Small Animal Dermatology, 3rd edition

174 DISEASES/DISORDERS

Decreases in epidermal ceramides and sphingosine-1-phosphate causing

increased transepidermal water loss and changes in cell signaling

Mutations in filaggrin (an important structural protein). Results in pene-

tration of allergens, microbes, and PAMPs into the epidermis where both

reaction to their presence and detection for immunological response are

enhanced.

Increased cellular reactivity in genetically predisposed individuals may include:

Increased expression by keratinocytes of TARC and TSLP, promoting a Th 2 -

lymphocyte response

Dendritic cells (DC) exposed to antigen in the presence of “danger sig-

nals,” including proteases and PAMPs, become activated to promote a T cell

response

Increased activated DC, Langerhans cells (LC) in the epidermis

Possible increased number of mast cells in atopic skin as well as mast cell

“hyperreleasability”

Altered ratio of CD4+to CD8+cells promoting a Th 2 over Th 1 response:

the role of Treg lymphocytes in atopic dermatitis is an area of active

research.

Reexposure in a sensitized animal induces pruritus, causing epidermal damage,

and elicits activated keratinocytes to release TARC, TSLP, and other cytokines,

promoting the recruitment of reactive immune cells into the epidermis and fur-

thering the inflammatory response.

The Role of IgE

 IgE has an essential role in type 1 hypersensitivity.

 Classic definition of atopy is an inflammatory dermatitis characterized by the devel-

opment of IgE to environmental allergens.

 The classic definition is being challenged by findings that include:
Elevated levels of IgE in asymptomatic individuals and reactivity to allergens in

individuals without detectable levels of IgE (atopic-like dermatitis)

Production of IgE is favored by Th

2 -lymphocyte proliferation

The development of clinical disease is not predicted by the level of detectable

IgE

Non-IgE antibodies (IgG

d) and a late-phase reaction may also be involved in

development of AD.

Th 1 /Th 2 /Th 17 /Tregand Cytokines

 AD is an imbalance in the activity and production of cytokines by various immune

(and other) cells.

 Th 2 activity (evidenced by increases in Th 2 -promoting cytokines) increases produc-

tion of IgE and recruitment of inflammatory cells.

 This has been used as justification for the concept of atopic disease as a Th 2 -polarized

immune response.