All of skin lesions/tumors and autoimmune

patch

greater than 5 mm macule:

nodule

greater than 5 mm papule

bulla

vesicle greater than 5 mm

urticaria: what cells?

immediate type I hypersensitivity: IgE and mast cell degranulation

when do you get response in type I and type IV hypersensitivity?

second exposure

urticaria: what does this do to blood vessels

histamine from mast cells cause BV to dilate (red and purple skin), permeable (edema)

clinical term caused by urticaria

plaque (raised skin lesion)

mast cell releases histamine → _____ → itchy

unmyelinated C fibers

urticaria: what part of skin does it affect?

• epidermis affected?

• what makes skin red/purple

• what raises the skin?

• unaffected epidermis

• dilated blood vessels

• superficial dermis edema (space between collagen)

how fast do lesions appear in urticaria

a few minutes in pre-exposed individual

acute eczematous dermatitis: what cells? what hypersensitivity?

allergic contact dermatitis: delayed type IV hypersensitivity, T cells

two main things happen when T cells release cytokines in allergic contact dermititis

inflammation: redness, dermal edema, itchy

keratinocyte apoptosis and breakage of intracellular adhesion molecules → edema in epidermis: spongiosis

allergic contact dermatitis skin lesions (2): from where?

vesicle (smaller) or bulla (bigger), epidermis

allergic contact has __ edema, urticaria has _ edema

allergic has both dermal edema and epidermal edema, urticaria just has dermal

how fast do lesions occur in allergic contact dermitis

several hours to days

Erythema Muliforme is a __ manifestation of inflammatory dermatoses:

two kinds?

acute

without mucosal disease: EM minor

with mucosal involvement: EM major

what can cause erthema multiforme

appears to be type IV, cell mediated, hypersensitivity rxn to 90% infectious agents, 10% of time to drugs

two kinds that can cause erythema multiforme:

main: herpes, mycoplasma pneumoniae

Erythema multiforme pathogenesis

1. Reactivation of HSV infection →

2. viral antigens deposit in skin or mucosa

3. recruitment of cytotoxic T cells

4. inflammation (edema and redness)

5. apoptosis/necrosis of basal epithelial cells with subepidermal blister

clinical features of erythema multiforme

1. bright red ring

2. paler, raised area (edema)

3. dusky or dark red central area with blister or crust

*target looking lesion

erythema multiforme: lesions appear __, resolve in _

3-5 days, 2 weeks

psoriasis: pathogenesis

• the cause is __: involves both _ and ?

• __ mediated - possibly _

• 1 inciting __ _ →

• 2. Activated ___ home to the __ and accumulate in the _

• 3. Release ___

• ___: → ___ and _

• ___

• multifactorial: genetic and enviornmental

• T cell, autoimmune

• 1. antigens

• 2. T cells, dermis, epidermis

• 3. Cytokines

• Inflammation: dilated BV, edema

• keratinocyte hyperproliferation

Continuation of psoriasis: pathogenesis

Keratinocyte hyperproliferation →

excess and rapid growth of epidermis → migration time from basal layer to susrface goes from 14 days to 4-7 → nuclei retained in cells at skin surface: parakerotosis

parakeratosis

stratum corneum: nuclei retained in cells at skin surface

ancanthosis, t cells, parakaratosis, dilated BV, downward extension of rete ridges

Psoriasis causes ? what layer

due to keratinocyte proliferation:

parakaratosis: corneum

acanthosis: thickening of epithelium?

hyperkeratosis: corneum thickening

psoriasis clinical features: raised or flat? colors?

plaque (rasied), red + silver/white, purple/brown and gray

psoriasis causes what clinical feature: where commonly?

plaque on scalp, knees, elbow

auspitz sign

multiple, minute bleeding points clinical sign of psoriasis

lichen planus: pathogenesis

1. autoimmune: antigen on cells in basal layer

2. CD8 →

3. TNF/Fas: apoptosis of keratinocytes

4. Chemokines: inflammation

in lichen planus: lesions are concentrated at the?

epidermal-dermal interface

Lichen planus histololigically:

saw tooth interface: epidermal hyperplasia, hyperkeratinosis, hypergranulosis

wickham striae

white lacelike markings of lichen planus

lichen planus clinical features: why?

Purple papule (small, less than 5 mm raised): from melanin released from keratinocytes

wickham striae: (white lacelike markings)

Lichen planus: what shape? rounded or flat topped? Shiny or scaly?

flat topped, shiny

is there oral inovlement with lichen planus?

yes: wickham’s striae (often asymptomatic), erosive form (ulcers)

two kinds of blistering (bullous disorders): both are what?

pemphigus, bullous pemphigoid, both autoimmune

Pemphigus vulgaris or foliaceus pathogenesis

autoantibodies to desmoglein 1 and 3 (cadherins) → loss of keratinocyte to keratinocyte adhesion

cadherins

desmoglein 1 and 3: related to pemphigus

Bullous pemphigoid pahthogensis

autoantibody to type XVII collagen (or other BM proteins) → damages basement membrane

location of demoglein 1 and 3 in epidermis in pemphigus foliaceus vs. pemphigus vulgaris

• upper part of epidermis: more desmogelin 1: Pemphigus foliaceus

• lower part of epidermis: more desmoglein 3: pemphigus vulgaris

cleft positions:

• pemphigus foliaceus

• Pemphigus vulgaris

• Bullous pemphigoid

• subcorneal

• suprabasal

• subepidermal

pemphigus foliaceus clinical featuer

bullae or blister (more superficial)

pemphigus vulgaris clinical feature

flaccid blisters and skin erosions (more erosive as blister is deeper than foliaceous), gingival erosion

bullous pemphigoid clinical features

tense bullae with clear fluid (more difficult to break than pemphigus), blisters/erosions in mucosa

how does immunofluoresence work to diagnose blistering disorder?

anti-desmoglein IgG (auto-antibody) incubate section with fluorescently tagged anti IgG antibody on epithelial cells

tumors: two kinds of benign and premalignant epithelial lesions

seborrheic keratosis and actinic keratosis (solar)

seborrheic keratosis: occurs where?

occurs in people __

sun related?

trunk, extremities, head, neck

greater than 50

no

seborrheic keratosis pathogenesis

cause unknown:

• somatic mutation in gene for fibroblast Growth factor receptor 3L (FGFR3)

• receptor on basaloid keratinocytes: increased proliferation, greater production of keratin

seborrheic keratosis histological features

• rete ridge pattern ablated (flat)

• Horn cysts in epidermis (keratin filled cysts)

• Acanthosis

seborrehic keratosis clinical features

tan to brown (melanin production in melaocytes), waxy, plaque

actinic keratosis: where does it occur? Why

balding scalp, face, lateral neck, distal or lower extremeties: sun related!

Actinic keratosis pathogenesis

uv light → DNA damage → mutates TP53 tumor suppressor → proliferation of atypical keratinocytes → intraepithelial dysplasia

skin tumors on white skin: actinic keratosis, squamous cell carcinoma in situ (in place epithelial layer), invasive SCC, basal cell carinoma main causes

sun, invasive SCC is usually other carcinogens but can be sun

common mutations in the pathway of skin tumors and other

actinic keratosis: TP 53

SCC in situ: HRas

invasice SCC: HRas (proto-oncogenes)

Basal cell carcinoma: hedgehog pathway (oncogene)

dysplasia

atypical cells in epithelium

is dysplasia malignant? Why?

no: confined to epithelium: can progress to malignancy, persist, or regress

Sun exposed skin tumors: clinical features

• actinic keratosis

• SCC in situ

• invasive SSC

• Basal cell carinoma

• macule or patch, scaly (hyperkeratosis)

• patch or plaque

• plaque or nodule

• papule

why can you get oral squamous cell carninoma in mouth?

stratified squamous epithelium

is there basal cell carcinoma in mouth?

no only on skin

main cause of invasive SCC in skin of color and basal cell carcinoma

where?

not sun usually: ulcers, scar, radiation, carcinogens: non-sun exposed skin like legs

basal is both exposed and non-sun exposed skin

invasive SCC skin of color features vs basal cell

dark scaly, plaque

pigemented, pearly, papule

melanocyte proliferations (3) and their cause? which can metasize (which is cancer?)

common nevus (mole), dysplastic nevus (dysplasia mole), melanoma: cancer

BRAF or NRAS

risk factors for melanoma besides sun

genetics

main location of melanoma in people of color

sole, under nail, mucosa

ABCD of melanoma vs mole

Melanoma

Assymetrical: yes

border: bumpy/irregular

color: variable

Diameter: large than 6 mm

why important to recognize melanoma early? (3)

much less common, aggressive and metasize to any organ, high morality rate

what causes systemic lupus ertyhematosus

antibodies against nuclear components (like DNA, histones) → immune complex forms (antigen + antibody) → deposits in tissue and causes damage

SLE is a ___ disease: _ and ?

variable presentation: what 5 main things

multisystem, relapsing and remitting

butterfly rash (malar)

photosensitvity

mouth ulcers

swollen, painful joint (joint inflammation)

fatigue and fever

does age and gender matter in lupus?

occurs more often in younger women

What causes myasthenia gravis

autoantibodies to nicotinic acetylcholine receptor on skeletal muscle → degradation of the receptor

if myasthenia gravis continues you get fewer receptors: what happens?

muscle weakness → flaccid paralysis

symptoms of myasthenia gravis (3)

muscle weakness:

• droopy eyelid

• droopy mouth

• difficulty chewing and swallowing

what is sjorgen syndrome

autoimmune destruction of Salivary and lacrimal glands

primary vs secondary forms of Sjogren

primary: just sjorgen (sicca)

secondary: associated with other autoimmune: Rheumatoid arthritis (RA), lupus

what symptoms suggest Sjogren syndrome (6)

dry mouth, mouth sores/ulcerations, dental caries, lump in neck by salivary glands (due to infilitration of lymphocytes), dry eyes, rheumatoid arthritis (60% have Sjoren and another)

gender and age of sjoren

90% occurs in women 35-45