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Read-Only Case Details Reviewed: Oct 2010



September 2019



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, there are foci of clumped, dark brown, granular to globular pigment (melanin) within the hair bulb matrix epithelium, within misshapen often fractured hair shafts, and to a lesser extent within the nonmatrical follicular epithelium and follicular lumina. Follicles are variably distorted in shape (follicular dysplasia) and are often ectatic, lined by attenuated follicular epithelium, and contain lamellations of keratin admixed with the previously described clumped melanin and 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 dermis, predominantly adjacent to hair shafts and bulbs, are moderate numbers of melanin-containing macrophages (pigmentary incontinence) and aggregates and clumps of free melanin. There are low numbers of perivascular lymphocytes and plasma cells in the superficial dermis. The overlying epidermis is multifocally mildly hyperplastic characterized by mild thickening of the stratum spinosum (acanthosis).


MORPHOLOGIC DIAGNOSIS: Haired skin: Follicular dysplasia, pigmentary, 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); 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 mongrels

·      Autosomal recessive in some breeds


·      Etiology unknown

·      Autosomal recessive transmission; the dilution gene -d, especially the allele -d1 may play an important role in the genetic transmission of color mutant alopecia, but alone this does not explain the syndrome because not all dogs with dilute coat colors develop alopecia; other disorders affecting the keratinization process may play a role (e.g. disorders of calcium ion conduction and protein kinase C activation)

·      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 (hair bulb germinal epithelium) are damaged by cytotoxicity of melanin precursor>hair follicle dysplasia>alopecia


·      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

o   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

o   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


·      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; hypotrichosis

·      Papules and pustules (secondary bacterial folliculitis) are frequent sequelae



·      Misshapen, fragmented anagen hair follicles

·      Melanin pigment clumping in follicular epithelium, hair bulb matrix cells, hair shafts, infundibular keratin, epidermis, and free in the dermis

·      Melanomacrophages are frequently present in the dermis around hair bulbs

·      Follicular hyperkeratosis, comedones

·      Fractured hair shafts

·      Secondary pyoderma, acanthosis, folliculitis, furunculosis

·      Possible hair follicle atrophy (secondary change)


·      Melanocytes and surrounding keratinocytes contain many mature melanosomes and macromelanosomes


·      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


Gross differentials in puppies:

·      Demodicosis (I-P07)

·      Dermatophytosis (I-F11)

·      Superficial pyoderma

·      Other inherited follicular dysplasias

Gross differentials in adults:

·      Endocrinopathies: hypothyroidism (I-M22), hyperglucocorticoidism (I-M23), growth hormone deficiency (I-M21)

·      Superficial folliculitis

·      Acquired pattern alopecia

Histologic differentials:

·      Black hair follicular dysplasia:

o   Localized form of color dilution alopecia that occurs only in the dark haired areas of light colored dogs with dark spots; onset is generally the first few weeks or months of life

o   Seen in bicolor and tricolor black and white dogs (Bassett Hounds, Beagles, Bearded Collies, Greater Munsterlanders, and mongrels); and in Holstein cattle (alopecia only affects the black-haired areas).

o   Pathogenesis: Thought to have a genetic component in some purebreds (Bearded Collie), and an autosomal inherited disorder in mongrels puppies; hair shaft defect appears to be associated with inadequate and disorganized melanosome transfer to keratinocytes resulting in melanin clumping in Greater Munsterlanders

o   Histologic lesions: Virtually identical to color-dilution alopecia except there may be a difference in melanin distribution (may be function of breed variation)

·      Perifollicular melanin clumping: Nonspecific secondary to inflammation 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

·      Other follicular dysplasias associated with pigment abnormalities:

·      Portuguese Water Dogs (these are not color-dilute dogs): follicular dysplasia occurs in the black or red color phase of this breed; generally occur between 3 months and 5 years

·      Black-and-red Doberman Pinchers (not phenotypically color dilute): reported to have a follicular dysplasia that is generally confined to the caudal dorsum; has an adult onset

·      Chesapeake Bay Retrievers: adult-onset alopecia disorder

·      Weimaraners: progressive alopecia of trunk with recurrent folliculitis/furunculosis in affected young adults

·      Cattle (all black and not color diluted): follicular dysplasia has been reported in black Angus-Brahman crosses


·      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

·      Reported in crosses involving Simmental, Gelbvieh, and Charolias cattle (most common in Simmental-Angus and Simmental-Holestein crosses)

·      Affected hair is short, curly, and sparse; white haired areas of the coat are unaffected

·      Histological lesions are virtually identical to canine color dilution alopecia

·      Coat color-linked hair follicle dysplasia of buckskin Holstein cows (color dilute tan and white): short abnormal hair in the tan areas


1.    Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat. 2nd ed. Oxford, England: Blackwell Science; 2005:518-522.

2.    Hnilica KA, Patterson AP. Small Animal Dermatology, A Color Atlas and Therapeutic Guide. 4th ed. St. Louis, MO:Elsevier Inc; 2017:337-338.

3.    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.

4.    Miller Jr WH, Griffin CE, Campbell KL. Muller & Kirk’s Small Animal Dermatology. 7th ed. Philadelphia, PA: WB Saunders Co; 2017:595-597.

5.    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.

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