Update on topical therapy (Proceedings)

I. Glycotechnology

a. Sugars are found on the surface of most cells including keratinocytes

i. They are important in

1. Cell to cell interactions

2. Immune signaling and fighting pathogenic microorganisms

b. Microorganisms attach to cells by means of glycoproteins called lectins; lectins recognize and bind to sugar moieties on the host cells.

i. Under normal circumstances this does not occur because of normal barrier function of the stratum corneum.

ii. If the barrier is disrupted, the bacteria can adhere.

iii. Exposing the bacteria to exogenous sugars blocks adhesion by sugars binding to the lectins.

iv. In vitro studies

1. A combination of 3 monosaccharides is able to decrease Pseudomonas adherence by 53%.

2. A polysaccharide decreases Staphylococcus intermedius adherence by 52%

3. A polysaccharide decreases Malassezia adherence by 42%.

c. Cytokines also interact with sugar moieties

i. Exogenous sugars may inhibit the binding of cytokines which then inhibits the release of more cytokines.

ii. In vitro study showed 75% decrease in tumor necrosis factor release.

d. Found in multiple Virbac products (Ketochlor®, Epi-soothe®, Hexadene®, and Keratolux® shampoos, Epi-Otic® Advanced)

II. T8 Keto Flush®

a. Contains tris-EDTA and 1% ketoconazole

b. Gentle antifungal with less acute contact irritation than other products

c. Non-drying

d. Not recommended for chronic maintenance due to the possibility of Malassezia resistance

III. Douxo Products® (Douxo seborrhea shampoo/spray/spot on, Douxo chlorhexidine shampoo)

a. Phytosphingosines

i. Sphingoid bases

1. Long-chained aliphatic amines

2. Defining structural unit of sphingolipids

ii. Commonly found in plant and skin associated ceramides

iii. Antimicrobial activity against

1. Staphylococcus aureus

2. Pseudomonas aeruginosa

3. Microsporum canis

4. Malassezia

b. Ceramide

i. Sphingolipid consisting of a sphingoid base linked to a fatty acid via an amide bond.

ii. Usually short lived key intermediate in the biosynthesis of more complex sphingolipids, except in the skin.

iii. Function in the skin

1. Make up 45-50% of the stratum corneum lipids.

2. Important in stratum corneum organization.

3. Essential for normal barrier function.

iv. Biological functions

1. Trigger apoptosis

2. Arrest cell growth and proliferation

c. Used for the treatment of

i. Idiopathic seborrhea

ii. Vitamin A responsive dermatosis

iii. Sebaceous adenitis

iv. Golden retriever ichthyosis

d. Douxo calm® shampoo/spray/gel

i. Ingredients

1. Phytosphingosine

2. Hinokitiol

a. Red cedar extract

3. Raspberry seed oil

a. Essential n-3 and n-6 fatty acids

ii. Useful for allergic dermatitis.

IV. Imiquimod (Aldara®)

a. Toll- like receptor agonist.

i. Receptors for bacterial/viral antigens

ii. Pathogen recognition system for innate immune response.

b. Mechanism of action

i. Enhances both innate and acquired immune response

ii. Stimulates monocytes and macrophages by binding Toll-like receptor 7.

iii. This leads to the production of several cytokines, including IFN-a and IL-1, 6, 10 and 12.

iv. This results in local antiviral, antineoplastic and immunoregulatory activity.

v. Stimulates natural killer cells and B cells.

vi. Enhances migration of Langerhans cells.

vii. Activates Th-1 reaction over Th-2.

c. Topical Uses

i. Antiviral

1. Papillomas

2. Herpes virus lesions

ii. Immunoregulatory

1. Atopic dermatitis

iii. Antineoplastic

2. Actinic dermatitis

3. Bowen's disease

4. Squamous cell carcinoma

5. Basal cell carcinoma

6. Mycosis fungoides

V. Tacrolimus (Protopic®)

a. Macrolactam immunomodulator

b. Mechanism of action.

i. Inhibits the maturation and activation of T-cells

ii. Inhibits calcineurin, which in turn inhibits the production of IL-1, 2, and 4, tumor necrosis factor and interferon gamma.

iii. Down regulates IL-8 receptors on keratinocytes, which decreases the chemotaxis of mast cells to the area.

iv. Down regulates high affinity IgE receptors on Langerhans cells and inflammatory dendritic cells in lesional skin.

v. Blocks degranulation of mast cells.

c. 100 times more potent than cyclosporine or betamethasone valerate.

d. Dog studies show that the 0.1% ointment is the most effective in reducing pruritus in the dog.

e. Uses

i. Discoid lupus erythematosus

ii. Pemphigus erythematosus

iii. Localized pemphigus foliaceus

iv. Perianal fistulas

v. Treatment of localized lesions of atopic dermatitis

vi. Feline idiopathic ulcerative dermatosis

f. Possible uses

i. Alopecia areata

ii. Contact allergy

iii. Cutaneous lupus lesions

iv. Dermatomyositis lesions

VI. Relief HC Spray®

a. 1% pramoxine and hydrocortisone

VII. LymDyp Spray®

a. 1:32 dilution of lime sulfur, same as 4 ounces per gallon

b. Must use within 6 weeks of opening

VIII. Chlorhexiderm HC Shampoo®

a. 4% chlorhexidine and 1% hydrocortisone

IX. Regulation of topicals

a. If facility/company produces FDA approved products, facilities and products are regularly checked

b. Otherwise, no.