Pre-Test:

1. What are the three layers of the skin: epidermis, dermis, hypodermis
2. What are two functions of the skin: permeability barrier, thermoregulation

Internal Medicine - Mariecon O, Escuadro-Chin, MD, DPDS, FPSVI

May 21 2015

THE SKIN 3. Subcutaneous Reactive Unit

a. Lobules
b. Septae
4. Hair Follicles & Glands***

*** There are only 3 reactive units of the skin but some
books include the 4th.

SUPERFICIAL REACTIVE UNIT

EPIDERMIS
Recall the 5 layers of the epidermis
1. Stratum corneum
2. Stratum lucidum
3. Stratum granulosum
4. Stratum spinosum
5. Stratum basale
Functions of the Skin
Function Tissue Layer Key Concepts
Permeability barrier Epidermis Epidermis is a dynamic tissue in which cells are
Protection from pathogens Epidermis constantly in non-synchronized motion
Dermis o From the basal layer, which is directly
Thermoregulation Epidermis attached to the dermis, the keratinocytes
Dermis mature  and  differentiate.  Once  it’s  in  the  
Hypodermis stratum corneum, they lose their nuclei
Sensation Epidermis through the process of differentiation and
Dermis keratinization.
Hypodermis Interconnected through forces of cohesion that
Ultraviolet protection Epidermis guarantees continuity of epithelium
Wound repair/regeneration Epidermis o In the spinous layer, there are
Dermis interconnections which are called
Physical appearance Epidermis desmosomes
Dermis
Hypodermis Homeostasis
1. Mitotic rate of terminative cells
KEY CONCEPTS 2. Desquamation rate of corneocytes
3. Generation time of epidermal cells
The Skin is composed of different tissue
compartments that interconnect anatomically &
interact functionally. Proliferation = Differentiation = Desquamation
However, the Epidermis, Dermis and Subcutis are To maintain homeostasis, these should be equal. If there is an
HETEROGENOUS leading to multiplicity of reaction imbalance, it will lead to the different pathology of the
patterns with in the tissue. epidermis.

Approaches to Clinical Dermatology EPIDERMAL PATHOLOGY

Anatomical Approach 1. Disturbance of Epidermal Cell Kinetics
o Reactive Units (on how they move)
Physiologic Approach 2. Disturbance of Epidermal Cell Differentiation
o Functional Failures (on how they move upward)
3. Disturbance of Epidermal Cohesion
REACTIVE UNITS OF THE SKIN
1. DISTURBANCE OF EPIDERMAL CELL KINETICS
1. Superficial Reactive Unit
Acanthosis
a. Epidermis
Enhanced cell proliferation
b. Junction
Enlargement of germinative cell pool
c. Papillary Body/Superficial Microvascular
Increased mitotic rate
Plexus
2. Dermal Reactive Unit
a. Reticular Dermis
b. Deep Dermal Microvascular Plexus
 3. DISTURBANCE OF EPIDERMAL COHESION
Desmosomes
Equilibrium of forming and dissociating intercellular
contacts
Guarantees continuity of epidermis
Adaptable to permit locomotion, permeability of
intercellular space and interactions

Intraepidermal Blisters
Classification of Intraepidermal Blisters by Anatomic
Level
Acanthosis in Psoriasis. There is also elongation of the rete Granular Layer Friction Blister
ridges, enlargement of the DE interface, and increased Pemphigus foliaceus
dermal-epidermal interaction. There is a thickened plaque Sub corneal pustular dermatosis
overlying the skin. The plaque is thick because the problem is SSSS/Bullous impetigo
in the epidermis. Spinous Layer Eczematous dermatitis
HSV
2. DISTURBANCE OF EPIDERMAL CELL DIFFERENTIATION Familial Benign Pemphigus
Parakeratosis Suprabasal Layer Pemphigus vulgaris
Faulty and accelerated cornification leading to Darier Disease
retention of pyknotic nuclei of epidermal cells Basal Layer Erythema multiforme
o Incomplete differentiation Lupus erythematosus
o Reduced transit time (maturation) Lichen planus
o Direct cell injury Epidermolysis bullosa

3 Morphologic Patterns of Intraepidermal Vesicles

1. Spongiosis
Secondary loss of cohesion due to influx of
fluid into the epidermis
Stellate-appearance: Spongelike
morphology

Parakeratosis in Psoriasis. There is reduced transit time which

does not permit complete cellular differentiation so there is
retention of nuclei.

Dyskeratosis
Apoptosis of keratinocytes 2. Acantholysis
o Eosinophilic cytoplasm Primary loss of cohesion
o Pyknotic nucleus Splitting & disappearance of desmosomes
o Keratin filaments in perinuclear aggregates Cavities  (2’to  fluid  influx):
o Suprabasal
o Midepidermal
o Subcorneal

Dyskeratosis in Darier Disease

Others:
o Actinic Keratosis
o Squamous Cell Carcinoma Pemphigus vulgaris. There is interaction of autoantibodies
o Direct Physical & Chemical Injury and Ag on keratinocytes. Clinically there is a very flaccid
o Erythema Multiforme blister since the lesion is superficial. Once it tears off there is
o Graft vs. Host Response erosion.
 DISTURBANCES OF THE D-E JUNCTION

Staphylococcal Scalded Skin Syndrome. The blister is in the

mid epidermis (the most superficial area). It is brought about JUNCTIONAL
by epidermolysin. Destroys the anchoring filaments

Bullous Pemphigoid

In Herpes Simplex Virus infection there is ballooning giant

cells and cytolysis. There is cleft formation at the lamina propria and Ag+Ab
reaction. The vesicle is more firm because of the overlying
3. Cytolysis epidermis.
Dissolution of cells
e.g. DERMOLYTIC
o Epidermolytic EB Destroys anchoring filaments, desmosomes,
o Epidermolytic Hyperkeratosis hemidesmosomes
o Bullous Congenital Ichtyosiform
erythroderma Recessive Epidermolysis Bullosa
o Ichtyosis Hystrix
o Hereditary Palmoplantart
keratoderma

DERMO-EPIDERMAL JUNCTION

Complete separation of the epidermis from the dermis;

reduced anchoring filaments and increased collagenase
production
OF
PATHOLOGIC REACTIONS FO THE SRU
Papillary Body
Here you can see that the epidermis is directly connected to Superficial Microvascular Plexus
the dermis through the hemidesmosome. o Highly reactive unit
Capillaries
Pre&post capillary vessels
Fibroblasts
Macrophages
Dendritic cells
Peripatetic lymphocytes
Loose connective tissue & ECM
Contact Dermatitis
Inflammatory reaction & spongiosis of epidermis;
cellular injury & parakeratosis
Spongiotic vesiculation
Chronic: acanthosis & epidermal hyperplasia
Psoriasis
Combined pathology of the epidermis, papillary
body, superficial venules & circulating cells
Initial lesions: perivascular accumulation of
lymphocytes and monocytoid elements within the
PB and SV & focal migration of leucocytes into the
epidermis
Asides from the acanthosis, parakeratosis, and elongation of
the rete ridges, there is superficial perivascular infiltration.
Lupus Erythematosus
Hallmark: inflammation, edema & lymphocytic
infiltrate in the papillary body and Superficial venular
plexus
Targets DE junction: broadening of basement
membrane zone (BMZ) + hydropic degeneration +
destruction of basal cells and atrophy
Hyperkeratosis, thinned epidermis & vacuolization of BMZ
Lichen Planus
Dense lymphocytic infiltrate in subepidermis and cytoid bodies
at the junction. There is hypergranulosis & hyperkeratosis.
Clinically it presents as a violaceous plaque.
Dermatitis Herpetiformis
IgA deposition & complement on tips of dermal papillae,
massive neutrophil infiltration
DERMAL REACTIVE UNIT
Strong fibroelastic tissue with network of collagen &
elastic fibers embedded in an ECM w/ high binding
capacity
Tightly interwoven
2 Areas
Superficial Microvascular System
o Acute inflammatory processes (E&DEJ)
o Chronic processes (perivascular)
Deep Dermal Vascular Networks
CHRONIC PROCESSES
Purpura Simplex
Lymphocytic infiltrate closely asstd with vascular
walls; vessel wall damage is less evident but integrity
is impaired, (+) phagocytosed materials inc iron

SUPERFICIAL PERIVASCULAR INFLAMMATION

Endothelial activation
Vascular dilation
Increased permeability
Edema
Reduced intravascular blood flow
Accumulation of RBC
Cellular infiltration of perivascular tissue

ACUTE INFLAMMATORY PROCESSES

Urticaria
Sparse perivascular lymphocytic infiltrate w/
eosinophils; edema of dermis & post capillary
DEEP PERIVASCULAR INFLAMMATION
venules

Larger vessels are involved; Papular & nodular lesions

Cutaneous Drug Reaction Lupus Erythematosus

Moderate to dense perivascular sleeves of Deep perivascular infiltrates
mononuclear cells, slight edema in the PB and
minimal interface dermatitis.

Polyarteritis Nodosa
Larger vessels are involved
Necrotizing Vasculitis
Necrosis, blistering & ulceration of the lesion
Neutrophilic and nuclear dusts around & in wall of
because it damages the large arteries that provide
venules; fibrin deposition
nutrients to the skin
SUBCUTANEOUS REACTIVE UNIT
Fat Lobules vs Septa
Small vessel vs Large vessel
Traumatic vs. inflammatory

This is an algorithm on how to deal with diseases of the subcutaneous layer.

SEPTAL LOBULAR
Erythema Nodosum Pancreatic Panniculitis
Edema, histiocytic reaction There is blistering, necrosis of fat lobules,
neutrophils & leucocytoclasia
FAILURE OF THE SKIN Common Autoimmune Skin Disease
The  requirements  of  the  skin  are  identified  in  its  failings… Target Antigen
Selected Requirements & Failings of Skin Diseases with Identified Autoantigens
Requirements Selected Failings Pemphigus foliaceus Desmoglein 1
Prevent infection via innate Infections,autoimmunity, Pemphigus Vulgaris Desmoglein 3 & 1
& adaptive immunity cancers Bullous Pemphigoid Collagen XVII, BPAG2
Maintain a barrier Infections, dehydration Epidermolysis Bullosa Acquisita Collagen VII
Repair injury Cancers, Leg ulcers Dermatitis herpetiformis Transglutaminase 3
Provide circulation Infarction ( embolization, Diseases with Unknown or multiple Antigens
vasculitis, occlusion) Subacute CLE Unknown
Communicate Sensory neuropathy, Chronic CLE
pruritus Psoriasis
Provide nutrition Vitamin D deficiency
Regulate temperature Hypo/Hyperthermia 3. FAILURE OF IMMUNITY: CANCER
Attract attention Photoaging, vitiligo, Strongest immune response to malignancy arise in
Alopecia the skin & lymphatic tissues
Squamous Cell Carcinoma
PREVENTING INFECTION: IMMUNOLOGIC o Well known complication of
1. Failure of Immunity: Infection immunosuppression in solid organ
2. Faulty Immunity: Autoimmunity transplant recipients
3. Failure of immunity: Cancer Melanoma
o therapy attempts to enhance immune
1. FAILURE OF IMMUNITY: INFECTION responsiveness
Warts
Trauma to stratum corneum interrupts physical MAINTAINING A BARRIER: PROTECTION
barrier, permits direct entry of offending agent 1. Failure of Protection against toxic chemicals: EHK &
(usually HPV) Darier's
Immunologic recognition: cytotoxic cellular 2. Failure to protect against dehydration & infection:
response, destruction & cure TEN
o Cure if you have intact immunity. If 3. Failure to protect against UV radiation: Albinism
immunocompromised, it will lead to growth
of the wart Function of the Barrier
Prevents fluid loss, electrolytes & other molecules
Dermatophytoses Prevents penetration of microorganism, toxic
Genetic susceptibility, immune responsiveness & materials & UV radiation
environmental circumstances
1. FAILURE OF PROTECTION AGAINST TOXIC
Opportunistic Infections in HIV CHEMICALS
Loss of immunologic integrity Epidermolytic Hyperkeratosis
M. Tuberculosis,Pneumocystis jiroveci, VZV & HSV Stratum corneum is defective in disorders of
keratinization
Hansen's Disease Prone to recurrent bacterial infection
Failure of Th1/Th2 paradigm:chronic infection
Structural barrier, immunologic recognition &
protective immunity

2. FAULTY IMMUNITY: AUTOIMMUNITY

Failure  in  distinguishing  “self”  from  infection
Target: epidermal basement membrane and
desmosomes

This is an example of Pemphigus.

There is deposition of Ab in Dsg 3, intercellular
2. FAILURE OF PROTECTION AGAINST DEHYDRATION PROVIDING CIRCULATION: NUTRITION
AND INFECTION Circulatory System
Toxic Epidermal Necrolysis 2-way hematologic system that conducts blood flow
Drug induced o Nutritional support (arteries, capillaries &
Rapidly progressive keratinocyte death →   veins)
detachment  of  epidermis  →  Fluid  &  electrolyte  loss   o Delivery of leucocytes
→  dehydration  → Infections: bacteria & yeast o Thermoregulation (anastomosing arteries &
veins)
1-way lymphatic system that returns leucocytes &
interstitial fluids to draining LN and central venous
system

FAILURE OF CIRCULATION
Embolic Occlusion of Most dramatic form of BV
arteries occlusion
Necrosis of all structures
distal to blockade
Vasculitis Asstd with: Rheumatic skin
disorders, DM, PM, RA, LE &
immune complex mediated
small vessel vasculitis
Occlusive vasculopathy Aberrant coagulation or
cold-related gelling
Venous insufficiency Most common vascular
3. FAILURE OF PROTECTION AGAINST UV RADIATION
problem
Albinism
Partial occlusion & valvular
Type 1 OCA- absence or reduction in tyrosinase
incompetence
activity & melanin production
Lymphatic Blockage Recurrent strep or staph
Hence, acute toxicity, photosensitivity,
infxn
immunosuppression, carcinogenesis & premature
Distal edema, widespread
aging
verrucous change
(Elephantiasis nostras
verrucosa)

INTERFACE BETWEEN EXTERNAL AND INTERNAL

ENVIRONMENT: COMMUNICATION
Mechanisms of Skin Communication
1. Nerve conduction via cutaneous fibers
2. Intercellular signaling mediated by cytokines &
hormones ( endocrine, paracrine & autocrine)
3. Physical  movement  of  “message-carrying”  cells

ABNORMALITY OF NEUROLOGIC COMMUNICATION

Excessive sensitivity (itching)
MAINTAINING THE INTEGRITY OF THE SKIN: REPAIR Excessive sweating (hyperhidrosis)
Injuries Decreased sensitivity (peripheral neuropathy)
o UV radiation: immunosuppression,
accelerated aging & carcinogenesis FAILURE OF CELLULAR & CYTOKINE COMMUNICATION
o Thermal injury Hormones ACTH- induced secretion of adrenal
Failure to effectively repair injury: Delayed wound corticosteroids
healing, Keloids, XP Vascular instability in Pheochromocytoma-
catecholamine hormones & precursors
FAILURE TO REPAIR INJURY (norepinephrine, epinephrine & dopamine)
Delayed wound healing Cushing’s  Disease-altered fat
o DM, aging distribution,vascular dilation & striae
Keloids Addison’s  Disease- inc adrenocortical
o Exuberant response to injury hormone; excessive ACTH
o Genetic & environmental hyperpigmentation
o Increased TGF-B activity on fibroblasts Cytokines IL-1.IL-8 & TGF-B (wound healing)
Xeroderma Pigmentosum TNF-a and IL-23: critical targets of
o Failure to repair UV radiation induced DNA immunobiologic agents for Psoriasis
damage
o UV radiation is dangerous; when DNA repair
are defective: Cancers such as Squamous
Cell Carcinoma
TEMPERATURE REGULATION: THERMOREGULATION
1. Failure of thermoregulation
a. Excessive heat
b. Excessive cold

EXCESSIVE HEAT
Requirement for Cooling
Central heating (external source or muscular
exertion)
Sustained local heating (protein denaturation)

Problem with
Innervation, circulation & sweating

Hypohidrotic Ectodermal Dysplasia

Complete absence of sweat glands
No capacity for cooling

EXCESSIVE COLD
Requirement for Heating
Response to heat loss to environment (hypothermia)
Exposure locally to sustained temperatures below
freezing (frostbite)

There is vascular constriction.

INTERPERSONAL COMMUNICATION: ATTRACTION

1. Conveys beauty
2. Attracts attention
3. Contributes to Self-Identity

FAILURE TO PRESENT AN ATTRACTIVE APPEARANCE

Proportioned, symmetric & unblemished skin

1. Pigmentary turmoil ( vitiligo & melasma)

2. Inappropriate hair distribution
a. Too much hair in wrong place:
hypertrichosis
b. Not enough hair: androgenetic alopecia in
men, female pattern hair loss & alopecia
areata
3. Undesirable fat distribution: hemifacial atrophy &
lipodystrophy

That in all things, God may be glorified.

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