7. DERMATOLOGIC DISEASES

direct immunofluorescence

when you suspect autoimmune disease + you have to do biopsy from the tissue itself, where you will find autoantibodies

indirect immunofluorescence

autoimmune disease is systemic + disseminated, autoantibodies are in the blood

all know histopathology, immunofluorescence result

for this chapter

all of these are incisional biopsy

LICHEN PLANUS

Common, chronic, Immunological mucocutaneous disorder

Middle-aged female adults more commonly affected

Skin lesions: Purple, pruritic, polygonal, papules

Fine, lace-like network of white lines - Wickham's striae

Extra oral: vulvae, glans penis, nails

normally seen with stress, never goes away completely

Two forms: Reticular and Erosive

RETICULAR LICHEN PLANUS

May present as papules, asymptomatic

Waxes and wanes over weeks or months

Dorsal tongue, more keratotic plaques

Much more common than erosive form

• white striae

Posterior buccal mucosa bilaterally usually

multifocal- similar lesions in multiple areas

you do not treat for this form, only inform pt

EROSIVE LICHEN PLANUS

Lesions symptomatic

also has white stria (wickhams)

Atrophic, erythematous areas with central ulceration

Atrophy/ulceration confined to gingiva = Desquamative gingivitis

very low malignant potential

lichen planus HISTOPATHOLOGIC FEATURES

Hyper-ortho and parakeratosis

Thickness of spinous layer varies

Rete ridges absent or hyperplastic, pointed or "saw-toothed”

Destruction of basal layer (hydropic degeneration)

Intense, band-like infiltrate of lymphocytes subjacent to epithelium

Degenerating keratinocytes - Civatte bodies

½ in formalin, ½ in michalins solution (live vs fixed)

d/d for desquamative gingiva

erosive lichen planus

mucous membrane pemphigoid

pemphigoid vulgaris

lichen planus DIAGNOSIS

Reticular: Clinical basis alone especially if classic lesions buccal mucosa bilaterally

Erosive: More difficult to diagnose clinically

Direct immunofluorescent – Fibrinogen positivity (fluorescent green area)

• IgG , IgA, IgM, c3 + fibrinogen tested for DIF)

lichen planus TREATMENT AND PROGNOSIS

Reticular - No treatment

Erosive - Corticosteroids

LICHENOID LESIONS: GRAFT-VERSUS-HOST DISEASE

Recipients of allogeneic bone marrow transplants bc HLA match not always exact

GRAFT-VERSUS-HOST DISEASE CLINICAL FEATURES

Tongue, labial/buccal mucosa affected

Burning - Candidiasis should be ruled out

Xerostomia - Due to immune response to salivary gland tissue

GRAFT-VERSUS-HOST DISEASE TREATMENT AND PROGNOSIS

Careful histocompatibility matching, immunosuppressant drugs

Topical corticosteroids

acute GRAFT-VERSUS-HOST DISEASE

Within first few weeks after bone marrow transplantation

Affects 50% of BM patients, 33-75% oral involvement

chronic GRAFT-VERSUS-HOST DISEASE

Continuation of acute or develops >100 days after bone marrow transplantation

May appear several years after procedure, >80% oral lesions

Reticular network of white striae resembling lichen planus

LICHENOID LESIONS: LUPUS ERYTHEMATOSUS

Systemic Lupus Erythematosus (SLE) - Multisystem disease

Genetic factors play a role in pathogenesis but precise cause unknown

Chronic Cutaneous Lupus Erythematosus: Primarily skin / oral

F>M, Average age – 31

Fever, weight loss, arthritis, general malaise

40-50% butterfly rash over malar area and nose

Sunlight often makes lesions worse

Kidneys and heart frequently affected (40-50%) serious sequelae

LUPUS ERYTHEMATOSUS ORAL MANIFESTATIONS

Oral lesions 5-25%, as high as 40%

Palate, buccal mucosa, lips, gingiva

May appear as lichenoid areas

Ulceration, pain, erythema, hyperkeratosis

LUPUS ERYTHEMATOSUS DIAGNOSIS & TREATMENT

Clinical, microscopic & immunologic studies

Direct immunofluorescence - IgM, IgG, or C3 in a shaggy or granular band at basement membrane zone

• direct + indirect possible

95% - Antinuclear antibodies (ANAs)

Acute episodes- Systemic corticosteroids, may be combined with other immunosuppressive agents

PEMPHIGUS VULGARIS

*not lichenoid

Most common of pemphigus disorders (Vulgaris is Latin for "common")

Oral lesions first sign of disease, most difficult to treat

Blistering - Autoantibodies against component of desmosomes

Immunologic attack causes intra-epithelial split

acantholysis: spinous layer cells are destroyed → blood fills

• vesiculobullous disease

Untreated often results in death

PEMPHIGUS VULGARIS CLINICAL FEATURES

60-70% initial lesions in oral cavity

Adults average age at diagnosis 50

Superficial, ragged ulcerations

Palate, labial / buccal mucosa, gingiva

Flaccid vesicles / bullae (blister) rupture quickly, leaving erythematous, denuded surface

Bulla induced on normal-appearing skin or oral mucosa by firm lateral pressure (+ve Nikolsky sign)

systemic disorder

PEMPHIGUS VULGARIS HISTOPATHOLOGIC FEATURES

Intraepithelial separation just above basal cell layer

Spinous cells fall apart, (acantholysis- not exclusive to this), cells become rounded "Tzanck cells"

Biopsy ulcerated mucosa- results inconclusive, lack of intact epithelium- connective tissue interface

Confirmed by direct immunofluorescence

Perilesional tissue placed in Michel’s solution

Antibodies between involved epithelial cells - IgG & C3

Indirect immunofluorescence- positive 80-90%, circulating autoantibodies in serum

PEMPHIGUS VULGARIS TREATMENT AND PROGNOSIS

Systemic corticosteroids - Often in combination with other immunosuppressive drugs (so-called "steroid-sparing" agents)

Success of therapy- Measure titers of circulating autoantibodies (indirect immunofluorescence)

Mortality rate 5 to 10% - Due to complications of long term systemic corticosteroid use

Mucous Membrane Pemphigoid

looks like pemphagus but not it

Chronic, blistering, mucocutaneous autoimmune disease (cicatrical pemphigoid) “Cicatricial”, meaning "scar."

Tissue-bound autoantibodies against components of basement membrane- Hemidesmosomes

SUBEPITHELIAL

Oral lesions do not scar

Similar to pemphigus, differs in prognosis / microscopic features

Gingival involvement - Desquamative gingivitis

Desquamative gingivitis seen in other conditions- Erosive LP, pemphigus vulgaris

Mucous Membrane Pemphigoid CLINICAL FEATURES

Older adults average age 60

Females > males by a 2:1 ratio.

Oral lesions in most patients

Conjunctiva, nose, esophagus, larynx, vagina / skin

Oral lesions begin as vesicles or bullae

Blister forms in sub epithelial location, thicker, stronger roof than pemphigus

Blisters rupture - large, superficial, ulcerated mucosa

Ulcers painful, persist for weeks to months

Most significant complication- ocular involvement - 14-25%

Conjunctiva becomes inflamed and eroded

Scarring between bulbar and palpebral conjunctiva

Adhesions called symblepharons result

Blindness occurs if not treated

Mucous Membrane Pemphigoid HISTOPATHOLOGIC FEATURES

Biopsy of perilesional mucosa - split between epithelium and connective tissue

Direct immunofluorescence testing to confirm diagnosis

Immunoglobulins at basement membrane zone – IgG & C3

Indirect immunofluorescence not helpful

nikolsky's sign

Bulla induced on normal-appearing skin or oral mucosa by firm lateral pressure (+ve Nikolsky sign)

seen in pemphigus vulgaris , mucous membrane pemphigoid + erosive lichen planus

Mucous Membrane Pemphigoid TREATMENT AND PROGNOSIS

Referral to an ophthalmologist

If only oral lesions, potent topical corticosteroids

Gingival lesions respond to oral hygiene measures

If topical steroids fail, systemic steroids or other immunosuppressive agents used

Aggressive therapy - Indicated with advancing ocular disease

ERYTHEMA MIGRANS (Geographic Tongue)

psoriasiform mucositis (another name)

Common condition primarily of tongue, Increased frequency in atopic individuals, patients with psoriasis

Usually asymptomatic, may be burning with spicy foods

If symptomatic - Topical corticosteroids

If fissured - Antifungals (yeast can grow in fissures)

Well-demarcated zones of erythema - Atrophy of filiform papillae

Atrophic areas surrounded by white serpentine borders

Lesions heal in a few days or weeks, then develop in another area

Infrequently occurs on other sites: (ectopic geographic tongue) can also been seen on palate

etiology unknown but ppl w allergies are more likely (atopic)

strong familial

no malignant potential

SYSTEMIC SCLEROSIS (SCLERODERMA)

Rare immunologically mediated condition

Dense collagen deposited in large amounts

• body gets stiff

Women three times men

First sign Raynaud's phenomenon, vasoconstriction

Vascular events and abnormal collagen deposition produce ulcers on fingertips

Flexion contractures produce shortened claw-like fingers

SYSTEMIC SCLEROSIS (SCLERODERMA) CLINICAL AND RADIOGRAPHIC FEATURES

Furrows radiating from mouth - "purse-string" appearance

Tongue stiff, board-like

Deposition of collagen in esophagus, difficulty in swallowing (dysphagia)

Microstomia (cant open mouth) from collagen deposition in perioral tissues

Subcutaneous collagen deposition in facial skin - "mask-like" facies

Diffuse widening of pdl space

Resorption of posterior ramus, coronoid process and condyle (20%)

SYSTEMIC SCLEROSIS (SCLERODERMA) Diagnosis & Treatment

Skin biopsy supportive of diagnosis

Anti-Scl-70 (Anti-Topoisomerase I)

D - penicillamine to inhibit collagen production

Prognosis is poor

CREST SYNDROME

Relatively mild variant of systemic sclerosis

Anti-Centromere Antibody (ACA)

Acronym for:

Calcinosis cutis

Raynaud's phenomenon

Esophageal dysfunction

Sclerodactyly (claw fingers, bc restricted movement)

Telangiectasia (dialated blood vessels)

HEREDITARY HEMORRHAGIC TELANGIECTASIA (RENDU-OSLER-WEBER DISEASE)

Autosomal dominant disorder

Multiple vascular defects – Telengiectasias

Epistaxis – Presenting symptom, begins in childhood

Bleeds of nose, GI, persistent anemia

Cutaneous & oral lesions – Mostly on tongue, lips

EPIDERMOLYSIS BULLOSA

Genetic mutations encoding structural proteins, lack of hemidesmosomes, defects in anchoring fibrils

Defect in attachment of epithelial cells to each other or to the connective tissue

23 forms of EB, mostly hereditary

Blisters in areas of minor trauma

EB Acquisita – Autoimmune

EPIDERMOLYSIS BULLOSA Oral Manifestations

Highly variable depending on EB type

Increased fragility

Ulceration of mucosa, lips, cheeks, tongue, palate

Obliteration of oral vestibule

Enamel hypoplasia, rampant caries

REACTIVE ARTHRITIS (Reiter’s Syndrome)

Immune mediated, triggered by infection

1-4 weeks after episode of dysentery / venereal disease

Non gonococcal urethritis, arthritis, conjunctivitis (cant see cant pee cant climb a tree)

Prevalent in young adult men

Glans penis - Balanitis circinata (geographic tongue lesion but on the penis)

Oral lesions - <20% of pts,similar to geographic tongue

Painless, erythematous papules

Skin lesions – Erythematous erosions with white scalloped boundary

if the skin is sloughed off

you do perilesional biopsy (around lesion) to compare where autoantibodies are