and the aortic valve. Clinical signs include syphilitic aortitis, aortic insufficiency, or aortic aneurysm. Syphilis (typically 15‒30 years after infection):
  • A consequence of vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus in the vasa vasorum Vasa vasorum Nutrient blood vessels which supply the walls of large arteries or veins. Arteries: Histology
  • Findings:
    • Aortitis Aortitis Inflammation of the wall of the aorta. Ankylosing Spondylitis
    • Aortic aneurysm Aortic aneurysm An abnormal balloon- or sac-like dilatation in the wall of aorta. Thoracic Aortic Aneurysms and aortic root dilation Aortic root dilation Aortic Regurgitation → aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • Coronary artery Coronary Artery Truncus Arteriosus narrowing
• Benign Benign Fibroadenoma tertiary gummatous syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis (may occur 1‒40+ years after infection; average of 15 years):
  • Gummas:
    • Soft, solitary, granulomatous lesions with central necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
    • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables in size
    • Destructive (leaves scars)
  • Occurs on skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, bones, or organs
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types involvement may cause deep, boring pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (worse at night).

Diagnosis

Screening Screening Preoperative Care^[7]

Screening Screening Preoperative Care asymptomatic individuals every 3‒12 months is recommended in individuals at high risk for disease. These individuals include:

• Individuals with a sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria partner with early syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis
• Sexually active MSM
• Individuals with HIV HIV Anti-HIV Drugs
• Individuals engaging in high-risk sexual behaviors:
  • Multiple partners
  • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria without condoms Condoms A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. Nonhormonal Contraception
  • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria with individuals with other sexually transmitted infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease ( STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs))
  • Commercial sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria work
• History of incarceration Incarceration Inguinal Canal: Anatomy and Hernias

Pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:

• All should be screened at the initial patient encounter.
• Individuals at high risk should have repeat screening Screening Preoperative Care at 28‒32 weeks of gestation and again at delivery.

General approach^[2‒5]

It is difficult to diagnose syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis. However, specific labs and the correlation Correlation Determination of whether or not two variables are correlated. This means to study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable. Causality, Validity, and Reliability of history and examination results can lead to a diagnosis.

• Types of testing:
  • Treponemal tests (TTs): detect antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions specific for T. pallidum
  • Nontreponemal tests (NTTs): detect antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against anticardiolipin, lecithin Lecithin A complex mixture of phospholipids; glycolipids; and triglycerides; with substantial amounts of phosphatidylcholines; phosphatidylethanolamines; and phosphatidylinositols, which are sometimes loosely termed as 1, 2-diacyl-3-phosphocholines. Lecithin is a component of the cell membrane and commercially extracted from soybeans and egg yolk. The emulsifying and surfactant properties are useful in food additives and for forming organogels (gels). Fatty Acids and Lipids, and cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism, which are released from damaged host cells
• Confirming the diagnosis typically requires a positive result on both treponemal and nontreponemal tests.
• Traditional approach:
  • Screening Screening Preoperative Care test (1st):  NTT
  • Confirmatory test (2nd): TT
• Newer approach, sometimes called “reverse sequence algorithm”:
  • Screening Screening Preoperative Care test (1st): TT
  • Confirmatory test (2nd): NTT
  • Will result in more false positives than the traditional approach
  • Recommended because it can identify syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis in individuals who would have been missed by the traditional approach, including:
    • Those with very early disease
    • The 15%‒25% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with late or latent syphilis Latent syphilis The stage of syphilis that occurs following the primary (chancre) and secondary stages. The patient is asymptomatic at the latent stage but remains seropositive for the spirochete. Syphilis whose NTTs become nonreactive over time
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should also be tested for other STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs).

Nontreponemal testing^[5]

• Tests are sensitive but not specific.
• Detects IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis or IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions antilipid antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
• Takes 1‒4 weeks after chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis appears to become reactive → will miss early-phase primary syphilis Primary Syphilis Syphilis
• May become nonreactive ( false negative False negative An FN test result indicates a person does not have the disease when, in fact, they do. Epidemiological Values of Diagnostic Tests) in late neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis (especially tabes dorsalis Tabes dorsalis Parenchymatous neurosyphilis marked by slowly progressive degeneration of the posterior columns, posterior roots, and ganglia of the spinal cord. The condition tends to present 15 to 20 years after the initial infection and is characterized by lightning-like pains in the lower extremities, urinary incontinence; ataxia; severely impaired position and vibratory sense, abnormal gait, optic atrophy; Argyll-Robertson pupils, hypotonia, hyperreflexia, and trophic joint degeneration. Syphilis)
• Options:
  • Rapid plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products reagin ( RPR RPR Treponema) test: 1st choice
  • VDRL VDRL Treponema:
    • Best initial test for CSF analysis CSF analysis Meningitis
    • Test of choice for neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis
  • Toluidine red unheated serum test ( TRUST Trust Confidence in or reliance on a person or thing. Conflict of Interest): used less frequently^[16,17]
• Tests may be:
  • Qualitative (reactive or nonreactive) 
  • Quantitative:
    • Tests provide titer levels.
    •  Results are used to follow titers → monitor treatment response
• False positive False positive An FP test result indicates that a person has the disease when they do not. Epidemiological Values of Diagnostic Tests results (because these conditions can produce the same antilipid antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions) can occur with:
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Rheumatic fever Rheumatic fever Acute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis. Acute rheumatic fever usually occurs 2-4 weeks after an untreated infection and affects the heart, skin, joints, and nervous system. Rheumatic Fever
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
  • Drugs

Treponemal testing^[5,17]

• Tests that detect antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions to Treponema Treponema Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. Treponema antigens
• Even after treatment, treponemal antibody titers are positive for life.
• Reported as “reactive” or “nonreactive”
• Does not distinguish between an active and a prior, treated infection
• Typically, becomes positive 5‒15 days after appearance of the chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis
• Options:
  • Fluorescent treponemal antibody absorption test Fluorescent treponemal antibody absorption test Serologic assay that detects antibodies to treponema pallidum, the etiologic agent of syphilis. After diluting the patient’s serum to remove non-specific antibodies, the serum is mixed on a glass slide with nichol’s strain of treponema pallidum. An antigen-antibody reaction occurs if the test is positive and the bound antibodies are detected with fluoresceinated antihuman gamma-globulin antibody. Syphilis (FTA-ABS):
    • Can be done on CSF to evaluate for neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis
    • Less specific than the CSF-VDRL test
    • Expensive, time-consuming, and difficult to read
  • Manual, cheaper options:
    • Microhemagglutination assay for T. pallidum ( MHA-TP MHA-TP Treponema); in Europe: T. pallidum haemagglutination test (TPHA)
    • T. pallidum particle agglutination test ( TPPA TPPA Syphilis)
  • Frequently automated, more expensive options (recommended 1st-line screening Screening Preoperative Care tests in UK):
    • T. pallidum enzyme immunoassay Enzyme immunoassay HIV Infection and AIDS ( TP-EIA TP-EIA Syphilis)
    • Chemiluminescence immunoassay Chemiluminescence Immunoassay Syphilis ( CIA CIA Syphilis)

Direct methods^[5]

Definitive tests using obtained specimens (such as exudates from mucosal lesions). However, use is limited since the tests are not routinely available.

• Darkfield microscopy:
  • A microscopy technique illuminating specimens against a dark background.
  • Motile spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema are seen.
  • Must be performed immediately after specimen collection
  • Sensitivity is < 50% (high false negative False negative An FN test result indicates a person does not have the disease when, in fact, they do. Epidemiological Values of Diagnostic Tests rate).
• Direct fluorescent antibody Direct Fluorescent Antibody A form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen. Congenital TORCH Infections (DFA) testing
• PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) to detect T.pallidum DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure.
  • Recommended over darkfield microscopy if using direct methods
  • Low sensitivity in blood

CSF assessment^[2,5,6]

• Tests are better at excluding neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis rather than diagnosing it.
• Should include:
  • TT (TPHA, MHA-TP MHA-TP Treponema, or TPPA TPPA Syphilis)
  • NTT (preferably VDRL VDRL Treponema, owing to its better sensitivity than RPR RPR Treponema in CSF)
  • Total protein Total protein Liver Function Tests 
  • Number of mononuclear cells or WBCs
• Indications:
  • Neurologic, ocular, and/or otic/auricular findings
  • Tertiary syphilis Tertiary Syphilis Syphilis
  • Treatment failure in any stage 
  • Consider in HIV HIV Anti-HIV Drugs patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (regardless of syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis stage), especially in those who:
    • Have RPR RPR Treponema or VDRL VDRL Treponema titers ≥ 1:32
    • Have a CD4+ count ≤ 350/ mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma³
    • Have detectable plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products HIV RNA HIV RNA HIV Infection and AIDS
    • Are not on antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs
  • Consider in follow-up of late syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship treated with alternative regimens (e.g., doxycycline)

Management

General management for syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis^[2–6,9]

• Treatment of choice is penicillin Penicillin Rheumatic Fever:
  • Bactericidal Bactericidal Penicillins levels should be maintained for 7‒10 days (longer with late syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis).
  • Long-acting penicillin Penicillin Rheumatic Fever G benzathine is the treatment of choice.
  • Typical dose: 2.4 million units (provides treponemicidal levels for up to 21 days)
• Consider other STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs):
  • Screen for HIV HIV Anti-HIV Drugs at the time of diagnosis.
    • Offer HIV HIV Anti-HIV Drugs preexposure prophylaxis Prophylaxis Cephalosporins to those who test negative.
    • In geographic areas with high prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of HIV HIV Anti-HIV Drugs, offer preexposure prophylaxis Prophylaxis Cephalosporins and retest for HIV HIV Anti-HIV Drugs in 3 months (if initial result is negative).
  • Screening Screening Preoperative Care for other STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs)
  • Offer vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination for hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus, if appropriate.
• Evidence of neurologic disease (e.g., meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, stroke):
  • Full neurologic exam
  • CSF assessment
• Evidence of ocular disease (e.g., uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea, optic neuritis Optic neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). Cranial Nerve Palsies):
  • Cranial nerve exam
  • Ocular slit-lamp exam
  • Ophthalmologic exam
  • CSF assessment is recommended by some expert guidelines.
• Testing and treatment for all sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria partners:^[2]
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship diagnosed with early syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis (primary, secondary, and early latent):
    • Presumptively treat all partners from the past 90 days.
    • Secondary syphilis Secondary Syphilis Syphilis: Test all partners from within the past 6 months; treat based on results.
    • Early latent syphilis Latent syphilis The stage of syphilis that occurs following the primary (chancre) and secondary stages. The patient is asymptomatic at the latent stage but remains seropositive for the spirochete. Syphilis: Test all partners from within the past 12 months; treat based on results.
  • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship diagnosed with late syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis (tertiary or late latent):
    • Test all partners from the past 1 year; treat based on results.
    • Test all long-term sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria partners; treat based on results.
• Abstain from sexual contact until:
  • All lesions are healed (if present).
  • 2 weeks after completion of treatment
• Follow-up:
  • Repeat clinical evaluation and serologic testing at 6 and 12 months:
    • Individuals with HIV HIV Anti-HIV Drugs are monitored more frequently.
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with late syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis should also be tested at 24 months.
  • Consider CSF assessment.
  • Compare titers to initial baseline levels to assess treatment response.
  • Evidence of treatment failure:
    • < 4-fold decrease in NTT titers lasting 6‒12 months after treatment 
    • Persistent low antibody titers ≤ 4 at 1–2 years after treatment 

Early syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis management

For primary, secondary, or early latent syphilis Latent syphilis The stage of syphilis that occurs following the primary (chancre) and secondary stages. The patient is asymptomatic at the latent stage but remains seropositive for the spirochete. Syphilis, the following antibiotics can be used:

• Preferred: IM penicillin Penicillin Rheumatic Fever G (single dose):^[2‒6,9]
  • Penicillin Penicillin Rheumatic Fever G benzathine 2.4 million units IM once
  • If penicillin Penicillin Rheumatic Fever G benzathine is not available: procaine Procaine A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. Local Anesthetics penicillin Penicillin Rheumatic Fever 600,000 units IM daily for 10‒14 days
  • Includes pregnant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and those with HIV HIV Anti-HIV Drugs
• For individuals with penicillin Penicillin Rheumatic Fever allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency, consider desensitization and/or skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions testing prior to starting an alternative agent.
• Alternative regimens:
  • Doxycycline (best-studied alternative) 100 mg by mouth twice a day for 14 days
  • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 1 g IM or IV once daily for 10‒14 days
  • Tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury 500 mg by mouth 4 times daily for 14 days
  • Amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins 3 g + probenecid Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Gout Drugs 500 mg twice daily for 14 days
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides (should be considered only as a last resort owing to resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing): 2 g by mouth once
  • Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides (a possibility per the WHO, but not recommended by US, UK, or European guidelines): 500 mg 4 times daily for 14 days
• Notes on treating syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides and erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides do not cross the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity well, so they are poor choices in pregnant women.
  • Doxycycline is teratogenic and is contraindicated.

Late syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis management^[2,5,6,9]

For late-latent syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis, tertiary syphilis Tertiary Syphilis Syphilis, or syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis of unknown duration, the following regimen is used:

• Preferred: IM penicillin Penicillin Rheumatic Fever G benzathine (3 weeks)
  • Penicillin Penicillin Rheumatic Fever G benzathine 2.4 million units IM once per week for 3 weeks (i.e., on days 1, 8, and 15)
  • If penicillin Penicillin Rheumatic Fever G benzathine is not available: procaine Procaine A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. Local Anesthetics penicillin Penicillin Rheumatic Fever 600,000–1.2 million units IM once daily for 17‒21 days 
• Alternative regimen:
  • Doxycycline 100 mg by mouth twice daily for 21‒30 days
  • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 2 g IV or IM daily for 10‒14 days

Neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis^{[2,5,6,9,10,14]}

• Treat for neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis only if the patient has clinical neurologic findings.
  • Invasion of T. pallidum into the CSF is common in primary and secondary syphilis Secondary Syphilis Syphilis, but the clinical significance of this is unclear.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with ocular and/or otologic findings should be treated for neurosyphilis Neurosyphilis Infections of the central nervous system caused by treponema pallidum which present with a variety of clinical syndromes. The initial phase of infection usually causes a mild or asymptomatic meningeal reaction. The meningovascular form may present acutely as brain infarction. The infection may also remain subclinical for several years. Late syndromes include general paresis; tabes dorsalis; meningeal syphilis; syphilitic optic atrophy; and spinal syphilis. General paresis is characterized by progressive dementia; dysarthria; tremor; myoclonus; seizures; and argyll-robertson pupils. Syphilis regardless of CSF findings.
• Preferred: IV penicillin Penicillin Rheumatic Fever G benzathine:
  • Aqueous crystalline penicillin Penicillin Rheumatic Fever G 18 million‒24 million units per day for 10‒14 days, administered as:
    • 3‒4 million units IV every 4 hours OR
    • Continuous infusion
  • Alternative regimen:
    • Procaine Procaine A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. Local Anesthetics penicillin Penicillin Rheumatic Fever G 2.4 million units IM once daily for 10‒14 days PLUS
    • Probenecid Probenecid The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. Gout Drugs 500 mg by mouth 4 times daily for 10‒14 days
• Alternative regimen: ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 2 g IV once daily for 10‒14 days
• Follow-up:
  • Serial neurologic examinations every 6 months
  • Consider CSF assessment (especially if treated with an alternative regimen).

Jarisch–Herxheimer reaction Jarisch–Herxheimer Reaction Syphilis^[9]

• Caused by an immune response to the antigens released by dying spirochetes Spirochetes An order of slender, flexuous, helically coiled bacteria, with one or more complete turns in the helix. Treponema
• Symptoms:
  • Rigors Rigors Fever
  • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
  • Rise in temperature
  • Increased respiratory rate Respiratory rate The number of times an organism breathes with the lungs (respiration) per unit time, usually per minute. Pulmonary Examination
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
• All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be monitored after therapy is initiated:
  • Occurs within 24 hours
  • Resolves within 12–24 hours
  • Seen in 10%–35% of cases
• Supportive care may be given:
  • Antipyretics (e.g., acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen, aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs))
  • IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids

Differential Diagnosis

• Chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid: STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) caused by Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop painful, necrotizing genital ulcers and inguinal lymphadenopathy Inguinal Lymphadenopathy Lymphadenopathy. Diagnosis is usually clinical, but PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) and cultures can help to confirm. Management is with macrolide antibiotics.
• Donovanosis Donovanosis Donovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region. Donovanosis: STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) caused by Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella granulomatis. Donovanosis Donovanosis Donovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region. Donovanosis is also known as granuloma inguinale Granuloma inguinale Donovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region. Donovanosis. The progressive, nodular genital lesions can form into painless ulcerations and cause tissue damage. Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy is uncommon. Diagnosis is confirmed with microscopic findings of Donovan bodies Donovan Bodies Donovanosis from the lesion. Management involves antibiotics, such as macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides, tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines, and trimethoprim-sulfamethoxazole.
• Lymphogranuloma venereum Lymphogranuloma venereum Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis. Chlamydial Infections: STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) caused by 3 strains of Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have a small, transient, painless genital ulcer followed by lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy ( bubo Bubo Yersinia pestis/Plague). Diagnosis is clinical, though PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) testing can help with confirmation. Management involves tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines or erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides.
• Genital herpes Genital Herpes Genital herpes infections are common sexually transmitted infections caused by herpes simplex virus (HSV) type 1 or 2. Primary infection often presents with systemic, prodromal symptoms followed by clusters of painful, fluid-filled vesicles on an erythematous base, dysuria, and painful lymphadenopathy. Labial and Genital Herpes: a common STI STI Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs) caused by HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 type 1 Type 1 Spinal Muscular Atrophy or 2. Prodromal symptoms often precede clusters of painful, fluid-filled vesicles Vesicles Female Genitourinary Examination on an erythematous base, which eventually form ulcers that can coalesce. Lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, dysuria Dysuria Painful urination. It is often associated with infections of the lower urinary tract. Urinary tract infections (UTIs), and severe neuralgia can occur. The diagnosis is generally clinical but confirmed with PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) and serologic testing. Management includes antiviral Antiviral Antivirals for Hepatitis B therapy.
• Genital warts Warts Benign epidermal proliferations or tumors; some are viral in origin. Female Genitourinary Examination (also called condylomata acuminata Condylomata Acuminata Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)): a human papillomavirus Human papillomavirus Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV) ( HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV)) infection causing a range of mucocutaneous findings, including broad-based smooth or velvety papules or rough verrucous or fungating plaques, in the anogenital region. The diagnosis is clinical. Management may include cytodestructive therapy ( podophyllotoxin Podophyllotoxin A lignan (lignans) found in podophyllin resin from the roots of podophyllum plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. Molluscum Contagiosum), immune-mediated therapy ( imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars), or surgical therapy.

Practical application in the clinic (checklist for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship presenting with a genital ulcer):^[4]

• Take a careful medical and sexual history.
• Examination of the genital, anal, and oral areas
• Perform testing for:
  • Syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis ( PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) from lesion and serologic TT and/or NTT)
  • Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( nucleic acid amplification Nucleic acid amplification Laboratory techniques that involve the in-vitro synthesis of many copies of DNA or RNA from one original template. Septic Arthritis test (NAAT) from lesion)
  • Consider other ulcerative diseases, including lymphogranuloma venereum Lymphogranuloma venereum Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. But is more widespread in developing countries. It is distinguished from granuloma venereum, which is caused by calymmatobacterium granulomatis. Chlamydial Infections, chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid, and donovanosis Donovanosis Donovanosis (also known as granuloma inguinale) is an STD caused by Klebsiella granulomatis and is mainly seen in tropical regions. The condition is characterized by chronic, progressive, ulcerating disease mostly affecting the genital region. Donovanosis.
• Provide same-day treatment for syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis and/or HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 based on history, point-of-care testing, and clinical findings.
• Screen for other STIs STIs Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs).
• Address safe sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, abstinence during and after treatment, and partner treatment.
• Adjust management based on test results when they become available.