Term
major immunobullous skin disorders
antibody-mediated blistering |
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Definition
pemphigus foliaceus
pemphigus vulgaris
bullous pemphigoig
epidermolysis bullosa aquisita (EBA) |
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Term
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Definition
glue that hold keratinocytes together
major protiens:
*DSG1
*DSG3 |
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Term
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Definition
anchor skin (basal layer) to basement membrane
major proteins:
*BPag1/BPag2
*Laminin 5
*alpha-6/beta-4 integrin |
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Term
| types of immunoflourescence testing for diagnosis of immunobullous disease |
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Definition
DIRECT - tests for antibodies in patient's SKIN
INDIRECT - tests for antibodies in patient's SERUM |
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Term
pemphigus foliaceus
location |
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Definition
blisters form in the granular layer
very superficial |
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Term
pemphigus foliaceus
skin lesion characteristics |
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Definition
"crusty corn flakes"
scaly, superficial, crusted erosions
frequently on an erythematous base |
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Term
pemphigus foliaceus
distribution |
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Definition
trunk, extremities
seborrheic distribution
oral involvement RARE |
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Term
pemphigus foliaceus
pathogenesis |
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Definition
autoantibodies disrupt function of desmosonal protein in the epidermal granular layer
specific antigen = Desmoglein 1 (DSG1) |
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Term
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Definition
the "glue" needed for proper cell-cell attachment via desmosomes
DSG1 expression is highest in the granular layer --> thus where pemphigus blisters form |
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Term
pemphigus foliaceus
course and treatment |
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Definition
-onset in elderly
-may be severely debilitating
-significant decrease in mortality today with corticosteroid use
topical or systemic steroid use depending on extent of involvement |
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Term
pemphigus vulgaris
location |
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Definition
| blisters in the spinous layer |
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Term
pemphigus vulgaris
skin lesion characteristics |
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Definition
flaccid blisters, usually on normal-appearing skin
painful, not pruritic
ruptured bullae produce erosions and crusting |
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Term
pemphigus vulgaris
distribution |
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Definition
anywhere on the skin, including scalp
most include ORAL/MUCOSAL involvement (sometime before skin lesions appear) |
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Term
pemphigus vulgaris
histology |
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Definition
subepidermal split within the spinous cell layer (deeper layer of the cleft)
"tombstoning" of basal keratinocytes |
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Term
pemphigus vulgaris
pathogenesis |
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Definition
autoantibodies disrupt function of desmosonal protein most abundant in the spinous layer of the epidermis
specific antigen = Desmoglein 3 (DSG3) |
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Term
pemphigus vulgaris
course and treatment |
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Definition
-onset in adulthood
-may be severely debilitating
-before steroid, very fatal
-tx with corticosteroids and steroid-sparing agent
if very severe: tx in burn unit, plasmapheresis, maybe rituxan |
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Term
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Definition
sere form of pemphigus neraly always associated with malignancy
very prominent ORAL involvement
frequently resistant to treatment |
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Term
paraneoplastic pemphigus
pathogenesis |
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Definition
| multiple tumor-related autoantibodies directed at desmosonal and hemidesmosonal proteins |
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Term
bullous pemphigoid
location |
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Definition
| blisters at the dermal-epidermal junction |
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Term
bullous pemphigoid
skin lesions |
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Definition
large, *TENSE BULLAE*
erythematous base
very pruritic (eosinophils!)
ruptured bullae may produce erosions and crusting |
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Term
bullous pemphigoid
distribution |
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Definition
trunk, extremities
mucosal involvement is RARE
widespread |
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Term
bullous pemphigoid
histology |
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Definition
subepidermal split just ABOVE the basement membrane - below basal cell layer
numerous eosinophils |
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Term
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Definition
| LINEAR IgG and C3 at dermal-epidermal junction |
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Term
bullous pemphigoid
pathogenesis |
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Definition
autoantibodies against hemidesmosomal proteins, which normally anchor keratinocytes to the basement membrane
specific antigens:
*BP antigen 1 (BPAG1)
*BP antigen 2 (BPAG2) |
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Term
bullous pemphigoid
course and treatment |
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Definition
-onset in elderly
-may be self limiting, resolving within 3 years
-topical or systemic steroid depending on severity |
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Term
cicatricial pemphigoid
skin lesions |
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Definition
ulcers, erosions
blisters sometimes seen
eventual scarring
very superficial |
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Term
cicatricial pemphigoid
distribution |
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Definition
mucous membranes (eyes, oropharynx, nasal cavity, larynx, esophagus)
skin involved in 25% of patients |
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Term
cicatricial pemphigoid
pathogenesis |
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Definition
autoantibodies against hemidesmosonal proteins, which normally anchor keratinocytes to the basement membrane
specific antigens:
*Laminin 5
*alpha-6/beta-4 integrin
*BP antigen 2 |
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Term
cicatricial pemphigoid
course |
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Definition
-onset in elderly
-generally slow progression, but severe flares/rapid progression is possible
-eye pain, foreign body sensation, photosensitivity
-impaired vision, blindness
-esophageal strictures
-laryngeal scarring |
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Term
cicatricial pemphigoid
treatment |
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Definition
-multidisciplinary approach needed (opthy, ENT, GI, rheum)
-corticosteroids (not always effective)
-dapsone, MTX, Cellcept, imuran
-IVIg, Rituxan if rapidly progressive
-surgery can trigger flares |
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Term
epidermolysis bullosa acquisita
location |
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Definition
| blisters at the dermal-epidermal junction |
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Term
epidermolysis bullosa acquisita
skin lesions |
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Definition
blisters and non-erythematous skin that hear with scarring and formation of milia (tiny cysts)
scars frequently seen in trauma-prone areas (knuckles, elbows, knees) |
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Term
epidermolysis bullosa acquisita
distribution |
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Definition
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Term
epidermolysis bullosa acquisita
histology |
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Definition
subepidermal split (below BM zone), usually with little inflammation
linear IG deposits at dermal-epidermal junction |
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Term
epidermolysis bullosa acquisita
pathogenesis |
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Definition
autoantibodies against type VII collagen, normally found in the anchoring fibrils beneath the basement membrane
reduces # of anchoring fibrils = adhesion defect and blister formation
specific antigen:
*Type VII collagen |
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Term
epidermolysis bullosa acquisita
course and treatment |
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Definition
-onset usually after age 40
-frequently self limiting, resolving within 3 years
(-occasionally patients have severe, generalized disease and prolonged course)
-poor response to treatment |
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Term
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Definition
-inherited disorders
-minor trauma leads to blister formation
-mutated genes affect epidermal cell and epidermal-dermal integrity
-wide spectrum of phenotypes (mild-fatal)
-no effective forms of conventional therapy yet |
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Term
epidermolysis bullosa simplex
location |
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Definition
| blister level in basal cell |
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Term
epidermolysis bullosa simplex
skin lesions |
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Definition
wide spectrum
mild: blisters in traumatized areas (hands, feet) (adults)
severe: generalized blisters in neonates |
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Term
epidermolysis bullosa simplex
distribution |
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Definition
| extremities most common in limited forms |
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Term
epidermolysis bullosa simplex
age of onset |
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Definition
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Term
epidermolysis bullosa simplex
pathogenesis |
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Definition
-AD
-mutations in gene encoding keratins, filamentous proteins required for maintaining keratinocyte structure
-defective keratinocytes form clumps instead of filaments |
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Term
epidermolysis bullosa simplex
genes mutates=d |
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Definition
*Keratins 5 and 14*
(help attach the keratinocyte to the hemidesmosome) |
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Term
epidermolysis bullosa simplex
course and treatment |
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Definition
ranges from mild to severe
no effective treatment
minimize trauma and practice good wound care |
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Term
junctional epidermolysis bullosa
location |
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Definition
| blister level at basement membrane |
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Term
junctional epidermolysis bullosa
skin lesions |
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Definition
blisters and erosions at birth
may affect ocular, respiratory, GI, GU epithelia
classic perioral granulation tissue |
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Term
junctional epidermolysis bullosa
distribution |
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Definition
generalized
tends to be more severe than simplex |
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Term
junctional epidermolysis bullosa
pathogenesis |
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Definition
-AD
-mutations in the genes encoding proteins within the basement membrane, required for normal adhesion |
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Term
junctional epidermolysis bullosa
genes mutated |
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Definition
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Term
junctional epidermolysis bullosa
course and treatment |
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Definition
ranges from very mild to severe, fatal disease
-some forms with greatly increased risk of sepsis and rare survival past infancy
no effective treatment; minimize trauma and practice good wound care |
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Term
dystrophic epidermolysis bullosa
location |
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Definition
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Term
dystrophic epidermolysis bullosa
skin lesions |
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Definition
blisters and erosions
may affect ocular, respiratory, GI, and GU epithelia
"mitten hand" deformity |
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Term
dystrophic epidermolysis bullosa
distribution |
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Definition
generalized
can affect all mucosal surfaces |
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Term
dystrophic epidermolysis bullosa
age of onset |
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Definition
at birth
some forms as late as early childhood |
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Term
dystrophic epidermolysis bullosa
pathogenesis |
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Definition
-AD/AR
-mutations in the gene encoding a structural protein within the anchoring fibrils, required for normal adhesion |
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Term
dystrophic epidermolysis bullosa
genes mutated |
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Definition
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Term
dystrophic epidermolysis bullosa
course and treatment |
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Definition
generally severe with extensive scaring
-malnutrition and growth retardation common
-aggressive squamous cell carcinomas may develop in areas of scarred skin --> 80% get SCC by age 40!
no effective treatment; minimize trauma and practice good wound care
preclinical attempts at gene therapy and stem cell transplant |
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