Dermatology

Pityriasis= scaly

Alba= white

Versicolor= many colors

Phemphigus= blister

Skin
Largest organ

1.7 meter square

Heaviest organ, nearly 5% of the body wt

Layers
3 layers

Epidermis

Dermis: skin proper

Subcutis: hypodermis:

Epidermis
5 layers

Base to top, inside to out

Stratum basale

Stratum spinosum

Stratum granulosum

Stratum lucidum

Stratum corneum

1st three layers form the Malphigian layer

Lucidum is usually an artifact, only on palms and soles

Stratum basale
Columnar cells

Mitotically active, thus give rise to all other layers

Expresses specific keratin

Keratin pair( keratin always is in pair, acidic and basic)

K5/14

Stratum spinosum

Polyhedral cells

Attached to one another via apparent spines on their surface

These spines are intercellular connection molecules

In the epidermis these are

Desmosomes

In desmosomes these are

Cadherins: Ca dependent adhesion molecule

plaque inside the cells have plakins

These form the desmosomal plaques

Keratinous tonofilaments attach to the nuclear membrane to the plasma

membrane

Desmogleins

Two types

Dsg 1

Present in sub corneal layers of the epidermis

Not expressed in the mucosa

Dsg 3

In basal layers of epidermis

Strongly expressed in the mucosa

If desmosomes are defective or damaged

Cells will separate from one another

On light microscopy:

Dissolution of spines seen: acantholysis is seen

Acantho: spines

The centrifugal forces are lost and only a central contracting force is left

Thus the cell shrinks

Round cells with large nucleus 7/8 of the cell

Peri nuclear halo is seen because of the contraction of the cytoskeleton

This is an Acantholytic cell called Tzanck cell

significance of acantholysis
Creation of intra epidermal blisters

It can either be

Primary Acantholysis: where the desmosomes are the primary target

Eg.

A. Pemphigus vulgaris

IgG Ab against Dsg 3

Thus there would be severe and early mucosal involvement

Supra basal cavity

B. Pemphigus foliaceous

IgG against Dsg 1

Thus no mucosa involvement

Sub corneal cavity

C. Paraneoplastic pemphigus

IgG and other Ig against

Desmogleins, desmocollins, plakins, basement membrane proteins

Thus the condition is polymorphic

D. Dariers disease

AD disease

Genetically defective ATP2A2 aka SERCA2A2( type of ATPase)

C/F

Greasy malodorous dirty looking warty papules over face, scalp, central
chest, upper back( basically in high sebaceous area)

Nails show V shaped nicks at the free edge, longitudinal ridges

histology

Acantholysis

Dyskeratosis: premature keratinization and cell death

These are known as

Corps Ronds in stratum spinosum

Corps grains in stratum corneum

E. Grover's disease

Idiopathic

F. Hailey Hailey disease

AD

ATP2C1 defect( ATPase)

G. Bullous impetigo and staphylococcal scalded skin syndrome SSSS

Both these are caused by epidermolytic toxin ET A and B

S. Aureus phage 2

These are proteases which cleave Dsg 1

If localized : bullous impetigo, flaccid blisters

If hematogenous spread: widespread peeling: SSSS

Only the stratum corneum peels o

Acanthocytes are derived from spinous layer in vulgaris

In foliaceous, granulosum

Secondary acantholysis
Desmosomes are not the primary target

Eg.

Burn

Herpes

Steven Johnson syndrome SJS

Toxic epidermal necrolysis TEN

Both above are severe drug reaction

Stratum granulosum

Flatter cells

Degenerating nuclei

Contain granules

Types of granules

1. Keratohyaline granules

Contains profilaggrin

Gets converted into filaggrin

And aggregates keratin filaments

These granules are absent in hard keratin eg. Nails and hair

They progress without the keratohyaline granules

2. Lamellar granules or membrane coating granules or odland bodies or

keratosomes

These contain lipids

This lipid has two functions

Aids to the water permeability barrier

Glues the stratum corneum cells together

Stratum lucidum
Artifact

Stratum Corneum

Horny layer of the skin

Completely flattened cells

Packed with keratin

Tough outer membrane made by cross linking of proteins

This outer membrane is called cornfield envelope

The cornfield envelope

Major components include

Loricrin

Involucrin

No nuclei in stratum corneum cells

No cytoplasmic organelles

Thus called the dead cells

Epidermal turnover time

Time taken for a basal cell to stratum corneum cell and get lost

Or

Time taken for a basal layer to completely replace itself

This is 28 days

14 days to reach corneum

And another 14 days to cover the corneum layer

Dermis
Made up of fibrillar proteins in a sea of extra cellular matrix

1. These fibers are mainly collagen
It makes 3/4 of the dry wt
Type 1 is 70%
Type 3 is 15%
Rest are other collagens

Collagen gives the tensile strength to the layer
Thus the ability to resist the deformation



2. Elastin
Only 5% of the dry wt
But very important
Elastin has characteristic Desmosine and isodesmosine linkages
which gives it a spring like structure which gives the recoil/ rebound
property



Collagen defect eg. EDS has hyper extensible skin which promptly
bounces back

Cutis laxa: skin problem with elastin defect
Skin hangs down, loose redundant, hanging folds
Blood hound, St. Bernard dog appearance





Subcutis/ hypodermis/ subcutaneous fat

The fat cells are arranged in lobules separated by collage nous septae















the structure is called Panniculus
It's inflammation is called Panniculitis

Septal Panniculitis: Erythema nodosum
It's a reactive Panniculitis
It is asso with
N: no cause, idiopathic: most common
O: orogenital ulcer( Behet's )
D: drugs( sulfonamides)
O: OCP, pregnancy, hormonal supplements
S: sarcoidosis
U: ulcerative colitis
M: microbes: streptococcal is most common cause after idiopathic
TB is second most common
Yersinia, campylobacter, histoplasmosis, blastomycosis,
coccidiomycosis






C/F
Painful , tender, erythematous subcutaneous nodules
Site: shin
Females>>>>> males
Associated with fever, arthralgia
Foamy histiocytes( phagocytosed lipid cells)
Most common Panniculitis
Heals in 4-6 weeks
With bruise like changes
And it may recur

Differentiate it from erythema nodosum leprosum
Lesions are widespread
Heals in 1 week
No sex predilection
Fragmented and granular AFB seen( solid AFB not seen)
Neutrophilic infiltrate is seen



Rx.
Treat the cause
Rest
NSAIDs
Steroids and KI in idiopathic cases


Sweet syndrome
Disease of neutrophils infiltrating the dermis
Histiocytic cells seen not foamy histiocytes





Lobular Panniculitis

A. Subcutaneous fat necrosis of the new born
Needle shaped clefts seen in lipocytes

B. Post steroidal Panniculitis
Features Mimic the above condition both clinically and histologically

C. Erythema induratum
Lobular Panniculitis that presents with nodules and ulcers on calves,
posterior part of legs

If associated with TB, called Bazin's disease
If asso with the non TB condition
Called erythema induratum of Whitfield

Histologically it shows
Lobular Panniculitis with vasculitis


D. Lupus Panniculitis
Asso with lupus erythematosis
Affects the upper part of the body: face, arm, chest, breast( May
mimic cancer here)
Histologically : Hyaline degeneration of adipocytes





E. Lipodermatosclerosis
It's a feature of venous ulcer or eczema
This seen near the malleoli
There are color changes

Histologically
Lipomembranous change
Degenerating adipocytes make elaborate designs














F. Sclerema neonatorum Vs Subcutaneous fat necrosis

Widespread woody induration
Child severely ill
Eg. Premature
High mortality
Histopathology
Needle shaped clefts in adipocytes plus giant cells
There is very little inflammation


Subcutaneous fat necrosis of the new born
Precipitated by cold environment
Localized nodules
Not very illMay be full term
Normal prognosis
Clefts only in adipocytes plus inflammation of lobules









Weber Christian disease
Waste basket diagnosis/ diagnosis of exclusion
Avoid making the diagnosis
Idiopathic, febrile, lobular Panniculitis




Basement membrane zone BMZ
aka dermoepidermal junction DEJ














































































bullous pemphigoid Ag 1 and 2
Anchoring filaments made up of Laminin 5




if skin is incubated in 1 molar solution of NaCl overnight
It cleaves through the lamina lucida
Producing a cavity called Salt split cavity
BPAG 1 and 2 will be present towards the roof of the cavity

If immunofluroscence is done on salt split cavity in bullous
pemphigoid: IF in roof

In Epidermolysis bullosa acquisita
In the floor
IgG against the type 7 collagen
Thus IF towards the floor of the cavity



Diseases associated with basement membrane zone

K5/14 pair defective( inherited) in Epidermolysis bullosa simplex

BPAG 1 and 2
IgG against them in bullous phemphigoid and other similar disease
Cicatricial BP
Herpes gestationis/ pimphigoid gestationis

IgA : linear IgA bullous pemphigoid
Chronic bullous disease of childhood is another variety


Alpha 6 4 integrin and Laminin 5(332)
Genetically defective in EB junctionalis


Type 7 collagen
If IgG against it: EB acquisita
If genetically/ inherited defective: ka EB dystrophicans





When hemidesmosomes are involved, the blister is called
subepidermal coz the defect is at the DJ or the BMZ






Non keratinocytic cells in epidermis

Keratinocytes makes the bulk of the epidermis: 90-95%
Others are

A. Langerhans cells
Origin: bone marrow( monocytic macrophage lineage)

Location : found in the upper stratum spinosum

Shape: dendritic

Structure: contains tennis racquet shaped bodies ka Birbeck granules

CD1a positive
CD 207 / langerin positive

Function: antigen presentation

These are intruder cells
Thus they do not form desmosomal adhesions





B. Melanocytes

Intruder
Origin: neural crest
Location: stays in the basal layer
Shape: dendrite
Granules: melanosomes
Function: melanin synthesis and distribution

Thus no desmosomes as it is an intruder cell

In basal layer, 1 melanocyte, after around 10 keratinocytes
But being dendritic, it transfers melanin to around 36 keratinocytes
This is ka epidermal melanin unit

The no of melanocytes is same in all
Thus the color of skin is dependent on degree of melanization and not
the no of melanocytes.




In vitiligo, melanocytes are immunologically destroyed, thus the no
is less

In albinism, the no is not reduced but the melanization is reduced
as the defect is in tyrosinase enzyme

UV exposure increases the melanin synthesis

Addison's disease
Pro opio melanocortin is increased
Which leads to increase in melanocyte secreting hormone( MSH)
and ACTH
The increase in MSH causes pigmentation






C. Merkel cells

Origin is controversial because of oresence of Neuropeptides like
VIP, serotonin etc. were considered neural crest cells

But since desmosomes are present, ectodermal origin is preferred

Shape: oval with microvilli
Connect at BMZ with free nerve endings
Located in the basal layer
Function is proprioception
Mainly seen in Palm, soles etc







Functions of skin
Protection
Mechanical barrier
Immunological
UV protection
Temperature regulation
Electrolyte regulation
Vit D synthesis: UV- B builds bone in basal layer+/- supra basal layer



Skin failure
Sepsis
Hypothermia
Hyperthermia
Fluid and electrolyte imbalance
High output cardiac failure
Leading to death
Causes are
Burns, SJS, TEN, pemphigus, erythroderma: widespread skin involved








Terminology
Primary skin lesions: which appear first in disease course

Secondary: modified primary

Primary include
Macule: change in color only
A large macule is referred to as a patch, best avoided

Papule: raised , solid, <0.5 cm

Plaque: raised, solid, >0.5, like a plateau

Nodule: round, solid lesion with a deep component, better palpated
than seen( gaanth)

Vesicle: fluid filled, <0.5 cm
Bulla: fluid filled, >0.5 cm
Pustule: pus filled, <0.5 cm
If large, could be called abscess

Wheal/ weal/ hives
Transient Intradermal edema
Usually itchy( urticaria)
Pale center, red halo

To be differentiated with angioedema which is sub cuticular and deep
dermal edema
Lip swelling, peri orbital edema, tongue and glottic edema


Burrow:
Linear and wavy tunnel in stratum corneum ending in a papule or a
vesicle, characteristically S shaped
Pathognomonic of Scabies






Secondary lesions
Denudation of the skin

Superficial is erosion
Ulcer is when the whole epidermis is gone

Fissure is deep vertical linear slit, crosses the BMZ, eg. Cracked heals











Excoriations
Scratch marks

Chronic itching or rubbing
Produces a triad of Lichenification
Thickening
Pigmentation
Accentuation of crease






sclerosis
Clinically: hide bound skin, tightly bound down: inability to pinch
Histologically: excess abnormal collagen deposition


Comedone: block of pilosebaceous gland
If covered by skin: white head, closed comedone
If no covering: black head: oxidized content and melanin, open
comedone


Histopathological terms

Thickened stratum corneum: hyperkeratosis
Without nuclei: orthokeratosis
Persisting nuclei: Parakeratosis, typically seen in psoriasis, actinic
keratosis and physiologically seen in oral mucosa




Increased granular layer: hypergranulosis
Focal hypergranulosis is seen in lichen planus

Reduced granular layer is called hypogranulosis

Agranulosis: no granular layer
Both above seen in psoriasis vulgaris

Increased spinous layer: acanthosis
Seen in lichen planus and psoriasis

Acantholysis
Dyskeratosis

Basal cell degeneration: vacuolar degeneration of basal cells
LE, dermatomyositis, graft vs host disease
Seen in LP


Granular degeneration
Vacuolar degeneration of upper spinous and stratum granulosum
Seen in inflammatory linear verrucous epidermal nevus(in 50% cases)
Related diseases
Vorners keratoderma
Bullous Ichthyosiform erythroderma
Epidermolytic hyperkeratosis