ANDREWS’DISEASES OF THE SKIN

Tenth Edition

Chapter 1The Skin: Basic Structure and Function

Elaine Miller, D.O., July 18, 2006

Basic Structure – 3 Layers

1. Epidermis

2. Dermis

3. Subcutaneous Fat

Considerable regional variation in their relative thickness

 Normal Skin: Trunk vs. Palm

Epidermis• The adult epidermis is composed of three

basic cell types:1. Keratinocytes

2. Melanocytes

3. Langerhans cells

• Adnexal structures: follicles and eccrine glands originate during the third month of fetal life

Epidermis: 1. Keratinocyte

• Principal cell of the epidermis (80%)

• Ectodermal origin• Produces keratin• Zones:

– Basal layer– Stratum Spinosum

Malphighian layer/prickle layer

– Granular layer– Stratum corneum

Epidermis: 1. Keratinocyte

• Mitotically active

• Changes as it moves upward through the epidermis

• Basal cell layer is generally one cell thick wherever its location

Epidermis: 2. Melanocyte

• Produce Pigment

• Derived from Neural Crest

• Found in the fetal epidermis in the 8th week

• Usually in the basal layer, approximately 1 for every 10 basal keratinocytes

• Numbers are same regardless of race or color

Epidermis: 2. Melanocyte

• Melanocytes are dendritic cells which are in contact with a number of keratinocytes thus forming the epidermal melanin unit

• Number and size of MELANOSOMES determines skin color!!!

• Melanocytes in dark skin synthesize larger melanosomes than those produced in light skin

• Larger melanosomes are also produced with chronic sun exposure

Epidermis: 2. Melanocyte• Melanocyte

Abnormalities: – Vitiligo – destruction

of melanocytes

– Albinism – melanocyte number is normal, but they are unable to synthesize fully pigmented melanosomes

Epidermis: 3. Langerhans Cell• Scattered among keratinocytes in the

stratum spinosum with no desmosome connections

• 3-5% of cells here

• Folded nucleus • Birbeck granules

• Originate in bone marrow• Functionally monocyte-macrophage lineage

Langerhans Cells have Birbeck Granules

Epidermis: Merkel Cell• Found in the basal layer

of the palms & soles, oral and genital mucosa, nail bed and follicular infundibula

• Located directly above the Basement Membrane

• Act as slow adapting touch receptors

Epidermal Appendages: The Adnexa

1. Eccrine Sweat Units

2. Apocrine Units

3. Pilosebaceous Units

Originate as down growths from the epidermis Adnexal structures serve specific functions All can functions as reserve epidermis, occurring

principally by virtue of migration

Adenexa: 1. Eccrine Sweat Unit

• Found at virtually all skin sites

• Most abundant on the palms, soles, forehead and axilla

• Cholinergic Innervation

• Regulates temperature by excreting sweat

Adenexa: 2. Apocrine Unit

• Develops as an outgrowth of the infundibulum or upper portion of the hair follicle

• Located in the axilla, areola, ano-genital area, external auditory canal, and eyelids

• Serves no known function in humans

• Secretion is mediated by adrenergic innervation

Adenexa: 3. Pilosebaceous Unit

• Pilosebaceous Unit: – 2-4 hairs

– associated sebaceous gland

– arrector pili muscle

– collagen

• Hair is composed of keratin

• Three types of hair: lanugo (fine), vellus, and terminal (coarse)

Adenexa: 3. Pilosebaceous UnitHair Follicles

• Infundibulum: from the uppermost portion to the entrance of the sebaceous duct

• Isthmus: from the sebaceous duct to the insertion of the erector pili muscle

• Inferior portion: the lowest part of the follicle and the hair bulb which cycles through involution and regeneration

• Hair shaft and the inner and outer root sheath develop from mitotically active undifferentiated cells of the matrix

Hair Follicle

Phases of Scalp Hair Growth 1. Anagen (growth)

~ 3-5 years (85-90% of hair) Pigmented bulb

2. Catagen (involution) ~ 2 weeks (1%) Apoptotic cells in outer root

sheath

3. Telogen (resting)

~ 3-5 months Lose 50-150 per day Club shaped hairs with non-

pigmented bulb and shaggy lower border

Adenexa: 3. Pilosebaceous UnitHair Follicles

• The cross-sectional shape of the hair depends on the arrangement of cells in the bulb

• Hair color depends on the distribution of melanosomes within hair bulb

• Black person’s hair = Big melanosomes

• White person’s hair = smaller melanosomes

• Red hair = Round melanosomes

• Gray hair = decreased melanocytes

Adenexa: 3. Pilosebaceous UnitSebaceous Glands

• Formed embryologically as an outgrowth from the upper portion of the hair follicle

• At all skin sites except palms and soles• Dense on the face and scalp• Always associated with hair follicles except at:

– Eyelids (meibomian glands)– Buccal mucosa – Vermilion border of the lip (Fordyce spots)– Prepuce (Tyson glands)– Female areolas (Montgomery tubercles)

• Holocrine Secretion under hormonal control (androgens)

Nails• Matrix keratinization

leads to the formation of the nail plate

• Keratin types found in the nail are a mixture of epidermal and hair types

• Fingernails grow an average of 0.1 mm/day, slower for toenails

Nails

• Abnormalities may serve as important clues to cutaneous and systemic disease

• Example:

A 72-year-old woman with diabetes, hypertension, and peripheral vascular disease was hospitalized with chest tightness and acute shortness of breath. She reported a four-month history of worsening dyspnea on exertion, orthopnea, and a progressive whitening of her fingernails

Antonarakis E. N Engl J Med 2006;355:e2

A 72-year-old woman with diabetes mellitus, hypertension, and peripheral vascular disease was hospitalized with chest tightness and acute shortness of breath

Acquired Leukonychia Totalis

• Acquired leukonychia totalis has been associated with several systemic diseases, including hepatic cirrhosis, chronic renal failure, congestive heart failure, diabetes mellitus, chronic hypoalbuminemia, and Hodgkin's lymphoma.

• The patient underwent coronary angioplasty with stent insertion in the affected artery. At follow-up six months later, the appearance of her nails had returned to normal.

The Dermoepidermal Junction

• Formed by the Basement Membrane Zone (BMZ)• Composed of four components

1. Plasma membranes of the basal cells with hemidesmosomes

2. Lamina lucida3. Lamina densa (Basal lamina)

mostly Type IV collagen

4. Fibrous components associated with the basal lamina: anchoring fibrils (Type VII Collagen), dermal micro-fibrils, and collagen

• BMZ is a semi-permeable filter• Serves as structural support for the epidermis

The Dermis

• The constituents of the dermis are of mesodermal origin, with the exception of nerves

• The principal component of the dermis is collagen, a family of fibrous proteins having at least 15 genetically distinct types in human skin

• Represents 70% of the dry weight of the skin

The Dermis• Fibroblast synthesize procollagen molecules that

are secreted by the cells and assembled into collagen fibrils

• Collagen is rich in the amino acids hydroxyproline, hydroxylysine and glycine

• Type I collagen is the major component of the dermis – it has a uniform structure

• Collagen fibers are loosely arranged in the upper dermis (papillary dermis)

• Tightly bundled in a fascicle-like pattern in the lower dermis (reticular dermis)

The Dermis

• Type VII collagen is the major structural component of anchoring fibrils and is produced predominantly by keratinocytes

• Fibroblast also synthesize elastic fibers and ground substance of the dermisDesmosine and isodesmosine are amino acids

that are unique to elastic fibersElastic fibers differ structurally and chemically

from collagen

Collagen

• It is the major stress-resistant material of the skin– Elastic fibers contribute very little to resisting

deformation and tearing of the skin, but have a role in maintaining elasticity

• Connective tissue disease is a term generally used to refer to a heterogenous group of autoimmune diseases that affect collagen and/or dermal mucin

Defects in Connective Tissue

• Defects in Collagen synthesisEhlers-Danlos syndromeX-linked cutis laxaOsteogenesis imperfecta

• Defects in elastic tissueMarfan syndromePseudoxanthoma elasticum

Vasculature of the Skin

• Consists of two main intercommunicating plexuses

1. Subpapillary plexus/upper horizontal network At the junction of the papillary and reticular

dermis Perfuses the dermal papilla

2. Lower horizontal plexus At the dermal-subcutaneous interface Larger blood vessels

• Adnexal structures of the dermis are well vascularized

Muscles of the Skin

• Smooth muscle:– Occurs in the skin as arrectores pilorum

– Comprises the muscularis of dermal and subcutaneous blood vessels

– Specialized aggregates are called Glomus bodies ocuring between arterioles and venules

• Glomus bodies are prominent on the digits and at the lateral margins of the palms and soles

• Striated (voluntary) muscle: – In the neck skin as the platysma muscle

– In the facial skin as the muscles of facial expression

Nerves of the Skin

• Neurovascular bundles - > VAN• Meissner corpuscles

– Mediate touch and pressure– Located in the dermal papillae especially in the hands and feet

• Vater-Pacini corpuscles– Mediate pressure– Located in the deeper dermis of weight-bearing surfaces and the

genitalia

• Temperature, pain and itch sensations are transmitted by unmyelinated nerve fibers which terminate in the papillary dermis and around hair follicles

Mast cells of the dermis

Mast Cells of the Dermis

• An important cellular constituent of the dermis

• Resemble fried eggs in histologic sections

• Contain up to 1000 granules which in turn contain heparin, histamine, and various other factors

• Surface contains up to to 500,000 glycoprotein receptor sites for IgE

• Respond to environmental changes, for example, in dry environments the number of mast cells increases as does the histamine content

Subcutaneous Tissue (Fat)

Subcutaneous Tissue (Fat)

• Beneath the dermis lies the panniculus, lobules of fat cells or lipocytes separated by fibrous septa composed of collagen and large blood vessels.

• Collagen in the septa is continuous with the collagen in the dermis

• It provides buoyancy, stores energy, and is an important site of hormone conversion

• Inflammatory conditions that affect the panniculus can be differentiated from each other based on whether it mainly affects the septa or the fat lobules themselves

CUTANEOUS SIGNS AND DIAGNOSIS

Chapter 2

CUTANEOUS SIGNS AND DIAGNOSIS

• The same disease may show variations under different conditions and in different people

• The appearance of lesions may have been modified by previous treatments or obscured by extraneous influences (scratching, secondary infection)

• Subjective symptoms may be the only evidence of disease (pruritis, pain)

CUTANEOUS SIGNS AND DIAGNOSIS

• Although history is important; however, in Dermatology, the diagnosis is most frequently made based on the objective physical characteristics and location or distribution of one or more lesions that can be seen or felt

• Careful physical exam is paramount

PRIMARY LESIONS

Macules and Patches

Papules, Plaques and Pustules

Nodules and Tumors

Vesicles and Bullae

Wheals (Hives)

Primary Lesions: 1. Macules

• Without elevation or depression

• Less than 1 cm in size

• Circular oval or irregular

• Circumscribed changes in the skin color

Primary Lesions: 2. Patches• A large macule

• 1 cm or greater in diameter

• Nevus flammeus or vitiligo

Primary Lesions: 3. Papules

• Circumscribed, solid elevations, varying in size from pinhead to 1 cm

• May be rounded, flat-topped, conical, or umbilacated

• May be soft or firm• Called papulosquamous

when capped by scales• May be discrete,

irregularly distributed or grouped

Primary Lesions: 4. Plaques

• A broad papule or a confluence of

papules

• 1 cm or more in diameter

• Generally flat

but may be

depressed

Primary Lesions: 5. Pustules

• Small elevations of the skin containing purulent material

• Similar to vesicles and have an inflammatory areola

• White, yellow or red • May start as pustules

or develop from papules or vesicles

Primary Lesions: 6. Nodules

• Morphologically similar to papules

• More than 1 cm in diameter

• Most frequently are centered on the dermis or the subcutaneous fat

Primary Lesions: 8. Wheals or Hives

• Evanescent, edematous, plateau-like elevations of various sizes

• Usually oval or arcuate contours

• Pink to red

• Surrounded by a pink areola

• May be discrete or coalesce

Primary Lesions: 9. Vesicles

• Circumscribed, fluid-containing, epidermal elevations 1-10 mm

• Apex may be rounded, acuminate, or umbilacated

• Discrete, irregularly scattered, grouped or linear

• May develop into bullae or pustules

• Unilocular or multilocular

Primary Lesions: 10. Bullae

• Rounded or irregularly shaped blisters containing serous or seropurulent fluid

• Greater than 1 cm

• Typically unilocular

• May be located in the epidermis or subepidermal

More About Bullae

• Nikolsky’s sign, diagnostic maneuver of putting lateral pressure on unblistered skin in a bullous eruption with shearing of the epithelium

• Absoe-Hansen’s sign, extension of a blister to adjacent unblistered skin when pressure is put on top of the blister

• Cellular contents of the bullae may be useful in confirming the diagnosis

SECONDARY LESIONS

Scales

Crusts

Excoriations and Abrasions

Erosions, Ulcers, Fissures

Scars

Secondary Lesions: 1. Scales

• Dry or greasy keratin laminated in masses

• Due to rapid formation of epidermal cells and pathologic exfoliation

• Vary in size & color

• May have a silvery sheen from trapping of air between layers

Secondary Lesions: 2. Crusts

• Collections of dry serum, pus, or blood, usually mixed with epithelial and/or bacterial debris

• Vary in size, shape thickness and color

• When they become detached the base may be dry or moist

Secondary Lesions: 3. Excoriations

• An excoriation is a punctate or linear abrasion produced by mechanical means, usually involving only the epidermis, but not uncommonly reaching the papillary layer of the dermis

• Caused by scratching

Secondary Lesions: 4. Abrasions

• If the damage is a result of mechanical trauma or constant friction – abrasion

• Frequently has an inflammatory areola

• May provide access for pyogenic organisms

Secondary Lesions: 5. Fissures

• Linear cleft through the epidermis or even into the dermis

• Single or multiple

• Microscopic to several centimeters in length

• Sharply defined

• May be dry, moist, red, straight, curved, irregular, or branching

Secondary Lesion: 5. Erosions

• Loss of all or portions of the epidermis alone

• May not become crusted

• Heals without a scar

Secondary Lesion: 6. Ulcers

• Rounded or irregularly shaped excavations that result from complete loss of the epidermis plus some of the portions of the dermis

• Various sizes, shallow or deep

• Heal with scarring

Secondary Lesions: 6. Scars

• Composed of new connective tissue that replaced lost substance in the dermis or deeper parts as a result of injury or disease, as part of the normal reparative process

• Characteristic of certain inflammatory processes

Secondary Lesions: 6. Scars

• Pink initially later becoming white and glistening

• Scars may be thin and atrophic or keloids

• May be smooth or rough, pliable or firm

Diagnostic Details of Lesions

Distribution of Lesions

• Few or numerous

• Local or diffuse

• Discrete or Coalesced to patches of peculiar configuration

• Dermatomes – Zoster

• Blaschko’s lines – epidermal nevi

Evolution of Lesions• Some stay the same

(nevi)

• Some start small and get bigger

• Some have characteristic changes with time (varicella)

Involution

• Lesions may disappear completely

• May leave characteristic residual pigmentation or scarring

• Keratotic papule of pleva

Grouping

• Characteristic of DH, herpes simplex, herpes zoster, and late syphilitic eruptions

• Linear (breakfast-lunch-and-dinner), flea and other arthropod bites

Configuration

• Annular• Linear• Serpiginous• Arcuate• Polycyclic• Guttate• Nummular• Unusual configurations

may be exogenously induced

Color

• The Tyndall effect modifies the color of the skin and the color of the lesions by the selective scattering of light waves of different wave-lengths. The blue nevus and mongolian spots are examples of this light dispersion effect

• Not advisable to place too much reliance on color

Color• Patches lighter in color

than normal skin may be completely depigmented or have lost only part of their pigment

• Hyperpigmentation may be a result of epidermal or dermal causes

• Hyperpigmentation following inflammation is most commonly the result of dermal melanin deposition

Consistency – Palpate the Lesion

• Blanchable

• Fluctuant

• Doughy

• Hot or cold

• Firm or calcified

The End