ORAL PATHOLOGY 2: VESICULAR LESIONS VESICULO-BULLOUS DISEASES Viral diseases Conditions associated with immunologic defects Hereditary diseases

ses 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 immunosurveillance 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)

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

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 Vincents 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

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 nervetrunk 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 FEATURES Varicella 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 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 lesions VARICELLA-ZOSTER INFECTIONS CLINICAL FEATURES Herpes Zoster Ramsay Hunt syndrome Involve the facial & auditory nerve Facial paralysis Vesicles of the ipsilateral external ear, Tinnitus Deafness Vertigo VARICELLA-ZOSTER INFECTIONS TREATMENT Varicella 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 patients 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

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: Kopliks 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

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

Etiologic agent: an unrelate virus of togavirus family Share some features with measles Fever Respiratory symptoms Rash No Kopliks 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

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 Nikolskys 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 (810% 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 longterm 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 vesiculobullous 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

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

CICATRICIAL PEMPHIGOIDDIFFERENTIAL DIAGNOSIS Pemphigus Detectable circulating & tissue-bound autoantibodies Desmosomes are the target tissues Affects mucosa, skin Presence of Nikolskys 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 Nikolskys 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 BULLOUS PEMPHIGOID CLINICAL FEATURES

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

Subsequent to rupture, superficial ulcers with a fibrinous base & surrounding zone of erythema Mild symptoms Lesions may involved keratinized and nonkeratinized 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

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

Exacerbation associated with ingestion of foods or drugs containing iodide compounds, or seasonal peak Oral manifestations Vesicles & bullae are evanescent in their presentation & duration

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 subbasement 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

Taken from Dr. Aggabaos lecture -Rosette Go 121310

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