Cutaneous Immunology

Question 1

Cutaneous physical defenses

Answer 1

• relatively impermeable stratum corneum
• continuous keratinization and dequamation
• antimicrobial peptides and secretions of free fatty acids through sebum

Question 2

Innate immunity

Answer 2

inherently programmed cells that destroy invading microbes before they establish infection

• non-specific and quick
• no long term memory
• mediated by phagocytic cells (neutrophils + macs)
• release inflamm mediators (mast cells + eosinophils) and also other cells like NK cells
• activated cells cause local tissue destruction and release cytokines (IL-1, TNF-a, IFN-y) for increased blood flow and fluid accum and recruit other immune cells

Question 3

Adaptive immunity

Answer 3

acquired response against specific antigens

• takes several days after initial stimulus
• subsequent exposures have faster and stronger response
• long-lived memory
• modulates response by altering cytokines released and cells recruited
• B-T lymphocytes and APCs (antigen presenting cells)

Question 4

Langerhans cells (LCs)

Answer 4

specialized dendritic cells (APC) that reside in epidermis

• phagocytose and process antigens
• encounter antigen –> migrate to regional lymph node to present antigen to T cells (form Cutaneous Lymphocyte Antigen cell-surface marker)
• if antigen specific T cell present, APC stimulate 2nd signal to activate T cell –> T cell proliferate/differentiate

Question 5

Dermal dendritic cells (DDCs)

Answer 5

Langerhan cells in the dermis

Question 6

TH1 cells

Answer 6

release IFN-y and TNF to stim cell-mediated immunity

• activate macrophages, dendritic cells, neutrophils and cytotoxic T cells
• clears viruses, tumors, intracellular pathogens
• Type IV (delayed) hypersensitivity

Question 7

TH2 cells

Answer 7

release IL-4, IL-5 and IL-10 to stim humoral immunity

• activate eosinophils and plasma cells for IgE production
• clears parasites and extracell microbes
• atopic dermatitis, urticaria + allergenic diseases

Question 8

TH17 cells

Answer 8

implicated in development of autoimmune diseases like Crohn’s disease, ulcerative colitis and psoriasis

Question 9

Allergic Contact Dermatitis (ACD)

Answer 9

adaptive cutaneous immune system producing exaggerated inflammatory response

• immune system creates local inflamm to destroy allergen
• AKA Type IV/delayed hypersensitivity
• itchy red papules and vesicles appear 24-48 hrs post exposure and worsen for 4-7 days
• mild erythema and scale to vesicles and bullae if severe acute or scale and lichenification if chronic
• allergens are usually haptens, which diffuse into epidermis and is phyagocytosed by LCs –> lymph node –> T cells –> TH1 reaction, clonal proliferation and migration of clones to skin (first time takes about 7-14 days, rexposure 24-48hrs)
• first exposure often doesn’t produce response

Question 10

Haptens

Answer 10

molecules too small to be recognized independently but capable of stimulating immune system after binding to native proteins

Question 11

Atopic Dermatitis

Answer 11

Eczema

• looks almost identical to ACD but due to TH2 dominance
• imbalance of immune system (assoc. with asthma and allergic rhinitis)
• genetic predisposition (filaggrin mutation), envi irritants/allergens (enters barrier disruption to initiate TH2 with positive feedback loop, impaired TH1), s. aureus
• generalized itchy skin and ill-defined erythematous papules and plaques with scale and crust (lichenification)
• Infants : affects face, scalp, extensor extremities
• Adults : affects face, flexural areas (antecubital/popliteal)

Question 12

Psoriasis

Answer 12

increased keratinization causing thickening epidermis

• erythematous, well-demarcated plaques with thick silvery-white scale resembling mineral mica
• some itching but less severe than in dermatitis
• extensor surfaces, trunk, extremities and genitals, nails
• associated with destructive arthritis (psoriatic arthritis)
• predominantly mediated by TH1 lymphocytes
• lymphocytes release cytokines to signal epidermis to proliferate rapidly causing thick plaques with scale
• controlled with chemotherapy targeting T cells or blocking TNF-a receptor
• TH17 involvement

Question 13

Koebner phenomenon

Answer 13

irritating or scratching of skin leads to outbreaks of psoriasis

Question 14

Guttate psoriasis

Answer 14

small round papules and plaques precipitated by strep infection

Question 15

Pustular psoriasis

Answer 15

numerous pustules localized to palms and soles

Question 16

Urticaria

Answer 16

Hives

• itchy, annular, edematous, pink papules/plaques (wheals)
• also can be linear wheals (dermatographism)
• deep in dermis = angioedema, causes painful swelling and often affects lips and face
• evanescence (lasts less than 24 hrs before resolving)
• type I (immediate) hypersensitivity
• Mast cells coated with IgE –> activation causes release of histamine, leukotrienes and prostaglandin
• histamine causes dilation of blood vessels and expansion of gap between endothelial cells –> fluid transudates to form localied edema
• histamine also works on nerves to cause itching
• fluid drained by lymphatics and substances broken down

Question 17

Mast cell degranulation

Answer 17

1. IgE Ab activation against allergen (Type 1 hypersensitivity)
2. drugs (opiates, ethanol)
3. physical stimuli (heat, cold, pressure, vibration, sunlight)

Question 18

Drug eruptions

Answer 18

Range from limited small fixed plaque to widespread blistering and sloughing of skin
-most commonly antibiotics, anticonvulsants and NSAIDs

Question 19

Exanthematous (morbilliform) drug eruptions

Answer 19

> 90% all drug eruptions (measle-like)

• drug metabolites cause delayed (type IV) hypersensitivity
• LCs phagocytose drug –> lymph node –> TH1 activation –> migration to skin
• takes 4-14 days after initiation of medication
• begin as erythematous macules/papules on trunk and upper extremities
• spreads outward to become confluent
• mildly itchy but not painful/isn’t morbid
• neither clinical appearance nor pathology can differentiate a viral exanthem from drug rxn nor identify drug responsible

Question 20

DRESS

Answer 20

drug eruption with eosinophilia and systemic symptoms

• characterized by exanthematous eruption with fever, lymphadenopathy and facial edema
• 15-40 days after drug with 5-10% mortality (fulminant hepatitis)

Question 21

Urticarial drug eruptions

Answer 21

subset of urticaria due to systemic medications

• 2nd most common cutaneous drug eruption
• occur within minutes of exposure when patient has IgEs
• immediate hypersensitivity (Type I)
• potential to be life threatening from airway compromise by angioedema or from widespread vasodilation and severe hypotension from anaphylaxis

Question 22

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

Answer 22

immune system activates cascade of apoptosis, causing widespread epidermal necrosis

• 7-21 days after exposure
• characterized by erythematous and dusky macules coalescing into patches on head, trunk and extremities
• mucosal ulcerations, bullae formation, sloughing of epidermis in sheets –> reveals dermis
• fever, systemic symptoms
• painful skin lesions + mortality complications