Localized keratinization syndromes (Proceedings)

There are a variety of keratinization defects that affect specific body locations, some of which are breed or species specific. The current discussion will cover acne, nasodigital hyperkeratosis, acne, stud tail, ear margin dermatosis, linear keratosis, schnauzer comedo syndrome and idiopathic facial dermatitis

Acne

Dogs and cats may both develop a disease referred to as acne. There is little to no work suggesting canine or feline acne has similarities to human acne. In humans acne is a complex disease and there is a role played by hormones, diet, the bacteria Propionibacterium acnes , sebaceous glands, and possible keratinocyte activation.(Heymann 2004; Adebamowo, Spiegelman et al. 2005; Nagy, Pivarcsi et al. 2005; Placzek, Arnold et al. 2005) Not only has little been done to study the disease in cats and dogs compared to humans we do not even no if it is the same in cats and dogs.

Canine

Canine acne is believed to relate to abnormal follicular keratinization resulting in comedones. It has been suggested that dogs are different because hairless breed comedones have fatty acid profiles suggesting epidermal derivation and not sebaceous. Work in dogs prone to acne has not been done. Some cases do have prominent sebaceous glands in dogs with acne. We do not know if canine acne relates to abnormalities in sebaceous secretions that cause a localized fatty acid deficiency. In humans the local fatty acid deficiency then causes the follicular hyperkeratosis. We do know in dogs that the abnormal follicles become infected, usually with staphylococcus intermedius. Follicular rupture (furunculosis) may also occur and contributes more to the inflammation by inducing a foreign body reaction. Trauma and ingrown impacted hairs may also play a pathologic role in some cases.

Acne is most common in short coated breeds with Boxers, Great Danes and Doberman pinschers being especially prone. Lesions include comedones, papules, pustules, nodules and furuncles on the chin, lips and muzzle. Cellulitis with larger plaques may be seen.

Treatment is not always needed in young or mildly affected dogs. Benzoyl peroxide shampoos and gels are often prescribed for milder cases or as adjunctive therapy in more severe cases. Topical mupirocin is also helpful. Recently the author has had success utilizing Douxo ® Seborrhea Spot-on with 1% phytosphingosine as a spot on application twice weekly. In severe cases systemic antibiotics are indicated. Doxycycline has been shown to be effective and whether this is due to antibiotic or other effects is still to be determined.(Bensignor and Guaguere 2004) Rarely topical or systemic glucocorticoids or retinoids may be needed. The author has also used tacrolimus in some cases with limited response. Pentoxifylline can also be of value in more scarring cases for help with tissue perfusion of systemic antibiotics.

Feline

Feline acne is a common finding though in many cases does not promote the client to seek veterinary attention. In some cases that do present, the condition is not clinically significant and treatment may not be warranted. Feline acne tends to be a long term problem and not outgrown as it may be in the dog. Histologically two forms are recognized by the author. One is a folliculitis/furunculosis, follicular hyperkeratosis syndrome. In the early phase there is just follicular hyperkeratosis. The other form has sebaceous adenitis present in addition to the follicular changes. A recent review described pyogranulomatous sebaceous adenitis in 23% of acne cats.(Jazic, Coyner et al. 2006) Whether this finding is represents a distinct subset is still to be determined.

Few studies have been done but so far there is no apparent breed or sex predilection. In one study of 22 cases the median age of onset was 4 years with a range of 6 months to 14 years.(Jazic, Coyner et al. 2006) However since subtle lesions may occur long before presentation this aspect requires further evaluation. Lesions include black follicular casts with comedones, erythema and crusting most commonly. Papules, pustules and occasionally furuncles and cellulitis or "chin edema" may also be seen and when present are also associated with alopecia. Pruritus is variable though rarely intense and when present often associated with folliculits. Some cases of feline acne have resolved in pregnant cats or with diet changes for a food allergy. Other owners have reported "outbreaks" of acne in multi-cat households. In a study of 13 cases from multi cat households 4 had another cat affected.(White, Bordeau et al. 1997) These observations suggest other factors may play a role in disease development. One must also be careful as some cats with mild acne are treated topically and then have more severe and persistent problems as they react to the topical therapy. Bacteria are most commonly found though occasionally Malassezia or dermatophytes may be cultured or detected in affected cats.(White, Bordeau et al. 1997; Jazic, Coyner et al. 2006) The role these play in disease is unknown. Feline calici virus was detected in the chin biopsy of one affected cat from a household with five affected cats.(Jazic, Coyner et al. 2006) In the study by Jazic, the histopathologic findings were lymphoplasmacytic periductal inflammation (86%), sebaceous gland duct dilation (73%), follicular keratosis with plugging and dilation (59%), epitrichial gland occlusion and dilatation (32%), folliculitis (27%), pyogranulomatous sebaceous adenitis (23%) and furunculosis (23%). Cases with concurrent sebaceous adenitis were not compared or contrasted to other histopathology findings in this study and this could be an important factor in relationship to response to therapy.

Treatment for feline acne is similar to canine acne however irritant reactions to topicals are more common. One study in cats showed 2% mupirocin gave excellent results in 63% of treated cats and 4% had a topical reaction. Other topicals include benzoyl peroxide gel (less than 5%), topical antimicrobial gels such as clindamycin, salicylic acid wipes, retinoic acid and Douxo ® Seborrhea Spot-on with 1% phytosphingosine. The option of no treatment and living with a few comedones should always be considered in mild cases or those refractory to treatment. Cases with folliculitis, furunculosis and sebaceous adenitis should be treated with appropriate systemic antibiotic therapy.

Stud Tail

This syndrome of cats is seen primarily as a clinical problem in intact male cats. However milder forms have been seen in females or castrated male cats. The dorsal tail is affected in the area of the "supracaudal organ". Numerous sebaceous glands are located here. Problem cases often have inflammation and associated folliculitis. Thinning or partial alopecia is common and hyperpigmentation may be seen. Comedones, greasy, waxy debris, matted oily hair, plaque formation, papules, pustules and furuncles may be seen. In some aspects this lesions may be similar to acne as it is associated with large active sebaceous glands and follicular hyperkeratosis. Though male cats are most often affected castration will not always alleviate the condition. Antibiotics, topical keratolytic shampoos, salicylic acid wipes, Retin A, Douxo ® Seborrhea Spot-on with 1% phytosphingosine, isotretinoin, glucocorticoids and progestational drugs have all been used both effectively and ineffectively as therapy.

Nasal Hyperkeratosis

Nasal hyperkeratosis is characterized by excessive keratin accumulation and thickening of the nasal planum. I see many cases with just nasal hyperkeratosis and I suspect that some cases that have combined symptoms of nasodigital hyperkeratosis have different underlying etiologies. To some degree it occurs commonly in older dogs and has been described as being a senile change. The disease may occur in young or middle aged dogs. Nasal hyperkeratosis has also been seen in dogs with dry eye or blocked lacrimal ducts. Fissures may occur in affected sites. Some cases will have a more yellowish crusting character to the hyperkeratosis and this should raise the index of suspicion about underlying inflammatory disease. Generally these cases do not depigment or loose normal markings. Other differential diagnosis includes pemphigus foliaceus and erythematosus, distemper virus, zinc responsive dermatosis, genetic dog food dermatosis and lupus erythematosus and leishmaniasis. Asymmetrical cases may be due to infectious disease and unilateral blocked tear ducts or nasal glands (xeromyteria). Xeromycteria is due to damage or absence of the nasal gland that functions to keep the nasal planum moist. Biopsy may be indicated to primarily rule out other differentials. Treatment consists of topical moisturizers such as petrolatum, propylene glycol and vitamin E. In refractory cases lactic acid moisturizers may be tried. In the most difficult cases a combination of urea/lactic acid and salicylic acid (Kerasolv, DVM Pharmaceuticals) or tretinoin gel may be helpful. Douxo ® Seborrhea Spot-on with 1% phytosphingosine as a spot on application twice weekly has also proven to be a palliative treatment in many cases.

Labrador retrievers are also affected by hereditary nasal parakeratosis.(Page, Paradis et al. 2003; Peters, Scott et al. 2003) This is believed to be an autosomal recessive trait and in one report 16 of 18 dogs shared common ancestors but none of the sires or dams of affected dogs were affected. (Page, Paradis et al. 2003) This clinically will appear as nasal hyperkeratosis though cytology and biopsy is characterized by parakeratosis and multiple intracorneal serum lakes and superficial interstitial-to-interface lymphoplasmacytic dermatitis.(Peters, Scott et al. 2003). Treatment is similar to other nasal hyperkeratotic syndromes but some may also respond to antibiotics and tacrolimus.

Footpad Hyperkeratosis – Hard Pad Disease

Footpad hyperkeratosis can be seen as a separate entity or in association with nasal hyperkeratosis. There are different types of hard pad disease seen. The first is a crusting, thickened pad. These cases are most common in pemphigus foliaceous, zinc responsive dermatosis, distemper infections and metabolic epidermal necrosis. These pads may be painful and cause lameness. Rare cases of pemphigus foliaceus present with just pad disease but most commonly these cases will have other lesions suggesting this etiology. Biopsies are the most helpful diagnostic procedure. Treatment will depend on the underlying cause. The second form is pads that have excessive fronds of normal appearing keratin. This is most obvious at the margins of the pads and represents overgrowth of the normal keratin mounds of the pads. Inflammation and exudate are not present. Lameness and pain are not detected. This condition appears more as if the pads just grow abnormally fast, do not desquamate normally or if there is conformational issues (improper wear). Familial footpad hyperkeratosis has been seen in Irish setters and the Dogue de Bordeaux and may have an autosomal recessive inheritance. Other breeds also seem to be over represented and these include the Kerry blue terrier, Labrador retriever and Golden retriever. The author has also seen this entity in a litter of Akitas. In the familial form of the disease symptoms are usually present by 6 months of age. Clinically all pads are usually affected and can create severe lameness with crusting, fissures and pronounced compact keratin that in some cases can produce horns. Histopathology shows moderate to severe hyperplasia with marked papillated and diffuse hyperkeratosis.

Treatment is symptomatic with topical emollients such as propylene glycol, phytosphingosine and keratolytics as mentioned in the nasal hyperkeratosis section. If papilloma virus is detected treatment with Imiquimod (Aldara, 3 M) or interferon may be helpful. Trimming excess pad tissue can also be of value.

Ear Margin Dermatosis

Canine ear margin dermatosis is a scaly, greasy condition of the margin of the pinnae. It is described mainly in dachshunds but other breeds may be affected, most of which have pendulous ears. I have seen this in erect eared dogs and dogs with ear crops as well. Follicular casts and partial alopecia are common. In severe cases secondary infections may occur. Severe cases may develop necrosis or fissures. The concern for a vascular component is then warranted. Usually these cases are asymptomatic unless infected, fissured or necrotic. Moisturizing agents and topical sulfur salicylic acid shampoos and topical hydrocortisone creams are most helpful in managing uncomplicated cases. Douxo ® Seborrhea Spot-on with 1% phytosphingosine as a spot on application twice weekly has also been used as a maintenance topical treatment with good success. Severe cases with a vascular necrosis respond best to partial pinnectomy though pentoxifylline at 20 - 30mg/kg q 12h may be beneficial and should be tried prior to surgery.

Linear Keratosis

Rare cases may present with linear scaly, crusty lesions.(White and al 1993; Scarampella, von Tscharner et al. 2000) These may be sharply marginated and appear to follow a dermatome. Follicular casts and fronds as in seborrhea may be seen. These lesions should be differentiated from a hamartoma and most likely represent some form of linear verrucous epidermal nevus. They are not progressive but are prone to secondary pyoderma. One report of linear pustular dermatitis that was methylprednisolone responsive suggests that biopsy is a worthwhile diagnostic procedure even if lesions seem characteristic and the prognosis is poorer for the nevus.(Beningo and Scott 2001) Histopathologic descriptions of multiple cases are not reported. Treatment is symptomatic and consists of topical keratolytic agents, phytosphingosine, glucocorticoids, retinoids or surgical excision of the lesion if possible. One report showed cryotherapy was successful.(Shibata, Nagata et al. 2002)

Schnauzer Comedo Syndrome

Schnauzer comedone syndrome is a follicular keratinization defect. It has been in the textbooks for many years but no one has ever published a paper on more than a case. Lesions are found primarily along the dorsal back within 2 inches of the midline. Comedones are most commonly seen but mild follicular casts and papules (2nd folliculitis) may also be found. Once infected, lesions may become painful and cause alopecia. Histologically follicular hyperkeratosis is the major change but when secondary infection intervenes then panniculitis, folliculitis and furunculosis may be seen. Treatment with topical benzoyl peroxide and phytosphingosine shampoo, spray or spot on formulations, or salicylic acid wipes or alcohol can often be effective. When topical therapy isn't effective then vitamin A at 8,000 to 10,000iu a day or isotretinoin 1-2mg/kg every 24 hours may be successful. It may also be worth trying topical adapalene, a potent topical retinoid preparation.

Idiopathic Facial Dermatitis of Persian Cats

An idiopathic and hereditary facial dermatitis of Persian and Himalayan cats has been described.(Bond, Curtis et al. 2000) Most cases present early in life less than one year of age with skin lesions confined to head and in particular with facial folds of periocular, perioral and chin regions. However, cervical areas and even other body locations such as axilla, groin and perineal have been seen by the author. The lesions appear as adherent black waxy exudates on the skin and hair shafts with moderate erythema to the skin. Pruritus and secondary infections with bacteria and yeast are common. Many cases have concurrent otitis externa. Histologically there is evidence of keratinization abnormalities with hyperkeratosis, epidermal and sebaceous hyperplasia. However, there is also crusting with a mixed perivascular to interface dermatitis noted suggesting other etiologies. Occasional sites of hydropic degeneration and dyskeratotic basal cells and intraepidermal eosinophilic microabscesses can be seen. Treatment is often palliative and many cases will respond to antimicrobial therapy. The author has been some partial responses to Douxo ® Seborrhea Spot-on with 1% phytosphingosine as a spot on application twice weekly. Care needs to be taken to avoid getting this product in the eyes. Cyclosporine at 5mg/kg q 24h has also been very effective in individual cases.

References

Adebamowo, C. A., D. Spiegelman, et al. (2005). "High school dietary dairy intake and teenage acne." J Am Acad Dermatol 52(2): 207-14.

Beningo, K. E. and D. W. Scott (2001). "Idiopathic linear pustular acantholytic dermatosis in a young Brittany Spaniel dog." Vet Dermatol 12(4): 209-13.

Bensignor, E. and E. Guaguere (2004). "Treatment of canine acne with doxycycline: an open trial." Vet Dermatol 15(s): 43.

Bond, R., C. F. Curtis, et al. (2000). "An idiopathic facial dermatitis of Persian cats." Vet Derm 11: 35-41.

Heymann, W. R. (2004). "Hyperandrogenism and the skin." J Am Acad Dermatol 50(6): 937-8.

Jazic, E., K. Coyner, et al. (2006). "An evaluation of the clinical, cytological, infectious and histopathological features of feline acne." Vet Derm 17(2): 134-140.

Nagy, I., A. Pivarcsi, et al. (2005). "Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors." J Invest Dermatol 124(5): 931-8.

Page, N., M. Paradis, et al. (2003). "Hereditary nasal parakeratosis in Labrador Retrievers." Vet Dermatol 14(2): 103-110.

Peters, J., D. W. Scott, et al. (2003). "Hereditary nasal parakeratosis in Labrador retrievers: 11 new cases and a retrospective study on the presence of accumulations of serum ('serum lakes') in the epidermis of parakeratotic dermatoses and inflamed nasal plana of dogs." Vet Dermatol 14(4): 197-203.

Pinnell, S. R. (2003). "Cutaneous photodamage, oxidative stress, and topical antioxidant protection." J Am Acad Dermatol 48(1): 1-19; quiz 20-2.

Placzek, M., B. Arnold, et al. (2005). "Elevated 17-hydroxyprogesterone serum values in male patients with acne." J Am Acad Dermatol 53(6): 955-8.

Scarampella, F., C. von Tscharner, et al. (2000). "Linear Organoid Nevus in a Dog." Vet Derm 11(1): 69-73.

Scott, D. and W. J. Miller (2000). "Congenital Follicular Parakeratosis in a Rottweiler and a Siberian Husky." Canine Pract 25(3): 16-19.

Scott, D. W., W. H. Miller, Jr,, et al. (2001). Muller and Kirk's Small Animal Dermatology . Philadelphia, W,B. Saunders.

Senter, D. A., D. W. Scott, et al. (2002). "Intracorneal vacuoles in skin diseases with parakeratotic hyperkeratosis in the dog: a retrospective light-microscopy study of 111 cases (1973-2000)." Vet Dermatol 13(1): 43-47.

Shibata, K., M. Nagata, et al. (2002). "Canine epidermal nevus treated with cryotherapy." Vet Dermatol 13(4): 229.

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White, S., P. Bordeau, et al. (1997). "Feline acne and results of treatment with mupirocin in an open clinical trial: 25 cases (1994–96)." Vet Dermatol 8(3): 157.