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HISTOLOGY OF THE SKIN ▪ consists of generally polyhedral cells having central

epidermis nuclei with nucleoli and cytoplasm actively
synthesizing keratins
▪ stratum germinativum
• combined zone of stratum basale and stratum
spinosum where some cells may divide
▪ tonofibrils
• assembled keratin filaments that converge and
terminate at numerous desmosomes
▪ cells extend slightly around tonofibrils on both sides of
each desmosome → short spines or prickles at cell
surfaces
▪ epidermis of thick skin subject to continuous friction
and pressure (such as foot soles) has thicker stratum
spinosum with more abundant tonofibrils and
desmosomes
o granular layer (stratum granulosum)
• consists mainly of a stratified squamous keratinized ▪ consists of three to five layers of flattened cells
epithelium composed of cells called keratinocytes ▪ undergoing keratinization
o also three much less abundant epidermal cell types ▪ cytoplasm filled with intensely basophilic masses
▪ melanocytes called keratohyaline granules
• pigment-producing • dense, noon-membrane-bound masses of filaggrin
▪ Langerhans cells associated with keratins of tonofibrils
• antigen-presenting ▪ lamellar granules
▪ Merkel cells • characteristic ultrastructural feature
• tactile epithelial cells • Golgi-derived
• forms major distinction between • small ovoid structures with many lamellae
o thick skin containing various lipids
▪ found on palms and soles • undergo exocytosis → lipid-rich, impermeable layer
▪ varies from 400-1400 µm around cells
o thin skin
▪ found elsewhere on body
▪ 75-150 µm
• stratified squamous epidermis lacks microvasculature
o cells receive nutrients and oxygen by diffusion from the
dermis
• layers of keratinocytes

+
o stratum lucidum
▪ found only on thick skin
▪ thin, translucent layer of flattened eosinophilic
keratinocytes held together by desmosomes
▪ nuclei and organelles lost
▪ cytoplasm consists almost exclusively of packed
keratin filaments embedded in an electron-dense
o basal layer (stratum basale) matrix
▪ single layer of basophilic cuboidal or columnar cells o stratum corneum
on basement membrane at dermal-epidermal junction ▪ 15 to 20 layers of squamous, keratinized cells filled
▪ hemidesmosomes in basal cell membranes join cells with birefringent filamentous keratins
to basal lamina ▪ keratin filaments synthesized during cell differentiation
▪ desmosomes bind cells together in lateral and upper in immature layers
surfaces • as they form, keratin tonofibrils become heavily
▪ intense mitotic activity and contains progenitor cells massed with filaggrin and other proteins in
for all epidermal layers keratohyaline granules
▪ human epidermis is renewed about every 15-30 days • by end of keratinization, cells contain only
• depends on age, region of body and other factors amorphous, fibrillar proteins with plasma
▪ keratins membranes surrounded by lipid-rich layer
• immediate filaments about 10 nm ▪ squames
• amount and type of keratin filaments increase when • fully keratinized or cornified cells
cells move upward during differentiation →until half • continuously shed at epidermal surface as
of protein in superficial keratinocytes desmosoes and lipid-rich cell envelopes break
o spinous layer (stratum spinosum) down
▪ normally thickest layer, especially in epidermal ridges

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o sensitive mechanoreceptors essential for light touch
sensation
o abundant in highly sensitive skin
▪ e.g. fingertips, bases of some hair follicles
o characterized by small, Golgi-derived dense-core
neurosecretory granules containing peptides
o basolateral surfaces contact expanded terminal discs of
unmyelinated sensory fibers penetrating basal lamina
dermis
• layer of connective tissue that supports epidermis and
binds to subcutaneous tissue
• melanocytes • thickness varies with region of body
o maximum of 4 mm on the back
• surface is very irregular and has many projections (dermal
papillae) that interdigitate with projections (epidermal pegs
or ridges) of epidermis
• basement membrane
o occurs between stratum basale and dermis
o follow contour of interdigitations
o consists of basal lamina and reticular lamina
• color of skin caused by many factors; most important is • sublayers
keratinocytes’ content of melanin and carotene +
number of blood vessels in dermis
o a specialized cell found among cells of basal layer and
in hair follicles
o eumelanins
▪ brown or black pigments produced by melanocyte
▪ pheomelanin → red hair
o neural crest derivatives that migrate into embryonic
epidermis’ stratum basale
▪ one melanocyte accumulates for every five or six o papillary layer
basal keratinocytes ▪ includes dermal papillae
o with pale-staining, rounded cell bodies attached by ▪ consists of loose connective tissue
hemidesmosomes to basal lamina ▪ with type I and II collagen fibers
▪ lacking attachments to neighboring keratinocytes ▪ with fibroblasts, scattered mast cells, macrophages
o with several long irregular cytoplasmic extensions that and other leukocytes
penetrate epidermis, running between cells of basal and ▪ with anchoring fibrils of type VII collagent inserting
spinous layer and terminating in invaginations of 5 to 10 into basal lamina
keratinocytes • helps bind dermis to epidermis
o although melanocytes produce melanosomes, o reticular layer
keratinocytes are melanin depot ▪ much thicker
▪ epidermal-melanin unit ▪ consists of dense, irregular connective tissue (mostly
bundled type I collagen)
▪ more fibers and fewer cells than papillary layer
▪ network of elastic fibers also present
• provides elasticity to skin
▪ with abundant proteoglycans rich in dermatan sulfate
• rich network of blood and lymphatic vessels
o subpapillary plexus
▪ between papillary and reticular dermal layers
▪ where branches of blood and lymphatic vessels form
a rich, nutritive capillary network just below epidermis
o deep plexus
▪ with larger blood and lymphatic vessels
▪ near interface of dermis and subcutaneous layer
• Langerhans cells o arteriovenous anastomoses
o mostly seen in spinous layer ▪ located between two plexuses
o represent 2-8% of epidermal cells ▪ involved in thermoregulatory function
o has cytoplasmic processes between keratinocytes of all ▪ decrease blood flow to minimize heat loss; increases
layers flow to facilitate heat loss
o bind, process, present antigens to T lymphocytes • also richly innervated
▪ microbes cannot penetrate epidermis without passing o sensory nerve fibers form network in papillary dermis
through these dendritic cells and around hair follicles
• Merkel cells o autonomic effector nerves to dermal sweat glands and
o also epithelial tactile cells smooth muscle fibers in skin of some areas are
postganglionic fibers of sympathetic ganglia
subcutaneous tissue
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• also hypodermis or superficial fascia hair
• consists of loose connective tissue that binds skin loosely • elongated keratinized structures that form within epidermal
to subjacent organs, making it possible for skin to slide invaginations (hair follicles)
over them • grows discontinuously
• contains adipocytes o with periods of growth followed by periods of rest
• extensive vascular supply promotes rapid uptake of insulin • hair bulb
of insulin or drugs injected subcutaneously o terminal dilation of growing hair follicle
o dermal papilla inserts into base of hair bulb
sensory receptors ▪ contains capillary network to sustain follicle
• unencapsulated receptors o keratinocytes generally similar to those in the basal and
o Merkel cells spinous layers
▪ each associated with expanded nerve endings ▪ divides rapidly → keratinization → melanin
▪ function as tonic receptors for sustained light touch accumulation → terminal differentiation
and sensing objects texture ▪ melanocytes in hair bulb matrix transfer melanosomes
o free nerve endings to epithelial cells that will later differentiate to form
▪ in papillary dermis and extending into lower epidermal hair
layers o outermost cells continuous with epithelial root sheath
▪ respond primarily to high and low temperatures, pain ▪ internal root sheath
and itching • completely surrounds initial part of hair root but
▪ also function as tactile receptors degenerates above level of attached sebaceous
o root hair plexuses glands
▪ web of sensory fibers surrounding hair follicles ▪ external root sheath
▪ detects movements of hair • covers internal sheath and extends to epidermis
• encapsulated receptors • continuous with basal and spinous layers
✓ all phasic mechanoreceptors
✓ responds rapidly to stimuli on skin
o Meissner corpuscles
▪ consists of sensory axons winding among flattened
Schwann cells arranged perpendicular to epidermis in
dermal papillae
▪ initiate impulses when light-touch low-frequency
stimuli against skin temporarily deform shape
▪ numerous in fingertips, palms and soles
o Lamellated (Pacinian) corpuscles
▪ found deep in reticular dermis and hypodermis
▪ with outer capsule and thin, concentric lamellae of
flattened Schwann cells and collagen surrounding a
highly branched, unmyelinated axon
▪ specialized in sensing coarse touch, pressure
(sustained touch) and vibrations
o Krause end bulbs • hair root
▪ simpler, encapsulated, ovoid structures with o keratinocytes continuous with those of basal epidermis
extremely thin, collagenous capsules penetrated by cover dermal papilla forms matrix of hair root
sensory fiber o in most thick hairs, large, vacuolated and moderately
▪ found in skin of penis and clitoris keratinized cells form central medulla of hair root
▪ sense low-frequency vibrations o heavily keratinized, densely packed cells make up
o Ruffini corpuscles cortex
▪ have collagenous, fusiform capsules anchored to o cuticle
surrounding connective tissue ▪ most per
▪ stimulated by stretch (tension) or twisting (torque) in ▪ ipheral cells
skin ▪ thin layer of heavily keratinized, squamous cells
covering cortex
• hair shaft
o part of hair extending beyond skin surface
• glassy membrane
o separates hair follicle from dermis
o acellular hyaline layer
• arrector pili muscle
o small bundle of smooth muscle cells
o extends from midpoint of fibrous sheath to dermal
papillary layer
o contraction → more erect hair
▪ in cold, in an effort to trap a layer of warm air
• hair growth cycle
o anagen
▪ long period of mitotic activity and growth
o catagen
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▪ brief period of arrested growth and regression of hair o sebocytes filled with small fat droplets → nuclei shrink,
bulb autophagy → disintegrate near ducts → release lipids
o telogen as main secretory product
▪ final long period of inactivity o sebum covers surfaces of both epidermis and hair
nails shafts
• sebum
o complex mixture of lipids – wax esters, squalene,
cholesterol, triglycerides
o hydrolyzed by bacterial enzymes after secretion
o helps maintain stratum corneum and hair shafts
o with weak antibacterial and antifungal properties
sweat glands
• develop as long epidermal invaginations embedded in
• hard plates of keratin on dorsal surface of each distal dermis
phalanx • eccrine sweat glands
• nail root o widely distributed in skin
o proximal part of nail o most numerous on foot soles – 620 glands/cm2
o covered by a fold of skin o can produce as much as 10 L/d
• cuticle o both secretory components and ducts are coiled with
o also eponychium small lumens
o extension of epidermal stratum corneum from nail root o secretory part has stratified cuboidal epithelium with
three cell types
• nail plate
▪ clear cells – produce sweat
o bound to a bed of epidermis, the nail bed
▪ dark cells – line most of lumen, secrete a poorly
▪ contains only basal and spinous layers
understood mixture of glycoproteins with bactericidal
• nail matrix
activity
o from which the nail root forms
▪ myoepithelial cells – contract to move secretion into
o where cells divide, move distally and become
duct
keratinized
o ducts have two layers of more acidophilic cells
o nail root → matures and hardens → nail plate
▪ absorb Na+ from secreted water to prevent excessive
o continuous growth in this area pushes nail plate forward
loss
over nail bed
o sweat pore
▪ 3 mm/mo for fingernails
▪ duct merges with stratum basale and sweat flows into
▪ 1 mm/mo for toenails
this spiraling channel
• hyponychium
• apocrine sweat glands
o epidermal fold at which the distal end of plate becomes
o largely confined to axillary and perineal regions
free of nail bed
o development depends on sex hormones
sebaceous glands
o with much larger lumens
o secretory component
▪ consists of simple cuboidal, eosinophilic cells with
numerous secretory granules that undergo exocytosis
o ducts similar to apocrine glands but open into hair
follicles in epidermis
▪ may contain protein-rich products

INTRODUCTION TO MORPHOLOGY
raised lesions
• papule
o solid, elevated lesion, in which significant portion
projects above plane of surrounding skin
• embedded in dermis over most of body, except in palms o <0.5 cm in size
and soles o surmounted with scales → papulosquamous lesions
• average of 100 glands/cm2 o clinical example: lichen planus
o increases to 400-900 glands/cm2 in face and scalp
• branched acinar glands with several acini converging at a
short duct that usually empties into upper portion of a hair
follicle
o hair follicle + associated sebaceous glands =
pilosebaceous unit
o in hairless regions, ducts open directly onto epidermal
surface
• holocrine secretion
o basal layer of flattened epithelial cells on basal lamina
→ proliferate → displaced centrally → differentiate into • plaque
sebocytes o solid plateau-like elevation that occupies a relatively
large surface area
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o >0.5 cm in diameter
o may form by extension or confluence of papules
o clinical example: psoriasis

• scar
• nodule o arises from proliferation of fibrous tissue that replaces
o five main types, depending on anatomic component previously normal collagen after a wound or ulceration
primarily involved breaches the reticular dermis
▪ epidermal o initially, deeper pink to red before becoming hypo- or
▪ epidermal-dermal hyperpigmented
▪ dermal • comedo
▪ dermal-subdermal o hair follicle infundibulum that is dilated and plugged by
▪ subcutaneous keratine and lipids
o solid, round or ellipsoidal palpable lesion o open comedo
o >0.5 cm in diameter ▪ when pilosebaceous unit is open to surface of skin
o depth of involvement and substantive palpability with visible keratinaceous plug
differentiates nodule from papule or plaque o blackhead
o tumor ▪ black color of comedo due to oxidized sebaceous
▪ general term for any mass, benign or malignant content of infundibiulm
o gumma o closed comedo
▪ granulomatous nodular lesion of tertiary syphilis ▪ follicular opening is unapparent
o clinical example: nodular basal cell carcinoma ▪ accumulates whitish keratin
o clinical example: comedonal acne

• cyst
o encapsulated cavity or sac lined with true epithelium
that contains fluid or semisolid material • horn
o spherical and oval shape  tendency of contents to o conical mass of cornified cells arising over an
spread equally in all directions abnormally differentiating epidermis
o clinical example: cystic hidradenoma o clinical example: verruca vulgaris
• calcinosis
o deposits of calcium in dermis or subcutaneous tissue
o hard, whitish nodules or plaques with or without visible
alteration of skin’s surface
o clinical example: cutaneous calcinosis
depressed lesions
• erosion
o moist, circumscribed depressed lesion that results form
loss of portion or all of viable epidermal or mucosal
• wheal lesion
o swelling of skin that is characteristically evanescent, o may result from: detachment of layers with maceration,
disappearing within hours rupture of vesicles or bullae, epidermal necrosis
o also: hives, urticaria o do not scar unless infected
o result of edema produced by escape of plasma through o clinical example: toxic epidermal necrolysis
vessel walls in upper portion of dermis
o pink to pale red in color
o angioedema
▪ deeper, edematous reaction that occurs in areas with
very loose dermis and subcutaneous tissue

• ulcers

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o defect in which epidermis and at least upper dermis has
been removed
o heals with scarring
o descriptions
▪ location
▪ borders – rolled, undermined, punched out, jagged or
angular
▪ base: clean, ragged, necrotic
• erythema
▪ discharge: purulent, granular, malodorous
o blanchable pink to red color of skin
▪ surrounding skin: red, purple, pigmented, reticulated,
o due to dilatation of arteries and veins in papillary and
indurated, sclerotic, infarcted
reticular dermis
o clinical example: pyoderma gangrenosum
o exists in different colors
o clinical example: dusky erythema, may be seen in fixed
drug eruption
• erythroderma
o generalized deep redness of skin (>90% of body
surface) within days or weeks
o clinical example: Sézary syndrome
• atrophy surface change
o diminution in size of cell, tissue, organ or part of body • scale, desquamation
o atrophic epidermis o flat plate or flake arising from outermost layer of stratum
▪ glossy, almost transparent, paper thin and wrinkled corneum
o atrophy of papillary or reticular dermal connective tissue o latent – when scale is observed only after scratching the
▪ depression of skin lesion
o atrophy of panniculus o clinical example: psoriasis vulgaris
▪ more substantial depression of skin
• poikiloderma
o combination of atrophy, telangiectasia, varied
pigmentary changes
o gives rise to dappled appearance to skin
o clinical example: chronic radiodermatitis
• sinus
o tract connecting deep suppurative cavities to each other
or to surface of skin
o clinical example: hidradenitis suppurativa
• hyperkeratosis
• striae
o excessive or thickened stratum corneum, often but not
o linear depressions of skin that result from changes to
always scaly
reticular collagen that occur with rapid stretching
• crusts (encrusted exudates)
o clinical example: striae distensae
o hardened deposits that result when serum, blood or
• burrow
purulent exudate dries on surface of skin
o wavy, threadlike tunnel through the outer portion of
o common colors
epidermis excavated by parasite
▪ yellow-brown  serous
o clinical example: scabetic burrow
▪ turbid yellowish-green  purulent
• sclerosis
▪ reddish-black  hemorrhagic
o circumscribed or diffuse hardening or induration of skin
o clinical example: impetigo
from dermal fibrosis
o clinical example: morphea
flat and macular lesions
• macule
o flat and perceptible only as an area of color different
from surrounding skin

• excoriation
o surface excavations of epidermis that result from
scratching
• fissure
o linear loss of continuity of skin’s surface or mucosa that
results from excessive tension or decreased elasticity at
• patch
involved tissue
o flat area of skin with different color form its surrounding
o clinical example: fissure on palm associated with
o >0.5 cm, may have fine, very thin scale
contact dermatitis
o clinical example: vitiligo, cutaneous T-cell lymphoma
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• lichenification ▪ white, yellow, or greenish-yellow in color
o reactive thickening of epidermis, with changes in o clinical example: superficial pyoderma
collagen of underlying superficial dermis
o clinical example: lichen simplex chronicus

• furuncle
o deep necrotizing folliculitis with suppuration
• keratoderma o inflamed follicle-centered nodule usually >1 cm with a
o excessive accumulation of scale → yellowish thickening central necrotic plug and an overlying pustule
of skin o may coalesce → carbuncle
o clinical example: plantar keratoderma in psoriasis • abscess
• eschar o localized accumulation of purulent material so deep in
o presence implies necrosis, infarction, deep burns, dermis or subcutaneous tissue that pus is usually not
gangrene, other ulcerating process visible on surface on skin
o clinical example: thermal burn o pink, erythematous, warm, tender, fluctuant nodule
fluid-filled lesions purpura/vascular lesions
• vesicle and bulla • purpura
o vesicle - ≤0.5 cm o extravasation of red blood from cutaneous vessels into
o bulla - >0.5 cm skin or mucous membranes results in reddish-purple
o fluid in cavity exerts equal pressure → spherical shape lesions
o contents may be visualized when cavity wall is thin and o erythema vs purpura
translucent enough ▪ diascopy on lesion
o arise from cleavage at various levels of the epidermis ▪ if redness in non-blanching under pressure of slide →
(intraepidermal) or of dermal-epidermal interface purpuric
(subepidermal) o as extravasated RVC decomposed over time, the color
o clinical example: vesicle – impetigo by toxin-producing of lesions change from bluish-red to yellowish-brown or
staphylococci; bulla – bullous pemphigoid green
o petechiae – small, pinpoint purpuric macules
o ecchymoses – larger, bruise-like purpuric rashes
o clinical example: leukocystoclastic vasculitis

• telangiectasia
o persistent dilations of small capillaries in superficial
dermis
o visible as fine, bright, nonpulsatile red lines or net-like
patterns on skin
• infarct
o area of cutaneous necrosis resulting from a bland or
• pustule inflammatory occlusion of blood vessels in skin
o circumscribed, raised cavity in the epidermis or o tender, irregularly shaped dusky reddish-gray macule or
infundibulum containing pus firm plaque
o purulent exudate o clinical example: cholesterol emboli
▪ composed of leukocytes with or without cellular debris
▪ may contain bacteria or may be sterile
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o serpentine or snake-like
o e.g. cutaneous larva migrans

shape or configuration of skin lesions • targetoid

• annular o target-like, with at least three distinct zones
o ring-shaped o e.g. erythema multiforme
o edge of lesion differs from center • whorled
o e.g. granuloma annulare, tinea corporis, erythema o with two distinct colors interspersed in a wavy pattern
annulare centrifugum o e.g. incontinentia pigmenti, hypomelanosis of Ito, linear
and worled nevoid hypermelanosis

• round/nummular/discoid
o coin-shaped
o round to oval lesion with uniform morphology
o e.g. nummular eczema, plaque-type psoriasis, discoid
lupus
arrangement of multiple lesions
• grouped/herpetiform
o lesions clustered together
o e.g. herpes simplex 1 reactivation

• polycyclic
o formed from coalescing circles, rings or incomplete rings
o e.g. urticaria, subacute cutaneous lupus erythematosus • scattered
• arcuate o irregularly distributed
o arc-shaped distributions of multiple lesions
o e.g. urticaria, subacute cutaneous lupus erythematosus • dermatomal/zosteriform
• linear o unilateral and lying in distribution of single spinal afferent
o resembling a straight line nerve root
o often implies an external contactant or Koebner o e.g. herpes zoster
phenomenon • blaschkoid
o e.g. scabies burrow, poison ivy dermatitis, bleomycin o following lines of skin cell migration during
pigmentation, lichen nitidus, lichen planus
embryogenesis
• reticular o e.g. incontinentia pigmenti, inflammatory linear verrucous
o net-like or lacy epidermal nevus
o with somewhat regularly spaced rings or partial rings with
sparing of intervening skin
o e.g. livedo reticularis, cutis marmorata

• serpiginous
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• contained in family of Arthrodemataceae amd represented
by 40 species in 3 genera
o Epidermophyton
o Microsporum
o Trichophyton
• dermatophytosis
o superficial fungal infections of skin, hair, nails
o due to dermatophytes’s ability to attach to and invade
keratinized tissue of animals and humans and utilize
degradation products as nutritional sources
taxonomy and epidemiology
• anthromophilic
o restricted of human hosts
o transmitted via direct contact
• lymphangitic o source reservoirs: infected skin or hair retained in
o lying along distribution of a lymph vessel clothing, combs, caps, socks, towels
• sun exposed o often epidemic in nature
o occurring in areas usually not covered by clothing o elicit a mild to noninflammatory host response
o e.g. photodermatitis, subacute cutaneous lupus o Trichophyton rubrum, T. tonsurans, T. inderdigitale, T.
erythematosus, polymorphous light eruption, squamous schoenleinii, T. rubrum, T. soudanense, T. violaceum, T.
cell carcinoma concentricum, Microsporum andounii, M. ferrugineum,
Epidermophyton floccosum
• sun protected
o occurs in areas covered by clothing • zoophilic
o e.g. parapsoriasis, mycosis fungoides o transmitted to humans from animals
o common sources of infection
• acral
▪ cats, dogs, rabbits, guinea pigs, birds, horses, cattle
o in distal locations
and other animals
o e.g. palmoplantar pustulosis, chilblains
o transmission
• truncal
▪ direct contact with animal
o occurring on trunk or central body
▪ indirectly via infected animal hair
• extensor
o tend to produce acute and intense inflammatory
o occurring over dorsal extremities, overlying extensor
responses
muscles, kness or elbows
o T. mentagrophytes, T. interdigitale, T. erinacei, T. simii,
o e.g. psoriasis
T. verrucosum, M. canis, M. amazonicum, M. gallinae, M.
• flexor nanum, M. persicolor
o overlying the flexor muscles of extremities, the
• geophilic
antecubital and popliteal fossae
o cause sporadic human infection upon direct contact with
o e.g. atopic dermatitis
soil
• intertriginous o potential for epidemic spread due to higher virulence of
o occurring in skin folds, where two skin surfaces are in geophilic strains + long-lived spores
contact, namely the axillae, inguinal folds, inner thighs,
• worldwide problem that affects >20-25% of population
inframammary skin, and under abdominal pannus
pathogenesis
o e.g. candidiasis
• initial steps: adherence to keratin → invasion and growth of
• localized
mycelial elements → keratin degradation → release of
o confined to a single body location
proinflammatory mediators → inflammatory response
o e.g. cellulitis
• adherence
• generalized
o the first step: successful adherence of arthroconidia –
o widespread
asexual spores formed by fragmentation
o exanthema (rash) – generalized eruption consisting of
o nonspecific lines of host defense
inflammatory lesions
▪ fungistatic fatty acids in sebum
o e.g. viral exanthems, drug eruption
▪ competing bacterial colonization
• bilateral symmetric o selective use of proteolytic armamentarium
o mirror-image symmetry on both sides of the body ▪ upregulation of multiple genes induced by contact with
o [Link], plaque-type psoriasis keratin
• universal • invasion
o entire cutaneous surface o trauma and maceration facilitate penetration
o e.g. erythroderma, alopecia universalis o secretion of specific proteases, lipases, ceramidases
o mannan show inhibitory effects on keratinocyte
DERMATOPHYTES proliferation and cell-mediated immunity
introduction
• host response
• Greek for “skin plant” o several lines of nonspecific mechanisms
▪ fungistatic fatty acids
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▪ increased epidermal proliferation → increases o favus
shedding ▪ longitudinally arranged hyphae and air spaces within
▪ secretion of inflammatory mediators hair shaft
▪ competition for iron by unsaturated transferrin ▪ arthroconidia not noted
o degree of host inflammation depends on host’s immune • clinical findings
status and natural habitat of dermatophyte o in general – hair loss, scaling, various degrees of
▪ anthropophilic dermatophytes induces a limited inflammatory response
cytokine profile o noninflammatory type
o cell-mediated immunity ▪ also seborrheic
▪ delayed type hypersensitivity response ▪ M. audouinii, M. ferrugineum
▪ associated with resolution ▪ arthroconidia sheath around hairs → graying →
▪ defective → chronic or recurrent breaking off just above level of scalp
▪ Th2 response not protective ▪ alopecia may be imperceptible
diagnostics ▪ patches often occur in occiput
• KOH-treated scale samples ▪ if ectothrix → green fluorescence
o quick and inexpensive tool
o septate and branching hyphae maybe visualized under
microscope with 10-20% KOH
o false-negatives in 15%
o scale collected by scraping involved area with dull edge
outward from advancing margins
▪ full thickness nail clippins should involve dystrophic
portion
▪ hairs should plucked
▪ placed on glass side and prepared with KOH →
coverslip o “black dot” tinea capitis
▪ warming slide for better penetration ▪ T. tonsurans, T. violaceum
o low-power microscopy → three possible patterns ▪ hairs broken off a level of scalp → grouped black dots
▪ ectothrix – arthroconidia sheath around hair shaft within patches of polygional shaped alopecia with
▪ endothrix - arthroconidia finger-like margins
• histopathology ▪ diffuse scaling
o not often employed ▪ minimally inflammatory
▪ some may develop follicular pustules, furuncle-like
• Wood’s light fluorescence
nodules, kerion
o examination of involved hair with Wood’s lamp (365 nm)
→ pteridine fluorescence of hair infected with particular
fungal pathogens
▪ hairs that fluoresce → further examination
▪ M. canis and M. audouinii (ectothrix) will fluoresce
▪ T. tonsurans (endothrix) will not fluoresce

DERMATOPHYTOSES
tinea capitis o inflammatory type
• dermatophyte infection of hair and scalp ▪ M. canis, M. gypseum, > verruucosum
o typically caused by Trichophyton and Microsporum ▪ result from hypersensitivity reaction to infection
• epidemiology ▪ present from follicular pustules to furunculosis or kerion
o most common in children 3-14 y.o. ▪ scarring alopecia
o transmission increased in ▪ pruritic or tender
▪ decreased personal hygiene ▪ posterior cervical lymphadenopathy – differentiates
▪ overcrowding tinea capitis from other inflammatory disorder of the
▪ low socioeconomic status scalp
o hair may harbor infectious organisms >1 year
• pathogenesis
o ectothrix
▪ only arthroconidia on surface of hair may be visualized
▪ cuticle is destroyed
▪ yellow-green fluorescence may be detected with
Wood’s light
o endothrix
▪ arthroconidia and hyphae remain within hair shaft
▪ cortex and cuticle intact
▪ “black dots”
▪ do not fluoresce
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▪ T. violaceum
▪ less inflammatory
▪ resembles tinea corporis or bacterial folliculitis
▪ active border – perifollicular papules and pustules, mild
erythema
▪ reversible alopecia

• histopathology
o PAS and methanemine silver stains reveal hyphae
around and within hair shafts
o dermis – perifollicular mixed cell infiltrate
o inflammatory
o markedly inflammatory lesions – polymorphonuclear
leukocytes
tinea favosa
• chronic dermatophyte infection of scalp rarely involving
glabrous skin or nails
o thick yellow crusts (scutula) within hair follicles →
scarring alopecia
• epidemiology
o acquired before adolescence
o associated with malnutrition and poor hygiene
• etiology ▪ T. interdigitale, T. verrucosum
o T. schoenleinii – most common ▪ most common
• clinical findings ▪ boggy-crusted plaques and seropurulent discharge
o early favus ▪ hairs – lusterless, brittle, easily epilated
▪ first 3 weeks ▪ perifollicular pustules → abscess-like collections of
▪ patchy perifollicular erythema with slight scaling and pus, sinus tracts, scarring alopecia
matting of hair tinea corporis
o progressive hyphal invasion → distends follicle → yellow- • dermatophytosis of glabrous skin except palms, soles and
red follicular papule → yellow concave crust (scutulum) groin
▪ unpleasant cheese-like or musky odor • epidemiology
• laboratory tests o transmission: direct from infected humans or animals,
o T. schoenlii fomites, autoinoculation
▪ subtle, blue gray fluorescence along entire hair o occlusive clothing, humid climate → more frequent and
▪ hyphae arranged lengthwise around and within hair severe eruptions
shaft, rare arthroconidia, vacant air spaces • etiology
o any, but commonly T. rubrum
• clinical findings
o annular or serpiginous plaque with scale across entire
active erythematous border

tinea barbae
• epidemiology
o occurs predominantly in males o border advances centrifugally
o decreased incidence d/t improved sanitation of barbers’ o center of plaque usually scaly but may be cleared
razors o Majocchi’s granuloma
o direct exposure to cattle, horses or dogs – now more ▪ superficial and subcutaneous dermatophytic infection
common mode of acquisition involving deeper portions of hair follicles
• etiology ▪ presents as scaly follicular papules and nodules that
o zoophilic strains of T. interdigitale, T. verrucosum, M. coalesce in annular arrangement
canis ▪ T. rubrum, T. interdigitale, M. canis
▪ common on legs in women after shaving or apply
• clinical findings
topical corticosteroids, among immunocompromised
o affects face unilaterally, involves beard area more often
patients
o superficial type

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o T. rubrum, T. interdigitale, E. floccosum
• clinical findings
o interdigital type
▪ most common
▪ scaling, erythema, maceration of interdigital and
subdigital skin of feet, esp. between lateral third and
fourth, fourth and fifth
tinea cruris ▪ spread to adjacent sole or instep
• dermatophytosis of groin, genitalia, pubic area, and ▪ occlusion, bacterial coinfection (Pseudomonas¸
perineal and perianal skin Proteus, S. aureus) → interdigital erotions + pruritus,
• epidemiology malodor
o second most common type of dermatophytosis
o spreads via direct contact, fomites
o exacerbated by occlusion and humid climates
o autoinfection common
o more common in men (3x)
• etiology
o T. rubrum, E. floccosum
• clinical findings
o well-marginated annular plaque with scaly raised border
▪ extends form inguinal fold on inner thigh o chronic hyperkeratotic (moccasin) type
▪ often bilateral ▪ patchy, diffuse scaling on soles and lateral and medial
o pruritus common aspects of feet
o pain when plaques are macerated or secondarily infected ▪ T. rubrum, E. floccosum, anthropophilic T. interdigitale
o E. floccosum – central clearing, limited to genitocrural
crease, medial upper thigh
o T. rubrum – plaques coalesce with extension to pubic,
perianal, buttock, lower abdominal areas
o genitalia infrequently affected

o vesiculobullous type
▪ zoophilic T. interdigitale
▪ tense vesicles >3 mm, vesiculopustles, bullae on soles
and periplantar areas

tinea pedis and tinea manuum

• tinea pedis – dermophytosis of feet
• tinea mannum – involves palmar and interdigital areas
• epidemiology
o most common worldwide
o attributed primarily to modern occlusive footwear
o incidence of tinea pedis higher among those using
communal baths, showers or pools
▪ host factors: immune response
o tinea manuum
▪ acquired through direct contact with person, animal,
soil or autoinoculation o acute ulcerative type
▪ only one hand is often involved ▪ zoophilic T. interdigitale + rampant bacterial
▪ concomitant infection of two feet-one hand syndrome superinfection with G(-) bacteria
• secondary infection of hand acquired from ▪ vesicles, pustules and purulent ulcers
excoriating and picking infected feet and toenails o tinea manus usually has noninflammatory presentation
with diffuse dry scaling and accentuation of creases
• laboratory tests
o KOH examination of blister roofs yield highest rate of
positive findings
• histopathology
o fungal organisms are highlighted in stratum corneum by
PAS or methanamine silver stains
• etiology

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COURSE: DERMATOLOGY
o there maybe a chronic, sparse perivascular infiltrate in o fiuconazole 200 mg daily for 4-6 weeks
dermis o systemic glucocorticoids used for first week of therapy in
treatment of dermatophytes cases with severe inflammation
• tinea capitis and favus • tinea corporis and tinea cruris
o involving hair-bearing skin → oral antifungal treatment o isolated plaques on glabrous skin → topical allylamines,
▪ penetration of follicle usually out of reach for topically imidazole, tolnaftate, butenafine, cicloprox
applied agents ▪ applied twice daily for 2-4 weeks
o griseofulvin o oral antifungals reserved for widespread or more
▪ in patients >4 years inflammatory eruptions
▪ 20-25 mg/kg/day in microsize form, 15 mgkg/day in o terbinafine 250 mg daily for 2-4 weeks, itraconazole 200
divided doses of ultramicrosize form for 8 weeks mg daily for 1 week, fluconazole 150-300 mg weekly for
▪ disadvantages: poor compliance, bitter taste 4 weeks > griseofulvin 500 mg daily
▪ common side effects: photosensitivity, headache, GI o for children
upset ▪ terbinafine 3-6 mg/kg/day for 2 weeks
▪ potent inducer of cytochrome P450 enzymes ▪ itraconazole 5 mg/kg/day for 1 week
o terbinafine ▪ ultramicrosize griseofulvin 10-20 mg/kg/day for up to 2-
▪ 3-6 mg/kg/day 4 weeks
• Trichophyton – for 2-4 weeks • tinea pedis and tinea manuum
• Microsporum – for 4-8 weeks o mild interdigital tinea pedis without bacterial involvement
▪ side effects: GI upset, reports of liver failure → topical allylamine, imidazole, ciclopirox, benzylamine,
▪ inhibitory effect on CYP 2D6 subset of cytochrome tolnaftate, undecanoic acid based creams
P450 system o terbinafine cream twice daily for 1 week effective in 66%
• interactions with beta-blockers and tricyclic of cases
antidepressants o oral medications
o itraconazole ▪ terbinafine 250 mg daily for 2 weeks
▪ 5 mg/kg/day for 2-4 weeks for Microsporum or ▪ itraconazole (adults) 400 mg daily for 1 week, 200 mg
Trichophyton daily for 2-4 weeks or 100 mg daily for 4 weeks
▪ side effects: GI upset, diarrhea with liquid formulation, ▪ itraconazole (children) 5 mg/kg/day for 2 weeks
peripheral edema (esp. when used with Ca2+ channel ▪ fluconazole 150 mg weekly for 3-4 weeks
blockers), hepatotoxicity ▪ topical or systemic corticosteroids for symptomatic
▪ better absorbed in presence of food relief during initial treatment of vesiculobullous tinea
▪ antacids may decrease absorption pedis
o fluconazole ▪ maceration, denudation, pruritus, malodor obligate →
▪ as both tablets and a pleasant-tasting liquid search for bacterial coinfection
▪ 6 mg/kf/day for 20 days for tinea capitis
▪ absorption not affected by gastric pH, GI side effects ALLERGIC CONTACT DERMATITIS
are less common epidemiology
▪ hepatitis reported, less common than with • age
ketoconazole o important cause of childhood dermatitis
▪ potent inhibitor of cytochrome P450 enzymes, esp. o equally likely in childhood as in adulthood
CUP 2C9 and 2C19 ▪ most common allergens differ between age groups
• less potential to interact with other medications ▪ fragrance mix allergy incidence increase with
except systemic imidazoles increasing age
o adjuvant therapy • gender and race
▪ selenium suilfide (1%, 2.5%), zinc pyrithione (1%, 2%), o gender differences largely unknown
povidone iodine (2.5%), ketoconazole (2%) as o role of race remains controversial
shampoo preparations – vs scalp dermatophytes of etiology and pathogenesis
children • represents contact dermatitis represents a classic cell-
• 2-4x weekly for 2-4 weeks mediated, delayed (type IV) hypersensitivity
▪ ketoconazole (2%), selenium sulfide (2.5%) 3x weekly o resulting clinical picture → erythema, edema and papulo-
by all household members vesiculation, in distribution of contact with instigating
o oral glucocorticoids allergen, with pruritus
▪ may reduce incidence of scarring associated with o sufficient contact with sensitizing chemical → repeated
markedly inflammatory tinea capitis contact with substance later
▪ appear to relieve pain and swelling ▪ important distinction to irritant contact dermatitis
▪ prednisone 1-2 mg/kg each morning during first week
of therapy
• tinea barbae
o oral antifungal usually necessary
o ultramicronized griseofulvin 500 mg bid for 6 weeks
o terbinafine 250 mg daily for 2-4 weeks
o itraconazole 200 mg daily for 2-4 weeks
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• sensitization phase • allergen testing
o most allergen are small, lipophilic, with low MW o commercially available patch-test screening tool, e.g.
o hapten – unprocessed allergen Thin-layer Rapid Use Epicutaneous (TRUE) Test
▪ penetrates skin → binds with epidermal carrier proteins
→ hapten-protein complex → complete antigen
o antigen-presenting cell of skin (Langerhans, dendritic)
take up hapten-protein complex → express as HLA-DR
molecule → migrates to lymphatics → present to naïve
antigen-specific T cells with CD3 complex that can
recognize antigen → T cells primed and differentiate into
• result interpretation
memory → clonal expansion → emigrate into circulation
o patch should be applied to healthy skin on patient’s back
o clones of CD4+ Th1, CD8+ type 1 cytotoxic T cells act as
for 48 hours
effectors
▪ reading carried out twice – 48 hours after application,
o generally lasts 10-15 days, often asymptomatic
and 96 hours after exposure
• elicitation phase
▪ instruct patients to report any other reactions
o both APCs and keratinocytes can present antigen →
appearing at day 5 or beyond
recruitment of hapten-specific T cells
o ICDRG recommends scoring system by Wilkinson et al
o T cells release cytokines → recruit inflammatory cells,
▪ + - weak nonvesicular reaction but with palpable
stimulates macrophages and keratinocytes to release
erythema
more cytokines
▪ ++ - strong reaction, edematous or vesicular
o proinflammatory state → redness, edema, papules,
▪ +++ - extreme reaction, bullous or ulcerative
vesicles, warmth
▪ ?+ - very weak or questionable reactions
clinical approach
▪ IR – irritant reactions
• history taking
treatment
o medical and environmental exposure history
• identification and removal of inciting agent should always
o site of onset and topical agents used to treat problem
be the goal in diagnosis and treatment
o history of skin disease, atopy and general health
o usage of personal care products
ATOPIC DERMATITIS
o patient’s avocations or hobbies
• chronically relapsing skin disease that occurs most
o occupation
commonly during early infancy and childhood
clinical manifestations
o assoc. with abnormalities in skin barrier function, allergen
• cutaneous findings
sensitization, recurrent skin infections
o pruritic, eczematous dermatitis localized to primary site of
epidemiology
allergen exposure
• since 1960s, > 3fold increase
o geometric, linear patterns, focal skin areas
o lesions vary depending on stage • prevalence in adults: 1-3%
▪ acute – edema, erythema, vesicle formation o much lower in agricultural regions
▪ vesicles rupture → oozing, papules, plaques • female preponderance
▪ subacute – erythema, scaly juicy papules and weeping o female/male ration – 1.3:1
▪ chronic – scaling, fissuring, lichenification • potential risk factors → hygiene hypothesis
o pruritus – key symptom for allergy o small family size
o increased income and education
o migration from rural to urban
o increased use of antinbiotics
etiology and pathogenesis
• highly pruritic inflammatory skin disease that results from
complex interactions between genetic susceptibility →
defective skin barrier, defects in innate immune system,
heightened immunologic responses to allergens and
microbial antigens
• decreased skin barrier function
o downregulation of cornified envelope genes (filaggrin,
loricrin)
o reduced ceramide levels
o increased levels of endogenous proteolytic enzymes
o enhanced transepidermal water loss
• topographic approach o soap and detergents → increased pH → breakdown of
o distribution usually single most important clue to barrier function
diagnosis of ACD o exposure to exogenous proteases from house dust mites
o area of greatest dermatitis = area of greatest contact with and S. aureus
offending allergen ▪ lack of inhibitors
patch testing • immunopathology of atopic dermatitis
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COURSE: DERMATOLOGY
o clinically unaffected → mild epidermal hyperplasia, ▪ source of thymic stromal lymphopoietin (TSLP) →
sparse perivascular T cell infiltrate activates DCs → prime naïve T cells to produce IL-4,
o acute eczematous skin lesions → marked intercellular IL-13
edema ▪ critical to skin’s innate immune responses
o dendritic APCs exhibit surface-bound IgE molecules • TLRs
o sparse epidermal infiltrate consisting of T lymphocytes • proinflammatory cytokines
o dermis of acute lesion → influx of T cells with occasional • antimicrobial peptides
monocyte-macrophages • in AD, reduced amount of antimicrobial peptides
o infiltrate consists predominantly of activated memory T • genetics
cells bearing CD3, CD4, CD5 RO o familially transmitted with a strong maternal
▪ normal mast cells numbers influence
o chronic lichenified lesions → o loss-of-function mutations in FLG (encodes
▪ hyperplastic epidermis with elongation of rete ridges filaggrin) – major predisposing factor
▪ prominent hyperkeratosis o variants in SPINK5 gene → LEKT1
▪ minimal spongiosis ▪ LEKT1 inhibits proteases involved in desquamation
▪ increased number of IgE-bearing LCs in epidermis and inflammation
▪ macrophages dominate dermal mononuclear cell ▪ implies that balance in protease vs protease inhibitor
infiltrate activity may contribute
▪ mast cells increase but fully granulated • basis of pruritus
▪ increased eosinophils – undergo cytolysis → release of o prominent feature of AD
franules ▪ cutaneous hyperreactivity
• cytokines and chemokines ▪ scratching
o inflammation orchestrated by local proinflammatory ▪ changes in humidity
cytokines and chemokines ▪ excessive sweating
o cytokines bind to receptors on vascular endothelium → o poorly understood mechanism
induction of vascular endothelial cell adhesion molecules o release of histamine not exclusive cause
→ tethering → activation → adhesion to vascular ▪ H1 antihistamine not effective
endothelium → extravasation of inflammatory cells o inflammatory cells may play important role
o in acute, production of Th2 cytokines (esp. Il-4, IL-13) → ▪ topical corticosteroids, calcineurin inhibitors help
mediate Ig isotype switching to IgE synthesis, upregulate clinical findings
expression of adhesion molecules • diagnosis is based on constellation of clinical features
o in chronic, increase in IL-5 – involved in eosinophil o major features
development and survival ▪ pruritus
▪ increased granulocyte macrophage colony-stimulating ▪ rash on face and/or extensors in infants and young
factor inhibits apoptosis of monocytes → persistence children
▪ maintenance also involves production of IL-12, IL-18, ▪ lichenification in flexural areas in older children
IL-11, TGF-1 ▪ tendency toward chronic or chronically relapsing
• key cell types in atopic dermatitis skin dermatitis
o APCs ▪ personal or family history of atopic disease: asthma,
▪ dendritic cells detect environmental allergens or allergic rhinitis, atopic dermatitis
pathogens via TLR o other common findings
▪ two high-affinity, IgE receptor-bearing myeloid DCs ▪ dryness
• Langerhans cells ▪ Dennie-Morgan folds
• inflammatory dendritic epithelial cells (IDEC)
▪ cell-bound IgE facilitate capture and internalization of
antigens into LCs before processing and presentation
to T cells
▪ IgE-bearing LCs that have capture allergen likely
activated memory Th2 cells
▪ stimulation of FcεRI on IDEC → release of
proinflammatory signals ▪ allergic shiners
▪ few can be detected within AD skin lesion ▪ facial pallor
o T cells ▪ pityriasis alba
▪ important role esp. in acute phase ▪ keratosis pilaris
▪ presence of Th2-like T cells in acute AD → cytokines ▪ ichthyosis vulgaris
→ enhance skin inflammation ▪ hyperlinearity of palms and soles
▪ chronic → switch to Th1-like cells → produce IFN-γ ▪ white dermatographism
• induce activation and apoptosis of keratinocytes ▪ conjunctivitis
o keratinocytes ▪ keratoconus
▪ secrete a unique profile of chemokines and cytokines ▪ anterior subscapular cataracts
after exposure to proinflammatory cytokines → e.g. ▪ elevated IgE
RANTES after stimulation with TNF-α, IFN-γ ▪ immediate skin test reactivity

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• cutaneous lesions complications
o intense pruritus and cutaneous reactivity as cardinal • ocular problems
features o eyelid dermatitis
▪ pruritus worse in early evening and night o chronic blepharitis
▪ consequences: scratching, prurigo papules, o atopic keratoconjunctivitis
lichenification, eczematous skin lesions o vernal conjunctivitis
o cataracts
• infections
o herpes simplex
o smallpox
o superficial fungal infections
o folliculitis
o pyoderma
• hand dermatitis
• exfoliative dermatitis
prognosis and clinical course
• natural history not completely known
• spontaneous resolution after age 5 years in 40-60% of
patients affected during infancy
• disappears in approximately 20% followed from infancy
until adolescence
o becomes less severe in 65%
treatment
o acute skin lesions
• systemic, multipronged approach
▪ intensely pruritic
o education about disease state
▪ erythematous papules associated with excoriation
o skin hydration
▪ vesicles over erythematous skin
o pharmacologic therapy
▪ serous exudate
o identification and elimination of flare factors
• topical therapy
o cutaneous hydration
▪ warm soaking baths for 10 minutes + occlusive
emollient or topical medication
▪ moisturizers
▪ topical therapy to replace abnormal epidermal lipids
• preparation with distinct composition of lipids and
ceramides
• nonsteroidal cream with palmitamide MEA
• hydrolipidic cream with glycerrhetinic acid
o chronic lesions ▪ hydration by baths or wet dressings
▪ thickened plaques of skin • promote penetration of topical glucocorticoids
▪ accentuated skin markings (lichenification) • topical anti-inflammatory therapy
▪ fibrotic papules (prurigo nodularis) o topical glucocorticoid therapy
o distribution and pattern vary according to age and ▪ most use topical glucocorticoids for acute
disease activity exacerbations
▪ infancy ▪ recent studies suggest, long-term control can be
• more acute maintained in subset with twice weekly applications of
• primarily involves face, scalp, extensor surfaces of topical fluticasone
extremities ▪ low-potency glucocorticoid preparation for face,
▪ older children or with long-standing disease genitalia and intertriginous areas
• chronic form ▪ ultrahigh-potency glucocorticoids for very short periods
• localization to flexural folds of extremities of time and in areas that are lichenified
▪ older ▪ midpotency glucocorticoids for longer periods of time
• usually subsides to treat chronic AD involving trunks and extremities
• skin is prone to itching and inflammation ▪ side effects
• laboratory tests • local
o not needed in routine evaluation and treatment of o develop of striae
uncomplicated AD o skin atrophy
o IgE elevated in 70-80% o perioral dermatitis
▪ assoc. with sensitization inhalant food allergies, o acne rosacea
concomitant rhinitis, asthma • systemic
o peripheral blood eosinophilia
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COURSE: DERMATOLOGY
o adrenal suppression – greatest risk in infants and o antimetabolites
young children ▪ mycophenolate mofetil
o topical calcineurin inhibitors • purine biosynthesis inhibitor
▪ topical tacrolimus, pimecrolimus as nonsteroidal • as monotherapy in adults with AD resistant to other
immunomodulators treatment
▪ side effect ▪ methotrexate
• transient burning sensation of skin • potent inhibitory effects on inflammatory cytokine
• rare cases of skin malignancy and lymphoma but synthesis and cell chemotaxis
controversial correlation • for adult AD patients with recalcitrant disease
• identification and elimination of triggering factors ▪ azathioprine
o general considerations • purine analog
▪ soaps, detergents, chemicals, smoke, abrasive • for severe AD
clothing, extremes of temperature and humidity • myelosuppression is significant side effect
▪ alcohol and astringents in toiletries • other therapies
o specific allergens o interferon-γ
▪ foods, aeroallergens ▪ suppress IgE responses, downregulate Th2 cell
▪ can be identified by taking careful history, skin-prick proliferation
tests, specific serum IgE levels ▪ influenza-like symptoms as common side effect
▪ avoidance measures: dust mite-proof encasings, o omalizumab
washing bedding in hot water weekly, removal of ▪ lack of efficacy in three adult patients, significant
bedroom carpenting, airconditioning improvement in three adolescent patients
o emotional stressors o allergen immunotherapy
▪ often exacerbates illness ▪ not proven to be efficacious
o infectious agents o extracorporeal photophoresis
▪ antistaphylococcal antibiotics for patients heavily ▪ passage of psoralen-treated leukocytes through
colonized or infected with S. aureus extracorporeal UVA light system
▪ systemic antibiotics for extensive superinfection o probiotics
▪ acyclovir for herpes simplex ▪ perinatal administration of Lactobacillus rhamnosus
o pruritus shows to reduce incidence of AD in at-risk children
▪ reduction of skin inflammation and dryness by topical during first 2 years of life
glucocorticoids and skin hydration ▪ children treated with two Lactobacillus strains for 6
▪ systemic antihistamine weeks show improvement
• sedating antihistamines, e.g. hydroxyzine or o Chinese herbal medications
diphenhydramine, may offer advantage with ▪ with severe AD may benefit
soporific side effects ▪ response is temporary and effectiveness may wear off
• doxepin hydrochloride – both tricyclic ▪ hepatic toxicity, cardiac side effects, and reactions
antidepressant, H1- and H2-histamine receptor- remain a concern
blocking effects o oral vitamin D
• tar preparations ▪ may improve innate immune responses of AD patients
o coal tar preparations may have antipruritic and anti-
inflammatory effects on skin LEPROSY
o useful in reducing potency of topical glucocorticoids in etiology
maintenance therapy • infectious disease caused by Mycobacterium leprae
• phototherapy o obligate intracellular bacillus
o natural sunlight beneficial o confined to humans, armadillos is certain locales and
o broadband UVB, broadband, UVA, narrowband UVB sphagnum moss
(311 nm), UVA-1 (340-400 nm) combined UVAB o acid-fast, ideally detected by modified Fite stain
phototherapy can be useful adjuncts o no known toxins
• hospitalization o well adapted to penetrate and reside within macrophages
o those appear erythrodermic or who have widespread • measure of M. leprae
severe skin disease resistant to outpatient therapy o morphologic index (MI) – a measure of AFB in skin
• systemic therapy scrapings
o systemic glucocorticoids o bacteriologic index (BI) – logarithmic-scaled measure of
▪ rarely indicated density in dermis
▪ may be appropriate for an acute exacerbation ▪ as high as 4-6+ in untreated
▪ important to taper dosage and begin intensified skin ▪ falls by 1 unit per year during effective antimicrobial
care to prevent rebound flaring therapy
o cyclosporine o rising MI or BI suggests relapse or drug resistance
▪ potent immunosupressiev drug that acts primarily on T • almost half of its genome contain nonfunctional genes
cells by suppressing cytokine transcription o only 1605 genes encode for proteins
▪ beneficial for severe AD refractory to conventional ▪ 1439 shared with M. tuberculosis
treatment o among lost genes
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COURSE: DERMATOLOGY
▪ catabolic and respiratory pathways ▪ ulnar
▪ transport systems ▪ posterior auricular
▪ pyrine, methionine, glutamine synthesis ▪ peroneal and posterior tibial nerves
▪ nitrogen regulation ▪ with hypesthesia and myopathy
o provides metabolic rationale for intracellular existence o T cells breach perineurium and destruction of Schwan
and reliance on host cells and axons may be evident → fibrosis of epineurium,
• cell wall contains large amounts of specific phenolic replacement of endoneurium with epithelial granulomas,
glycolipid (PGL-1) caseous necrosis
o unique trisaccharide binds to basal lamina of Schwann ▪ pathognomonic for leprosy
cells o strong T cell and macrophage activation → localized
• one of the few bacterial species that still has not been infection
cultivated on artificial medium or tissue culture
• grows best in cooler tissues
o skin, peripheral nerves, anterior chamber of eye, URT,
testes
epidemiology
• demographics
o almost exclusively a disease of developing world
o within endemic locales, distribution is uneven, with areas
of high prevalence bordering on areas with little or no
disease
o estimates range from 0.6-8 million affected individuals
• lepromatous leprosy
o estimated 500,000 new cases annually
o associated with poverty and rural residence
o most individuals appear to be naturally immune to leprosy
and do not develop manifestations after exposure
o time of peak onset: second and third decades of life
o lepromatous form is twice as common as among men vs
women, rarely in children
• transmission o present with symmetrically distributed nodules
o remains uncertain ▪ raised plaques or diffuse infiltration
o may be multiple ▪ on face → leonine facies
▪ nasal droplet ▪ loss of eyebrows and eyelashes
▪ contact with infected soil ▪ pendulous earlobes
▪ amoeba insect vectors ▪ dry scaling of skin
clinical, histologic and immunologic spectrum o bacilli are numerous in skin
• incubation period can vary between 2-40 years ▪ found in large clumps – globi
o generally 5-7 years in duration ▪ also in peripheral nerves – initially invade Schwann
o extremely long doubling time cells → foamy degenerative myelination and axonal
• presents as spectrum of clinical manifestations that have degeneration → Wallerian degeneration
bacteriologic, pathologic, and immunologic counterparts o bacilli also plentiful in blood system and in all organ
o polar tuberculoid (TT) → borderline tuberculoid (BT) ↔ systems, except lungs and CNS
mid-borderline (BB) ↔ borderline leprosy (BL) ↔ polar o diffuse lepromatosis
lepromatous disease (LL) ▪ without visible skin lesions but with diffuse dermal
• tuberculoid leprosy infiltration and demonstrably thicker dermis
o symmetric nerve enlargement and damage
▪ from actual bacillary invasion
▪ more insidious but more extensive
▪ acral, distal symmetric peripheral neuropathy
▪ tendency toward nerve-trunk enlargement
o s/sx related to URT, anterior chamber of eye and testes
o in untreated px, lymphocytes fail to recognize M. leprae
o encompasses TT and BT disease ▪ seems to be antigen-specific
o symptoms confined to skin and peripheral nerves • reactional states
o skin lesions o type 1 lepra reactions – downgrading and reversal
▪ one or a few hypopigmented macules or plaques reactions
▪ sharply demarcated and hypesthetic ▪ in almost half of patients with borderline forms
▪ erythematous or raised borders ▪ classic signs of inflammation within previously involved
▪ devoid of normal skin organs macules, papules and plaques
▪ dry, scaly and anhidrotic ▪ on occasion, appearance of new skin lesions, neuritis
o AFB generally absent or few and fever
o asymmetric enlargement of peripheral nerves
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COURSE: DERMATOLOGY
• esp. ulnar nerve at elbow – painful and exquisitely • loss of dorsal interosseous musculature in affected
tender hand
▪ if affected nerves not treated with glucocorticoids, • loss of sensation
irreversible damage as early as 24 h ▪ median nerve involvement →
• foot drop when peroneal nerve is involved • impairs thumb opposition and grasp
▪ radial nerve dysfunction – rare →
• wrist drop
▪ plantar ulceration – most common complication of
leprous neuropathy
• therapy – careful debridement, antibiotics,
avoidance of weight-bearing until healed,
progressive ambulation
▪ downgrading reactions – precedes initiation of therapy
▪ peroneal nerve palsy → footdrop
→ becomes more lepromatous
▪ reversal reactions – after initiation of therapy → more • treated with simple nonmetallic brace in show or
tuberculoid surgical correction by tendon trasnfors
▪ edema is most characteristic feature of type 1 lepra ▪ Charcot’s joints, esp. of foot and ankle – uncommon
reacions ▪ loss of distal digit
• conscientious protection of extremities and initiation
of therapy to prevent
o nose
▪ bacillary invasion → chronic congestion and epistaxis
▪ saline nose drops may help
▪ untreated → saddle-nose deformity, anosmia
o eye
▪ cranial nerve palsies → lagophthalmos, corneal
o type 2 lepra reactions: erythema nodosum leprosum insensitivity → trauma, infection, corneal ulcerations and
▪ occurs exclusively in patients near lepromatous end of opacities
leprosy spectrum (BL/LL) – nearly 50% • eye drops and ointments may protect
▪ 90% of cases, it follows chemotherapy, within 2 years ▪ uveitis → cataracts, glaucoma
▪ crops of painful erythematous papules that resolve o testes
spontaneously resolve ▪ orchitis in ENL
▪ mild to severe testicular dysfunction in LL → elevation
of LH, FSH, decreased testosterone, aspermia
diagnosis
• leprosy presents with characteristic skin lesions and skin
histopathology
• should be suspected when patient from endemic area has
▪ malaise, and fever suggestive skin lesions or peripheral neuropathy
▪ may also experience neuritis, lymphadenitis, uveitis, • should be confirmed by histopathology
orchitis and glomerulonephritis o tuberculoid – lesions, esp. advancing edge, must be
▪ may develop anemia, leukocytosis and abnormal LFT biopsied
▪ skin biopsy reveal vasculitis or panniculitis, sometimes o lepromatous – nodules, plaques and indurated areas are
with leukocytes or PMNL optimal, but normal appearing skin also diagnostic
o Lucio’s phenomenon treatment
▪ those with diffuse lepromatosis • antimicrobial therapy
▪ recurrent crops of large, sharply marginated, ulcerative o active agents
lesions ▪ dapsone (50/100 mg/d)
• may be generalized → frequently fatal as result of • sulfone, folate antagonist
secondary infection and sepsis • mainstay of therapy
▪ histology: ischemic necrosis of epidermis and • skin lesions resolve and numbers of viable bacilli
superficial dermis, heavy parasitism of endothelial cells reduced
with AFB and endothelial proliferation and thrombus • primarily bacteriostatic
formation in larger vessels of deeper dermis • resistance-related relapse of only 2.5%
▪ probably mediated by immune complexes • when discontinued in lepromatous patients who had
• complications been smear-negative for years → relapses in first
o extremities year after cessation and occur 1% annualy for next
▪ consequence of neuropathy → insensitivity, myopathy nine years (total of 10%)
▪ insensitivity affects fine touch, pain and heat receptors • generally safe and inexpensive
▪ most commonly involved: ulnar nerve at elbow → • side effects: reduced red cell survival, Hgb decrease,
• clawing of fourth and fifth fingers sulfone syndrome

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▪ clofazimine (50-100 mg/d, 100 mg three times weekly, o vaccination at birth with bacilli Calmette-Guérin has
300 mg monthly) proved variable effective – from total inefficiency to 80%
• causes red-black skin discoloration that accumulates efficacy
▪ rifampin (600 mg daily or monthly) – bactericidal • chemoprophylaxis
• relapses begin only after 6 years and most o not recommended even for household contacts
commonly after 10 years • isolation
• induces microsomal enzymes → increased doses of o hospitalized patients need not be isolated
glucocorticoids and OCs
o choice of regimens HERPES SIMPLEX
▪ tuberculoid leprosy is easiest form to treat, cured epidemiology
reliably with finite course of chemotherapy • common worldwide
▪ lepromatous leprosy requires prolonged or even • caused by two closely related types of HSV
lifelong chemotherapy o HSV-1 → orofacial disease
▪ other issues o HSV-2 → genital and perigenital infection
• even without therapy, TT may heal spontaneously • incidence of HSV-1
and dapsone monotherapy is curative o greatest during childhood – when 30-60% of children are
• in TT, no bacilli is common; thus, no measure for tx exposed to virus
success o rates of infection increase with age and reduced
• in LL, commonly harbor viable persisters that socioeconomic status
become source of relapse → prolonged follow-up is o majority of >30 y.o. are seropositive
necessary • incidence of HSV-2
▪ antimicrobial regimens recommended for treatment of o acquisition correlates with sexual behavior and
leprosy in adults (WHO) prevalence of infection in sexual partners
form of leprosy intensive WHO regimen o antibodies vs HSV-2 are rare in people before onset of
regimen sexual activity
tuberculoid dapsone (100 dapsone (100 o prevalence is 22% in >12 y.o.
(paucibacillary) mg/d) for 5 yrs mg/d) + rifampin o >70% of transmission is assoc. with asymptomatic and
(600 mg/month) subclinical reactivation and shedding
for 6 months o rate of acquisition is higher for women vs men
lepromatous rifampin (600 dapsone (100 etiology and pathogenesis
(multibacillary) mg/d) for 3 mg/d) plus
• the virus
years + clofazimine (50
o members of Herpesviridae family
dapsone (100 mg/d), and
mg/d) rifampin (600 ▪ lipid-enveloped double-stranded DNA viruses
indefinitely mg) + ▪ both are members of α-Herpesviridae subfamily
clofazimine • infect multiple cell types in culture
(300 mg) • grow rapidly
monthly for 1-2 • efficiently destroy host cells
years o infection in host is characterized by lesions in epidermis
• therapy for reactions ▪ → spread into nervous system → latent infections in
o type 1 neurons
▪ glucocorticoids (prednisone, initially 40-60 mg/d) • herpesvirus replication
▪ as inflammation subsides, glucocorticoid dose can be o after infection → immediate-early genes are transcribed
tapered but must be continued for at least 3-6 months → proteins → upregulate expression of early proteins
▪ indications are strictly limited required for genome replication
• intense inflammation a threat of ulceration ▪ late [HSV-2→HSV] genes encode virion structural
• at cosmetically important sites components
• in which neuritis is present • three stages of HSV infections in vivo
• otherwise, reaction should be tolerated o acute infection
o type 2 ▪ virus replicates at site of inoculation → primary lesions
▪ mild – may be treated with antipyretics alone → spreads to infect sensory nerve terminals →
▪ with many skin lesions, fever, malaise, other tissue retrograde axonal transport → neuronal nuclei in
involvement – glucocorticoids (initially 40-60 mg/d) regional sensory ganglia
▪ if despite two courses, recurring and persisting → o establishment and maintenance of latency
thalidomide (100-300 mg nightly) should be initiated ▪ in a subset of infections
▪ lower doses of thalidomide (50-200 mg nightly) is ▪ viral DNA is maintained as an episome
effective in preventing relapses ▪ gene expression severely restricted
o Lucio’s phenomenon o reactivation of virus
▪ optimal wound care and therapy for bacteremia are ▪ replication with anterograde axonal transport →
indicated peripheral site, or near point of entry
prevention and control ▪ HSV-1 reactivates most efficiently  usually trigeminal
• vaccination ganglia

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▪ HSV-2  from sacral ganglia o trigger factors
• immune response ▪ emotional stress, illness, exposure to sun, trauma,
o risk of severe HSV disease, recurrence rate correlates fatigue, menses, chapped lips, season
with immune competence ▪ other include UV irradiation, trigeminal nerve surgery,
o role for CD8+ and CD4+ T cells, NK cells and oral trauma, epidural administration of morphine,
inflammatory cytokines abrasive, laser, chemical facial cosmetic procedures
clinical findings o HSV-2 → indistinguishable from HSV-1
• orofacial infections ▪ usually in adolescents and young adult and following
o HSV-1 → herpetic gingivostomatitis, pharyngitis genital-oral contact
o herpetic gingivostomatitis ▪ 120x less likely reactivate than HSV-1 disease
▪ may resemble those of aphthous stomatitis • genital infection
▪ ulcerative lesions involving hard and soft palate, o major clinical presentation of HSV-2
tongue and buccal mucosa, neighboring facial areas ▪ HSV-1 in 10-40%, usually oral-genital contact
▪ clinical course of acute first-episode genital lesions
similar with HSV-1 and HSV-2 infections
▪ different stages of evolution – vesicles, pustules,
erythematous ulcers
▪ may require 2-3 weeks to resolve
▪ in males – on glans penis or penile shaft

o pharyngitis
▪ ulcerative and exudative lesions of posterior pharynx
▪ other: fever, malaise, salivation, myalgias, dysphagia,
irritability, cervical adenopathy
o reactivation involves perioral facial area
▪ outer one-third of lower lip being most commonly
affected
▪ two-thirds of labial lesions involve vermillion border
▪ in females – vulva, perineum, buttocks, vagina, cervix
(80%)
▪ accompanying pain, itching, dysuria, vaginal and
urethral discharge, tender inguinal lymphadenopathy
▪ systemic s/sx – fever, headache, malaise, myalgias
▪ others: herpetic sacral radiculomyelitis with urinary
retention, neuralgias and constipation
▪ HSV cervicitis in 80%
• purulent or bloody vaginal discharge
• diffuse or focal friability and redness, extensive
o herpes labialis
ulcerative lesions, necrotic cervicitis
▪ prodrome in 45-60% - pain, burning or itching at site of
subsequent eruption

o progression
▪ development stages
• prodromal
• erythema
• papule
▪ disease stages
▪ HSV-2 reactivate approximately 16x more frequently
• vesicle
• tend to be more frequent in first months to years
• ulcer
▪ recurrent HSV-2 infection
• hard crust
• small, but grouped vesicular lesions in genital area
▪ resolution stages
• prodrome of tenderness, itching, burning or tingling
• dry flaking
• less severe
• residual swelling
• usually heal in 6-10 days
▪ usually resolve within 5-15 days
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▪ headache, fever, stiffneck, mild photophobia,
lymphocytic pleocytosis
▪ mostly HSV_2
▪ resolves spontaneously in 2-7 days
▪ assoc. with primary genital HSV-2 infection
o other symptoms
▪ sacral nerve involvement, numbness, pelvic pain,
tingling, urinary retention, constipation, CSF
pleocytosis
o HSV encephalitis
▪ acute onset of focal neurologic symptoms and fever
treatment
laboratory tests • education
• method of choice dependent on clinical presentation o all sexually active persons should be educated
o history and clinical findings may be sufficient regarding nature and risks of acquiring and transmitting
• cell culture STI’s
o px with lesions o recognition of s/sx
o typical cytopathic effects o safe sex practices
o positive within 48-96 hours after inoculation • antiviral therapy
o 60-70% of fresh genital lesions are culture-positive o many require no specific treatment at all
o most successful when lesions are cultured during ▪ keeping lesions clean and dry while they heal by
vesicular stage themselves
• PCR o warranted for infections likely to prove protracted, highly
o more sensitive symptomatic or complicated
o acyclovir
• direct fluorescent antibody staining of lesion scrapings and
▪ acyclic guanosine analogue
antigen detection assays – less sensitive thatn viral culture
▪ preferential activation in infected cells and preferential
• Tzanck smear – less sensitive than culture and antibody
inhibition of viral DNA polymerase
staiing
▪ must be phosphorylated to be active, requires viral
o positive in <40% of culture proven cases
thymidine kinase (TK) for initial phosphorylation
o scraping base of freshly ruptured vesicle → stain with
o vancyclovir
Giemsa or Wright stain → examination for
▪ L-valyl ester of acyclovir
multinucleated giant cells – both HSV and VZV cause
▪ higher bioavailability after oral administration
these changes
o docosanol (10% cream)
▪ long-chain saturated alcohol that inhibits entry of lipid-
enveloped virus into cell
o choice of antiretrovirals
▪ disseminated, severe: IV acyclovir, 5-10 mg/kg q8h
▪ life-threatening HSV infection (e.g. encephalitis): IV
acyclovir, 15 mg/kg q8h
▪ neonatal herpes: IV acyclovir, 20 mg/kg q8h
• serologic detection ▪ first episode of genital HSV-2 infections: oral
o differentiating a primary episodes from a recurrent acyclovir, famciclovir, valacylovir
infection ▪ primary HSV gingivostomatitis: oral acyclovir
complication ▪ recurrent herpes labialis: penciclovear 1% cream q2h
• immunocompromised host while awake for 4d, docosanol 10% cream 5x/d, oral
o usually more severe, more extensive, difficult to treat, acyclovir 400 mg 5x/dx5d, famiclovir 500 mg 3x/dx5d,
more frequent recurrence valacyclovir 2g 2x/dx1d
• ocular infections prevention
o leading cause of recurrent keratoconjunctivitis → • antiviral therapy
corneal opacification and visual loss o acyclovir, famciclovir and valacyclovir decrease both
▪ HSV-1 symptomatic and subclinical shedding of HSV-2
o herpetic eye disease • vaccines
▪ blepharoconjunctivitis, dendritic or geographic o best public health strategy
epithelial ulcer with pain and blurred vision → stromal o however, no vaccine has proved to protect adequately
keratitis, iritis against acquisition of HSV
o acute retinal necrosis – rare
▪ retinal arteriolar sheathing, uveitis, peripheral retinal ACNE VULGARIS
opacification • self-limited disorder of the pilosebaceous unit seen
• neurologic disorders primarily in adolescents
o meningitis • pleomorphic array of lesions of varying extent and severity
o comedones
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o papules • presence and activity of Propionibacterium acnes
o pustules o Gram (+), anaerobic, microaerobic bacterium found in
o nodules sebaceous follicle
epidemiology o cell wall contains carbohydrate antigen → stimulates
• sufficiently common that it often has been termed antibody development
physiologic ▪ those with severe acne – highest antibody titers
o acne often heralds onset of puberty ▪ antipropionobacterial antibody → activating
▪ in girls, may precede menarche compliment → cascade of proinflammatory events
• prevalence hits its peak during middle-to-late teenage o elicits a delayed type hypersensitivity response →
period lipases, proteases, hyaluronidases, chemotactic factors
o >85% of adolescents affected ▪ neutrophils → ROS, lysosomal enzymes
o in very young, comedones as most predominant lesion o binds to TLR-2 on monocytes and PMNCs → stimulates
• acne severity seems to be familial expression of cytokines → release of proinflammatory
o twin studies: 81% of variance due to genetic factors cytokines – IL-1α, IL-8, IL-12, TNF-α
etiology and pathogenesis o adolescents with acne have high concentrations of P.
• follicular epidermal hyperproliferation acnes
o → formation of microcomedo clinical findings
o epithelium of infundibulum → hyperkeratotic, increased • history
cohesion o gradual onset of lesions around puberty
o excess cells → plug in follicular ostium → downstream o abrupt onset
concretions of keratin, sebum, bacteria → accumulate in ▪ consider hyperandrogenism – when severe in onset,
follicle → dilation of upper hair follicle → microcomedo assoc. with hirsutism, irregular menstrual periods
o stimulus is unknown o medication history
▪ androgens stimulation? ▪ some medications can cause abrupt onset of
• dihydrotestosterone (DHT) – potent androgen, may monomorphous acneiform eruption
play role in acne ▪ anabolic steroids, corticosteroids, corticotropin,
• dehydroepiandrosterone sulfate (DHEA-S) → phenytoin, lithium, isoniazid, vitamin B complexes,
androgen DHT via 17-β hydroxysteroid halogenated compounds, EFFR inhibitors
dehydrogenase (HSD), 5-α reductase • cutaneous lesions
• follicular keratinocytes have increased 17-β HSD, o primary sites: face
and 5-α reductase → increased DHT production ▪ lesser degree: back, chest, shoulders
▪ decreased linoleic acid? o characterized by several clinical lesion types
• essential fatty acid in skin ▪ one type of lesion may predominate
• decreased in subjects with acne ▪ noninflammatory – comedos
▪ increased IL-1 α activity • open comedo – flat, slightly raised lesion with central
▪ effects of Propionibacterium acnes dark-colored follicular impaction of keratin and lipid
• excess sebum production
o patients with acne produce more sebum – quality is the
same
o components of sebum may play role – triglycerides and
lipoperoxides
o triglycerides → free fatty acids by P. acnes → promote
further bacterial clumping, colonization → inflammation
→ comodogenic? • closed comedones – pale, slightly elevated, small
o lipoperoxides → proinflammatory cytokines, activate papules
peroxisome proliferator-activated receptors (PPAR)
pathway → increased sebum
o androgen hormones → bind to and influence sebocyte
activity
o other hormones: estrogen? CRH?
• inflammation
o expansion of comedone with densely packed keratin,
sebum and bacteria → follicular wall rupture → brisk ▪ inflammatory lesions – from small papules to pustules
inflammatory response to nodules
o predominant cell type within 24 hrs: lymphocyte
▪ CD4+ around pilosebaceous unit
▪ CD8+ found perivascularly
o 1-2 days after rupture → neutrophil becomes
predominant cell type
o dermal inflammation may actually comedo formation
▪ biopsies from acne-prone skin demonstrate increased
inflammation
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o cleansing
▪ twice daily with gentle cleanser followed by application
of better treatments
▪ overcleansing, using alkaline soaps → disrupt skin pH,
cutaneous lipid barrier, compound irritancy potential of
acne treatments
▪ medicated cleansers (with benzoyl peroxide or salicylic
o scarring – four general types acid) offer convenience as a wash
▪ ice pick o topical agents
• narrow, deep scars that are widest at surface and ▪ sulfur/sodium sulfacetamide/resorcinol
taper to a point in dermis • inhibition of PABA, essential for P. acnes growth
▪ rolling • inhibits formation of free fatty acids
• shallow, wide scars with undulating appearance • presumptive keratolytic properties
▪ salicylic acid
• with comedolytic properties, but weaker than retinoid
• causes exfoliation of stratum corneum though
decreased cohesion of keratinocytes
▪ azelaic acid
• antimicrobial, comedolytic
• competitive inhibitor of tyrosinase → may decrease
postinflammatory hyperpigmentation
• safe in pregnancy
▪ benzoyl perozide
• antimicrobial agent through decreasing bacterial
population and hydrolysis of triglycerides
▪ topical antibiotics
▪ boxcar • erythromycin, clindamycin, dapsone
• wide, sharply demarcated scars ▪ retinoids
• width similar at surface and base • bind to and activate retinoic acid receptors →
▪ hypertrophic activate specific gene transcription → cell
proliferation, differentiation, melanogenesis →
modification of corneocyte accumulation and
cohesion
• comedolytic, anti-inflammatory
• tretinoin, adapalene, tazarotene
• systemic therapy
o antibiotics and antibacterial agents
laboratory tests ▪ tetracyclines
• not indicated unless hyperandrogenisms is suspected • decreases concentration of FFA, esterified fatty acid
o serum levels of androgens – serum DHEAS, total content increases
testosterone, free testosterone o mostly preventive
o serum LH, FSH, LH:FSH ratio • direct suppression of P. acnes
o serum 17-hyderoxyprogesterone • taken on empty stomach, 1 hour before or 2 hours
prognosis and clinical course after meals to promote absorption
• age of onset varies • common side effects: GI upset, esophagitis,
o as early as 6-8 years of age, may not appear until age of pancreatitis
20 or later • uncommon side effects: hepatotoxicity,
• several years’ duration followed by spontaneous remission hypersensitivity reactions, leukocytosis,
in majority thrombocytopenic purpura, pseudomotor cerebri,
• extent of involvement varies, and with spontaneous may increase uremia
fluctuations in degree of involvement • should not be administered to pregnant women
o in women, often associated with menses – flare just • not safe for use in children <9 years
before onset of menstruation • derivatives can be taken with food – doxycycline,
treatment minocycline
• mechanism of action of most common treatments can be • doxycycline side effects – photosensitivity reactions
categorized • minocycline side effects – blue-black pigmentation,
o correct the altered pattern of follicular keratinization vertigo
o decrease sebaceous gland activity ▪ macrolides
o decrease the follicular bacterial population • azithromycin
o exert an anti-inflammatory effect o hepatic metabolism
• local therapy o side effects – GI upset, diarrhea
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▪ trimethoprim-sulfamethoxazole • in severe truncal involvement – up to 2 mg/kg/day
• potential for side effects is greater with use → should • typical course is 20 weeks, but not absolute
be used only when no response to other antibiotics • initial dosing should be low
• common side effects – GI upset cutaneous o diet
hypersensitivity reactions ▪ role of chocolates, sweets, milk, high-glycemic index
• serious side effects – SJS/TENS, aplastic anemia foods, fatty acids in acne enquires further study
▪ cephalexin ▪ restricting food firmly thought by patient as a trigger is
• first generation cephalosporin not harmful, as long as nutritional well-being is not
• penetrates poorly into pilosebaceous unit compromised
▪ clindamycin and dapsone • acne surgery
• hormonal therapy of acne o its use today is primarily restricted to those patients who
o oral contraceptives do not respond to comedolytic agents
▪ four main mechanism • intralesional glucocorticoids
• decrease amount of gonadal androgen production o dramatically decreases size of deep nodular lesions
by suppressing LH production o 0.05-0.25 mL per lesion of triamcinolone acetate
• decrease amount of free testosterone by increasing suspension
production of sex hormone binding globulin • phototherapy and lasers
• inhibit activity of 5-α reductase activity
• progestins can block androgen receptors on SCABIES
keratinocytes and sebocytes
▪ two progestines have demonstrated antiandrogenic
properties – cyproterone acetate, drospirenone
o glucocorticoids
▪ use is restricted to severely involved patient
▪ ordinarily used for limited periods of time →
recurrences common epidemiology
▪ low-dose prednisone, dexamethasone orally at • affects all ages, races and socioeconomic levels
bedtime → suppress adrenal androgen production
• infested host usually harbors 3-50 oviparoud mites
o gonadotropin-releasing hormone agonists
• prime route of transmission: close personal contact
▪ act on pituitary gland to disrupt cyclic release of
o sometimes considered as sexually transmitted
gonadotropins → suppression of ofvarian
o via inanimate objects, esp. in crusted scabies
steroidogenesis in women
• notoriously contagious
▪ used in treatment of ovarian hyperandrogenism
etiology and pathogenesis
▪ limited by side effects – menopausal symptoms, bone
• infestation of Sarcoptes scabiei var. homini
loss
o highly host-specific
o antiandrogens
o family Sarcoptidae, class Arachnida
▪ spironolactone – aldosterone antagonist
• mite is pearl-like, translucent, white, eyeless and oval in
• androgen-receptor blocker and 5-α reductase
shape
• reduces sebum production, improve acne
o with four pairs of stubby legs
• side effects: diuresis, potential hyperkalemia,
irregular menstrual periods, breast tenderness,
headache, fatigue
▪ cyporoterone acetate – progestational antiandrogen
• blocks androgen receptor
▪ flutamide
• androgen receptor blocker
• monitor LFTs • able to live for 3 days away from host in sterile test tubes
o isotretinoin o 7 days if placed in mineral oil mounts
▪ approved for use with severe recalcitrant nodular acne • cannot fly or jump
▪ MOA not clear • life cycle completely on human skin
• profound inhibition of sebaceous gland activity o female mite → chewing, body motions → sloping burrow
• decrease, but transient, in P. acnes in stratum corneum to boundary with stratum granulosum
• anti-inflammatory activity o along path, lays 2-3 eggs a day during life span of 30
• maybe an effect on pattern of follicular keratinization days
▪ side effects – cheilitis, dryness of mucous membranes o eggs hatch in 10 days → mature on skin surface
and skin, eczematous dermatitis, thinning of hair, o male mite lives on surface and enters burrows to mate
ophthalmologic findings (xerophthalmia, night clinical findings
blindness, conjunctivitis, keratitis, optic neuritis, • suspected by findings of
corneal opacities, hearing loss), pseudotumor cerebri, o pruritus
GI symptoms uncommon, osteopenia, teratogenic ▪ appears 4-6 weeks after initial infestation
▪ daily dosage of isotretinoin in range of 0.5-1 mg/kg/day o characteristic distribution of lesion
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o epidemiologic history ▪ rash and pruritus may persist for up to 4 weeks →
• physical examination postscabetic itch
o excoriations o excessive washing of skin with harsh soaps aggravate
o eczematous dermatitis that favors iriritation
▪ interdigital webs o permethrin 5% cream
▪ sides of fingers ▪ apply for 8 hours, repeat in 7 days
▪ volar aspects of wrists and lateral palms o lindane 1% lotion
▪ elbows ▪ apply for 8 hours, repeat in 7 days
▪ axillae o crotamiton 10% cream
▪ scrotum ▪ apply for 8 hours on days 1,2,3, 8
▪ penis ▪ with antipruritic qualities
▪ labia ▪ marginal effectiveness
▪ areolae o precipitated sulfur 5-10%
o head and neck usually spared in adults ▪ apply for 8 hours on days 1, 2, 3
o indurated, crusted nodules in children on intertriginous ▪ safe in neonates and during pregnancy
areas o benzyl benzoate 10% lotion
• crusted scabies ▪ apply for 24 hours
o hyperkeratotic plaques on palmar and plantar regions o ivermectin 200 μg/kg
o dystrophy of toenails and fingernails ▪ taken orally on day 1 and 8
prevention
• all family members and close contacts whould be treated
simultaneously
• treated individuals should wear clean clothing
• all clothing, pillow cases, towels, and bedding used during
previous week should be washed in hot water, dried at high
heat
• nonwashables should be dry-cleaned, ironed, put in clothes
dryer without washing or stored in sealed plastic bag in warm
area for 2 weeks
• burrow • floors, carpets, upholstery and furniture should be carefully
o pathognomonic lesion vacuumed
o thin, thread-like, linear structure
o 1-10 mm SEBORRHEIC DERMATITIS
o tunnel caused by movement of mite • common, chronic papulosquamous disorder
o best seen in interdigital webs and wrists characteristically found in regions of body with high
• definitive diagnosis: microscopic identification of scabies concentration of sebaceous follicles and active sebaceous
mites, eggs or fecal pellets (scybala) glands – face, scalp, ears, upper trunk and flexures
o drop of mineral oil over burrow → scraping longitudinally • presents with pink to erythematous, superficial patches and
with no. 15 scalpel blade → glass slides → examined plaques with yellow, branny and sometimes greasy scale →
under LPO excessive flaking
o other diagnostics: confocal microscopy, dermoscopy, epidemiology
skin biopsy • two age groups
complications o infantile self-limited form
• secondary impetiginization o chronic adult form
• PSGN from scabies-induced pyodermas • male predominance in all ages
• lymphangitis and septicemia in crusted scabies o no horizontal transmission
• bullous pemphigoid • prevalence is 3-5% in young adults, 1-5% in general
treatment population
• treated with combination of scabicide and fomite control etiology and pathogenesis
o in insecticidal therapies, second application is required to • exact pathogenesis is yet to be fully elucidated
reduce potential for reinfestations o linked with Mallasezia
o all household and close contacts must be simultaneously o immunologic abnormalities
treated o sebaceous activity
• topical scabicides o patient susceptibility
o applied overnight to entire skin surface with special • people with seborrheic dermatitis show high skin surface
attention to lipid levels of triglycerides and cholesterol, lower levels of
▪ finger and toe creases FFA and squalenes
▪ cleft of buttocks o Malassezia, P. acnes have lipase activity that transforms
▪ belly button triglycerides → FFA
▪ beneath fingernails and toe nails • all seven species of Malassezia are lipophilic
o relief within 3 days usually o except M. pachydermatis

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COURSE: DERMATOLOGY
• FFAs and ROS produced → antibacterial activity → alters ▪ scalp (cradle cap), trunk (flexures, napkin area),
normal skin flora Leiner’s disease (nonfamilial and familial C3/C5
• immunology dysfunction)
o many patients have normal levels of Malassezia but have o adult
an abnormal immune response → depressed helper T ▪ scalp, face, eyelids (blepharitis), trunk (petaloid,
cell response, less production of phytohemagglutinin and pityriasisform, flexural, eczematous, follicular,
concavilin generalized, erythrodermic)
o elevated levels of IL-10, drop in IL-2 and IF-γ prognosis and clinical course
o Malassezia → stimulates alternative complement • self-limited with good prognosis in infants vs chronic and
relapsing in adults
pathway
• generalized flares and erythroderma can occur
o inflammation on skin  metabolic products, complement
seborrheic dermatitis in infants vs adults
activation
• infantile form
• physical factors
o occurs during first few weeks to 3 months of life
o seasonal fluctuations in humidity and temperature flare
o self-limited
disease
o commonly concentrated on vertex of scalp
o low humidity and cold temperatures in winter
▪ adherent, yellow-brown, greasy scale
o facial psoralen + ultraviolet radiation (PUVA) treatments
▪ can sometimes spread to entire scalp – inflammatory,
and facial trauma
erythematous, oozing crusts
• microbial effects
o lesions on face, neck → disseminated to trunk and
o presence or imbalance of microbial flora likely plays a role
extremities
in disease
▪ inflammatory glistening plaques in intertriginous sites
o some have cultures of Candida albicans, Staphylococcus
aureus, P. acnes
o none have been linked to pathogenesis
o number of yeasts does not correlate with severity
• drugs
o several drugs are known to trigger
o griseofulvin, cimetidine, lithium, methyldopa, arsenic,
gold, auranofin, aurothioglucose, buspirone,
chlorpromazine, ethionamide, haloperidol, interferon-α,
phenothiazines, stanozolol, thiothixene, psoralen, • adult form
methoxsalen, trioxsalen o chronic, can persist from 4th-7th decade
• neurotransmitter abnormalities ▪ peak at age 40
o many neurologic disorders have been associated with o lesions may be seen on face
seborrheic dermatitis → resulting in some facial ▪ prominent symmetry
immobility and sebum accumulation ▪ medial eyebrows, forehead, upper eyelids, nasolabial
o Parkinson’s, Alzheimer’s, syringomyelia, epilepsy, folds, lateral nares
cerebrovascular infarcts, postencephalitis, mental
retardation, poliomyelitis, quadriplegia, trigeminal nerve
injury and other facial nerve palsies
o depression and emotional stress reported to be triggers
• aberrant epidermal proliferation
o patients may have epidermal hyperproliferation or
dyskeratinization related to increased activity of
calmodulin ▪ other sites: retroauricular regions, external auditory
• nutritional disorders canal, auricle, conchae bowl, scalp, occiput, neck
o not proven to be associated with vitamin deficiency
• genetic factors
o family history is often reported
o mutation encoding zinc finger protein (C2H2) has been
described resulting in a seborrhea-like dermatitis
• psoriasis and seborrheic dermatitis
o sebopsoriasis
▪ overlap of psoriasis and seborrheic dermatitis
o lesions on trunk – presternal region, upper back,
▪ tends to localize to scalp, face, presternal chest
umbilicus → petaloid or arcuate with fine pink scale
▪ margins better defined, more erythematous and with
o intertriginous sites show less scale
thicker scales
▪ may mimic intrtrigo
▪ biopsy can be indistinguishable from psoriasis
o erythema, pruritus common
clinical findings
▪ other symptoms: burning or tingling sensitivity
• clinical patterns o Pityrosporum folliculitis can be seen
o infantile
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COURSE: DERMATOLOGY
▪ with diffuse monomorphic tiny pustules and papules o blanch with pressure
with peripheral erythema on trunk o characterized by dilated blood vessels and increased
▪ diagnosis via KOH preparation permeability – involves venular plexus
o typically begins during puberty – corresponds with epidemiology
androgen activity • acute – if <6 weeks
treatment o most are due to adverse reactions to medications, foods
• infantile or viral illnesses
o responds readily to shampoos, emollients and mild • chronic – if >6 weeks – combined incidence of 0.5%
topical steroids o chronic autoimmune urticaria (45%)
o prolonged inflammation on scalp or intertriginous areas o chronic idiopathic urticaria (55%)
→ low potency topical corticosteroids (hydrocortisone 1% o 50% of px with chronic urticaria are free of lesions within
cream or lotion) → followed by topical imidazole (2% 1 year, 65% within 3 years, 85% within 5 years
ketoconazole cream, lotion or 1% shampoo) • 85% of children experience urticaria in absence of
o mild, baby shampoos can help remove thick, stubborn angioedema
scale on scalp • 40% of adult patients with urticaria also experience
o secondary infections should be treated angioedema
• adult pathogenesis
o aim of treatment will be control rather than cure • mast cell and histamine release
o scalp → o mast cell as major effector cell
▪ shampoos containing zinc pyrithione o mast cell adhere to fibronectin and laminin via VLA β1
▪ selenium sulfide (1-2.5%) integrins VLA-3, -4, and -5 and to vitronectin via αvβ3
▪ imidazoles (1-2% ketoconazole shampoo, creams, integrin
lotions, foams) o cutaneous mast cells release histamine in response to
▪ cicloprox (cream, gel shampoo) compound 48/80, C5a, morphjne and codeine
▪ salicylic acid (shampoos, creams) o substance P, vasoactive intestinal peptide (VIP),
o severe and thick scale on scalp → somatostatin activate mast cells for histamine secretion
▪ topical corticosteroids with shower cap occlusion as o release of mast cell products (histamine, leucotrienes,
needed cytokines, chemokines) → alterations in
▪ Baker’s P&S solution vasopermeability, upregulation of adhesion molecules on
▪ tar shampoo endothelial cells, rolling and attachment of blood
▪ salicylic acid leucocytes → chemotaxis, transendothelial cell migration
o avoid aggressive hair manipulation o intracutaneous injection of specific antigen → biphasic
o with severe inflammatory disease that fail above response
regimens → ▪ transient, pruritic, erythematous, wheal-and-flare
▪ systemic glucocorticoids reaction
▪ caution patient of side effects and rebound flares after ▪ tender, deep, erythematous, poorly demarcated area
discontinuation of swelling
o face, trunk, ears → • autoimmunity and chronic urticaria
▪ short courses of low potency topical glucocorticoids → o increased incidence of antithyroid antibodies
suppress initial inflammation ▪ 15-24% in patients with urticaria
▪ topical calcineurin inhibitors ▪ most are euthyroid
• pimecrolimus, tacrolimus • cellular infiltrate
▪ topical antifungals have been used with varying o perivascular infiltrate that surrounds small venules within
success superficial and deep venular plexus
▪ sulfur or sulfunomide combination, propylene glycol ▪ predominance of CD4+ T lymphocytes
topical ▪ no B cells
▪ benzoyle peroxide wash 5-10% o resembles allergic late-phase reaction
o seborrheic blepharitis ▪ neutrophils and monocytes relatively more prominent
▪ warm to hot compress in urticaria
▪ washing with baby shampoo → gentle cotton tip o presence of C5a distinguishes lesion from typical
debridement of thick scale allergen-induced cutaneous late-phase reaction
▪ avoid ocular glucocorticoids • basophil releasibility
o alternative treatments o basophils hyporesponsive to anti-IgE in chronic urticaria
▪ oral antifungals for severe and refractory cases ▪ due to augmented levels of SHIP phosphatase that
limits phosphorylation reaction critical for histamine
URTICARIA secretion
• skin lesion consisting of a wheal-and-flare reaction in which ▪ appears to reverse when patient remits → marker for
localized intracutaneous edema (wheal) is surrounded by disease activity?
an area of redness (erythema) that is usually pruritic • role of the extrinsic coagulation cascade
o can last from 30 minutes to 36 hours o presence of D-dimer and prothrombin 1 and 2 fragments
o can be as small as a millimeter or 6-8 inches in diameter ▪ indicates activation of prothrombin to thrombin,
(giant urticaria) digestion of fibrinogen by thrombin
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o dependent on tissue factor rather than factor XII – ▪ arise from 3-6 hours after sustained pressure has been
extrinsic applied to skin
• bradykinin: role in angioedema ▪ peak prevalence un 3rd decade
o kinins ▪ may be associated with fever, chills, arthralgias,
▪ low-MW peptides that participate in inflammatory myalgias, elevated ESR, leukocytosis
processes by virtue of their ability to activate o vibratory angioedema
endothelial cells → vasodilation → increased vascular ▪ described in families with autosomal dominant pattern
permability → production of NO, mobilization of • often accompanied by facial flushing
arachidonic ▪ typical symptom: hives across back when toweling off
▪ stimulate sensory nerve endings → burning shower
dysesthesia o cold urticaria
▪ e.g. bradykinin ▪ idiopathic or primary acquired cold urticaria
o generation of bradykinin – two pathways • may be assoc. with headache, hypotension,
▪ via tissue kallikrein and kininogen syncope, wheezing, SOB, palpitations, nausea,
▪ one is initiated by intrinsic coagulation pathway → vomiting, diarrhea
factor XII → factor XIIA ▪ attack occur within minutes after exposures that
• substrates: prekallikrein and factor XI, both complex include changes in ambient temperature, direct contact
with high-MW kininogen (HK) with cold object
• → plasma kallikrein and factor Xia ▪ diagnostic cold contact test – wheal after application of
clinical findings ice
• circumscribed, raised erythematous, usually pruritic o cholinergic urticaria
evanescent areas of edema that involve superficial portion ▪ develops after an increase in core body temperature
o extension into deep dermis or subcutaneous and ▪ highest prevalence in individuals aged 23-28 years
submucosal layers → angioedema ▪ distinctive, pruritic, small, 1-2-mm wheals surrounded
▪ commonly affects face or portion of extremity by large areas of erythema
▪ painful but not pruritic ▪ systemic features: dizziness, headache, syncope,
flushing, wheezing, SOB, nausea, vomiting, diarrhea

• immunologic: IgE- and IgE receptor-dependent o local heat urticaria

o atopic diathesis ▪ rare form in which wheals develop within minutes after
▪ episodes that occur in persons with personal or family exposure to locally applied heat
history of asthma, rhinitis, eczema o solar urticaria
o specific antigen sensitivity ▪ pruritus, erythema, wheals that develop within minutes
▪ common: shellfish, nuts, chocolate; penicillin; after exposure to sun or artificial light sources
aeroallergens; Hymenoptera venom ▪ systemic features: headache, syncope, dizziness,
• physiologic urticaria wheezing, nausea
o dermographism ▪ six subtypes – in response to specific wavelengths
▪ most common form o exercise-induced anaphylaxis
▪ appears as lineal wheal with flare at site in which skin ▪ pruritus, urticaria, angioedema, respiratory distress,
is briskly stroked with firm object syncope distinct from cholinergic urticaria
▪ transinent wheal appears rapidly and fades within 30 ▪ resemble hives seen in acute or chronic urticaria
min ▪ some are food-dependent – exercise will lead to
▪ may become pruritic → itch-scratch sequence episode only if food was ingested within 5 hours of
▪ prevalence in 1.5-4.2% exercise
▪ not associated with a topy o adrenergic urticaria
▪ peak prevalence in 2nd-3rd decades ▪ wheals surrounded by white halo that develop during
emotional stress
o aquagenic urticaria and aquagenic pruritus
▪ small wheals reminiscent of cholinergic urticaria
• contact urticaria
o may be IgE mediated or nonimmunologic
o appears within minutes
▪ IgE mediated → may be associated with systemic
o pressure urticaria manifestations
▪ erythematous, deep, local swellings, often painful
• papular urticaria
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o episodic, symmetrically distributed, pruritic, 3-10-mm ▪ without B cells or NK cells
urticarial papules • increased TNF-α and IL-3  acute urticaria, chronic
o reaction to bites of insects idiopathic urticaria, delayed pressure urticaria
• urticarial venulitis • major basic protein, eosinophil cationic protein 
o urticaria may be nmanifestation of cutaneous necrotizing eosinophil granules
venulitis o around blood vessels, dispersed in dermis of acute
o associated features: fever, malaise, arthralgia, abdominal urticaria, CIU, delayed-pressure urticaria, cholinergic
pain urticaria, solar urticaria
▪ less common: conjunctivitis, uveitis, • P-selectin, E-selectin, ICAM1, VEAM1  CHIU,
glomerulonephritis, obstructive and restrictive dermographism
pulmonary disease, benign intracranilal hypertension • MHC class II upregulated on endothelial cells of chronic
• serum sickness urticaria
o adverse reaction that resulted from administration of • papular urticaria → epidermis is thick with intercellular
heterologous serum to humans but may also occur after edema and lymphocutes
administration of drugs o dermis has edema with infiltrate containing T cells,
o occurs 7-21 days after administration of offending agent macrophages, eosinophils and neutrophils
o manifested by fever, urticaria, lymphadenopathy, treatment
myalgia, arthralgia, arthritis • acute urticaria
o usually self-limited and last 4-5 days o antihistamines
• reactions to the administration of blood products o if relief provided by nonsedating antihistamines
o result of immune complex formation and complement insufficient → hydroxyzine, diphenhydramine 25-50 mg
activation → direct vascular and smooth muscle qid
alterations and mast cell mediator release via o course of corticosteroid can be used 40-60 mg/day for 3
anaphylotoxins days, taper by 5-10 mg/day
• infections o epinephrine indicated if laryngeal edema is present
• urticaria/angioedema after direct mast cell degranulation o ideal treatment is identification and removal of its cause
o opiate, analgesics, polymyxin B, curare, d-tubucurarine • chronic urticaria
induce release of histamine from mast cells and o measures that provide symptomatic relief
basophils o antipruritic lotions, cool compresses, ice packs may
• urticaria/angioedema relating to abnormalities of provide temporary relief
arachidonic acid metabolism o H1-type antihistaminic drugs are mainstays
o intolerance to aspirin and NSAIDs manifested as ▪ second- and third-generation H1-type antihistamines
urticaria/angioedema as drugs of choice
• chronic idiopathic urticaria and idiopathic angioedema • newer, low-sedating
approach to the patient • reduced sedative and anticholinergic effects
• comprehensive history and physical examination ▪ should be taken on a regular basis
o appearance ▪ if ineffective → agent from different pharmacological
▪ small wheals with large erythematous flare → class, combine antihistamines or increase dose
cholinergic urticaria • if ineffective → hydroxyzine, diphenhydramine 25-50
▪ linear wheals → dermographism mg qid may be tried
▪ localization to exposed areas → light- or cold-induced ▪ cold urticaria → cyproheptadine at 4-8 mg tid/qid
urticaria seems particularly effective
o special PE technique
▪ dermographism → brisk stroke EPIDERMAL NECROLYSIS
▪ delayed-pressure urticaria → use of weight • toxic epidermal necrolysis (TEN) and Stevens-Johnson
▪ cold-induced urticaria → application of cold stimulus syndrome S(JS) are acute life-threatening
▪ localized heat urticaria → application of heat stimulus mucocutaneous reactions characterized
▪ cholinergic urticaria → exercise • by extensive necrosis and detachment of epidermis
o timing, onset o characterized by skin and mucous membrane
▪ when present for days or weeks at a time or occurs involvement
recurrently for similar intervals → allergic reactions to epidemiology
food or drugs • rare
▪ hives last less than 2 hours → dermatographism, o overall incidence: 1-6 cases per million person-uears
cholinergic urticaria, cold urticaria (SJS), 0.4-1.2 cases per million person-years (TEN)
▪ lasting 12-36 hours, first appear 3-6 hours after stimuli o can occur at any age
→ delayed pressure urticaria ▪ risk increasing with age after fourth decade’
▪ longer than 6 weeks → chronic urticaria o more frequently affects women
histopathology ▪ ratio at 0.6
• chronic urticaria o overall mortality: 20-25%
o dermal infiltrating inflammatory cells may be sparse or ▪ SJS – 5-12%
dense ▪ TEN – >30%
▪ CD4 > CD8, neutrophils, eosinophils basophils
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▪ poor prognosis: increasing age, significant comorbidity, o initially symmetrically distributed on face, upper trunk,
greater skin involvement proximal part of limbs
▪ SCORTEN – prognosis score for EN
etiology
• pathophysiology is still unclear
• drugs are most important etiologic factors
o high risk drugs
▪ antibacterial sulfonamides, aromatic anticonvulsants,
allopurinol, oxicam NSAIDs, lamotrigine and
nevirapine
▪ risk confined to first 8 weeks of treatment
▪ slow dose escalation decreases rate of rash in
lamotrigine and nevirapine, but no evidence it
o distal portions are relatively spared by can extend within
decreases risk of EN
few days or hours
o lower risk drugs
o erythematous, dusky red, purpuric macules → coalesce
▪ non-sulfonamide antibiotics such as aminopenicillins,
o atypical target lesions with dark centers can be observed
quinolones, cephalosporins, tetracyclines
o Nikolsky sign – dislodgement of epidermis by lateral
• role of infectious agents much less prominent pressure
o there cases of EN associated with Mycoplasma ▪ positive on erythematous zones
pneumoniae infection, viral disease and immunization o lesions → flaccid blisters
• cases reported after bone marrow transplantation ▪ spread with pressure and burst easily
o some are extreme form of acute graft-versus-host ▪ necrotic epidermis easily detached at pressure points
disease or by frictional trauma → reveals large areas of
• lupus erythematosus is associated with an increased risk of exposed, red, oozing dermis
EN
• radiotherapy in addition to treatment with antiepileptic drugs
→ trigger EN with lesions localized at sites of radiation
treatment
o phenytoin, phenobarbital or carbamazepine
pathogenesis
• early lesions → cell-mediated cytotoxic reaction against
keratinocytes → massive apoptosis
o presence of cytotoxic cells – natural killer T cells, drug-
specific CD8+ T cells
o monocytes, macrophages, granulocytes also recruited
o amplification of cytokines
▪ TNF-α, Fas-L → factors activating death receptors on
cell membranes → apoptosis of keratinocytes
▪ granulolysin as principal soluble death mediator
• little is known on what are initial and intermediate steps
• most drugs associated with high risk can induce milder and
more frequent reactions
o abnormal regulation of immune response → TEN/SJS? o classified according to total area in which epidermis is
o CD25+ T cells have been demonstrated to be potentially detached or detachable
important in prevention of severe epidermal damage ▪ <10% of BSA – SJS
clinical findings ▪ 10-30% of BSA – SJS/TEN overlap
• history ▪ >30% of BSA – TEN
o clinically begins within 8 weeks after onset of drug • mucous membrane involvement
exposure for first time o nearly always on at least 2 sites
o nonspecific symptoms o observed in 90% of cases
▪ fever, headache, rhinitis, cough, malaise o begins with erythema → painful erosions of oral, ocular
▪ may precede lesions by 1-3 days and genital mucosa → impaired alimentation,
o pain on swallowing or burning or stinging of eyes photophobia, conjunctivitis, painful micturition
progressively develop o oral cavity and vermilion border of lips → painful
▪ heralds mucous membrane involvement hemorrhagic erosions coated by grayish white
o a third begin with nonspecific symptoms, another third pseudomembranes and crusts of lips
begin with mucous membrane involvement, last third with
an exanthema
o rapid progression, additional signs, severe pain and
constitutional symptoms should alert one
• cutaneous lesions

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prognosis and clinical course
• epidermal detachment progresses for 5-7 days
• plateau phase – progressive reepithelialization
o few days to few weeks
o life-threatening complications may occur
• increased mortality in 3-month period following hospital
discharge
treatment
• prompt withdrawal of offending agent
o approx.. 80% have conjunctival lesions → pain, • symptomatic treatment
photophobia, lacrimation, redness, discharge → o with limited skin involvement, SCORTEN = 0,1
epithelial defect corneal ulceration, anterior uveitis, ▪ can treated in nonspecialized wards
purulent conjunctivitis ▪ maintain hemodynamic equilibrium and prevent
• extracutaneous symptoms complications
o assoc. with high fever, pain, weakness ▪ same aims as extensive burns
o visceral involvement possible o fluid replacement
laboratory tests ▪ volumes usually less than for burns because interstitial
• laboratory values edema is absent
o no laboratory test to support diagnosis ▪ peripheral venous lines are preferred
o for evaluation of severity and daily management o environment should be raised to 28-30°C
o evaluate RR and ABG levels o early nutritional support via nasogastric tube
▪ serum bicarbonate < 20 mM → poor prognosis ▪ promote healing and decrease risk of bacterial
o serum electrolytes, serum BUN translocation
▪ massive transdermal fluid loss → electrolyte o regular skin, blood and urine specimens collected for
imbalances, hypoalbuminemia, hypoproteinemia → bacterial and fungal cultures
mild and transient AKI, prerenal azotemia common o prophylactic anticoagulation
▪ raised BUN → marker of severity o no standard policy on wound dressings and antiseptics
o CBC o eyes should be examined daily by ophthalmologist
▪ anemia usual ▪ emollients, antibiotic or antiseptic eye drops and
▪ mild leukocytosis vitamin A every 2 hours
▪ thrombocytopenia ▪ mechanical disruption of early synechiae
▪ neutropenia an unfavorable prognostic factor o mouth rinsed several times a day with antiseptic or
• histopathology antifungal solution
o early stages • specific treatment in acute stage
▪ sparse apoptopic keratinocytes in suprabasal layers → *none has clearly proved its efficacy
full-thickness necrosis and subepidermal detachment o corticosteroids
o moderately dense mononuclear cell infiltrate of papillary o IV IG
dermis – CD8+ lymphocytes and macrophages o cyclosporine A
complications and sequelae o plasmapheresis or hemodialysis
• acute phase o antitumor necrosis factor agents
o sepsis
▪ epithelial loss predisposes to infections STAPHYLOCOCCAL SKIN INFECTIONS
▪ S. aureus, Pseudomonas, gut enterobacteriae epidemiology
o multiorgan system failure, pulmonary complications • Staphylococci
• after acute, EN behaves as a chronic disease o coagulase-negative Staphylococci
o posttraumatic stress disorder o coagulase-positive Staphylococci – S. aureus
▪ psychiatric consultation and/or psychological support • individuals carry at least 10-24 combined temporary and
necessary in majority resident S. epidermidis (most common CoNS)
o late ophthalmic complications • S. aureus
▪ functional alteration of conjunctival epithelium with o permanently colonizes anterior nares in approx.. 20% of
dryness and abnormal lacrimal film → chronic population
inflammation, fibrosis, entropion, trichiasis, o transient or intermittent in others
symblepharon o other sites: axillae, perineum, pharynx, hands
▪ long-term irritation → metaplasia of corneal epithelium o predisposing conditions – atopic dermatitis, DM, dialysis,
with painful uclerations,scarring, altered vision IV drug use, liver dysfunction, HIV infection
o hypopigmentation and/or hyperpigmentation o aggressive pathogen – most common cause of primary
o nail bed changes pyodermas and STIs
o mouth complications • transfer of organisms predominantly via hands
o vulvar and vaginal complications etiology and pathogenesis
▪ dyspareunia, genital adhesions • colonization may be transient or represent a prolonged
o chronic lung disease → bronchiolitis obliterans carrier state

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o S. aureus → cellular components and extracellular
products
o host factors – immunosuppression, glucocorticoid
therapy, atopy
o preexisting tissue injury or inflammation is important in
pathogenesis
• some strains produce one or more exoproteins
o staphylococcal enterotoxins – SEA, SEB, SECn, SED,
SEE, SEG, SEH, SEI
o exfoliative toxins – ETA, ETB
o TSS toxin-1
o leucocidin o bullous impetigo
• TSST-1, staphylococcal enterotoxins ▪ phage group II S. aureus strains 77, 55 → bullous
o pyrogenic toxin superantigens impetigo, exfoliative disease (SSSS), staphylococcal
o binds directly to expressed HLA-DR on antigen- scarlet fever
presenting cells without processing → 5-30% of resting T • varying cutaneous responses to exfoliatin A and B
cells activated → massive release of cytokines, esp. IL- ▪ cutaneous lesions
2, IFN-γ, TNF-β • occurs more commonly in neubworn and in older
• evasion of immune clearance infants
o chemotaxis inhibitory protein – inhibits neutrophil • rapid progression of vesicles → bullae
chemotaxis
• (-) Nikolsky sign
o protein, A, staphylokinase, capsular polysaccharide,
• initially contain clear yellow fluid → dark yellow and
fibrinogen binding protein, clumping factor A →
turbid
avoidance of being opsonized and phagocytosed
• margins sharply demarcated without erythematous
o staphylokinase, aureolysin → bind, cleave antimicrobial
halo
peptides
• superficial → rupture within day or 2 → thin, light-
• drug resistance
brown to golden-yellow crusts
o methicillin resistance
• immunity
o primary defense is innate immunity provided by
neutrophils
o antimicrobial peptides
▪ dermicidin, LL-37, protegrin, α-defensins, β-defensins,
lacrtoferricin, cascocidin
o however, S. aureus can invade and survive in many types
of host cells
clinical findings
• superficial staphylococcal pyodermas
o pyodermas – infections in epidermis, just below stratum
corneum or in hair follicle
o impetigo
▪ bullous vs nonbullous ▪ laboratory tests
▪ bullous impetigo caused by S. aureus • exudates reveal Gram (+) cocci in clusters
o nonbullous impetigo o prognosis and clinical course
▪ accounts for more than 70% of cases of this pyoderma ▪ infection → cellulitis, lymphangitis, bacteremia →
▪ history osteomyelitis, septic arthritis, pneumonitis, septicemia
• S. aureus spreads from nose to normal skin (11 days o treatment
later) → develop into skin lesions (after another 11 ▪ mild to moderate
days) • local treatment with mupirocin ointment or cream
• pruritus or soreness common • removal of crusts
▪ cutaneous lesions • good hygiene
• initial: transient vesicle or pustle → honey-colored • retapamulin 1% ointment effective
crusted plaque • fusidic acid also effective
• surrounding erythema ▪ extensive or bullous lesions
• constitutional symptoms absent • dicloxacillin, 250-500 mg PO qid
• regional lymphadenopathy in prolonged infection • erythromycin 250-500 mg qid
• erythromycin-recsitant → coamoxiclav, cephalexin,
cefaclor, cefprozil, clindamysin
• CA-MRSA → TMP-SMX and rifampin, clindamycin,
and tetracycline
• staphylococcal ecthyma

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o cutaneous pyoderma characterized by crusted erosions
or ulcerations
o usually consequence of impetigo
▪ evolves from impetigo occluded by footwear and
clothing
o most commonly on lower extremities
▪ poor hygiene and neglect are key elements
o ulcer with “punched-out” appearance when dirty grayish-
yellow crust and purulent material are debrided o carbuncles
▪ margin indurated, raised and violaceous ▪ more extensive, deeper, communicating and infiltrated
▪ base extends deeply into dermis lesion that develops when suppuration occurs in thick
o slow to heal inelastic skin when multiple furuncles coalesce
o management usually systemic – same agents as
impetigo

▪ extremely painful lesion

▪ fever and malaise often present
▪ involved area is red, indurated
▪ multiple pustules appear on surface → draining
externally around multiple hair follicles
▪ develops yellow-gray irregular crater at center
o prognosis and course
▪ bacteremic spread of infection and recurrence
▪ lesions about lips and nose → facial and angular
emissary veins → cavernous sinus
▪ invasion of bloodstream → osteomyelitis, acute
endocarditis, brain abscess
• folliculitis o treatment
o pyoderma that begins within hair follicle ▪ simple furunculosis
o superficial folliculitis • local application of moist heat
▪ also: follicular or Bockhart impetigo ▪ with cellulitis, with associated fever – systemic
▪ small, fragile, dome-shaped pustule at infundibulum of antibiotics
hair follicle • staphylococcal paronychia
o individuals exposed to hand trauma or chronic moisture
predisposed
o usually around fingernails, often originating from break in
skin
o skin and soft tissue of proximal and lateral nail fold are
red, hot and tender
o management – oral and topical antibiotics, incision,
o deep folliculitis
drainage of abscesses
▪ sycosis barbae – deep folliculitis with perifollicular
inflammation occurring in bearded areas of face and
upper lip
▪ local treatment with warm saline compresses and local
antibiotics (muciprocin, clindamycin) may be sufficient
▪ in fungal infections → hairs may be broken or loosened
• furuncles and carbuncles
o furuncles
▪ deep-seated inflammatory nodule that develops
around hair follicle, usually from preceding folliculitis →
often evolving into abscess
▪ arise in hair-bearing sites, esp. in regions subject to • staphylococcal whitlow (felon)
friction, occlusion, perspiration o purulent infection or abscess involving bulbous distal end
▪ systemic host factors of finger
• obesity, blood dyscrasias, defects in neutrophil o portal of entry – traumatic injury or extension of
function, treatment with glucocorticoids and cytotoxic paronychia
agents, Ig deficiency states
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o finger bulb is red, hot, tender and edematous with o treatment
possible abscess formation ▪ topical treatment is valuable adjunct
o management – surgical drainage of loculated abscesses, • removal of dirt, crusts, debris by soaking soap and
IV antibiotic therapy water
▪ mupirocin ointment as effective as parenteral or oral
penicillin
▪ retapamulin 1% ointmenet also effective
▪ penicillin is drug of choice
• as single injection of long-acting benzathine
penicillin or orally
▪ erythromycin is suitable alternative
• intertriginous streptococcal infections
o streptococcal pyodermas occur much less commonly in
occluded sites
o treatment – oral antibiotics or topical mupirocin
STREPTOCOCCAL SKIN INFECTIONS
• epidemiology
o usually spread by transfer of organisms through close
personal contact
▪ major source: patients with URTIs
o approx. 10% of normal population carry asymptomatically
• etiology and pathogenesis
o all GAS strains are β-hemolytic
o bacitracin disk sensitivity has been widely used as
presumptive test for GAS
o M protein
▪ inhibits phagocytosis, promotes adherence to host
cells, allows bacterial growth in human blood
▪ highly polymorphic
o other virulence factors
▪ cell surface molecules - hyaluronic acid capsule, C5a
peptidase, opacity factor, streptococcal inhibitor of
complement
▪ secreted proteins – streptolysins O and S, cysteine
proteinase, pyrogenic exotoxins, streptokinase,
hyaluronidase
o hallmarks of invasive GAS infection
▪ profuse edema
▪ rapid spread through tissue planes
▪ relatively thin exudative response
▪ may spread via lymphatic or hematogenous routes →
fulminant clinical course
• impetigo
o etiology and pathogenesis
▪ GAS appear on skin approx.. 10 days before
development of impetigo
• not recovered from nose and throat until 14-20 days
after skin acquisition of organism
▪ preexisting lesions predispose
▪ other factors: crowding, poor hygiene, neglected minor
skin trauma
▪ inflammatory process is superficial → unilocular
vesicopustules located between stratum corneum and
stratum granulosum
• usually situated near opening of hair follicle
• organisms, leukocytes and cell debris fill vesicle
o clinical findings
▪ crusted superficial infection of skin
▪ vesicular phase described but rarely detected
▪ clinically indistinguishable from impetigo caused by S.
aureus
▪ pruritus and burning may occur, but usually painless
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