Genodermatoses and newly recognized skin diseases (Proceedings)

Recognizing breed associated or genetic dermatologic conditions can prove quite challenging on a daily basis. Such conditions are more obvious when multiple animals from a single litter are affected at birth, however clinical signs of many of these conditions are not present until adulthood and many animals have dispersed to new homes. In such cases the genetic link may not be quite so obvious. Pedigree analysis and additional genetic testing have provided much insight as to the mode of inheritance of many of these conditions, however facts regarding pathogenesis of the disease state in most cases remains unclear.

Adult-onset hair loss in Chesapeake Bay retrievers

This coat disorder has been recently reported in the literature. Both intact and neutered animals are affected with a form of adult-onset alopecia. In the cases reported, all animals have been otherwise healthy except for a non-pruritic progressive symmetrical hair loss affecting the axillae, the thorax (lateral to ventral aspects), and the flank region extending to include the caudal dorsum and caudal thighs. The extremities are typically spared with a normal hair coat in these regions. The distribution of hair loss described in this syndrome is consistent with a non-inflammatory (endocrine) pattern of alopecia. The age of onset for clinical signs ranges from 5 months to 4 years and hair loss ranges from thinning in some areas to complete alopecia in others. Routine lab work (CBC, Chemistry panel, urinalysis) results are typically within normal limits; evaluation of thyroid hormones, urine cortisol: creatinine ratios and ACTH stimulation testing fails to reveal significant abnormalities to explain the adult-onset hair loss.

• Diagnosis: Treat and resolve any secondary infections.

Rule out endocrinopathies and systemic illnesses

Submit biopsies for histopathology—Infundibular orthokeratotic hyperkeratosis is a consistent finding along with follicular atrophy.

• Treatment: None reported

• Pedigree analysis: Common ancestors in the sire and dam line of most affected dogs examined.

• Mode of inheritance and pathogenesis unknown; potentially a hair cycle disorder or a type of follicular dysplasia.

Hypotrichosis and alopecia in Irish Water Spaniels

Special coat characteristics are associated with this breed, resulting in the selective breeding of animals possessing such traits. These characteristics include focal areas that are smooth coated interspersed with a mostly curly coat. Recently coat abnormalities have been noted within the breed and include more generalized areas of alopecia and thinly haired regions that extend to include the dorsum, flank region, caudal thighs as well as much of the neck. Both intact and neutered male and female dogs are affected. This is a non-pruritic adult-onset progressive condition affecting middle-aged dogs most commonly. The age of onset ranges from 1-6 years of age, with an onset of 5-6 years of age considered typical. Routine lab work (CBC, Chemistry panel, urinalysis) results are typically within normal limits; evaluation of thyroid hormones, sex hormones (elevated 17-OHP) and ACTH stimulation testing fails to reveal significant abnormalities to explain the adult-onset hair loss.

• Diagnosis: Treat and resolve any secondary infections.

Rule out endocrinopathies and systemic illnesses.

Submit biopsies for histopathology—Infundibular orthokeratotic hyperkeratosis is a consistent finding along with follicular atrophy and pigment clumping within the hair shaft and/or hair follicle.

• Treatment: None reported

• Pedigree analysis: Not reported.

• Mode of inheritance and pathogenesis unknown.

Exfoliative cutaneous lupus erythematosus of German Short-haired pointers

This condition has previously been referred to as a type of lupoid dermatosis and is considered unique to the breed. It is an acquired, adult-onset condition, affecting dogs between the ages of 6 months to 4 years. The predominant clinical sign associated with this disease is an exfoliative, scaling skin disease that will also include alopecia in some cases. It is generalized in distribution and may initially affect the face, pinnae and dorsum and then will progress to involve the remainder of the body. Most dogs have secondary bacterial and yeast infections and are pruritic. Some dogs are systemically ill as well, presenting with pyrexia, peripheral lymphadenopathy and pain or lameness. A stilted or abnormal gait has also been noted. Results of routine lab work (CBC, Chemistry panel, UA) are inconsistent between animals with thrombocytopenia and mild nonregenerative anemia reported in some cases. Lymph node aspiration in some dogs has revealed lymph node hyperplasia.

• Diagnosis: Submit biopsies for histopathology—Lymphocytic interface dermatitis and mural folliculitis with sebaceous adenitis.

• Treatment: Limited success with immunomodulatory drugs (prednisone, cyclosporine, azathioprine) plus topical antiseborrheic treatments.

• Pedigree Analysis: Common ancestor in the sire line for some dogs.

Mode of inheritance currently unknown; autosomal recessive or polygenic recessive mode suggested based on limited pedigree data.

• Pathogenesis: Unknown. Both circulating and tissue fixed antibodies (IgG) detected, thus a cytotoxic T-cell mediated process against basal cells is suggested.

Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the cavalier King Charles spaniel

One scientific report describing this breed specific syndrome exists. It is described as a congenital condition, however the dermatologic lesions tend to progress with age. Clinical signs consist of bilateral keratoconjunctivitis sicca, noted in some cases at 10-11 days of age, with the reported coat abnormalities present at birth. The hair coat is described as curly or wavy rather than silky as expected for this breed and the vibrissae are reported to be shorter than normal. A seborrheic skin condition is reported within the first week of life and abnormalities of the footpads, the claws and the claw folds develop and progress from normal in appearance at birth to become severely affected in many animals.

• Diagnosis: Dermatologic signs present at birth with development of concurrent KCS

Submit skin biopsies for histopathology— Irregular epidermal hyperplasia with marked hyperkeratosis and a mild perivascular inflammatory dermatitis.

• Treatment: Symptomatic therapy.

• Pedigree analysis: Autosomal recessive mode of inheritance suspected. Common ancestor on both the sire and dam sides of the pedigree of affected animals. This condition has been noted in all coat colors of this breed.

• Pathogenesis: Unknown.

Hereditary nasal parakeratosis in Labrador Retrievers

This is a newly described syndrome and must be differentiated from other causes of nasal hyperkeratosis. These animals are otherwise healthy except for their dermatological disease. Clinical signs consist of accumulations of keratin along the dorsal aspect of the nasal planum that can progress to fissures and erosions. Footpads may be mildly affected as well. This syndrome is differentiated from the idiopathic form of nasal parakeratosis namely by the age of onset and the breed specificity. The age of onset is 6-12 months in most cases and both Labrador Retrievers and their crosses are affected.

• Diagnosis: Submit skin biopsies for histopathology— Marked parakeratotic hyperkeratosis with regular to irregular epidermal hyperplasia and accumulation of intercellular fluid (protein-rich) with a mild to moderate lymphoplasmacytic perivascular to interface dermatitis.

• Treatment: Symptomatic therapy consisting of propylene glycol and/or petroleum topically.

• Pedigree analysis: Unknown mode of inheritance.

• Pathogenesis: Unknown.

Epidermolytic Hyperkeratosis (heritable keratinization defect) in Norfolk Terriers

This is another newly reported heritable skin condition and was identified in a group of related Norfolk terriers. In contrast to other genodermatoses, the pathogenesis of this disease has been identified and confirmed. All dogs are otherwise healthy except for their mild dermatologic disease. Clinical signs noted at birth include excessive scaling of the skin of the ear margins and an abnormal grayish pigmentation to the skin. Initially superficial lesions of the inguinal and axillary regions are noted which occur with even very mild trauma and are consistent with a fragile epidermis. Symptoms progress with age to include severe hyperpigmentation, generalized scaling and malodor as a result of frequent secondary bacterial and yeast infections.

• Diagnosis: Submit skin biopsies for histopathology—Orthokeratotic hyperkeratosis with moderate regular hyperplasia and hyperpigmentation. Areas of separation are evident in the upper granular cell layer of the epidermis.

• Treatment: Symptomatic therapy.

• Pedigree analysis: Autosomal recessive mode of inheritance.

• Pathogenesis: Spontaneous mutation of keratin 10.

Sebaceous Adenitis

Sebaceous adenitis was originally described in the 1980's and has now been reported in the Standard Poodle, the Akita, as well as many other breeds including the Samoyed and the Vizsla. This condition has also been reported in rabbits and a horse. Clinical signs range from a moth-eaten patchy alopecia to complete alopecia with hyperpigmentation primarily affecting the trunk and sparing the extremities, however the legs, pinnae and head can be affected. Scaling and follicular casts are hallmark findings. This is a non-pruritic condition, however secondary bacterial infections are common and will induce symptoms of pruritus. This is an adult-onset progressive condition, affecting young to middle-aged dogs most commonly.

• Diagnosis: Submit skin biopsies for histopathology—Nodular pyogranulomatous to granulomatous inflammation targeting the sebaceous gland. In chronic or end-stage cases the sebaceous glands may be absent.

• Treatment: Symptomatic therapy; success has been reported with vitamin A therapy, oral cyclosporine and topical "sebum replacements".

• Pedigree analysis: Autosomal recessive mode of inheritance with variable expression is suspected in the Standard Poodle, Autosomal recessive mode of inheritance suspected in the Akita.

• Pathogenesis: Currently unknown.

Hair cycle arrest (Alopecia X) update

This condition has been known by many names and until recently was thought to be caused by aberrant production of adrenal steroid hormone intermediates. This proposed pathogenesis has been questioned and it has now been shown that many dogs with this condition do not have abnormalities associated with the production of adrenal steroid hormones or their intermediates. In addition, it has also been demonstrated that hair regrowth is not associated with changes in adrenal steroid hormone concentrations.16 Additional mechanisms contributing to the manifestation of this disease are currently under investigation.

Dermal arteritis of the nasal philtrum

This condition has been reported in related dogs as well as dogs of various breeds with no known affected relatives. Clinical signs include a focal ulcerative lesion that is well circumscribed, V-shaped and located at the nasal philtrum. The most compelling reason for seeking medical attention is the repeated arterial bleeding episodes, varying from mild to severe and life threatening. The age of onset ranges from 3-6 years.

• Diagnosis: Submit biopsies for histopathology—Idiopathic proliferative arteritis.

• Treatment: Surgical intervention for hemostasis if necessary and symptomatic therapy; success has been reported with topical glucocorticoids, oral tetracycline and niacinamide, potentially topical tacrolimus.

• Pedigree analysis: None.

• Pathogenesis: Currently unknown.