Glossary of UmmsDermatology

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keritinizing stratified squamous epithelium
4 cell types of Epdermis
keatinocyte (80%)
Melanocyte (10-15%)
Langerhans (3-5%)
Merkel cell (<1%)
Keratinocytes form 4 layers
Basal layer
spinous layer
granular layer
cornified layer
Basal layer
single proliferative layer
basophilic columnar to cuboidal cells
cells divide and migrate up
spinous layer
usually thickest layer
polygonal cells with eosinophhilic cytoplasm
dermosomal spines often visible
granular layer
1-4 cells thick
basophillic keratohyaline granules
cornified layer
outermost layer
cells lose their nuclei and flatten to form dead plates of keratin (roof shingles); shed as dead skin
Tiem to go from basal layer to stratum corneum
30 days
 Neural crest origin
 Found in basal layer
 Dendritic cell with stellate projections
 Ratio of melanocytes to basal cells is 1:4 to 1:10
 Cuboidal cells with eccentrically located, crescent-shaped nuclei; no desmosomes
 Function: produce protective melanin pigment
 Melanin packaged in melanosomes  transported to spinous layer keratinocytes
 Dark skin and light skin have same number of melanocytes; melanosomes more evenly dispersed in dark skin accounting for increased pigmentation.
Langerhans Cells
 Bone marrow derived
 Dendritic cell with stellate projections
 Found in suprabasilar epidermis and dermis
 Antigen presenting cell; mediator of skin immune response (i.e. delayed hypersensitivity reactions)
 Surface markers for Fc, C3 and Ia (immune response-associated) antigens
 Numbers decrease following UV exposure
 Birbeck’s granules, distinctive cytoplasmic organelles, seen ultrastructurally
Merkel Cell
 Found in epidermis and dermis
 Cells aggregate to form tactile corpuscles (slow-adapting touch receptors) associated with peripheral nerves
 Origin of cell unknown
 Function of solitary cells unknown
 Membrane bound dense core granules, similar to neurosecretory granules of APUD system, seen ultrastructurally
Basement membrane zone function
attaches dermis to epidermis
3 layers of the basement membrane zone
lamina lucida
lamina densa
sublamina densa
Lamina lucida
a. Electron-lucent zone
b. Anchoring filaments course through this zone, connecting the overlying basal cell at its hemidesmosome attachment plaque to the underlying lamina densa.
Lamina densa (basal lamina)
a. Made of Type IV collagen
b. Anchoring fibrils (made of Type VII collagen) and dermal microfibril bundles attach lamina densa to underlying dermis.
Sublamina densa
a. Intertwines with dermal collagen bundles
 Pilosebaceous Unit – 3 components
1. Hair follicle
2. Sebaceous gland
3. Arrector pili muscle
Apocrine Gland
Eccrine Gland
Hair growth – 3 phases
1. Anagen (growth) phase
3-4 years, 85-90% hairs
2. Catagen (involutional) phase
3 days, 1% hairs
3. Telogen (resting) phase
3 months, 10-14% hairs
3 portions of hair folicle
hair folicle
 Develops from downward proliferation of epidermal cells
 Outer root sheath – glycogenated
 Internal root sheath – Huxley’s layer, Henle’s layer, cuticle
 Hair – cuticle, cortex, medulla
Sebaceous gland
 Found everywhere except palms/soles
 Most abundant on face, chest, back and scalp
 Become functionally active at puberty
 Gland secretes sebum (lipid oily mixture) to provide emollients to hair/skin
 Structure
 Multilobular structure that connects to the infundibulum of the hair follicle
 Peripheral germinative cell layer
 Central lipid-laden cells with clear to foamy cytoplasm
Arrector pili muscle
 Smooth muscle that inserts into perifollicular connective tissue
 Sympathetic contraction makes hair “stand up” (goose-bumps)
Apocrine Gland
 Located in axillae, groin, eyelids (Moll’s glands), external auditory canal (ceruminous glands)
 Odorless secretion (odorous due to cutaneous microorganisms)
 Unknown function
 Enlarge and become active at puberty
 Stimulated by excitement/fear (adrenergic innervation)
Apocrine Gland: 2 structures
1. Secretory coiled gland
 Outer myoepithelial layer
 Inner cuboidal/columnar layer
 Apocrine decapitation secretion
 Found in deep dermis/superficial fat

2. Straight duct – connects to hair follicle (as part of pilosebaceous unit) or skin surface
Eccrine Gland
 Found everywhere except mucous membranes
 Dense on palms, soles, axillae, forehead
 Stimulated by thermal, mental, gustatory stimuli (cholinergic innervation)
Eccrine Gland structure
1. Secretory coiled gland
 Outer myoepithelial layer
 Inner secretory layer with 2 cell types: larger glycogen-rich pale cells and smaller, darker-staining cells
 Found in deep dermis/superficial fat
 Smaller than apocrine gland
2. Coiled duct
3. Straight duct
4. Spiraled duct (Acrosyringium)
 Intraepidermal portion
 Opens to skin surface
Connective tissue layer between epidermis and subcutaneous fat
parts of dermis
Papillary dermis - superficial dermis
- relatively thin
- Type III collagen
 Reticular dermis - deeper dermis
- thicker
- Type I collagen
Connective tissue matrix components of dermis
-Elastic tissue
-Ground substance
-Fibroblasts, mast cells, dermal dendrocyte (antigen-presenting cell)
Additional parts of dermis
 Epidermal appendages, blood vessels, nerves, cells (fibroblasts, mast cells, inflammatory cells) found in dermis
 Synthesized by fibroblasts
 Provides mechanical strength and extensibility
Collagen types
 Type I collagen - most abundant, tightly bundled
- reticular dermis
 Type III collagen - more fine, loosely arranged
- papillary dermis
 Type IV collagen - basement membrane (lamina densa)
 Type VII collagen - basement membrane (anchoring fibrils)
Elastic tissue
 Synthesized by fibroblasts
 Provides recoil and elastic properties
 Composed of the protein, elastin and a microfibrillar matrix containing fibrillin
 Desmosine and isodesmosine – amino acids unique to elastin protein
Ground Substance (Extracellular matrix)
 Synthesized by fibroblasts, possibly mast cells
 Important in skin hydration, preserves tensile elasticity, redistributes pressure forces
 Composed of fibronectin and glycosaminoglycans (hyaluronic acid, chondroitin sulfate, dermatan sulfate)
 Chief cell in dermis
 Produces collagen, elastin, and ground substance
 Contractile cell during wound healing
1. Free nerve endings – temperature, pain, pruritus
2. Meissner’s corpuscle – fine touch
3. Merkel cell complex – slow adapting touch
4. Pacinian corpuscle – deep pressure, vibration
1. Deep vascular plexus
2. Superficial vascular plexus (subpapillary plexus)
Deep vascular plexus
 Located at dermal-subcutaneous interface
 Arterioles arise from this plexus to supply epidermal adnexal structures and superficial vascular plexus
Superficial vascular plexus (subpapillary plexus)
Located in papillary dermis
 Supplies capillaries, end arterioles, and venules to dermal papillae
thickness of epidermis and dermis varies in different regions

The epidermis is thickest on palms and soles. The dermis is thinnest on eyelids and thickest on the back.
layers of the epidermis

Basal layer (stratum basale)
Spinous layer (stratum spinosum)
Granular layer (stratum granulosum)
Cornified layer (stratum corneum)
Melanocyte dendrites extend ...

Melanocyte dendrites extend in all directions, especially laterally along the basal cell layer and upward between the keratinocytes in the spinous layer. Once melanin is formed, it is transferred from melanocytes into keratinocytes by apocopation.
melanocytes in difft races

epidermal melanin unit in dark (left) and light (right) skin.
schematic representation of the epidermal basement membrane zone

bullous pemphigoid antigens are transmembrane proteins of the hemidesmosomes. Underlying them are anchoring filaments, about which very little is known. Laminin is a cruciate molecule that mediates adhesion of the cell to underlying matrix molecules. type IV collagen forms the lamina densa. Type IV collagen monomers arrange themselves to form a diamond-shaped mesh in which heparan sulfate proteoglycan is embedded. Type VII collagen forms the dermal anchoring fibrils that interact with sub-lamina densa domains of type IV collagen to form "hoops" through which the banded type I and type III collagen fibrils interwine. Each of these molecules contribute to the adhesion of the overlying basal cell to the dermis
three I's of pilar anatomy

infundibular, isthmus, and inferior
Differentiation of cells of hair matrix along six separate lines of development

from outside inward, Henle’s layer, only one cell thick and first to cornify; Huxley’s layer, characterized by brightly eosinophilic-staining trichohyalin granules and but two cells thick; cuticle of inner root sheath; cuticle of hair; hair cortex; and hair medulla. Surrounding the central core of these products of matrix is pale-staining, relatively broad, outer root sheath. Through the narrow outlet at distal end of bulb, the papilla emerges to become continuous with connective tissue sheath that envelops entire follicle
Loc of glands
3 gland types

eccrine sweat unit

The eccrine sweat unit is a simple hollow tube bounded distally by an opening onto the skin surface and proximally by a cul-de-sac. Both ends of the tube are wound and connected by a straight duct. The proximal portion coils in regular fashion, whereas the distal portion spirals through the epidermis.
cutaneous innervation

The cutaneous innervation includes (1) unmyelinated efferent sympathetic nerves that supply arterioles, eccrine glands, apocrine glands, and hair erector muscles, and (2) mostly myelinated somatic sensory nerves that supply specialized end-organs (e.g., Meissner corpuscles and Pacini corpuscles), Merkel cells, hair follicles, and free dermal nerve endings.
Relationship of the superficial and deep
vascular plexuses.

Relationship of the superficial and deep
vascular plexuses.
Major Immunobullous Skin Disorders
Pemphigus vulgaris
Paraneoplastic pemphigus
Pemphigus foliaceus
Bullous pemphigoid
Ocular cicatricial pemphigoid
Epidermoylsis bullosa acquisita (EBA)
skin layers (4) and disease (4)
Cornified = pemphigu foliaceus
Granular = pemphigus vulgaris
Spinous = bullous pemphigoid
Basal = epidermolysis bullosa acquisita (EBA)
how are there connections in the dermal sheet
kertain in cells anchors to desmosomes which holds stuff together
Ds depends on
1) where in the skin Ab are found(cell layer)
2) which immunoreactants are present (IgG, IgA, C3)
3 tests
take tissue perilesional to blister
1) Direct immunofluorescence--> Ab
2) light microscopy

collect serum
3) indirect immunofluorescence for serum ab
Indirect Immunofluorescence
examine patients serum to look for circulating ab for confirming a ds of immunobullous disease and testing different dilutions of patients serum --> circulating ab titer which can help assess response to tx
1) diuted serum is added to normal tissue to allow for binding of any path ab present in serum
2) wash to remove serum and then sections are reacted with fluorescent ab
pemphigus foliaceous:
sx and demog
demog: elederly
sx: scaly superficial crusted erotions that are frequently erythemitous
LOc: distributed on trunk, extremtitis (rarely orally)
pemphigus foliaceous:
split high in epidermis in the granular layer
pemphigus foliaceous:
IgG on keratinocyte cell surface especially in granular cell layer . indirect immunofluorescence shows presence of circulating anti-keratinocyte Ab.
can produce blisters in newborn mice proving they cause the disease
pemphigus foliaceous:
pathogenic autoAb directed agains desmosomal protein in epidermal granular cell keratinocytes

Anti - Desmoglian 1 (Dsg1)
Pemphigous folliaceous
course: may be severly debilitating (was fatab b4 steroids but not fatality is <10%)

Tx: for localized and ltd ds, topical coticsteroids by be ok but if its serious give oral corticosteroids and a steroid sparing agent (cell sept, imuran or cytoxin)
Pemphigus vulgaris:
demog and sx
demog: usually in adults
sx: primary lesions are flaccid blisters usually on normal appearing sking (painful not pruritic)
ruptured bullae give rise to erosions and crusting ...sometimes preceding skin lesions by many monts
oral ds --> reduced intake and wt loss

Loc: anywhere on skin including scalp. most have oral lesions
Pemphigus vulgaris:
intraepidermal split, in lower epidermis (spinous cell layer)
Pemphigus vulgaris:
IgG on keratinocyte cell surface. Indirect immunofluorescence show presence of circulating antikeratinocyte Ab. May corr with ds activity
Pemphigus vulgaris:
Ab agains Desmoglein 3 (Dsg-3)
Pemphigus vulgaris:
may be severely debilitating
(prior to steroids was always fatal but now <10%
Pemphigus vulgaris:
corticosteroids and a steroid sparing agent (cellsept, imuran or cytoxan)

sever cases in the burn unit with plasmaphoresis used t acutely decrease circulaton of path Ab but rebound can occur unless cytoxan is used to prevent B lymphocyte clones from producing even higher levels of paht Ab than b4 tx
Paraneoplasic pemphigus
a varient caused by a pathogenic ab to a variety of antigens including desmoplakins I and II, bullous pemphigoid antigen I, evoplakin, periplakin, and HD1/plectin. Mucosal involvment is exp severe and resistant to tx (may also FX GI and resp tract)
All patients have an underlying malignancy
Bullous pemphigoid:
sx and demog
demog: elderly

sx: large tense bullae on erythematous base ; very pruritic
loc: trunk extremities (rare mucosal inhovement)
Bullous pemphigoid:
subepidermal split, with mixed infiltrate of inflammcells in dermis that includes eosinophils.
Split high in basement memb (non scarring), based on electron microscopy and immunolocalization studies
bullous pemphigoid:
IgG and C3 at the dermal epidermal jct in a linear pattern
bullous pemphigoid:
pathogenic autoAb directed against proteins in basal keratinocyte hemidemosomes, which normally anchor the cells to the bm

Anti: BP antigen (BPAG1 or BPAG2)
bullous pemphigoid:
Course and Tx
Course: frequently selfltd resolving iwthin 3 yrs with occasional pt having severe generalized ds with prolonged course

Tx: potent topical steroids may be ok.
If systemic, use prednisone or combined tx with tetracycline (has anti-inflammatory FX) and niacinamide.
Prednisone is very effective and in severe cases (relatively severe for bullous pemphigoid) a steroid sparing agen may be req
Epidermolysis Bullosa Acquisita
demog: usually >40
sx: blisters on non-erythemitous skin that heals with scarring and formation of milia (tiny cysts).
Loc: distal extremities
Epidermolysis Bullosa Acquisita:
subepidemal split usually with little inflammatory cells. Split below the basement membrane (scarring) based on em and immunolocalization studies
Epidermolysis Bullosa Acquisita:
pahtogenic autoantibodies directed against type VII col which is normally found in anchoring fibrils loc beneath the basement membrane. These patients have reduced numbers of anchoring fibrils and therefore an adhesion defect at the dermal-epidermal jct

Anti-TypeVII col
Epidermolysis Bullosa Acquisita:
IgG at the dermal-epidermal jct in a linear pattern
Epidermolysis Bullosa Acquisita:
Course and tx
Course: frequently self-ltd resolving within 3 years. Occasional patients have severe generalized ds and prologned course

Tx: poor response to tx
Mechanobullous BDiseases
what are these
What: diseases in which relatively minor trauma leads to blister formation
Caused by: 1) proteins req for maintenance of epidermal integrity or 2) epidermal-dermal adhesion
Ds: based on clinical findings, histology (inclu detection of relevant struct proteins and electron microscopy) and DNA analysis to screen for gene alterations responsible for disease (req genetic counciling)
Mechanobullous Ds
1) Epidermolysis Bullosa Simplex
2)Junctional Epidermolysis Bullosa
3)Dystrophic Epidermolysis Bullosa
Epidermolysis Bullosa Simplex:
demog and sx
demog: neonatal period or adulthood
mild EBS --> blisters in traumatized areas (hands feet) in adults
severe EBS--> generalized blisters in neonates with extremities commonly involved
Loc: extremeties most common
Epidermolysis Bullosa Simplex:
cleavage within epidermal basal cell layer
Epidermolysis Bullosa Simplex:
mutations in genes encoding keratin proteins which spontaneously assemble into filaments. Keratin filaments, part of the cytoskeleton, are req for maintaining the structural integrity of keratinocytes Defective keratin form clumps instead of filaments

Anti-Keraitin 5 or 14 (K5 or K14)
Epidermolysis Bullosa Simplex:
course and tx
course: range from mild to severe
tx: minimize trauma and practice good wound care. No effective treatment
Junctional Epidermolysis Bullosa
sx and demog
demog: at birth
sx: blisters and erosions.
may also affect ocular repiratory, GI, and GU epithelia. Some subtypes carry a greatly increased risk of sepsis with rare survival past infancy.
Junctional Epidermolysis Bullosa:
cleavage within the basement membrane
Junctional Epidermolysis Bullosa
mutations in genes encoding proteins within the basement membrane
Junctional Epidermolysis Bullosa
Course and Tx
course: range from mild to severe
Tx: minimize trauma and practice good wound care. No effective tx
Dystrophic Epidermolysis Bullosa
sx and demog
demog: at birth (some as late as early childhood)
sx: blisters and erosions may also affect ocular, repiratory, GI/GU epithelia. Some subtypes carry a greatly increased risk of sepsis with rare survival past infancy
Loc: generalized in some forms most mucosal surfaces are involved
Dystrophic Epidermolysis Bullosa:
Subepidermal cleavage
Dystrophic Epidermolysis Bullosa:
mutations in gene encoding protein within the anchoring fibrils

gene mutated --> type VII col
Dystrophic Epidermolysis Bullosa
Course and tx
Course: generically severe with extensive scarring. Malnutrition and growth retardation are common. Pts can develop aggressive squamous cell carcinomas in areas of scarred skin.

Tx: Minimize trauma and practice good wound care. Early attemps at gene therapy.
Loc of cleavage planes in three major forms of epidermis bullosa:
1) EB simplex (mutations in keratins K4 or K14): within the basal layer of epidermis
2) Junctional EB (mutaitons in lamanin 5): within the lamina lucida of the basement memb
3) Dystrophic EB (type VII col mutation): beneath the basement membrane with a deficiency of anchoring fibrils
Chronic Plaque PSoriasis:
skin sx (4)
sx: 4 prominent features:
1)Sharp demarcation
2) Silvery micaceous scale
3) Glossy erythema under scale
4) Auspitz sign=
-pinpoint hemorrhage seen when scale removed
-Not seen in inverse or pustular
-May help distinguish psoriasis from other similar dermatoses

Loc: Elbows & Knees, Scalp, Gluteal cleft, Hands & feet, Retroauricular, Periumbilical
Inverse psoriasis
-Psoriatic plaques can be localized to skin folds: Axillae, Genital, inframammary
-Absent scale
-Sharply demarcated, glossy erythema
Koebner phenomenon
- ~25% of pts
- Psoriasis develops in areas of skin injury
Other forms of skin injury can also cause: Sunburn, Drug eruptions, Viral exanthems
-Seen in some other dermatoses as well
Eruptive/Guttate psoriasis
-Mult small papules (5-15 mm)
-Upper trunk & proximal extremities
-Younger patients
-Often follows strep throat or viral URIs
-Better prognosis
Erythrodermic psoriasis
-Generalized disease
-Reason to hospitalize
-Patients acutely ill: Fevers/chills, Total body erythema,Fine scale
-Diagnose by history: Known psoriasis, Characteristic nail changes
Pustular psoriasis
-Generalized OR localized forms
-Sterile pustules on red skin
-Triggers: Pregnancy (impetigo herpetiformis), Withdrawal from corticosteroids, Infection
-Generalized pustular psoriasis has systemic findings: Short episodes of fever, Weight loss, increased WBC, hypocalcemia, increased ESR
Psoriasis and Nail involvement
-10-78% of patients
-Fingers > toes
-Pits: nail matrix
-Oil spots: nailbed
-Splitting/thickening/onycholysis: distal nailbed
-Nail loss (anonychia): pustular involvement
Psoriatic arthritis
-5-30% of patients with cutaneous psoriasis
-In some pts(10-15%), appears before skin lesions
Common (95%):asymmetric oligoarthritis in the Small joints of hands/feet(DIP near pathognomonic) and in the Large joints of legs
-Uncommon (5%):arthritis mutilans
- ~2% of the US population
-Average age of onset 27-29 y.o.
- Peaks at age 22.5; smaller peak at age 55
-Earlier onset (before age 15)implies 1)Worse disease
because theres greater surface area involvement and worse response to therapy
and 2) Greater probability of affected family members
Genetic predisposititon
- Twin studies (MZ > DZ twins)
- ~1/3 of patients have relative with disease
- Parents with psoriasis:
1 parent—8.1% of offspring have disease
Both parents—41% of offspring have disease
Psoriasis and HLA
HLA-Cw6: have guttate psoriasis or early onset patients (85%)

HLA-B27: Pustular psoriasis and psoriasis with peripheral arthritis

Psoriasis gene
HLA-Cw6 is the PSORS-1 gene
This gene confers increased likelihood of early-onset psoriasis
Psoriasis pathogenesis
Shortening of epidermal cell cycle (8-fold): (from 311hrs to36hrs)
More cells produced per day: (from 1218 to 35,000)

Has to do with T cell activation
Psoriasis and T cells
1) Many T-cells in active lesions
2)Bone marrow transplantation
(clean donor then Psoriasis resolves, psoriatic donor then Psoriasis develops)
3) If you suppress T-cells, psoriasis improves so you tx with:
-Ultraviolet light depletes skin of immune-competent cells, especially T-cells
Lymph node t-cell activation
Requires 2 things:
1) Interaction of MHC and T-cell receptor
2) Interaction between costimulatory molecules
(ICAM-1 and LFA-1, LFA-3 and CD2, CD40 and CD40L, B7 and CD28)
Psoriasis Tx
Non-targeted therapy: Serendipitous discoveries
These treatments are used for the majority of psoriasis patients

1) Topical steroids
2) Vitamin D analogues
3) UV phototherapy
4) Retinoids
5) Methotrexate
6) Cyclosporine
Steroids in psoriasis
- Mainstay of anti-inflammatory treatment

-Inhibits transcription of:
[proinflammatory cytokines, Chemokines, Adhesion molecules (ICAM, VCAM)]
Biological Therapies in Psoriasis Tx:
1) block t cell activation and co-stimulation
2)block t cell proliferation and survival
3)Cytokine Blockade
4)Immune deviation
Block t cell activation and co stimulation:
2 ways
1. Alefacept (Amevive)—fusion protein (LFA-3 and human IgG1); blocks CD2/LFA-3 interaction
2.) Efalizumab (Raptiva)—antibody to CD11a component of LFA-1 on T-cells; blocks binding to ICAM-1 on APC
- Also blocks binding of LFA-1 to ICAMs on endothelial cells, preventing T-cell migration into skin

These drugs are FDA-approved for treatment of psoriasis
block t cell proliferation and survival
1. Daclizumab and basiliximab—antibodies to components of IL-2 receptor; block IL-2 binding and T-cell proliferation

2. Limited efficacy in psoriasis (drugs not in general clinical use)
Cytokine Blockade in psoriasis
1. Etanercept (Enbrel)—fusion protein of two TNF-a receptors—binds TNF-a

2.Infliximab (Remicade)—chimeric antibody to TNF-a—binds TNF-a

3.Adalimumab (Humira)—fully human antibody to TNF-a—binds TNF-a

These drugs are FDA-approved for treatment of psoriasis
Immune Deviation in Psoriasis
-Psoriasis is a Th1 process

-Goal— increase Th2 response, decrease Th1
-Recombinant IL-4 (RhuIL-4)
-Recombinant IL-10 (Tenovil)

These drugs not in general clinical use
Th1 -Th2 paradigm in psoriasis
Th1 cells:
-Promote macrophage activation (cell-mediated immunity)
-Differentiation stimulated by IFN-γ and IL-12, inhibited by IL-4, IL-5, IL-10

Th2 cells:
-Promote antibody production (humoral immunity--IgM, IgA, IgE)
-Differentiation stimulated by IL-4, inhibited by IL-12, IFN-γ

Key Th1/Th2 Cytokines in Psoriasis vs Atopic Dermatitis
Psoriasis: (Th1) IL-12, IFNgamma, IL-2

Atopic Drmatitis: (Th2) IL-4, IL-5, IL-10

very unusal to see both in the same patient
Atopic dermatitis:
labs on blood show..
demog: Early infancy and childhood
frequency: increased incidence, esp. in industrialized countries
freq: prevalence 10-20% in children, 1-3% in adults
Genetics: 73% give a family history of atopy
Labs: Pts have increased blood eosinophilia and increased IgE
what ds are in the atopic triad
Atopic Dermatitis
Allergic rhinitis
sx of Atopic Dermatitis
-Intense pruritus --> SCRATCHING
-Cutaneous reactivity: reduced threshold for pruritus
(Allergens, reduced humidity, excess sweat, irritants exacerbate pruritus and scratching)

Clinical manifestations Acute AD
-More frequent in infancy: (Face, Scalp , Extensor extremities)
Clinical manifestations Subacute AD
Dry skin
Clinical manifestations Chronic AD
- Thickened plaques
- Accentuated skin markings (lichenification)—due to rubbing & scratching
-Fibrotic papules (prurigo nodules)
-Dry skin
-In older children and adults: (Flexures of extremities, Chronic hand dermatitis)
Pathogenesis of AD
1. IgE bound to Langerhans cells (LC) binds allergen
2. Allergen-triggered LC and mast cell release IL-4 and IL-10 --> Th2
3. Meanwhile, Th2 cells circulate in blood of AD patients, lead to:
increased IgE increased Eosinophils
Atopic Dermatitis : Normal Skin
Even unaffected skin is not normal.

-Increased dryness; increased water loss from skin
-Greater irritant skin response
-Sparse perivascular T cell infiltrate with increased Th2 cells present
Hygiene hypothesis of atopy
- Recent increases in atopy, especially in industrialized nations
- Early infections or exposure to microbial material early in life may prevent development of Th2-driven allergic disease
- Reduced microbial exposure environment may lead to enhanced Th2 response
Triggers for AD flares
1. Allergens:
- Food allergens can cause a flare in nearly 40% of children with AD
- Aeroallergens: inhalation of allergens can cause flares, esp in more severe AD
2. Microbes:
Staphyloccus aureus overgrowth
Risk for infection in atopic dermatitis
Increased risk of infection

- increased bacterial, viral, and fungal skin infections
Th1 = good cell-mediated immunity
Th2 = poor cell-mediated immunity
- 90% of AD skin lesions harbor S. aureus (vs. 5% of normal controls)
- In studies of mice undergoing either Th1 or Th2 inflammatory responses, S. aureus binds better to Th2 skin sites
- If superinfected, antistaphyloccal treatment can lead to significant improvement in AD

Herpes simplec --> eczema herpeticum
Smallpox vaccination --> eczema vaccinatum
-CDC recommends against vaccination in patients with AD
Treatment of AD
6 real dx and some preventative
-- Moisturize: dry, cracked skin is a portal for infection and allergens
-- Mild soaps and cleansers
--Avoidance of irritants and allergens (if identified)

1. Topical steroids—cornerstone of therapy
2. Anti-infective therapy
3. Antipruritics/antihistamines
4. Topical immunomodulators:
5. Tacrolimus (FK506)
6. Pimecrolimus (ASM 981)
Topical immunomodulators for AD
1. Tacrolimus (FK506)
- Interferes with T-cell activation
- Interferes with Th1 and Th2 cytokine transcription

2. Pimecrolimus
- Interferes with T-cell activation
- Decreases Th1 and Th2 cytokine expression
future directions for AD
As in psoriasis, better understanding of mechanisms underlying AD leading to investigation of new drug therapies

-- IgE antibodies to keep IgE from binding to mast cells
-- Recombinant human IFN-γ to boost Th1 response
-- Treatment with microbial probiotics to boost Th1 immune response
-- Cytokine modulation: anti-IL-5 antibodies
Cytokines in Psoriasis vs AD
Th1 pattern predominates in psoriasis
Key cytokines: IFN-γ, IL-12, IL-2

Th2 pattern predominates in AD
Key cytokines: IL-4, IL-5, IL-10
Biologic Therapy (2 and their targets)
1. Etanercept/Infliximab/Adalimumab—bind TNF-α

2. Alefacept/efalizumab—block T-cell activation and co-stimulation
T cell activation:
on what
what is result
req 2 things
on&to: naive t cell -->mature t cell

1. Interaction of MHC and T-cell receptor
2. Interaction between costimulatory molecules
- ICAM-1 and LFA-1
- LFA-3 and CD2
- CD40 and CD40L
- B7 and CD28
T cell activation-- Th1 vs Th2
pix mc pix
Th1 vs Th2 paradigm
Th1 cells:
--Promote macrophage activation (cell-mediated immunity)
-- Differentiation stimulated by IFN-γ and IL-12, inhibited by IL-4, IL-5, IL-10

Th2 cells:
-- Promote antibody production (humoral immunity--IgM, IgA, IgE)
-- Differentiation stimulated by IL-4, inhibited by IL-12, IFN-γ

-- Erythematous plaques with excoriations
-- Common sites-forehead,neck
-- Periorbital pigmentation
-- Dennie-Morgan sign
Atopic Dermatitis
Erythema vs hyperpigmentation
Both w/scale
Wrist and antecubital fossa
Atopic Dermatitis
Reaction pattern, more common in blacks and asian children; discrete follicular papules, pruritic; some pts have associated nickel allergy (jeans)
Follicular Eczema
mild exzematous dermatosis, mostly face and upper arms of children, mainly cosmetic concern is darkly pigmented skin
Pityriasis Alba

Alba=white, pityriasis=scaling
--Heliotrope rash- erythematous in caucasians

--Slight hyperpigmentation- less distinctive
--Well demarcated
--Erythematous to violaceous
--Plaques (can develop bulla or erosion)
--Lesions recur @ same site
Fixed Drug Eruption (white)
Well demarcated
Hyperpigmented instead of erythematous
Plaques-can also develop bulla
Fixed Drug Eruption
Hypo or hyperpigmentation in darker pigmented skin
May be confused with SLE
Seborrheic dermatitis
Erythematous --> purplish plaques
White lacy marks (wickham stria)
Lichen Planus
Major Determinants of Skin Pigmentation
Melanin : most important
Oxyhemoglobin: red hue to skin
Deoxyhemoglobin: blue tint to skin
Carotene: orange hue to skin and conjuctiva
Skin Color : Constitutive vs Facultative
Constitutive skin pigmentation refers to "baseline" genetically determined color in the absence of sun exposure or other factors

Facultative skin pigmentation refers to that which results after secondary melanin induction.

The most potent and relevant inducer of melanin pigmentation is solar ultraviolet (UV) irradiation.
Skin phototypes:
Method to classify people’s responses to UV exposure based on ability to sunburn or tan

SPT1: Always burns easily, never tans
SPT2: Always burns easily, tans minimally and with difficulty
SPT3: Burns minimally, tans gradually and uniformly (light brown)
SPT4: Burns minimally, tans well (moderate brown)
SPT5: Rarely burn, tans very well (dark brown)
SPT6: Almost never burns, tans profusely
Erethema Action Spectrum and sunlight
UVA longer wavelength– increased pigmentation; has less energy (20 j/cm2 of uva required to get same effect as 20 mJ/cm2 of uvb)

UVB shorter wavelength- induces erythema and sunburn
Melanocytes derived from neural crest cells
Melanin production determined by activity of Tyrosine
Key regulatory enzyme: tyrosinase
Tyrosinase activity increased in darkly pigmented individuals
Melanin is most prevalant in basal cells
Melanosomes (stage I-IV)
Melanocytes in dark skin
Melanosomes are larger and more evenly dispersed in dark skin --> increased pigmentation
Tyrosinase activity
Tyrosinase activity is more than doubled in dark-skinned individuals
More constitutive pigment – increased probability of developing dyspigmentation
May be hyper or hypopigmentation
Cytokines associated w/inflammation cause melanocytes to make more or less melanin
May take months-yrs to resolve
Post-inflammatory dyspigmentation
Treatment for pigmentation changes
goal : Treatment for pigmentary changes aimed at shortening the time to natural resolution by reducting the inflammatory processes

Topical retionoids speed up resolution-
After time, DLE resolves to look like ..
DLE resolves with hypopigmentation, hyperpigmented borders
Retinoic Acid on hyperpigmentation in darker skin tones
RA lightens hyperpigmentation in 40 weeks

Overall facial lightening

lighening begins at 4 weeks with RA but 24 weeks without :(
skin is completely depigmented vs hypopigmented
believed to be autoimmune process which mediates melanocyte death
Sunscreen is essential to both involved and uninvolved skin
Koebnerization by UV burn
Uninvolved skin may tan --> more dramatic difference

Involved skin is no longer protected by melanin--> UV --> koebnorization --> worsening
Normal skin UV can cause inflammation --> loss of pigment
Unrestrained growth of scar tissue- benign

± Trauma- may grow beyond injury site

Common sites – ear lobes, neck, face, and shoulders

Usually asymptomatic but may be painful or itchy
Keloids: Tx
Intralesional steroids
Kenolog 5-40 mg/ml
Compression – Keloid Klips
Idiopathic, chronic, granulomatous inflammation that affects many organs

Primary lesions- lung, skin, eye, liver, brain

Histology- look like granulomas in all affected organs

In US- more common in people of African descen
Diseases/conditions that occur almost exclusively in darkly pigmented patients with very curly hair
Acne keloidalis nuchae
Pseudofolliculitis barbae
Follicular degeneration syndrome
Traction alopecia
Nape of neck/occipital area
Papular and pustular lesions‡ may develop hypertrophic/keloidal scars
Etiology- shaving very curly hair close to scalp
Hair grows into skin ‡ elicits a foreign body reaction
Acne Keloidalis Nuchae
papular and pustuar lesions --> may develop hypertrophic / keloidal scars

BEARD area
Pseudofolliculitis Barbae
female > male
Certain hairstyles put physical stress on hair
Occurs in crown and at the hair line
+/- permanent change
Traction Alopecia
Due to hot oil on scalp and hair
May also be seen with chemical relaxer use
Usually vertex scalp
May lead to scarring alopecia (poor regrowth)
Follicular Degeneration Syndrome
Drug reaction timing
Most reactions occur within 1 week of exposure to the medication.

Exception: semi-synthetic penicillins and ampicillin
50% begin 1 week after exposure or later
Pathogenesis of the cutaneous rash:

non-immunologic reactions vs immunologic reactions
Non-immunologic reactions
Destabilize mast cell membranes
Mast cell mediator release

Immunologic reactions
Smaller meds must bind with a hapten to cause reactions
IgE-dependent or immune complex
Most common medication reaction

Urticaria (hives)
Non-immunologic reactions
Mast cell and basophil mediator release
Itching, urticaria, bronchospasm, anaphylactic shock
immunologic reactions: IgE dependant
Circulating antigen
~6 days after exposure to synthesize sufficient antibodies (IgG or IgM)
Antibody complexes
Serum sickness
Immunologic reactions: Immune complex
Maculopapular reactions
Ampicillin during the prodrome of infectious mononucleosis (Epstein-Barr virus) can cause a generalized maculopapular reaction;

patients are NOT allergic to the antibiotic after the disease is over.
Top 10 Dx to cause rxns

Semi-synthetic penicillins*
Whole blood+
Penicillin G*
Packed red blood cells+
Urticaria (hives)
Dermal pink papules and plaques

Very itchy

Most medications have been reported

Angioedema may be life threatening
erythema multiforme
An acute eruption of macules, papules, or subdermal vesicles presenting a multiform appearance, the characteristic lesion being the target or iris form of lesion over the dorsal aspect of the hands and forearms; its origin may be allergic, seasonal, or from drug sensitivity, and the eruption, although usually self limited, may be recurrent or may run a severe course, sometimes with fatal termination (Stevens-Johnson syndrome).
bullous form of erythema multiforme that may be extensive, involving the mucous membranes and large areas of the body; it may produce serious subjective symptoms and may be fatal.
Prodrome of fever, pruritus, conjunctivitis
Progressive toxemia with mucosal erosions (oropharynx, eyes, genitalia)
Cutaneous lesions are painful, plaques, target lesions or ill-defined erythema
Sheet like loss of epidermis and Nikolsky’
Toxic Epidermal Necrolysis
Toxic Epidermal Necrolysis Tx
Withdrawal of culprit drug
IVF/supportive care
Burn center
Corticosteroid use is controversial
--May retard wound healing
--Patients may be more susceptible to infection
--Anecdotal reports suggest there may be value
Ocular lesions need to be assessed
Palpable purpuric lesions on the legs

Heart, liver, kidney may be involved

May be fatal

Thiazide diuretics
tx of Vasculitits
Thiazide diuretics
Looks like lupus

Serology is positive for anti-histone antibodies
Medication-induced lupus
Medication-induced lupus Tx
Tx (2)

Thiazide diuretics
Bluish-gray color

Drug deposits in skin
Pigmentary changes
dx assoc with pigmentary changes
Recur in the same site each time drug is administered

Round plaques of edema, erythema, blister

Leads to post-inflammatory hyperpigmentation

Limbs and genitalia
Fixed drug eruption
Treatment of Drug Rash
Withdrawal of offending agent
Antihistamines and topical steroids
Systemic corticosteroids
Penicillin desensitization (Allergy Department)
Patient education
--Drug rash may persist for weeks after withdrawal
Potassium Hydroxide (KOH) Preparation tests for what
Fungi — long, branching hyphae;

Yeast — thin hyphae (and budding yeasts)

Tinea versicolor — “spaghetti and meatballs”
what is the KOH test
Add a drop of potassium hydroxide (KOH; dissolves the epidermal cell walls) to the skin scrapings on a slide.
Examine under microscope.
Fungal Culture :
Indications — Verification of fungal infection.

Methods — Suspected material (scale, hair) is sent to lab in sterile cup or placed directly on agar.
Fungal Culture
Various pathogens identified by gross morphology of fungus that grows out.
Candida spp. are fast-growing (3-7 days) and have a mucoid look and a yeasty smell. Fungus may take up to 4 weeks to grow in culture.
Mineral Oil Preparation
Indications — Scabies

Choose site (small dot beyond burrow in finger web for scabies).

Transfer scrapings to the slide. Add mineral oil. Put on a cover slip and examine under microscope.

Results — Live scabies mites; eggs; feces
Direct Observation (as a diagnostic method)
Indications — Pubic lice and head lice.

Methods — Look for lice (creepy-crawlies), or nits. Don’t forget the eyelashes.

Results — Lice and nits are directly visible.
Viral Testing looks for
Herpes simplex
Herpes (varicella) zoster
Varicella (chickenpox)
Viral Testing of skin lesions
Must have an intact vesicle for reliable results.

Scrape the base of the lesion. Send to lab for rapid direct fluorescent antibody (DFA) test (1 hour) and viral culture (3 days).
Tzanck Smear
Must have an intact vesicle for reliable results. Scrape the base of the lesion. Add a nuclear stain. Examine under the microscope.

Multinucleated giant cells
Wood's Lamp
Erythrasma (Corynebacterium minutissimum) — scale fluoresces coral-red.

Porphyrias — urine, feces, blood will fluoresce in the various porphyrias. The color is bright coral pink.

Pigmentary disturbances
Wood's lamp will enhance the color differences

Examples: vitiligo (depigmentation), melasma (hyperpigmentation)
Patch Testing
Evaluation of contact dermatitis.

Suspected allergens are placed on test discs that are taped on the skin. Patches are left in place for 48 hours, then read.
Positive results range from erythema to vesicles.

Add ultraviolet for photopatch testing for photoallergy.
Diagnostic Surgical Techniques: punch technique
For lesions suspicious for melanoma; measuring the depth of the lesion is important in determining prognosis

Used for lesions in which the significant pathology is below the epidermis
Diagnostic Surgical Techniques: Shave technique
For diagnosis of epidermal tumors like basal cell and squamous cell carcinomas
Diagnostic Surgical Techniques:
Routine histopathology—”H + E”
what it sounds like
Diagnostic Surgical Techniques: Immunofluorescence
Fluorescein-tagged anti-IgG, anti-IgA, and anti-C3

Shows where immunoglobulins and complement are attached to proteins in the skin
Skin scrapings may show
Skin scrapings may show hyphae of fungi or yeast; mites or eggs of scabies; organisms or eggs of lice; or herpesvirus infection
Fungal cultures can demonstrate
the specific fungus, usually within a month
(common pimples); Nodulocystic acne (severe form)
Acne vulgaris
(papules and redness, usually in adults, usually in central 1/3 of face)
Acne rosacea = Rosacea
(papules and redness around the mouth)
Perioral dermatitis
Agents for Topical Acne
3 agents and their SideFX
1. Benzoyl peroxide; azelaic acid; many other unrelated agents
SE – irritation

2. Retinoids (drugs with vitamin A-like activity):
tretinoin (Retin-A); adapalene (Differin); tazarotene (Tazorac)
SE - dermatitis (retinoid reaction)

3. Antibiotics, usually clindamycin; metronidazole for rosacea
MA - Reduces Propionibacterium acnes in follicle, reducing inflammatory byproducts
SE - dryness from usually alcoholic vehicle
Oral agents for Acne
3 agents
1. Antibiotics, usually tetracycline, erythromycin, or minocycline
MA - Reduces P. acnes in follicle, reducing inflammatory by-products; direct anti-inflammatory action?
SE - nausea; vaginal yeast infections

2. Oral contraceptives
For women only; all have variable efficacy

3. Isotretinoin (Accutane, others)
MA - exactly how it works in acne is unknown. For severe, nodulocystic acne. After 4 to 6 month course, many patients achieve permanent clearing of severe acne.
SE - Typical for retinoids: dermatitis;hyperlipidemia;(NOT a mutagen, so can be taken before future pregnancy, as long as NOT taken during pregnancy)*; black box warning; depression and suicide associated with use (causality unclear)
ex ds
ie: when skin is thick
ex ds: Psoriasis
Psoriasis Topical Tx
A. Tars, salicylic acid (OTC agents for psoriasis must have one or other)

B. Vitamin D derivative: calcipotriene
SE - irritation
Psoriasis Systemic Tx
Retinoid: acitretin (Soriatane)
MA - Affects epidermal cell differentiation
SE - Retinoid toxicity: dermatitis, hyperlipidemia;
— under some circumstances, has long half-life so should not be given to women of child-bearing potential except in exceptional circumstances
Disorders: 1) Psoriasis, 2) seborrheic dermatitis, 3) Contact dermatitis (like poison ivy), 4) Eczema, atopic dermatitis, 5)Lichen planus
3 types
1.Coritcosteroids (topical, local, systemic)
2. Phototherapy
3. Calcineurin inhibitors
Corticosteroids (glucocorticoids) are also called corticoids but usually called steroids (poor term, confuses because of mineralocorticoids)
MA - Inhibits inflammation
ex, sidefx
ex: Hydrocortisone(available without a prescription)
SE: Unlikely, but effectiveness is low, too

Potency: More potent corticoids are metabolized more slowly in skin or made more potent by altering molecular structure (often by adding one or more fluorine molecules, i.e., fluorinated corticosteroids)

SE - thinning (atrophy) of skin; systemic absorption can lead to hypothalamic-pituitary-adrenal (HPA) axis suppression
Corticosteroids: Systemic
Prednisone and others
SE - Suppression of HPA axis. Short-term use (up to one month)reduces risks and is widely used without problems.
Ultraviolet therapy
Medical use is controlled; tanning parlors are unregulated

SE - sunburn, skin cancer, early signs of aging skin

use for
names are (2)
Disorders: Atopic dermatitis, eczema

Tacrolimus (Protopic); pimecrolimus (Elidel)

MA - prevents T-cell activation

Labeled for use for treating psoriasis and for preventing rejection of transplanted organs
SE – nephrotoxicity

ds used for
side fx
Urticaria (hives)
Itching conditions
MA - reversibly occupy the histamine receptor on cells so histamine effects are reduced; do not directly affect histamine release.
SE - Those that cross blood-brain barrier can cause drowsiness (desirable for itchy patients). Low-sedating antihistamines don't cross blood-brain barrier easily.
ANTI-INFECTIVES: classes (4)
1. antifungals and anticandidal agents
2. antivirals
3. antibacterials
4. antiparisitics
antifungals and anticandidal agents:
MA - most interfere with fungal synthesis of sterols which are required to maintain the fungal cell wall

Disorders: Athletes' foot, jock itch, etc. Dermatologists use the term "tinea" to mean fungal infection (e.g., tinea pedis meaning fungal foot).
topical: many
1. Griseofulvin
2. Itraconizole
3. Terbinafine
antifungals and anticandidal agents: systemics
Name all 3
what are they used for
side effects
1. Griseofulvin
2. Itraconizole/ Ketoconazole, fluconazole
use: Effective for ordinary tineas and Candida species
SE: Azoles have many drug-drug interactions because they inhibit a major drug metabolizing cytochrome enzyme CYP3A4. A careful drug history is important if using azoles.

3. Terbinafine
use: Effective for ordinary tineas
SE - Rare liver toxicity
Anti-fungal and Anti-candidal agents for SYSTEMIC INFECTIONS
For systemic fungal infections, use I.V. antifungals
1. Herpes simplex (cold sores, genital herpes, herpetic whitlow [infection of finger pad occurring most often in health care workers]) Eczema herpeticum

2. Varicella (chickenpox): Varicella zoster (reactivation of chickenpox causing blisters of skin along a nerve root; also called herpes zoster or shingles)
Antivirals: systemic
Names: Acyclovir ; valacyclovir (converts to acyclovir); famciclovir
MA - interferes with viral DNA synthesis; present in infected cells
SE - rare
Disorders: Minor skin wounds, infections, etc.
Topical Antibacterials
Mupirocin (Bactroban)
Neomycin, bacitracin, polymixin B

SE - contact dermatitis fairly common to neomycin
Systemic antibacterials
Impetigo, folliculitis, cellulitis, etc.

A. Numerous antibiotics
Disorders: Scabies, Lice/Crabs
MA - basically insecticides, affect parasite nervous system
topical antiparisitics
Permethrin (Elimite); malathion (Ovide)
oral antiparasitics
2 ex and what theyre used for
1. Ivermectin
use: Given orally for scabies or lice resistant to topical therapy

2. Albendazole, thiabendazole
Given orally or applied to skin for cutaneous larva migrans, a parasite from dog feces — often contracted by medical students on the beach during winter break — No dogs on beach!

SE - essentially none when used topically
Antibodies or fusion proteins
MA - interact with receptors at cell surface
Antisense molecules
MA - complementary to small portions of DNA or mRNA; inhibit the effects of a single specific gene.
Methotrexate, azathioprine (Imuran), cyclophosphamide (Cytoxan); antimalarials (e.g., hydroxychloroquine [Plaquenil]); mycophenolate mofetil (CellCept)
MA - immunosuppressives by various mechanisms
-- drugs can have widely disparate indications
use for
2 examples with mech and sidefx
Disorders: The pigmentary changes and wrinkling that come with the passage of time and especially sun exposure

1.) Retinoids: topical tretinoin(Retin-A; Renova = creamy base)
MA - retinoid effects at DNA level generate collagen synthesis Insurance companies generally refuse to pay for this use of the drug; considered “not medically necessary”
SE - Retinoid side effects

2. Alpha-hydroxy acids: glycolic or lactic acid; "fruit acids"; (also cosmetics with collagen, ground-up placentas, etc.)
Marketed as cosmetics — not supposed to claim physiologic action so they claim to "help improve the signs of aging", etc.
2ex and side effects
Disorder: Balding
1. Topical minoxidil (Rogaine)

SE – Irritation

2. Finasteride (Propecia) [lower dose of Proscar for prostatic hypertrophy]
MA - inhibits local testosterone in hair follicles
SE - Decreased libido
drug classes
Disorders:Delusions of parasitosis, Self-mutilation
clas: Antipsychotics
Many treatments for acne; most powerful is
isotretinoin (Accutane) but concerns about teratogenicity and depresion/suicide.
Corticosteroids can be constructed of various potency for inflammatory conditions; but there is a concern of
concerns about skin atrophy.
Anti-virals are useful if
enough reaches the site of infection, usually requiring systemic therapy.
Anti-histamines block the histamine receptor; reduce itch
but probably by inducing somnolence.
A self-limited disease involving the sebaceous follicles (greatest density on face and scalp)
How does Acne work
Sebaceous gland produces sebum (lipids including triglycerides)

androgens increase the secretion

bacteria: triglycerides --> ffa

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