JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 2327342): 2-year-old male blue Doberman pinscher
HISTORY: This dog had a history of chronic keratoconjunctivitis and bilaterally symmetrical hair loss.
HISTOPATHOLOGIC DESCRIPTION: Haired skin: Diffusely, hair follicles are moderately distended by lamellations of keratin which occasionally entrap small clumps of dark brown granular to globular pigment (melanin), are variably distorted in shape (follicular dysplasia), and often contain fragmented hair shafts. Multifocally, melanocytes within the epidermis, the follicular epithelium, and in the perifollicular dermis are engorged with small clumps of melanin. In the superficial and deep dermis, adjacent to hair shafts and bulbs, as well as in the panniculus carnosus, are moderate numbers of melanin-containing macrophages (pigmentary incontinence) and aggregates and clumps of free melanin. The follicular epithelium is diffusely hyperkeratotic. The overlying epidermis is multifocally mildly hyperplastic characterized by mild thickening of the stratum spinosum (acanthosis).
MORPHOLOGIC DIAGNOSIS: Haired skin: Follicular dysplasia, diffuse, moderate, with intrafollicular and intraepidermal melanin clumping, pigmentary incontinence, and hyperkeratosis, Doberman pinscher, canine.
CONDITION: Color dilution alopecia
SYNONYMS: Color mutant alopecia; blue dog disease
- Uncommon hereditary skin disease of dogs with color-diluted coats (blue, fawn)
- Most common in Doberman Pinschers (57.9% blue; 89.5% fawn), but also reported in other breeds including Yorkshire terriers, miniature pinschers, great Danes, whippets, Italian greyhounds, salukis, chow chows, dachshunds, silky terriers, Boston terriers, Newfoundlands, Bernese mountain dogs, Shetland sheep dogs, schipperkes, Chihuahuas, poodles, Irish setters, German setters, and crossbreed dogs
- Autosomal recessive in some breeds
- Etiology unknown
- Color dilution alopecia is based on autosomal recessive gene transmission; the dilution gene -d, especially the allele -d1 may play an important role in the genetic transmission of color mutant alopecia
- Other alleles and other factors should be taken into consideration, such as disorders of calcium ion conduction and protein kinase C activation, which play an important role in the keratinization process, because not all dogs with dilute coat colors develop alopecia
- Dilute hairs have large pigment granules (macromelanosomes), likely due to abnormal melanin transfer and storage
- Dilute hairs contain as much or more melanin than their normal counterparts
- Matrix hair cells damaged by cytotoxicity of melanin precursor>hair follicle dysplasia>alopecia
TYPICAL CLINICAL FINDINGS:
- Alopecia, poor quality haircoat, and secondary pyoderma in color-dilute areas
- Affected dogs are born with a normal haircoat
- Most dogs develop the syndrome between 4-months and 3-years of age
- More color dilute>greater magnitude of alopecia
- Alopecia most severe on dorsal trunk
- There are two patterns of development
- Recurrent folliculitis form:
- Recurrent dorsal papules and pustules from bacterial folliculitis
- Involved hair follicles have poor to no hair regrowth
- Alopecia becomes more widespread with repeated infection
- Initial hair loss form:
- Gradual onset of dry, dull, poor-quality haircoat
- Initial hair loss results from fractured hair shafts
- Secondary pyoderma may occur but the hair loss develops first
- Recurrent folliculitis form:
TYPICAL GROSS FINDINGS:
- This condition is limited to color-diluted hair (diluted black or brown areas), with sparing of white and tan areas
- Dry, dull, poor-quality haircoat
- Papules and pustules (secondary bacterial folliculitis) are frequent sequelae
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Misshapen, fragmented anagen hair follicles
- Melanin pigment clumping in follicular epithelium, hair bulb matrix cells, hair shafts, infundibular keratin, and epidermis
- Melanomacrophages are frequently present in the dermis around hair bulbs
- Follicular hyperkeratosis
- Fractured hair shafts
- Secondary pyoderma, acanthosis, folliculitis, furunculosis
- Melanocytes and surrounding keratinocytes contain many mature melanosomes and macromelanosomes
ADDITIONAL DIAGNOSTIC TESTS:
- Microscopic examination of plucked hairs reveals numerous irregularly sized and shaped macromelanosomes distributed unevenly along the hair shaft; the cuticle may be absent or fractured over the pigment clumps
- Grossly, color mutant alopecia in puppies needs to be differentiated from demodicosis, dermatophytosis, superficial pyoderma, and other inherited follicular dysplasias; in adults, differential diagnoses include endocrinopathies (hypothyroidism, hyperglucocorticoidism, growth hormone deficiency dermatosis) and superficial folliculitis or acquired pattern alopecia
- Black hair follicular dysplasia is a localized form of color dilution alopecia that occurs in the dark haired areas of light colored dogs with dark spots; there are differences in melanin distribution between the two diseases (may be function of breed variation) but this is believed to be a related to breed differences in deposition rather than a disease difference
- Only affects the dark patches and not the light colored areas
- Black hair follicular dysplasia breeds include: bearded collie, border collie, beagle, basset hound, papillon, saluki, Jack Russell terrier, American cocker spaniel, Cavalier King Charles spaniel, dachshund, Gordon setter, large Munsterlander, pointers, and mongrels
- Perifollicular melanin clumping is a nonspecific finding in inflammatory and other dysplastic follicular diseases involving the hair bulb; the presence of melanin within the follicle with color mutant alopecia differentiates it from inflammatory follicular disease
- Normal-coated color diluted dogs: There is melanin clumping, but normal hair shaft architecture is preserved
- Cats with blue or cream-colored hair coats carry the Maltese dilution gene, and have spontaneous truncal hypotrichosis or alopecia; histologic changes are similar to those described in dogs (clumped melanin in the follicular epithelium and hair shafts), but dysplastic changes in the hair follicles and shafts are rare
- Cross-related congenital hypotrichosis occurs in cross breeds of European cattle, especially Simmental-Angus and Simmental-Holstein crosses; the ears, muzzle and ventrum are primarily affected; white areas are not affected; color-dilute animals have short, curly hair coats that may be sparse; histologic lesions are almost identical to canine lesions
- Coat color-linked hair follicle dysplasia of buckskin Holstein cows (color dilute tan and white); short abnormal hair in the tan areas
- Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Oxford, England: Blackwell Science; 2005:518-522.
- Mauldin E, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA:Elsevier; 2016:539-541.
- Medleau L, Hnilica KA. Small Animal Dermatology, A Color Atlas and Therapeutic Guide. 2nd ed. Louis, MO:Elsevier Inc; 2006:253-254.
- Parego R, Proverbio D, Roccabianca P, Spada E. Color dilution alopecia in a blue Doberman pinscher crossbreed. Can Vet J. 2009:50(5):511-14.
- Scott DW, Miller WH, Griffin CE. Muller & Kirk’s Small Animal Dermatology. 6th ed. Philadelphia, PA :WB Saunders Co; 2001:966-970.