Spirochete Infections

Slide 1 · Spirochete Infections

Syphilis: pathogenesis, morphology, clinical stages and diagnosis

An integrated clinicopathologic lecture

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Explain spirochete structure and the biologic basis of treponemal persistence.

Relate proliferative endarteritis and inflammation to organ injury in syphilis.

Distinguish acquired stages and congenital manifestations using morphology.

Interpret the complementary roles of treponemal and nontreponemal tests.

Slide 3 · Etiologic identity of syphilis

Treponema pallidum subsp. Pallidum causes chronic, multisystem sexually transmitted infection.

The organism is slender, microaerophilic and difficult to propagate in routine culture.

The clinical spectrum reflects dissemination, host inflammation and potential persistence.

Transplacental infection creates a distinct pattern of fetal and childhood disease.

Slide 4 · Spirochete architecture: Movement within an outer sheath

Slender helical body

Periplasmic flagella

Outer sheath

Schematic: Corkscrew-shaped gram-negative bacteria; Axial flagella lie between the protoplasm and outer sheath.

Slide 5 · Closely related treponemes: Distinct diseases

Organism

Associated disease

T. Pallidum subsp. Pallidum

Syphilis

T. Pallidum subsp. Pertenue

Yaws

T. Pallidum subsp. Carateum

Pinta

Slide 6 · Why routine bacterial visualization is difficult

Direct tissue visualization

Too slender for conventional Gram-stain recognition

Silver stains can highlight organisms in tissue

Immunofluorescence techniques may demonstrate bacteria

Laboratory growth

T. Pallidum is not easily maintained in standard culture

Diagnosis therefore relies heavily on serologic testing

Results need clinical and stage-specific interpretation

Slide 7 · Routes of treponemal spread

Inoculation at mucosa or skin

Local chancre with abundant treponemes

Lymphatic and hematogenous dissemination

Multisystem infection

Schematic — conceptual sequence based on the source text

Slide 8 · Disease expression follows both organism and host

Microbial behavior

Early local multiplication

Widespread dissemination

Prolonged persistence

Host-mediated injury

Plasma cell–rich inflammation

Proliferative endarteritis

Ischemia and eventual scarring

An initially limited lesion does not exclude systemic infection.

Slide 9 · The defining lesion: Proliferative endarteritis

Small vessels develop endothelial activation and intimal proliferation.

A surrounding chronic inflammatory infiltrate is characteristically rich in plasma cells.

Progressive intimal fibrosis may narrow or obliterate the vascular lumen.

This vascular reaction contributes to lesions at multiple clinical stages.

Slide 10 · From endarteritis to ischemic tissue injury

Endothelial activation

Intimal proliferation → fibrosis

Restricted tissue perfusion

Ischemia and organ injury

Schematic — conceptual sequence based on the source text

Slide 11 · An inflamed small artery develops luminal narrowing

Intimal proliferation + inflammation

Progressive narrowing of lumen

Downstream tissue ischemia

Simplified vascular cross-section — schematic, not histology or a scale drawing

Slide 12 · Why plasma cells matter histologically

Plasma cells are a recurring component of the inflammatory reaction in syphilis.

Primary chancres show plasma cells mixed with macrophages and lymphocytes.

Secondary lesions commonly retain this pattern, sometimes less intensely.

Plasma cell predominance supports consideration of syphilis but is not pathogen-specific.

Slide 13 · Cellular response at superficial infection sites

T lymphocytes

Prominent infiltrate

CD4+ Th1 cells participate

Protection remains incomplete

Macrophages

Infiltrate infected tissue

Engulf antibody-opsonized treponemes

Contribute to local microbial control

Plasma cells / antibodies

Specific antibodies develop

Complement activation

Facilitate phagocytosis

Slide 14 · Immune containment is not necessarily eradication

Local cellular and antibody response

Reduction in bacterial burden

Regression of visible lesion

Persistent systemic organisms in some patients

Schematic — conceptual sequence based on the source text

Slide 15 · Antigenic diversification of TprK

Silent donor sequences

Gene conversion at tprK

Altered TprK antigenic regions

Reduced recognition by existing antibodies

Schematic — proposed contribution to antibody escape, not proof of a single causal mechanism

Slide 16 · Persistence: Several reinforcing processes

Treponemes can disseminate despite a prominent local inflammatory infiltrate.

Host immunity reduces organism numbers but does not consistently sterilize infection.

TprK variation is a proposed mechanism of antibody escape.

T. Pallidum attachment to activated platelets may contribute to dissemination; This remains a suggested mechanism.

Slide 17 · Three acquired stages and an intervening latent phase

Phase

Dominant clinical picture

Central pathologic concept

Primary

Painless indurated chancre

Local treponemes and endarteritis

Secondary

Multisite mucocutaneous lesions

Hematogenous spread and inflammation

Latent

No overt active lesions

Persistent infection with seroreactivity

Tertiary

Aortitis, neurosyphilis, gummas

Chronic inflammatory injury and scarring

Slide 18 · Primary syphilis: Onset and anatomic distribution

Classically appears approximately 2–6 weeks after infection.

The first lesion develops at the site of initial treponemal invasion.

Common sites include genital mucosa and skin, cervix, vagina and anus.

Lesion healing does not imply microbiologic cure.

Slide 19 · Chancre: The gross morphology of a firm ulcer

Elevated erythematous papule

Surface erosion

Clean-based shallow ulcer

Firm indurated margin: Hard chancre

Schematic — conceptual sequence based on the source text

Slide 20 · Histology of the primary chancre

A dense infiltrate of plasma cells with lymphocytes and macrophages occupies the lesion.

Small vessels show proliferative endarteritis.

Endothelial activation is followed by progressive intimal fibrosis.

Treponemes are numerous in the primary lesion and permit transmission.

Slide 21 · Regional lymph nodes in primary infection

Clinical consequence

Regional lymphadenopathy may accompany the chancre

Nodal changes often reflect reactive inflammation

Microscopic reactions

Acute or chronic nonspecific lymphadenitis

Plasma cell–rich infiltrates may be seen

Granulomatous responses are also described

Slide 22 · Why disappearance of a chancre is misleading

Visible lesion heals

Local inflammation subsides

Organisms may already be disseminated

Untreated systemic infection can progress

Schematic — conceptual sequence based on the source text

Slide 23 · Case: A painless indurated genital ulcer

An adult presents with a solitary painless, firm genital ulcer.

Findings to interpret

A clean superficial ulcer lies within an indurated base.

The lesion arose weeks after a potential exposure.

The associated local node is enlarged.

Primary syphilis is a major clinicopathologic consideration.

Slide 24 · Secondary syphilis: Clinical transition

Secondary manifestations follow dissemination from the primary focus.

They typically arise weeks after the original chancre in untreated infection.

Lesions are widely distributed on skin and mucous membranes.

Systemic inflammatory symptoms commonly accompany the eruption.

Slide 25 · Secondary rash: More than one morphology

Common appearances

Discrete red-brown macules

Maculopapular eruption

Scaly or annular lesions

Other patterns

Follicular lesions

Pustular variants

Distribution may be widespread

Slide 26 · Palms and soles are diagnostic clues

Cutaneous lesions frequently affect palmar and plantar surfaces.

These sites are informative when evaluating an otherwise nonspecific eruption.

Morphology is variable: Macular, papular, scaly or pustular.

The distribution should be interpreted together with mucosal changes and serology.

Slide 27 · Condylomata lata: Broad moist plaques

Clinical setting

Moist intertriginous or anogenital sites

Inner thighs and axillae may also be affected

Lesion identity

Broad-based elevated plaques

Part of secondary syphilitic mucocutaneous disease

Distinguish conceptually from a primary chancre

Slide 28 · Secondary mucosal involvement

Superficial silvery-gray erosions can involve oral, pharyngeal or genital mucosa.

Lesions may be painless and easy to overlook without examination.

Red mucosal lesions may harbor many organisms and be especially infectious.

Mucosal disease and skin lesions often coexist.

Slide 29 · Systemic inflammatory manifestations

Lymphatic

Generalized lymphadenopathy

Local inflammatory reactions

Constitutional

Low-grade fever and malaise

Possible weight loss

Neurologic

CNS invasion may occur early

May be asymptomatic

Slide 30 · Microscopic pattern in secondary lesions

Plasma cell–rich chronic inflammation resembles the reaction in the primary chancre.

Small-vessel obliterative endarteritis can persist as a central microscopic clue.

The density of the infiltrate may be lower than in primary lesions.

Clinical distribution is essential because microscopic findings alone are not specific.

Slide 31 · CNS dissemination need not await tertiary disease

Treponemes can involve the CNS during relatively early infection.

Some infections are neurologically silent despite CSF changes.

Symptomatic disease may include meningitis, visual disturbance or hearing change.

The classic tertiary categories do not define the earliest possible timing of CNS involvement.

Slide 32 · Clinical case: Rash plus mucosal lesions

A patient has a generalized eruption involving palms and soles.

Findings to interpret

Broad, moist plaques are present in the anogenital region.

A painless superficial oral lesion is noted.

The patient reports malaise and generalized lymphadenopathy.

Secondary syphilis integrates the distribution, mucosal lesions and systemic findings.

Slide 33 · Latency: Persistent infection without florid lesions

What changes

Chancre and secondary lesions may regress

The patient may become clinically asymptomatic

What does not follow

Disappearance does not prove organism elimination

Serologic investigation remains central

Late organ manifestations can arise in untreated infection

Slide 34 · Tertiary syphilis: Three major patterns

Cardiovascular

Syphilitic aortitis

Aortic root / arch sequelae

Neurologic

Meningovascular disease

Tabes dorsalis / general paresis

Gummatous

Nodular necrotizing lesions

Skin, bones and internal organs

Slide 35 · Tertiary injury may follow years of latency

Tertiary disease can emerge after a prolonged clinically latent interval.

Cardiovascular, neurologic and gummatous manifestations may occur separately or together.

The scarcity of organisms in some late lesions highlights the importance of host inflammation.

Treatment has made gummatous complications less frequent.

Slide 36 · Syphilitic aortitis: The relevant vascular target

Endarteritis of aortic vasa vasorum

Reduced nourishment of proximal aortic media

Medial scarring and loss of elastic support

Progressive aortic dilation

Schematic — conceptual sequence based on the source text

Slide 37 · Vasa vasorum occlusion initiates medial injury

Intimal proliferation + inflammation

Progressive narrowing of lumen

Downstream tissue ischemia

Simplified vascular cross-section — schematic, not histology or a scale drawing

Slide 38 · Aortic root dilation: Major functional outcomes

Inflammatory medial damage

Aortic root / proximal arch dilation

Valve coaptation failure

Aortic regurgitation and aneurysmal change

Schematic — conceptual sequence based on the source text

Slide 39 · Coronary ostial narrowing in aortitis

Subintimal scarring may constrict the coronary arterial openings.

Ostial narrowing limits myocardial blood supply.

Ischemic manifestations may therefore coexist with proximal aortic dilation.

Both consequences arise from chronic remodeling rather than simply a bacterial mass.

Slide 40 · Neurosyphilis: Diverse presentations

Form

Recognized manifestation

Asymptomatic

CSF inflammatory or serologic abnormalities without recognized neurologic symptoms

Meningovascular

One designated form of symptomatic neurosyphilis

Tabes dorsalis

One designated late neurologic form

General paresis

One designated late neurologic form

Slide 41 · Asymptomatic neurosyphilis: CSF clues

Inflammatory CSF abnormalities may precede obvious neurologic symptoms.

Described changes include pleocytosis, increased protein or reduced glucose.

CSF testing for syphilis-associated antibodies supports the diagnostic assessment.

Neurosyphilis evaluation matters because central nervous system involvement changes clinical management.

Slide 42 · Gummas: The distribution and gross lesion

Gummas are rubbery, white-gray lesions varying from microscopic foci to tumorlike masses.

They can occur singly or in multiples.

Favored locations include skin, subcutis, bone, joints and other viscera.

They may cause tenderness, swelling, ulceration or pathologic fracture depending on site.

Slide 43 · Gumma: Central necrosis and reactive margin

Central coagulated necrotic material

Palisading macrophages + fibroblasts

Outer mononuclear infiltrate: Plasma cells

Schematic of described architecture; Treponemes are sparse in established gummas

Slide 44 · Why organisms are hard to find in a gumma

Longstanding host inflammatory response

Coagulative necrosis and fibrosis

Low visible treponemal burden

Diagnosis rests on context and ancillary evidence

Schematic — conceptual sequence based on the source text

Slide 45 · Hepar lobatum: Gummatous hepatic scarring

Hepatic gummas can heal with irregular scarring.

The resulting distortion produces the characteristic lesion termed hepar lobatum.

The source illustration uses trichrome to highlight fibrosis; The actual image is not included here.

This is a tertiary manifestation, distinct from diffuse congenital hepatic fibrosis.

Slide 46 · Tertiary patterns: Lesion and consequence

Pattern

Pathologic lesion

Main consequence

Aortitis

Vasa vasorum endarteritis; Medial scarring

Root dilation, valve regurgitation, aneurysm

Neurosyphilis

CNS inflammatory disease

Variable neurologic syndrome

Gumma

Necrotic center; Macrophages, fibrosis, plasma cells

Focal destruction and scarring

Slide 47 · Congenital infection: Transplacental spread

Maternal treponemal infection

Organisms cross placenta

Generalized fetal spirochetemia

Multiorgan inflammation and fibrosis

Schematic — conceptual sequence based on the source text

Slide 48 · Why maternal disease stage matters

Congenital transmission is most frequent with maternal primary or secondary syphilis.

Organism burden is greatest during these clinically active phases.

The fetal effects may include pregnancy loss and severe neonatal illness.

That appropriate maternal penicillin treatment greatly reduces transmission and adverse outcomes.

Slide 49 · Untreated congenital syphilis: Fetal outcomes

Pregnancy consequences

Late abortion

Stillbirth or perinatal death

Severe fetal infection

Surviving infants

Early multisystem inflammation

Skin and bone involvement

Potential later stigmata

Slide 50 · Early congenital syphilis: Snuffles

Nasal discharge and obstruction may develop during the first months of life.

This presentation is traditionally termed snuffles.

Nasal mucosal involvement accompanies systemic congenital infection.

It must be interpreted with maternal history, infant examination and appropriate testing.

Slide 51 · Infantile skin injury can be severe

A bullous or desquamating eruption may involve palms and soles.

Epidermal sloughing can also affect perioral and perianal skin.

The rash is often more severe than typical acquired secondary syphilis.

Cutaneous changes should trigger consideration of disseminated fetal infection.

Slide 52 · Congenital skeletal abnormalities: Two mechanisms

Osteochondritis

Disturbed endochondral bone formation

Epiphyseal widening and disordered cartilage position

Periostitis

New bone formation on long-bone surfaces

Prominent lesions in lower legs

Characteristic deformities can follow

Slide 53 · Vomer injury and saddle-nose deformity

Syphilitic osteochondritis / osteitis

Destruction of nasal vomer

Loss of nasal bridge support

Saddle-nose contour

Schematic — conceptual sequence based on the source text

Slide 54 · Tibial periostitis and saber shin

Syphilitic periostitis of tibia

Excess anterior periosteal bone growth

Anterior tibial bowing

Saber-shin deformity

Schematic — conceptual sequence based on the source text

Slide 55 · Congenital hepatic disease: Diffuse fibrosis

The liver may show fibrosis that traverses lobules and separates hepatocytes into small nests.

Lymphoplasmacytic inflammation and vascular abnormalities accompany the fibrosis.

Hepatomegaly is a frequent clinical correlate.

Early hepatic gummas are possible but diffuse fibrosing injury is the central pattern.

Slide 56 · Pneumonia alba: Fetal pulmonary involvement

Congenital infection may produce diffuse pulmonary interstitial inflammation and fibrosis.

In an affected stillborn infant, the lungs may appear pale and airless.

This gross appearance is termed pneumonia alba.

The process is part of systemic spirochetemia rather than an isolated airway infection.

Slide 57 · Other affected fetal organs

Visceral involvement

Pancreas and kidneys

Heart and spleen

Endocrine organs

Immune / nervous sites

Thymus

Central nervous system

Diffuse interstitial inflammation

Slide 58 · Late congenital syphilis: Hutchinson triad

Eye

Interstitial keratitis

Corneal inflammatory injury

Dentition

Hutchinson teeth

Small, notched incisors

Hearing

Eighth-nerve deafness

Neurologic tissue injury

Slide 59 · Additional late congenital features

Ocular changes may include choroiditis and abnormal retinal pigmentation.

Hutchinson incisors are reduced in size, peg- or screwdriver-shaped and may be notched.

Eighth-nerve injury and optic atrophy may arise in the setting of meningovascular disease.

Late manifestations reflect damage that becomes evident during childhood.

Slide 60 · Congenital disease differs by time of expression

Infantile / early

Childhood / later

Snuffles and bullous rash

Interstitial keratitis and hearing loss

Osteochondritis or periostitis

Saddle nose and saber shin may persist

Hepatic and pulmonary fibrosis

Characteristic Hutchinson teeth

Slide 61 · Syphilis diagnosis: Combine clinical stage and serology

Serologic assays are the principal laboratory approach.

Treponemal and nontreponemal tests measure different antibody responses.

Diagnostic algorithms use both classes rather than relying on one test alone.

Test performance and interpretation vary by disease stage and treatment history.

Slide 62 · Nontreponemal tests: Reaction to a lipid antigen

Antigenic target

Cardiolipin–cholesterol–lecithin complex

Not exclusive to T. Pallidum

Common tests

Rapid plasma reagin (RPR)

Venereal Disease Research Laboratory (VDRL)

Clinical interpretation

Results can be quantified as titers

Useful for response monitoring

Slide 63 · Treponemal tests identify organism-directed antibodies

These assays detect antibodies directed against T. Pallidum antigens.

Examples in the source include the fluorescent treponemal antibody absorption test.

T. Pallidum enzyme immunoassays also serve as treponemal tests.

Many treponemal tests remain reactive after adequate therapy and are not suitable for monitoring treatment response.

Slide 64 · Traditional syphilis serologic algorithm

Screen: Nontreponemal RPR / VDRL

If reactive: Specific treponemal assay

Interpret concordant results

Consider clinical stage and history

Schematic — conceptual sequence based on the source text

Slide 65 · Reverse-sequence serologic algorithm

Screen: Treponemal immunoassay

Follow with nontreponemal assay

Reconcile discordant results as needed

Interpret with clinical history

Schematic — conceptual sequence based on the source text

Slide 66 · Test sensitivity depends on clinical phase

Early infection

Antibody tests may not yet be reliably reactive

A negative early test does not settle a strong clinical suspicion

Clinical follow-up and repeat evaluation may be required

Established infection

Both classes of tests perform well in secondary disease

Treponemal tests generally remain useful in latent or tertiary disease

Prior treatment changes serologic interpretation

Slide 67 · Follow-up: Antibody titers are not interchangeable

Nontreponemal assays

Treponemal assays

Quantitative titers can be followed

Commonly provide qualitative reactivity

Titers often fall after successful treatment

Reactivity may persist after treatment

Useful for monitoring response

Useful for evidence of exposure/infection history

Slide 68 · False positives and discordant tests

Nontreponemal antibody responses are not fully specific to T. Pallidum.

False-reactive results can accompany pregnancy, autoimmune disease or other infections.

Treponemal tests can also produce false-positive results.

Discrepant serology requires interpretation of both assays and the clinical context.

Slide 69 · Histopathology across acquired stages

Stage

Typical lesion

Shared microscopic features

Primary

Hard chancre

Plasma cells; Proliferative endarteritis

Secondary

Skin / mucosal eruption

Plasma cells; Obliterative endarteritis

Tertiary

Aortic lesions or gumma

Vessel injury / necrosis / fibrosis; Organisms often sparse

Slide 70 · Interpretation: The same vascular lesion, different organs

Syphilitic vascular injury

Skin / mucosa: Ulcer or rash

Aorta: Medial scarring

Ischemia and fibrosis shape late injury

Schematic — conceptual sequence based on the source text

Slide 71 · Case: Chronic ascending aortic disease

A patient with untreated historical infection has progressive proximal aortic dilation.

Findings to interpret

Vasa vasorum show chronic obliterative vascular injury.

The proximal aortic media is scarred.

The aortic valve has become incompetent.

Syphilitic aortitis links vasa vasorum disease to root dilation and regurgitation.

Slide 72 · Case: Congenital multisystem involvement

A neonate has nasal discharge, a bullous palmar eruption and hepatomegaly.

Findings to interpret

Maternal syphilis was active during pregnancy.

The rash is accompanied by prominent skin desquamation.

Bone abnormalities appear on clinical evaluation.

The combination supports congenital syphilis with systemic involvement.

Slide 73 · Clinicopathologic synthesis: five anchors

T. pallidum is difficult to culture and can persist despite host immunity.

Plasma cell–rich inflammation and proliferative endarteritis recur across stages.

Chancres, disseminated mucocutaneous disease and late organ injury form a spectrum.

Congenital infection preferentially produces skin, bone, liver, lung and later sensory lesions.

Clinical stage and paired serologic test classes are crucial for interpretation.