Management of canine keratinization (seborrheic) disorders (Proceedings)

Keratinization and seborrheic disorders are both used interchangeable to describe microscopic and gross changes resulting from multiple etiologies. Most seborrheic lesions are secondary to ectoparasites, allergies, pyoderma, fungal infections, cutaneous neoplasia or endocrinopathies. There are a limited number of primary seborrheic disorders such as Vitamin A or zinc responsive dermatoses, idiopathic primary seborrhea and sebaceous adenitis. The clinical signs are predominantly the result of three major changes associated with keratinization disorders including changes in keratinization, lipid film and skin flora.

Keratinization refers to the process involved in the development of keratin. The keratinocyte or epidermal cell proceeds through a maturation process from the basal cell layer, spinosum (prickle cell) layer, granular cell layer and terminating in the corneal layer. Each epidermal layer has different major function in the maturation of the keratinocyte. In the basal cell mitosis is the primary activity. In the stratum spinosum and stratum granulosum, differentiation predominates while exfoliation or desquamation occurs in the stratum corneum. There are many factors that influence the keratinization process. Theses include arachidonic acid metabolism and eicosanoids that influence the production of proinflammatory (LTB4, PGE2) mediators. They also increase epidermal mitotic activity and cell proliferation. Many cytokines produced by the keratinocytes influence epidermal cell proliferation. (IL-1, IL 2, IL 6) The keratinocytes provide a microenvironment in which many of the immunologic events take place. They play a very active role in the initiation and amplification of antigen-driven responses elicited in the skin. Interleukin 1 is abundant in the epidermis. Minor trauma to the stratum corneum elicits release of preformed IL-1. Ultraviolet irradiation, mitogens and contact irritant substances may initiate release of IL-1 from the keratinocytes.

The surface lipid film is a complex emulsion comprised of 90% sebaceous gland and 10% sweat gland secretions. It has multiple functions including epidermal protection, waterproofing and regulating skin pH. In seborrheic conditions lipid film composition is changed with increased levels of free fatty acids and cholesterol and a fall in ceramide levels. These changes decrease the bacteriostatic effect of the lipid film and encourage bacterial and fungal growth. Free fatty acids are irritants that promote hyperkeratosis leading to scaling and strong odor.

The bacterial and Malassezia overgrowth in seborrheic disorders may be marked. The lipophillic yeast play a role in perpetuating seborrhea by increasing the release of free fatty acids and increasing non-specific inflammation. The majority of the gross lesions associated with keratinization (scales, greasiness, inflammation, dyskeratosis-lichenification, hyperpigmentation, hyperkeratosis)) are chronic or recurring due to the primary or secondary etiologies that are occurring with the individual keratinocytes or within the microenvironment of the epidermis.

Therapy

Topical medications are routinely used as symptomatic treatment. They are usually referred to as antiseborrheic agents. Systemic treatment is usually directed at eliminating or controlling the primary cause(s).

Topical agents:

There are a relative small number of topical agents used for symptomatic treatment of keratinization disorders and concurrent secondary problems. Usually two or more specific agents are incorporated in vehicles with moisturizing properties. There are several specific properties to look for when selecting topical medications. Some properties will be beneficial while others may be detrimental depending on the specific gross findings and underlying etiologies.

Keratolytic activity facilitates the breaking of the bond or cohesion among corneocytes. This results in increased desquamation and softening of the stratum corneum. Keratoplastic activity helps normalize the keratinization process (mitosis, maturation and desquamation). The basal cell layer of the epidermis is the site of most keratolytic activity. Some agents have strong degreasing properties. An agent with follicular flushing activity helps remove follicular secretions and bacteria and to decrease follicular hyperkeratosis. Antibacterial and antifungal activity may help normalize the surface flora and prevent excessive colonization of microorganisms on the skin surface.

Specific antiseborrheic agents:

Coal tar is considered a strong antiseborrheic agent with keratolytic, keratoplastic and mild degreasing activities. It is usually combined with sulfur and/or salicylic acid at a 1-2 % concentration. There is more potential for surface irritation as the concentration increases. Coal tar preparations at a concentration of 10% are used on local hyperkeratotic lesions to promote desquamation and alter the mitotic activity.

Sulfur at a concentration of 2-4% has moderate keratoplastic, keratolytic, antibacterial and antifungal activity. It has mild follicular flushing activity. Sulfur is has minimal degreasing activity.

Salicylic acid at a concentration of 1-2% has moderate keratoplastic and bacteriostatic and mild antipruritic activity. At a 3-6% concentration, there is moderate keratolytic activity. Salicylic acid and sulfur are frequently combined to enhance their synergistic activity.

Benzoyl peroxide is a strong keratolytic, degreasing and antibacterial agent with a strong follicular flushing action. Adverse effects include excessive drying, bleaching of hair and clothing and contact irritation.

Selenium sulfide is a strong degreaser with moderate keratolytic and keratoplastic activity. It also has good anti-yeast properties.

Phytosphingosine is a pro-ceramide, a natural component of the epidermis that has antiinflammatory and antimicrobial properties (Douxo®, Sogeval).

Moisturizing agents:

Moisturizers may lubricate, rehydrate and soften the skin. Both emollients and humectants are useful for symptomatic treatment of keratinization disorders. Emollients decrease transepidermal water loss and cause moisturization due to occlusive properties. They smooth roughened skin surface and increase skin pliability. Emollient agents include olive, coconut and cottonseed oils, fats (lanolin), hydrocarbons (petrolatum, paraffin) and essential fatty acids. Humectants attract transepidermal water to the surface as well as draw water from the environment if >70% humidity. Humectant agents include propylene glycol, sodium lactate, glycerin, urea and lactic acid. Emulsifiers are vehicles for other moisturizer or humectants. Emulsifiers include PEG-4, dilaurate, lecithin and cetyl alcohol.

Drugs with specific activities may be incorporated into moisturizing preparations. Chlorhexidine, diphenhydramine, colloidal oatmeal (hydroscopic) and pramoxine (antipruritic) are frequently used. Both specific antiseborrheic and moisturizing agents are available in several forms of topical preparations including shampoos, rinses, dips, gels, ointments and creams.

Systemic therapy:

Managing keratinization and sebum secretion problems with systemic treatment is limited. Vitamin A at doses of 400 to 700 IU/day for 3-4 months may be indicated in Vitamin A metabolism disorders, West Highland White Terrier (WHWT) dysplasia, idiopathic primary seborrhea and acne.

Acetretin (Soriatiane, Roche) is indicated for disorders of epithelial or follicular development or keratinization. These diseases include WHWT dysplasia, idiopathic seborrhea and acne. The recommended dose is 1 mg/kg/day. A higher dose of 3 mg/kg/day has been recommended for sebaceous adenitis.

Isotretinoin (Accutane. Roche) has been used primarily for diseases that require alteration or normalization of adnexal structures. Some epidermal diseases may respond. Diseases in which Isotretinoin has been used include idiopathic seborrhea, Schnauzer comedone syndrome, epidermal cysts, ichthyosis, mycosis fungoides and sebaceous adenitis.

Adverse reactions to the synthetic retinoids include keratoconjunctivitis, hyperactivity, pruritus, pedal and mucocutaneous junction erythema, stiffness, vomiting, diarrhea and blood abnormalities including hypertriglyceridemia, hypercholesterolemia and increased levels of liver enzymes.

Essential fatty acids and Vitamin E (15 mg/kg/day) may be beneficial.

Summary of therapeutic protocols:

Topical treatment should be considered in all seborrheic disorders. It helps to eliminate skin debris, reestablish the skin's ecosystem and restore hydration. The objectives of treatment include cleansing, moisturizing and softening of skin, to normalize keratinocyte activity (keratoplastic effect), to encourage elimination of excess layers of the stratum corneum (keratolytic effect), to limit sebum production and to control bacterial and fungal complications.

The frequency and selection of specific topical agents or forms (shampoos, rinses, etc) will be determined by the gross lesions, owner compliance and clinical progress. The treatment protocol must be adapted to each patient. Changes will be needed in the protocol with frequent evaluations required to assess clinical progress or lack thereof.

Systemic therapy should be directed to specific needs such as antibacterial, antiyeast, modulation of the keratinization process and controlling allergies or endocrinopathies.