Spirochaetal Infections

PRIMARY SYPHILIS

The typical primary chancre usually begins as a single painless papule that rapidly becomes eroded and usually becomes indurated, with a characteristic cartilaginous consistency on palpation of the edge and base of the ulcer.

In heterosexual men, the chancre is usually located on the penis. In homosexual men, it is often found in the anal canal or rectum, in the mouth, or on the external genitalia. In women, common primary sites are the cervix and labia.

Multiple primary lesions may be more common among men with concurrent HIV infection.

Regional lymphadenopathy usually accompanies the primary syphilitic lesion, appearing within 1 week of the onset of the lesion.

The nodes are firm, non-suppurative, and painless. Inguinal lymphadenopathy is bilateral and may occur with anal as well as with external genital chancres.

The chancre generally heals within 4 to 6 weeks (range: 2 to 12 weeks), but lymphadenopathy may persist for months. Atypical primary lesions are produced by small inoculums of the organism - small papule.

Differential Diagnosis of genital ulcers: Herpes simplex, primary genital herpes, Trauma, chancroid, donovanosis.

SECONDARY SYPHILIS

Protean manifestations

Localized or diffuse symmetric mucocutaneous lesions and generalized non-tender lymphadenopathy.

The healing primary chancre is still present in 15% of cases, and the stages may overlap more frequently in persons with concurrent HIV infection than in those without this coinfection.

The skin rash consists of macular, papular, papulosquamous, and occasionally pustular syphilides; often more than one form is present simultaneously.

Initial lesions are bilaterally symmetric, pale red or pink, non-pruritic, discrete, round macules that measure 5 to 10 mm in diameter and are distributed on the trunk and proximal extremities.

After several days or weeks, red papular lesions 3 to 10 mm in diameter also appear.

These lesions, which may progress to necrotic lesions (resembling pustules) in association with increasing endarteritis and perivascular mononuclear infiltration, are distributed widely, frequently involve the palms and soles, and may occur on the face and scalp. Tiny papular follicular syphilides involving hair follicles may result in patchy alopecia, with loss of scalp hair, eyebrows, or beard in up to 5% of cases.

In warm, moist, intertriginous body areas, including the perianal area, vulva, scrotum, inner thighs, axillae, and skin under pendulous breasts, papules can enlarge and become eroded to produce broad, moist, pink or gray-white, highly infectious lesions called condylomatalata; these lesions develop in 10% of patients with secondary syphilis. Superficial mucosal erosions, called mucous patches, occur in 10 to 15% of patients and may involve the lips, oral mucosa, tongue.

Constitutional symptoms that may accompany or precede secondary syphilis include sore throat (15 to 30%), fever (5 to 8%), weight loss (2 to 20%), malaise (25%), anorexia (2 to 10%), headache (10%), and meningismus (5%).

Acute meningitis occurs in only 1 to 2% of cases, but numbers of cells and levels of protein in CSF are increased in >30% of cases. T. pallidum has been recovered from CSF during primary and secondary syphilis in 30% of cases; this finding is often but not always associated with other CSF abnormalities.

Less common complications of secondary syphilis include:

• Hepatitis - usually ASYMPTOMATIC. Pt has abnormal liver function test.
• Nephropathy - produces proteinuria associated with an acute nephrotic syndrome (or rarely with hemorrhagic glomerulonephritis.
• Gastrointestinal involvement (hypertrophic gastritis, patchy proctitis, ulcerative colitis, or a rectosigmoid mass).
• Arthritis,
• Periostitis.

Ocular findings that suggest secondary syphilis include otherwise-unexplained pupillary abnormalities, optic neuritis, and a retinitis pigmentosa syndrome the classic iritis (especially granulomatous iritis) or uveitis.

Like those of primary syphilis, the manifestations of the secondary stage resolve spontaneously, usually within 1 to 6 months.

LATENT SYPHILIS

Positive serologic tests for syphilis, together with abnormal CSF examination and the absence of clinical manifestations of syphilis, indicate a diagnosis of latent syphilis.

The diagnosis is often suspected on the basis of a history of primary or secondary lesions, a history of exposure to syphilis, or the delivery of an infant with congenital syphilis.

Early latent syphilis encompasses the first year after infection, whereas late latent syphilis (beginning >1 year after infection in the untreated patient) is associated with relative immunity to infectious relapse.

However, T. pallidum may still seed the bloodstream intermittently during the latent stage, and pregnant women with latent syphilis may infect the fetus in utero.

Moreover, syphilis has been transmitted through the transfusion of blood from patients with latent syphilis of many years’ duration.

It was previously thought that untreated late latent syphilis had three possible outcomes: (1) it could persist throughout the lifetime of the infected individual; (2) it could end in the development of late syphilis; or (3) it could end with the spontaneous cure of infection, with reversion of serologic tests to negative.

It is now apparent, however, that the more sensitive treponemal antibody tests rarely, if ever, become negative without treatment.

About 70% of untreated patients with latent syphilis never develop clinically evident late syphilis, but the occurrence of spontaneous cure is in doubt.

Involvement of the Central Nervous System

Traditionally, neurosyphilis has been considered to be a late manifestation of syphilis, but this view is inaccurate.

CNS syphilis represents a continuum encompassing early invasion (usually within the first weeks or months of infection), months to years of asymptomatic involvement, and, in some cases, development of early or late neurologic manifestations.

ASYMPTOMATIC NEUROSYPHILIS

The diagnosis of asymptomatic neurosyphilis is made in patients who lack neurologic symptoms and signs but who have CSF abnormalities including mononuclear pleocytosis, increased protein concentrations, or a reactive Venereal Disease Research Laboratory (VDRL) slide test.

This occurs in 25% of pts with untreated latent syphilis. These are the patients who are known to be at risk for neurologic complications.

In patients with untreated asymptomatic neurosyphilis, the overall cumulative probability of progression to clinical neurosyphilis is about 20% in the first 10 years but increases with time; the likelihood is highest among patients with the greatest degree of pleocytosis or protein elevation.

SYMPTOMATIC NEUROSYPHILIS

Although mixed features are common, the major clinical categories of symptomatic neurosyphilis include meningeal, meningovascular, and parenchymatous syphilis. The last category includes general paresis and tabes dorsalis.

The onset of symptoms usually comes <1 year after infection for meningeal syphilis, at 5 to 10 years for meningovascular syphilis, at 20 years for general paresis, and at 25 to 30 years for tabes dorsalis.

However, symptomatic neurosyphilis, particularly in the antibiotic era, often presents not as a classic picture but rather as mixed and subtle or incomplete syndromes including:

• Meningeal syphilis may involve either the brain or the spinal cord, and patients may present with headache, nausea, vomiting, neck stiffness, cranial nerve involvement, seizures, and changes in mental status. This condition may be concurrent with or may follow the secondary stage.
• Patients presenting with uveitis or iritis frequently have meningeal syphilis.
• Meningovascular syphilis reflects diffuse inflammation of the pia and arachnoid together with evidence of focal or widespread arterial involvement of small, medium, or large vessels. The most common presentation is a stroke syndrome involving the middle cerebral artery of a relatively young adult; however, unlike the usual thrombotic or embolic stroke syndrome of sudden onset, meningovascular syphilis often becomes manifest after a subacute encephalitic prodrome (with headaches, vertigo, insomnia, and psychological abnormalities), which is followed by a gradually progressive vascular syndrome.
• General paresis The manifestations of general paresis reflect widespread late parenchymal damage and include abnormalities corresponding to the mnemonic paresis:
  • personality
  • affect
  • reflexes (hyperactive)
  • eye (e.g., Argyll Robertson pupils)
  • sensorium (illusions, delusions, hallucinations)
  • intellect (a decrease in recent memory and in the capacity for orientation, calculations, judgment, and insight), and
  • speech.

Tabes dorsalis is also a late manifestation of syphilis that presents as symptoms and signs of demyelination of the posterior columns, dorsal roots, and dorsal root ganglia.

Symptoms include ataxic wide-based gait and footslap; paresthesia; bladder disturbances; impotence; areflexia; and loss of position, deep pain, and temperature sensations.

Trophic joint degeneration (Charcot’s joints) and perforating ulceration of the feet can result from loss of pain sensation. The small, irregular Argyll Robertson pupil, a feature of both tabes dorsalis and paresis, reacts to accommodation but not to light.

Optic atrophy also occurs frequently in association with Tabes.

Other manifestations of late syphilis

1. Cardiovascular syphilis- attributable to endarteritis obliterans of the vasa vasorum, which provide the blood supply to large vessels. This condition results in uncomplicated aortitis, aortic regurgitation, saccular aneurysm, or coronary ostial stenosis, with symptoms usually appearing 10 to 40 years after infection. Linear calcification of the ascending aorta on chest x-ray films suggests asymptomatic syphilitic aortitis.
2. Late benign syphilis (Gumma)- Gummas may be multiple or diffuse but are usually solitary lesions that range from microscopic in size to several centimeters in diameter. Histologic examination shows a granulomatous inflammation with a central area of necrosis. Gummas of the skin produce painless and indurated nodular, papulosquamous, or ulcerative lesions that are usually indolent. Can occur on the bone, Upper resp tract causing palatal or nasal septum perforation
3. Congenital syphilis

Organism can’t be detected by culture.

1. Dark field microscopy- Examination of lesion exudates. The identification of a single characteristic motile organism by a trained observer is sufficient for diagnosis.
2. The direct fluorescent antibody T. pallidum (DFATP) test- uses fluorescein-conjugated polyclonal anti-treponemal antibody for the detection of T. pallidum in fixed smears prepared from suspect lesions
3. Polymerase chain reaction
4. Serologic tests-
   1. Non-Treponemal tests- Used for initial screening. They measure IgG and IgM directed against a cardiolipin-lecithin-cholesterol antigen complex. These include
      1. Rapid Plasma Reagin (RPR) Test
      2. VDRL
   2. Treponemal tests- Used for confirmation of reactive non-treponemal results
      1. The fluorescent treponemal antibody–absorbed (FTA-ABS)
      2. microhemagglutination assay for T. pallidum (MHA-TP). The above 2 now replaced by Serodia TP-PA test
      3. T. pallidum hemagglutination test (TPHA)

The RPR and VDRL tests are equally sensitive and may be used for initial screening or for quantitation of serum antibody. The titer reflects the activity of the disease. Titers rise during the evolution of early syphilis; VDRL titers usually reach 1:32 or higher in secondary syphilis. A persistent fall by two dilutions (fourfold) or more after treatment of early syphilis provides essential evidence of an adequate response to therapy. VDRL titers do not correspond directly to RPR titers, and sequential quantitative testing (as for response to therapy) must employ a single test.

The three uses of serologic tests for syphilis:

1. Testing of large numbers of sera for screening or diagnostic purposes (e.g., the RPR or VDRL test)
2. Quantitative measurement of antibody titer to assess the clinical activity of syphilis or to monitor the response to therapy (e.g., the RPR or VDRL test)
3. Confirmation of the diagnosis of syphilis in a patient with a positive non-treponemal antibody test or with a suspected clinical diagnosis of syphilis (e.g., the FTA-ABS test or the Serodia TP-PA test)

False-Positive Serologic Tests for Syphilis

Because the antigen used in non-treponemal tests is found in other tissues, the tests may be reactive in persons without treponemal infection, although rarely do titers exceed 1:8 in such patients.

Evaluation for Neurosyphilis

Involvement of the CNS is detected by examination of CSF for pleocytosis (>5 white blood cells/mm3), increased protein concentration (>45 mg/dL), or VDRL reactivity.

CSF abnormalities can be demonstrated in up to 40% of cases of primary or secondary syphilis and in 25% of cases of latent syphilis.

The CSF VDRL test is highly specific but is insensitive and may be nonreactive even in cases of progressive symptomatic neurosyphilis.

A. Penicillin G is the drug of choice for all stages of syphilis.

T. pallidum is killed by very low concentrations of penicillin G, although a long period of exposure to penicillin is required because of the unusually slow rate of multiplication of the organism.

The efficacy of penicillin against syphilis remains undiminished after 50 years of use.

B. Other antibiotics effective in syphilis include the tetracyclines, erythromycin, and the cephalosporins.

C. Contact tracing is important

Jarisch-Herxheimer Reaction:

A dramatic though usually mild reaction consisting of fever (average temperature elevation, 1.5°C), chills, myalgias, headache, tachycardia, increased respiratory rate, increased circulating neutrophil count, and vasodilation with mild hypotension may follow the initiation of treatment for syphilis.

In patients with secondary syphilis, erythema and edema of the mucocutaneous lesions but may increase.

Patients should be warned to expect such symptoms, which can be managed with symptombased treatment.

Steroid and other anti-inflammatory therapy is not required for this mild transient reaction.

Introduction:

Yaws, also known as pian, framboesia, or bouba, is a chronic infection caused by Treponema pallidum subspecies pertenue. It is typically acquired in childhood.

Clinical Characteristics:

• The disease begins with the development of one or several primary lesions, known as the "mother yaw."
• These primary lesions are followed by the appearance of multiple disseminated skin lesions.
• Early lesions can persist for months, are infectious, and tend to recur during the early years of infection.
• Late manifestations of yaws can be destructive, involving the skin, bone, and joints.

Transmission:

The infection is transmitted through direct contact with infectious lesions. Transmission can also be facilitated by disruptions of the skin caused by insect bites or abrasions.

High-Risk Group:

Children with open lesions and without covering clothing are most likely to transmit the infection during play or group sleeping.

Clinical Progression:

• After an average incubation period of 3 to 4 weeks, the first lesion appears as a papule, typically on an extremity.
• These primary lesions enlarge, especially in warm, moist weather, and take on a "raspberry-like" appearance.
• Regional lymphadenopathy develops, and primary lesions usually heal within 6 months.
• Dissemination is believed to occur during the early weeks and months of infection.
• A generalized secondary eruption, often with various forms (macular, papular, or papillomatous), may appear concurrently or following the primary lesion.
• Secondary lesions can become secondarily infected with other bacteria.
• Painful papillomatous lesions on the soles of the feet result in a crab-like gait ("crab yaws").
• Periostitis can lead to nocturnal bone pain and polydactylitis.

Late Yaws:

Late yaws is recognized in less than 10% of untreated patients and is characterized by:

• Gummas on the skin and long bones
• Hyperkeratosis of the palms and soles
• Osteitis and periostitis
• Hydrarthrosis
• Gangosa, a condition involving the destruction of the nose, maxilla, palate, and pharynx, similar to the lesions seen in leprosy and leishmaniasis.

Treatment for Yaws:

First-Line Treatment (Preferred):

• IM Benzathine Penicillin
• Dosage: 1.2 million units (MU) administered as a single dose.

Alternative Treatment Options:

• Erythromycin
• Tetracycline
• Doxycycline

Causative Agent: Treponema carateum
Geographic Distribution: Primarily found in Central and South America
Clinical Characteristics:

• Milder compared to other treponematoses
• Limited to skin involvement

Primary Lesion:

• Description: Pruritic (itchy) red papule
  Common Locations: Typically appears on the hand or foot
  Characteristics: May develop scaling but does not ulcerate
  Associated Features: Often accompanied by regional lymphadenopathy

Later Stages:

• Description: Similar lesions can continue to appear for up to 1 year
  Features: Generalized lymphadenopathy

Resolution:

• Outcome: Lesions eventually heal
  Resulting Skin Changes: Hyperpigmented or depigmented patches

Alternative Names: Bejel, Siti, Dichuchwa, Njovera, Skerljevo
Causative Agent: Treponema pallidum subspecies endemicum
Geographic Distribution: Primarily found in Africa and the Middle East
Characteristics:

• Chronic infection acquired in childhood
• Early lesions localized to mucocutaneous and mucosal surfaces
• Transmission through direct contact, kissing, or sharing utensils; insect transmission suggested but unproved
• Primary lesion uncommon
• Resembles syphilis in late stages, with rare cardiological and neurological manifestations

Symptoms:

• Initial Lesion:
  • Typically an intraoral papule
  • Often goes unrecognized
  • Followed by mucous patches on the oral mucosa
  • Mucocutaneous lesions resembling secondary syphilis's condylomata lata
• Duration:
  • Eruption may last for months or years
  • Treponemes readily demonstrated in early lesions
• Common Features:
  • Periostitis
  • Regional lymphadenopathy
• Late Manifestations:
  • May include osseous and cutaneous gummas
  • Destructive gummas, osteitis, and gangosa more common compared to late yaws
  • Gummas of the nipples in women who have previously had endemic syphilis and breast-feed infants with oral lesions
  • Late lesions may result from repeated exposure of a sensitized host

Diagnosis and Treatment:

• Diagnosis:
  • Usually clinical in endemic areas
  • Causative organism can be identified from exudative lesions under dark-ground microscopy
  • Serological tests for syphilis are positive and do not differentiate between the conditions
• Treatment:
  • Long-acting penicillin (e.g., intramuscular benzathine penicillin, 1.2 million units) given as a single dose
  • Single-dose oral azithromycin gives good results
  • Doxycycline is used when penicillin is ineffective or contraindicated