12. Immune-mediated Disorders of the Oral Mucosa Flashcards by J L

•
Structural organization of SSE
From bottom to surface
– Stratum ____ (Basal or germinative layer)
– Stratum ____ (Spinous layer)
– Stratum ____ (Superficial layer, stratum corneum, keratin layer)

• Bulk of SSE > stratum \_\_\_\_
• In oral mucosa > non-ketatinized or para > the surface is stratum \_\_\_\_
	○ Para: \_\_\_\_ palate, attached gingi, \_\_\_\_ (both non and para for tongue, para are at tips, while valleys are non-keratinized)

basal
spinosum
superficiale

spinosum
superficiale
hard
tongue

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Lichen planus
• Type ____ hypersensitivity reaction

• Immune-mediated disorders - type IV
• Type I - anaphylaxis - mediated by \_\_\_\_
• Type II - antibody-antigen - disrupts functionality (\_\_\_\_)
• Type III - \_\_\_\_ deposition - antibodies bind to antigen, but what causes diseases it activates PMNs which cause the damage
• Type IV - \_\_\_\_, lymphocytes - delayed type hypersensitivity reaction
	○ Poison ivy, contact allergy, latex
	○ LICHEN PLANUS IS TYPE \_\_\_\_, not sure what cells are reacting to
• Lesion in skin - purple, pruitic, polygonal and papular

IV
IgG
myasthenia gravis
immune complex
cell-mediated
IV

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Oral lichen planus

• Reticular
– Usually ____
– Interlacing white lines (____)
– History of waxing and waning

• Erosive
– ____
– Ulcerated mucosa
– May be restricted to ____

• \_\_\_\_ always warrants therapy - ulcerations; may see white striations, but often times you don't

asymptomatic
wickham's striae
symptomatic
gingiva
erosive

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Reticular LP

* ____ striations, lace-like pattern

white

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• LP of ____ tongue

○ Disregard hyperkeratosis in middle, but peripherally you see ____-like pattern

dorsal

lace

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LP of lips
- ____
- Esthetically displeasing, but not concerning as clinicians; doesn’t really warrant ____

asymptomatic

treatment

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____ LP
- Tongue, buccal mucosa
- May see ____ (middle) surrounding the ulceration

erosive/ulcerating

striations

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Desquamative gingivitis
• Non-specific ____ term
– Gingiva appears ____ and ulcerated
• May be due to variety of different diseases

desquamative gingivitis is NOT a diagnosis; there is an array of diseases that manifests with same ____ manifestation; most common one being erosive LP

if you have PT who has focal or diffusively, peeling painful raw gums, it’s called ____ gingivitis- it’s a descriptive term not a diagnosis
NOT a diagnosis, just a description term
like the terms leukoplakia and erythroplakia ( white or red lesion)

clinical
clinical
desquamative

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Desquamative gingivitis
so we are adding ____ to this Differential Diagnosis list this List will grow as we learn more disorders.. as we move to D2 year we will keep on adding on to the list.

erosive lichen planus

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Biopsy

Excisional
Incisional

Biopsy of ulceration MUST include portion of adjacent intact ____

• Excisional is \_\_\_\_

mucosa

curative

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L: look at basal layer, you don’t see prominent basal cells; they undergo ____ degeneration > undergo damage
- M: pink circlular structures > ____ bodies, or civatte bodies > represent apoptotic cells > epi cells
- R: inflam infiltrate > loads of ____ > at the interface bt the epi and connective tissue

hydropic
colloid
lymphocytes

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Basement membrane

• Lymphos are recruited via chemokines and other chem mediators, and these cells are typically \_\_\_\_ (cyto T) > physically damaging the epithelium > some cells undergo apoptosis (\_\_\_\_ bodies)
• Treatment with \_\_\_\_ > prevent the formaiton/syntehsis of lymphocytes > how you treat LP
	○ If lesion is localized/diffsue > skin mucosal lesion: systemic steroid; oral cavity: topical steroid, liquid or cream form 
	○ High potency, int potency, low potency
		§ High: \_\_\_\_
		§ Int: \_\_\_\_

CD8+
colloid
steroids
clobetzole
fluocinode

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LP-like lesions
Lichenoid mucositis
– \_\_\_\_ allergy
– \_\_\_\_ allergy
Systemic conditions
– \_\_\_\_ erythematosus
– Graft vs host disease

• Arises as lichen planus clinically > LM > umbrella of diagnoses
	○ Contact: \_\_\_\_, peppermint, metal/alloy/gold
	○ Drug: \_\_\_\_, hypertension, and some for transplant rejection prevention

* Drug reaction - \_\_\_\_ - hypothyroidism
* Discoid lupus/lupus erthematosus
* GvH disease > can mimic LP clinically, but \_\_\_\_ it's different

contact
drug
lupus
cinnamon
hyperthyroid

synthryoid
microscopically

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Lichenoid mucositis
• Medications
• Flavoring agents
• Dental materials

• Interface reaction, and you have a \_\_\_\_ infiltrate > lympho's are wrapped around BV deep within the tissue
• Superficial, and a \_\_\_\_ perivascular (in LP you do not see the deep perivascualr infiltrate) > here, you see, auotomatically you're thinking some kind of a reaction (due to drug, contact, etc.)
	○ \_\_\_\_ taking is critical (cinnamon, peppermint, meds)
	○ Still treated with roids
• Have to understand cause - if you can link to medication (\_\_\_\_) > changing the medication
• If restoration > do not replace unless you have to > \_\_\_\_ first, if doesn't go away > may warrant reevaluation for that tooth

perivascular
deep
history
temporally
treat

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L: ____ restoration

* R: chewing cinnamon gum > erosive lichenoid pattern involving ____ of tongue

gold

dorsum

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Desquamative Gingivitis
Erosive lichen planus
Lichenoid mucositis
Graft vs host disease

• And \_\_\_\_, can manifest with desquamtive gingivitis
	○ Gums are peeling red and raw

lupus

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Hemidesmosomes
• Physically attach ____ cells to basement membrane
• Cytokeratin molecules in cytoplasm are connected to ____
– Via Bullous pemphigoid ____ and ____ (BP230 and BP180) and ____
• Extracellular domain of integrin crosses plasma membrane to bind ____ in basement membrane

• Protein structures that link basal cells to BM
	○ Linked from within via \_\_\_\_
• Hemidesmosome composed of proteins that link cytokeratin within cell; cytokeratin binds to PB230, 180 and plectin and all binds to integrin a6b4 which crosses cell membrane into external environment (basement membrane, binding laminin 5)
	○ Any protein disruption > detachment

basal
intergin alpha6beta4
230
180
plectin
laminin 5
cytokeratin

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Benign mucous membrane pemphigoid

____, vesiculobullous disease
Similar to Type ____ hypersensitivity
____ women
Usually limited to ____ membranes
Lesions heal with scarring
____ consult is mandatory
- Vesiculobullous - blisters - separation of epi from connective tissue > will rupture giving rise to ulceration
- TII > ____ generated unknwon > binds antigen (any of proteins within hemidesmo) > destruction of hemidesmo and reuslting in separationf rom CT
- Mucuous membranes, not just oral cavity (can be ocular, genital, etc.); very rarely you will get ____ lesions
- ____ pemphigoid > another word for scar (heal with scarring, esp in eyes)

autoimmune
II
older
mucous
ophtlamology

antibody
skin
sicotritial

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Mucous membrane pemphigoid

• Over time you get scar tissue > to point that scars connect lower eyelid to the actual globe > \_\_\_\_ (scar tissue that connects lower eyelid to the lobe) > hard time moving eye > \_\_\_\_ > fixed globe (can't move eye at all)

symblepharon

ankylobepharon

Mucous membrane pemphigoid

____ autoantibodies
Several possible antigens
- Develop autoantibodies against antigen > unknown eitology > the trigger can be ____, laminin 5, ____ in pemphigoid
- MMP pemphigoid, ____ disease > array of genes that result in same phenotype that result in separation of tissue

IgG
BP230
BP180
heterogenous

Mucous membrane pemphigoid

• Antibodies bind anitgen within \_\_\_\_ > destruction of hemi > lost and separated from CT > subethelial cleavage

hemidesmosome

Epi is completely separated from underlying CT > ____ cleavage
- ____ to establish diagnosis

subepi

biopsy

Direct immunofluoresence
Antibodies have variable region (which recognizes antigen) and a constant region

• Important to establish diagnosis
• Blue > piece of \_\_\_\_ tissue on the slide
• The structures are antibodies (white, etc.)
• If patient has pemhp > tissues have ab's to the \_\_\_\_ (autoab's)
• Each class of ab, the \_\_\_\_ regions are the same (all IgG have the same region)
	○ Fab varies within class
• Can exploit the Fc reigons by producing ab synthetically tor \_\_\_\_ all human IgG Fc
	○ Tagging the synthetic ab with a fluorochrome > detect fluoro with immunofluoresence

biopsy
hemi
Fc
recognizing

Membrane mucous pemphigoid

• \_\_\_ pattern of fluorescene, bc tha tnibody bind at the BM (the hemidesmosome)
• Finding directly evident from patient \_\_\_ > direct immunofluoresscence
• Steroids prevent \_\_\_ cells from forming, prveenting formaitno of plasma and prveent fomratnion of ab
	○ Similar to LP, but that's for lympho's

linear
tissue
B

Desmosomes • Protein structures that bind actual cells to one another (including ___ cells) • Composed of ___, desmocollin, ___, desmoplakin ○ (which are ___) to adjacent cells. ○ ___ and ___ connect cytokeratins in the cells • Cytokeratin > DP, PK > DG and DC cross cell membrane > outside of cell interdigitate with ___ to form a tight zipper

``` basal desmoglein plakoglobin intracellular PG DP adjacent cells ```

Desmosomes 1. ___ (bundles of tonofilaments) connect to... 2. Intracellular thickenings composed of ___ and plakoglobin 3. ____ and desmocollin penetrate intercellular space 4. Attach to their counterparts from opposite cells

tonofibrils desmoplakin desmoglein

Pemphigus vulgaris • No ____ predilection • Fragile vesicles or bullae – Positive ____ sign • Skin, dysphonia, dysphagia * Similar to Type ____ hypersensitivity * ____ autoantibodies * ____ is antigenic • Still vesiculobullous > blisters are extremely fragile > rearley see blisters in this disease • Can eliciit blister formation with ____ trauma > postiive nikoslky sign ○ Cotton swab/back end of mirror > minor twisitng on skin/mucosa > causes blistering ○ Can do with pemphigoid but takes much more to do • Skin mucosa > affects any SSE linign (laryngeal, esophageal) > ____ (altered voice, deeper) and ____ (difficulty eating, traumatize esophagus) • Type II > IgG binding to an autoantigen > unlike PG > only ____ antigen > DG3

``` sex nikolsky II IgG desmoglein 3 ``` minimal dysphona dysphagia one

* Nikossky sign | * Stopped ____ bc disease was so uncomfortable

brushing

* Diffuse oral disease of palate | * Ask questions about lesions on skin > chest/back ____ > placing on ____ separated skin

soreness | bra

``` Desquamative gingivitis • Erosive lichen planus • Lichenoid mucositis • Mucous membrane pemphigoid • ____ • Graft versus host disease ```

pemphigus vulgaris

Pemphigus vulgaris • ____ cleavage • Acantholysis • ____ cells • Antibodies bind DG3 > lost cell attachment • ____ cells are physically separating from each other ____ cells sometimes we have individual cells floating around in the blister

suprabasilar tzanck acantholysis tzanck

* individual cells falling apart is called ____ cell | * ____ is Acantholysis

tzanck | separation

* Cellsa ttached to BM, everything above is separated | * R: ____ cells

Tzanck

• Basal cells have ____, stilla ttached to BM, but they're standing ____ Tombstone!

desmosomes | alone

Direct IF - pemphigus vulg • ____ pattern > black is actual cells, and the green around is the ab binding around the cells ○ ____ for PV

chicken wire | pathoneumonic

Indirect IF • Unlike PG, can use indirect • Use patients ____ (draw blood sample, spin it down) > if have PV will ab at ____ enough concentration in their serum • Patients serum has autoab's in the serum, and incubate with a ____ anti-human IgG ○ Apply it to another ____ (mouse, monkey, etc.) > mouse SSE all contain desmosomes with DG3 that is similar to human DG3 If pt has antibodies, you will see same chicken wire pattern. antibody will bind to desmoglein • Why use indirect? • We can tirtrate terament based on ____ of antibodies..we can see if pt is responding to therapy by taking ____ instead of biospy every time! • 100 ab in serum today > after month of therapy > down to 50 ab in serum > therapy is working ○ Can take blood samples occasioanlly to gauge response to therapy

``` serum high secondary tissue concentration blood ```

Pemphigus vs. Pemphigoid table ``` Pemphigus Circ. ab: ____ Loc of antigen: ____ Loc of blister: ____ Anatomic surfaces: ____ Nikolsky sign: ____ Txt: ____ Prognosis: ____ ``` ``` Pemphigoid Circ. ab: ____ Loc of antigen: ____ Loc of blister: ____ Anatomic surfaces: ____ Nikolsky sign: ____ Txt: ____ Prognosis: ____ ``` • Pemphigus is a disease of ____ - periods of remission, etc; was once a life threatening disease ○ ____ • much harder to elicit blister in ____ • dont use indirect with diagnosis of pemphigoid - low ____ of auto antibodies • Pemphigoid > disease is limited and more easily ____

``` yes desmosome suprabasilar mucosa and skin +++ systemic meds fair-good ``` ``` no hemidesmosome subepithelial mainly mucosa + topical/systemic meds good-excellent ``` ``` life steroids pemphigoid concentration treated ```

* pathognomonic for Pemphigus V (____ pattern) | * linear pattern shown here is not pathognomonic of ____ (____ also shows linear pattern of fluorescence)

chicken wire mucus membrane pemphigoid lupus

``` Lupus erythematosus • ____ group of diseases • Three main types – ____ lupus – Chronic cutaneous lupus (____ lupus) • Type ____ hypersensitivity ``` • Three categories > heterogenous > 2 main: systemic lupus, and discoid lupus ○ Systemic - affects array of tissue/organ types (skin, kidney, heart, GI, brain) ○ Discoid - more limited in phenotype, primariily ____ mucosa • TIII > aggregate of ab-antigen > many anitgens > this doesn't cause damage, but he recruitment of complement and ____ causes the damage (BV, skin, epi, glomeruli, etc.)

heterogenous systemic discoid III skin PMNs

``` SLE • ____ rash • Oral lesions may resemble ____ • Antinuclear antibodies • Positive ____ antigen • Anti-____-stranded DNA antibodies • Lupus band test – + DIF of ____ and normal ____ ``` • Very characteristically with butterfly type of face; not pathognomonic but characteristic to skin ○ May feature ____ • Heterogenous - ab's that are autoreactive, to DNA to ribonucleoprotein > smith antigen, and to dsDNA ○ The ____ of cells exposed to external enviornemtn > anitgenic in patients • Diagnosied by only ____ fluoresncen > lupus band test > both lesional and non-lesional tissue ○ Occurs in both lesional and non-lesional ○ Band is at BM

``` malar "butterfly" lichen planus smith lesional mucosa ``` balding nuclei direct

SLE • ____ gingivitis • can be diagnosed with Direct immunofluorescence ONLY ____ ○ it is called Lupus band test • both ____ and not ____ tissue is biopsied • both lesional and non lesional will be ____ toward immunofluro you have a positive lupus band test- band at the ____ area • ____ pattern of fluorescence at the BM area

``` desquam. direct lesional lesional reactive BM ``` linear

``` Discoid lupus • Mainly affects ____-exposed skin • Heals with scarring • ____ oral lichenoid lesions • Positive ____ in minority of cases • Positive Lupus band test only of ____ tissue ``` • More likely effects ____ than males, but if it is a male it's much ____ • Limited to skin mucosa > heal with scarring > manifest in areas where you're exposed to sun > mimic ____ in the oral cavity ○ Biospy is warranted so you know what you're dealing with ○ Lupus treated with ____ rather than LP > treated with a diff class of medications

sun erosive ANAs lesional females worse LP steroids

Discoid Lupus * R: desquamative gingivits * add this disease (DLE)to the list too! * Both SLE and Discoid lupus (DLE) can cause desquamative gingivitis * DLE can mimic ____

lichen planus

Discoid lupus * L: looks like LP under microscope, but in direct fluoresnce you see ____ band that you don't see in LP; lupus is autoimmune and not a DTH disease, so you have the presence of ____ * DLE only shows in the ____ tissue, not non-lesional (SLE does both)

linear autoab's lesional

``` Desquamative Gingivitis (FULL) • ____ • Lichenoid mucositis • ____ • Pemphigus vulgaris • Graft versus host disease • ____ • Discoid lupus erythematosus ```

erosive lichen planus mucous membrane pemphigoid systemic lupus erythematosus