ORAL PATHOLOGY 2: VESICULAR LESIONS

VESICULO-BULLOUS DISEASES Viral diseases Conditions associated with immunologic defects Hereditary diseases

VIRAL DISEASES Virus are composed of an inner nucleic acid core of

either DNA or RNA that represents their genetic code

VIRAL DISEASES Herpes simplex infections Varicella-zoster infections Hand-foot & mouth diseases Herpangina Measles (rubeola)

HERPES SIMPLEX INFECTIONS PATHOGENESIS Typical route of HSV inoculation is physical contact

with an infected individual Primary infection: few percentage of individuals show

clinical signs & symptoms Incubation period after exposure- several days to 2

weeks

HERPES SIMPLEX INFECTIONS CLINICAL FEATURES Primary Herpetic Gingivostomatitis Secondary Herpetic Gingivostomatitis Herpetic Whitlow

PRIMARY HERPETIC GINGIVOSTOMATITIS Usually seen in children Adults who have not been previously exposed to HSV Vesicular lesion may appear:

Skin Vermillion Oral mucosa ( any mucosal surface)

Accompanied by fever, arthralgia, malaise, headache and cervical lymphadenopathy

After the systemic primary infection runs its course of about 1 week to 10 days

Lesions heal without a scar Virus may have migrated to the trigeminal ganglion to

reside in a latent form

SECONDARY OR RECURRENCE HSV INFECTIONS Represents reactivation of latent virus 90%- have antibodies to HSV 40%- develop secondary herpes Due to breakdown in focal immuno-surveillance Due to an alteration in local inflammatory mediators

that allows the virus to replicate

Prodromal symptoms in the site which lesions will appear:

Tingling Burning Pain

Multiple fragile & short-lived vesicles appear that become ulcerated & coalesce to form a map-like superficial ulcers

Lesions heal without scarring in 1-2 weeks Number of recurrences is variable (one or more per

year) Typically occur at or near the same site with each

recurrence Intraorally, occur on the hard palate or gingiva Regionally, occur on the vermillion and surrounding

skin (herpes simplex labialis)

HERPETIC WHITLOW A primary or secondary HSV infection involving the

finger(s) Pain, redness and swelling are prominent Vesicles or pustules break to become ulcers Axillary or epitrochlear lymphadenopathy may be

present

HERPES SIMPLEX INFECTIONS HISTOPATHOLOGY Intraepithelial vesicles containing exudate,

inflammatory cells and some virus-infected epithelial cells

HERPES SIMPLEX INFECTIONS DIFFERENTIAL DIAGNOSIS Streptococcal pharyngitis

Does not involve lips or perioral tissues Erythema multiforme

Oral ulcers are larger without vesicular stage

Vincent’s infection Limited to gingiva

HERPES SIMPLEX INFECTIONS TREATMENT For any drug to be effective, treatment must be

initiated as soon as possible ( no later than 48 hours from the onset)

5% Acyclovir ointment Oral Acyclovir tablets: 400mg, 5 x a day for 7 days –

primary genital herpes Supportive treatment: fluids, rest, oral lavage &

antipyretics

VARICELLA-ZOSTER INFECTIONS ETIOLOGY VZV- one of the herpesviruses that is pathogenic for

human Primary infection in the seronegative individual is

known as varicella ( chicken pox) The secondary or reactivation of latent VZV is known

as herpes zoster (shingles) The ability of the virus to remain quiescent in sensory

ganglia for indefinite periods a primary infection is common

VARICELLA-ZOSTER INFECTIONS PATHOGENESIS Varicella

Mode of transmission: Through inspiration of contaminated

droplets Direct contact

Incubation period- 2 weeks Recovery – 2 to 3 weeks

Herpes Zoster Reactivation is uncommon Occurrence follows:

Immunosuppressive state from malignancy Drug administration Radiation or surgery of the spinal cord Local trauma

Prodromal symptoms: Pain or paresthesia develop & persist for

several days ( as the virus infect the sensory nerve- trunk or head & neck)

Vesicular skin lesion become pustular & ulceration follows

Disease last for several days & may be followed by a troublesome post-herpetic neuralgia

VARICELLA-ZOSTER INFECTIONS CLINICAL FEATURESVaricella

Childhood disease Fever, chills, malaise & headache Rash that involve the trunk , head & neck Rash develops into a vesicular eruption that becomes

pustular & eventually ulcerates Self- limiting- last several weeks Oral manifestations

Multiple shallow ulcers that are preceded by evanescent vesicles in the oral mucosa

Complications: Pneumonitis Encephalitis Inflammation of other organs If occur during pregnancy, fetal

abnormalities may occur

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If occur in adults, symptoms are more severe with more complications

Herpes Zoster Affect adult population

Risk: compromised immune responses Affect sensory nerves of the trunk & head & neck Trigeminal nerve: unilateral oral, facial or ocular

lesionsVARICELLA-ZOSTER INFECTIONS CLINICAL FEATURESHerpes Zoster

Ramsay Hunt syndrome Involve the facial & auditory nerve

Facial paralysis Vesicles of the ipsilateral

external ear, Tinnitus Deafness Vertigo

VARICELLA-ZOSTER INFECTIONS TREATMENTVaricella

Supportive therapy for normal individual For immunocompromised individual

Virus-specific drugs Acyclovir ( Zovirax®) Vidarabine Human leukocyte interferon

Herpes Zoster Acyclovir (Zovirax®) – 800mg/ 5x a day for 7- 10 days Analgesics for pain & fever Topical virus-specific drugs

HAND, FOOT & MOUTH DISEASE Etiologic agent: Cocksackie virus ( picornavirus) type A

16 Highly contagious viral infection Mode of transmission:

Airborne spread Oral-fecal contamination

This virus have predilection for mucous membranes of the mouth, cutaneous regions of the hands and feet

Occurs in epidemic or endemic proportions Affects predominantly children under 5 years of age Short incubation period The lesions resolve after 1-2 weeks Signs & symptoms are moderate in intensity

Low-grade fever Malaise Lymphadenopathy Sore mouth

Pain from oral lesions is often patient’s chief complaint

Oral lesions Begins as vesicles that quickly rupture to

become ulcers covered by yellow fibrinous membrane surrounded by erythematous halo

Multiple lesions which occur anywhere Favored sites: palate, tongue & buccal

mucosa Cutaneous lesions

Appear concomitant with or shortly after the oral lesions

Multiple maculopapular lesions Progress to a vesicular state and eventually

become ulcerated and encrusted Typically on the feet, toes, hands and fingers

HAND, FOOT & MOUTH DISEASE DIFFERENTIAL DIAGNOSIS Primary herpetic gingivostomatitis Varicella Virus culture cone to confirm clinical impression

HAND, FOOT & MOUTH DISEASE TREATMENT Symptomatic treatment

Disease is self- limiting & of short duration Non-specific mouthwashes may be used to alleviate

oral discomfort

HERPANGINA Etiologic agent: Cocksackie type A virus Mode of transmission:

Contaminated saliva Contaminated feces

HERPANGINA CLINICAL FEATURES Usually endemic Outbreaks typically during summer or early fall Occur most often in children Symptoms:

Fever, malaise, dysphagia & sore throat Oral lesions:

Vesicular eruptions on the soft palate, faucial pillars and tonsils

A diffuse erythematous pharyngitis is also present

HERPANGINA TREATMENT Treatment is not required Self-limiting, mild and of short-duration & causes few

complications

MEASLES RUBEOLA Etiologic agent: measles virus ( paramyxovirus) Mode of transmission: airborne droplets through the

respiratory tract

MEASLES RUBEOLA CLINICAL FEATURES Predominantly a disease of children Often appearing in winter and spring Incubation period: 7-10 days Prodromal symptoms: 1-2 days

Fever, malaise, coryza, conjunctivitis, photophobia & cough

Pathnognomonic signs: Koplik’s spots- small , erythematous

macules with white necrotic centers on the buccal mucosa

Precedes skin lesions by 1-2 days Skin rash Initially affects the head & neck Followed by the trunk & extremities Complications:

Encephalitis Thrombocytopenic purpura Otitis media pneumonia

MEASLES GERMAN MEASLES OR RUBELLA A contagious diseases Etiologic agent: an unrelate virus of togavirus family Share some features with measles

Fever Respiratory symptoms Rash

No Koplik’s spots Ability to cause congenital defects in developing fetus

MEASLES GERMAN MEASLES OR RUBELLA TREATMENT No specific treatment Supportive therapy

Bed rest Fluids Adequate diet analgesics

CONDITIONS ASSOCIATED WITH IMMUNOLOGIC DEFECTS Pemphigus vulgaris Cicatrical pemphigoid Bullous pemphgoid Dermatitis herpetiformis Linear IgA disease

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PEMPHIGUS A general term for a group of mucocutaneous diseases

characterized by intraepithelial blister formation Results from a breakdown or loss of intercellular

adhesion, producing acantholysis Acantholysis- epithelial cell separation

PEMPHIGUS VULGARIS Most frequently encountered pemphigus

Pemphigus vegetans Pemphigus folicaceus Pemphigus erythematosus

Auto-immune etiology Presence of circulating antibodies of IgG type

responsible for the earliest morphologic event- dissolution or disruption of intercellular junctions and loss of cell-cell adhesion

PEMPHIGUS VULGARIS CLINICAL FEATURES Lesions present as ulcers preceded by bullae 60% - first signs in the oral mucosa

Precede the onset of cutaneous lesions by period of up to 1 year

Ulcers range in appearance from a small aphthous-like lesions to large map-like lesions

Gentle traction on clinically unaffected mucosa may produce a stripping or epithelium, called Nikolsky’s sign

Affects the soft palate, buccal mucosa and floor of the mouth

Affects both gender Most cases noted within the 4th and 5th ecade Common in some racial and ethnic groups: Ashkenazic

jews May occur with other auto-immune diseases:

myasthenia gravis, lupus erythematosus, rheumatoid arthritis, etc.

PEMPHIGUS VULGARIS HISTOPATHOLOGY Pathognomonic features: acantholytic lesion that

present squamous epithelial cells lying free within the bulla of the vesicle cavity

Tzanck cells- acantholytic epithelial cells

PEMPHIGUS VULGARIS DIFFERENTIAL DX Bullous and cicatrical pemphigoid Erythema multiforme Bullous lichen planus Dermatitis herpetiformis Pemphigus vegetans

Contain abundant eosinophils Diagnosis made by biopsy examination and direct

immunofluorescence testing

PEMPHIGUS VULGARIS TREATMENT Early or stable phase

Steroid (prednisone)- intermediate dose Generalized involvement

High dose of prednisone Immunosuppressant agent: azathioprine,

methotrexate or cyclophosphamide

PEMPHIGUS VULGARIS TREATMENT & PROGNOSIS High morbidity and mortality rates reduced due to the

introduction of systemic corticosteroid Iatrogenic morbidity associated with

chronic corticosteroid use (8-10% per 5 years- secondary to long-term steroid therapy)

The major clinical problem once the disease is brought under control:

Lifelong treatment commitment required and the potential long-term dug effects

CICATRICIAL PEMPHIGOID Represents a chronic blistering disease AKA

Benign mucous membrane pemphigus Ocular pemphigus Childhood pemphigoid Mucosal pemphigoid

Cicatricial Pemphigoid Affects the gingiva, the terms gingivosis &

desquamative gingivitis have been uses Idiopathic etiology Considered as auto-immune disease Presence of immunoglobulins and complement

components along the basement zones on direct immunofluorescence testing

CICATRICIAL PEMPHIGOID CLINICAL FEATURES Affects adults and elderly Tend to affect women more than men Oral mucosal presentation are variable:

From incipient erosion or desquamation of attached gingival tissues to large areas of vesiculo-bullous eruption involving the alveolar mucosa, palate, buccal mucosa, tongue & floor of the mouth

Lesions are chronic and may heal with scarring (cicatrix)

Extraoral sites in order of frequency following oral mucosa:

Conjunctiva Larynx Genitalia Esophagus

Skin- appear in the head & neck & extremities but are uncommon

Gingival lesions are the most common form of oral presentation

Manifested as patchy erythema with mild discomfort to intense generalized erythema & ulceration extending to & beyond the attached alveolar mucosal junction

Severity of surface desquamation parallels the level of pain

With chronicity, pain typically diminishes in intensity Gentle massage uninvolved tissue will produce a

vesicle or desquamation

CICATRICIAL PEMPHIGOIDDIFFERENTIAL DIAGNOSISPemphigus

Detectable circulating & tissue-bound auto-antibodies Desmosomes are the target tissues Affects mucosa, skin Presence of Nikolsky’s sign Systemic steroids with other immunosuppressive

agents Fair to good prognosis

Pemphigoid No detectable circulating antibodies Detectable tissue-bod auto-antibodies Basement membrane is the target tissues Affects oral mucosa ( esp. gingiva), eyes & genitals Presence of Nikolsky’s sign Treatment is systemic or topicall steroid therapy Good to excellent prognosis

CICATRICIAL PEMPHIGOID HISTOPATHOLOGY No evidence of acantholysis and epithelial

degenerative change

CICATRICIAL PEMPHIGOID TREATMENT Prednisone with disappointing results High-potency topical steroids are soften used Rinsing with chlorhexidine is an adjunct

CICATRICIAL PEMPHIGOID PROGNOSIS Benign Self-limiting Do not produce mortality Significant debilitation and morbidity can occur Prognosis in children is good

BULLOUS PEMPHIGOID Share etiologic and pathogenetic factor with cicatrical

pemphigoid Detectable circulating auto-antibodies which will bind

to tissue antigens

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BULLOUS PEMPHIGOID CLINICAL FEATURES Found primarily in the elderly (7th & 8th decades) Skin lesions: trunk and limb distribution Tense vesicles and bullae preceded or associated by

erythematous papular eruption Oral mucosal lesions

Similar with cicatricial pemphigus Areas of involvement: Soft palate, buccal mucosa & floor of the mouth

BULLOUS PEMPHIGOID TREATMENT Periods of remission noted Systemic corticosteroids used to control this disease Non-steroidal immunosuppressive agents used to

effect control of the disease Recently, antibiotics ( tetracycline & erythromycin) &

niacinamide are use with some success

DERMATITIS HERPETIFORMIS Unknown cause Cell-mediated immunity may play a significant role in

pathogenesis No circulating auto-antibodies are noted Deposits of IgA are evident in the skin and mucosa Affects skin, mucosa & jejunum Defective fat absorption resembling that in celiac

disease & sensitivity to gluten

DERMATITIS HERPETIFORMIS CLINICAL FEATURES A chronic disease Seen in young & middle aged adults Slight male predilection Essentially a cutaneous disease Rarely involves the oral mucosa Periods of exacerbation & remission Cutaneous lesions Formation of papular, erythematous, pruritic lesions

that most often are vesicular Lesions are usually symmetric in the distribution over

extensor surfaces Elbows, shoulders, sacrum & buttocks

Frequent involvement of the scalp & face (diagnostic significant)

Lesions are usually aggregated ( herpetiform) Involvement varies from periodic development to

generalized involvement Healed areas may become hyperpigmented with very

slow fading Exacerbation associated with ingestion of foods or

drugs containing iodide compounds, or seasonal peak Oral manifestations

Vesicles & bullae are evanescent in their presentation & duration

Subsequent to rupture, superficial ulcers with a fibrinous base & surrounding zone of erythema

Mild symptoms Lesions may involved keratinized and

non-keratinized mucosa

DERMATITIS HERPETIFORMIS HISTOPATHOLOGY Presence of neutrophils, eosinophils and fibrin on the

dermis IgA are also found in the connective tissue

DERMATITIS HERPETIFORMIS TREATMENT Chemotherapeutic agents

Dapsone Sulfoxone Sulfapyridine

Gluten-free diet

DERMATITIS HERPETIFORMIS PROGNOSIS Response to chemotherapy is usually prompt Elimination of gluten from the diet will reduce small

bowel pathology Within 2 months, a return to normal small

bowel function A lifelong condition, often exhibiting periods of

remission

LINEAR IgA DISEASE Chronic autoimmune disease of skin Affects mucous membranes Not associated with gluten-sensitve enteropathy Skin lesions may be urticarial, annular, targetoid or

bullous Oral lesions are generally ulcerative preceded by bullae Ocular lesions are seen in majority of the cases

Ulcers and scans Patients respond to sulfones or to corticosteroids

HEREDITARY DISEASES Epidermolysis Bullosa

EPIDERMOLYSIS BULLOSA General term encompasses one acquired and several

genetic varieties ( dystrophic, junctional or simplex) of disease that are basically characterized by the formation of blisters at the site of minor trauma

Acquired form- epidermolysis acquisita IgG deposits found in sub-

basement membrane Hereditary form

Circulating antibodies are not apparent

EPIDERMOLYSIS BULLOSA CLINICAL FEATURES Bulla formation from minor provocation Found usually over areas of stress

Elbows Knees

Onset of disease Hereditary type- infancy or early childhood Acquired type – adulthood

Severity is generally greater with the inherited form Blisters maybe widespread and severe

resulting to scarring and atrophy Nails may be dystrophic

Oral lesions- common & severe in inherited form (recessive dystropic epidermolysia bullosa

Bullae that heal with scar Constricted oral orifice from scar Hypoplastic teeth

EPIDERMOLYSIS BULLOSA TREATMENT Avoidance of trauma Supportive measures Chemotherapeutic agents ( not effective)

Corticosteroids Vitamin E Phenytoin Retinoids Dapsone Immunosuppressives

EPIDERMOLYSIS BULLOSA PROGNOSIS Dependent upon the subtype Ranges from life threatening one of the recessive

forms ( junctional epidermolysis bullosa) to debilitating in most other forms

Taken from Dr. Aggabao’s lecture-Rosette Go 121310

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