Immune related & inherited disorders of skin I&II - Zaloga

Question 1

melanocytes

Answer 1

• pigment cells in basal layer that produce melanin

- disperse melanin to be held in keratinocytes (contain granules)

Question 2

desmosomes and hemidesmosomes

Answer 2

-connect cells

Question 3

layers of skin

Answer 3

1. stratum basale - bassement membrane (type 4 collagen), single cell, hemidesmosomes in basal lamina, mitotically active, progenitors
2. stratum spinosum - thickest, produce keratins, contain desmosomes
3. stratum granulosum - final differentiation and maturation of keratins, basophilic, keratohyaline granules
4. stratum lucidum - only thick skin, thin, eosinophilic keratinocytes, no nuclei/organelles
5. stratum corneum - no nuclei, only keratin, basket weave pattern, lipid rich, continuous shedding

Question 4

skin repair

Answer 4

• stratum basale and inflammatory cells (neutrophils and Macs) migrate to wound site –> blood clot forms and leukocytes clean wound –> form granulation tissue from fibroblasts –> new epithelium
• excess collagen forms scar tissue

Question 5

skin lesions

Answer 5

slide 5-6

Question 6

inflammatory dermatoses

Answer 6

1. acute lesions - days to weeks, neutrophil infiltrate, edema
2. chronic lesions - months to years, lymphocyte and macrophage infiltrate, atrophy, fibrosis, hyperplasia, most are autoimmune

Question 7

acute inflammatory dermatoses

Answer 7

1. urticaria (hives) - affects dermis
2. erythema multiforme - affects basement membrane
3. SJS and toxic epidermal necrolysis (TEN) - affects the basement membrane
4. acute eczematous dermatitis - affects epidermis

Question 8

urticaria (hives)

Answer 8

• mast cell degranulation**
• dermal microvascular hyperpermeability
• edematous plaques (wheals)
• antigen induced activation of immune system –> release vasoactive substance from mast cells (degranulation) –> inflammation and dilation of blood vessels
• type 1 hypersensitivity (IgE)
• edema in dermis separates collagen
• risk factors: collagen vascular disorder, nonhodgkin lymphoma, hereditary angioneurotic syndrome

Question 9

erythema multiforme

Answer 9

• self limited hypersensitivity due to infections (herpes mainly) and drugs**
• affects dermal/epidermal layer –> interface dermatitis
• T cells recognize unknown antigens (CD8 centrally, CD4 peripherally) –> epidermal necrosis w/ blister and targetoid lesion
• head and distal extremities (acral regions), limited hypersensitivity, targetoid lesions, <10% of body SA**

Question 10

Steven johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)

Answer 10

• both are interface dermatitis (dermal/epidermal junction) –> keratinocyte necrosis –> blisters
• due to medication**, begin as erythema multiforme targetoid lesions
• both affect mucous membranes**
• skin changes of neck and trunk**
• TEN more severe - slough skin –> tissue necrosis –> organ failure or infection
• SJS in children - 10-30% of body SA
• TEN in elderly - >30% of body SA affected

Question 11

acute eczematous dermatitis

Answer 11

• contact dermatitis –> exposed antigen produces inflammatory rxn
• affects the epidermis**
• type 4 hypersensitivity (T cell mediated)
• produces yellow crust and spongiosis (spongiotic dermatitis) –> edema fluid breaks keratinocytes desmosomes
• if persistent –> develop reactive acanthosis and hyperkeratosis

Question 12

ichthyosis

Answer 12

• non-inflammatory scaling lesion disorder
• epidermal maturation of keratinocytes –> chronic hyperkeratosis of stratum corneum
• ichthyosis vulgaris primary
• defective desquamation of keratinocytes
• steroid sulfatase deficiency in X-linked form –> build up of cell adhesion
• fish scales

Question 13

vitiligo

Answer 13

• depigmentation areas of skin (patchy); might itch
• autoimmune (CD4,8 T cells) –> destroy melanocytes
• no melanin on basal layer but preserved on hair follicles
• risk factors: alopecia, other autoimmune diseases, pernicious anemia, hyperthyroidism
• extremities

Question 14

psoriasis

Answer 14

• erythematous lesions with silvery plaques
• autoimmune –> HLA-Cw0602, unkown antigen
• sensitized CD4 T cells, activated CD8 T cells –> keratinocyte proliferation –> thickening of skin(acanthosis)
• may have psoriatic arthritis –> affect joints
• elbows, knees, scalp, sacrum
• parakeratotic stratum corneum
• dilated vessels in dermal papillae (auspitz sign)
• neutrophils infiltrate –> micro abscesses and spongiform pustules
• Koebner phenomenon –> psoriatic lesions from trauma

Question 15

blistering (bullous) diseases

Answer 15

• autoantibodies affect proteins that bind keratinocytes aka desmosomes/hemidesmosomes –> separation of keratinocytes (acantholysis)
• pemphigus –> Dsg1
• pemphigoid –> BPAG2 (hemidesmosome)
• dermatitis herpetiformis –> proteins in basal layer

Question 16

Desmogleins

Answer 16

• structural proteins that are part of the desmosomes and hemidesmosomes
• Dsg3 more deep
• Dsg1 more superficial

Question 17

pemphigus diseases

Answer 17

• autoantibodies (IgG) against desmogleins
• all show acantholysis and blister formation
• treat with immunosuppressants
  1. vulgaris –> most common, suprabasilar, rupture easily, shallow lesions, antibodies against Dsg 1,3
  2. foliaceus –> subcorneal (superficial), superficial erosion, antibodies against Dsg 1
  3. erythematosus –> localized, less severe than foliaceus
  4. vegetans –> rare, wart like plaques, suprabasilar

Question 18

bullous pemphigoid

Answer 18

• autoantibodies against BPAGs of hemidesmosomes
• subepidermal layer (below basal layer) –> separate dermal/epidermal junction
• tense bullae with clear fluid
• no acantholysis bc no epidermis
• superficial dermal edema

Question 19

dermatitis herpetiformis

Answer 19

• urticaria, grouped plaques, and vesicles
• IgA autoantibodies in dermal papillae against dietary gluten –> antibodies cross react with reticulin –> sub epidermal blister
• associated with celiac disease and gluten
• treat: remove gluten from diet

Question 20

porphyria

Answer 20

• non-inflammatory blistering disorder
• subepidermal
• no autoantibodies
• inherited or acquired porphyrin metabolism deficit
• release of molecules from porphyrin ring degradation –> inflammation –> urticaria and vesicles
• porphyrin in dermal papillae
• activated by sunlight –> inflammatory response
• hyalinized dermis vessels

Question 21

acne vulgaris

Answer 21

• epidermal appendage disorder
• induced by drugs, oils, and cosmetics –> clog pores of hair follicles (infundibulum) –> inflammatory response and necrosis
• causes: keratin plug, hypertrophy of sebaceous glands, bacteria (propionibacterium) in hair follicle
• inflammatory and non-inflammatory types
• open comedones –> infundibulum open –> black keratin plug
• closed comedones –> infundibulum closed –> keratin plug deeper and trapped –> rupture follicle (inflammation) –> abscesses and scarring

Question 22

Panniculitis

Answer 22

• inflammatory rxn in subcu tissue**
• affects lobules of fat or connective tissue that separates fat (septa)
• associated with infections (beta hemolytic strep, TB), drugs, and IBS
• delayed hypersensitivity rxn (type 4 - T cell mediated)
• lesions and bruising on legs
• erythema nodosum is common form –> red plaques and nodules