12. Immune-mediated Disorders of the Oral Mucosa Flashcards
•
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
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
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
- Reticular LP
* ____ striations, lace-like pattern
white
• LP of ____ tongue
○ Disregard hyperkeratosis in middle, but peripherally you see ____-like pattern
dorsal
lace
- LP of lips
- ____
- Esthetically displeasing, but not concerning as clinicians; doesn’t really warrant ____
asymptomatic
treatment
- ____ LP
- Tongue, buccal mucosa
- May see ____ (middle) surrounding the ulceration
erosive/ulcerating
striations
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
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
Biopsy
- Excisional
- Incisional
Biopsy of ulceration MUST include portion of adjacent intact ____
• Excisional is \_\_\_\_
mucosa
curative
- 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
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
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
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
- L: ____ restoration
* R: chewing cinnamon gum > erosive lichenoid pattern involving ____ of tongue
gold
dorsum
Desquamative Gingivitis
Erosive lichen planus
Lichenoid mucositis
Graft vs host disease
• And \_\_\_\_, can manifest with desquamtive gingivitis ○ Gums are peeling red and raw
lupus
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
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
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
- ___ (bundles of tonofilaments) connect to…
- Intracellular thickenings composed of ___ and plakoglobin
- ____ and desmocollin penetrate intercellular space
- 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
