Abnormal Pigmentation

Definition

The following terms are used when discussing pigmentation and pigmentary abnormalities.⁷

• Melanin is a brown-black, light-absorbing, insoluble pigment formed in many organisms by specialized cells called melanocytes.

• Hyperpigmentation is an excessive tissue deposition of pigment, usually melanin.

• Hypopigmentation refers to less than normal pigmentation and can be congenital or acquired.

• Leukoderma (hypomelanosis) is a partial or total acquired loss of melanin pigment from the skin. The term vitiligo also refers to an acquired loss of melanin from the skin but is often reserved for a specific type of leukoderma found in humans.

• Leukotrichia is an acquired loss of pigment from the hair.

• Albinism is a congenital lack of pigment in all tissues.

Mechanisms of Pigmentation Abnormalities

Cutaneous pigmentation results from the interaction of melanocytes and keratinocytes. The degree of “baseline” pigmentation observed in an animal is genetically controlled. Melanocytes are of neural crest origin and migrate from this site during embryologic development. They are present in nearly all tissues but occur in the highest numbers in the epidermis, mucous membrane epithelium, dermis, hair follicles, leptomeninges, uveal tract, and retina. Epidermal melanocytes are found in the basal cell layer, and each melanocyte is pre­sumed to supply melanin to 10 to 20 keratinocytes. Melanin is usually found in the deeper layers of the epidermis, although darkly pigmented animals may have melanin throughout the epidermal layers.

Melanocytes produce membrane-bound organelles called melanosomes that fuse with vesicles containing the enzyme tyrosinase. Melanin, a black-brown pigment, is produced from tyrosine in the presence of tyrosinase and copper. It is deposited on the protein matrix in the melanosomes.

phase.⁷

In general, mechanisms associated with pathologic pigmen­tary disturbances in large animals are poorly understood. Hyperpigmentation results from increased amounts of melanin in the epidermis or dermis or both. The melanin may be present in melanocytes, keratinocytes, or melanophages (dermal macrophages that have phagocytized melanin pigment). Hyperpigmentation is an uncommon problem in horses because most normally have darkly pigmented skin. Hyperpigmentation may be reversible: with removal of the pigment-promoting stimulus, it tends to decline over time to the baseline level.

MSH may stimulate hyperpigmentation. MSH acts by affect­ing the levels of cyclic adenosine monophosphate (cAMP), result­ing in increased tyrosinase activity. MSH also causes increased dispersion of melanosomes into melanocyte dendritic processes, where they are phagocytized by keratinocytes. Increased levels of ACTH, estrogens, progesterones, and androgens may also affect pigmentation, although the importance and mode of action in large animals are not clear.

Inflammation from a variety of causes and persistent cutane­ous trauma from friction induce hyperpigmentation. Stimuli that may be factors in large animals include physical cutaneous damage (trauma, friction); chemicals (primary irritants, allergic sensitizers, photosensitizers); infectious agents; and nutritional disturbances.

Hypopigmentation is the result of a decreased amount of melanin in the epidermis or dermis (or both) and may be congenital or acquired (depigmentation). Possible mechanisms include decreased melanin production (defects in melanocyte migration during embryogenesis or disorders of melanin synthesis), decreased dispersion of melanin granules (defective transfer of melanin to keratinocytes), and increased loss of melanin (accelerated desquamation of epidermal melanin, epidermal pigment loss caused by disruption of the basement membrane with resultant pigmentary incontinence, or immu­nologic destruction of melanin or melanocytes).

Several congenital genetic abnormalities that result in partial or total hypopigmentation have been identified in large animals. Albinism is a recessive condition in which a normal complement of melanocytes is present but a biochemical defect results in lack of ability to synthesize tyrosinase, so melanin is not produced. There is complete lack of melanin in all tissues in a true albino. Pseudoalbinism, in which there is ocular pigmenta­tion, may be more common. Other genetic disorders include abnormal melanosome production and abnormalities in melanocyte development and migration from the neural crest (piebaldism).^7,9

Acquired hypopigmentation (leukoderma) may be caused by several factors, including genetic abnormalities, trauma, inflammation, dietary imbalances, hormonal influences, and immunologic disorders. In some cases acquired hypopigmenta­tion is idiopathic. Juvenile Arabian leukoderma appears to have a genetic basis because of the predilection for the Arabian breed and the occurrence of the disease in young animals.¹⁰ Trauma and inflammation are the most common factors associ­ated with depigmentation, particularly in the horse. The intensity of the inflammatory reaction may bear little relation to the degree of postinflammatory leukoderma. Dietary abnormalities, particularly molybdenum toxicity and copper deficiency, are associated with faded or washed-out coat color in food animals. Severe protein deficiency, such as occurs in kwashiorkor in humans, can lead to deficient melanin pigmenta­tion. Melatonin is a hormone produced by the pineal gland that antagonizes MSH, thus causing decreased pigmentation, although an association with pathologic hypopigmentation in large animals has not been documented. Immunologic destruc­tion of melanocytes has been documented in humans and is suspected of being a factor in acquired hypopigmentation in the dog but has not yet been documented in large animals. Idiopathic leukodermas are noted in all species.

Leukotrichia is the result of decreased amounts of melanin in the hair shaft. In most cases the pathogenesis is speculative, and the actual factors are unknown. Melanocytes in the hair bulbs can be affected independently of melanocytes in the epidermis, and leukotrichia without a coexistent leukoderma is common. Leukoderma, however, is usually accompanied by leukotrichia; thus when the two conditions are seen in combina­tion, their pathogenesis is the same. Several leukotrichias that occur independently of leukoderma appear to be genetically induced because of breed predilections (e.g., reticulated leu- kotrichia of Quarter Horses).

Approach to Diagnosis of Pigmentation Abnormalities

The initial approach to diagnosis of pigmentary abnormalities is to determine whether the defect is congenital or acquired. Congenital pigmentary abnormalities are almost always caused by a genetic defect, whereas acquired abnormalities most commonly do not have a hereditary basis. If the abnormality is acquired, the clinician must determine if it is a primary pigmentary abnormality or if it is associated with some other pathologic change such as inflammation or trauma. If associated changes are a feature of the disease, differential diagnosis should focus on the initial pathologic changes (Box 11.7).

The following steps are a guide to the diagnosis of pigmenta­tion abnormalities in horses and ruminants:

1. History (see Fig. 11.1)

a. If the pigmentary change is congenital, determine if related animals are affected and if the lesions have

■ BOX 11.7

Most Common Causes of Abnormal Pigmentation in Horses and Ruminants

Loss of Pigmentation

Burns and other trauma

Idiopathic Ieukotrichia and leukoderma (horses) Copper deficiency (ruminants)

Increase in Pigmentation

Pruritus

Melanoma

progressed or regressed since birth. Take note of the patient's signalment and determine if that breed has been documented to have congenital pigmentary abnormalities.

b. If the pigmentary change is acquired, determine if the animal has been subjected to cutaneous trauma that could result in posttraumatic pigmentary change. Determine if other cutaneous lesions in addition to the pigmen­tary changes have been observed (e.g., inflammation, ulceration).

c. Determine if the animal's diet is nutritionally complete and balanced.

d. Determine if the animal has been exposed to any toxic substances.

e. Determine if contact animals of the same or different species are affected. Because feed and environment are shared, if contact animals are affected, dietary imbal­ances and toxicities should be included in the differential diagnosis.

f. If the affected animal is a horse, determine what para- siticidal agents have been administered and if they are effective in the treatment or prevention of onchocerciasis.

2. Physical examination (see Fig. 11.2)

a. Check for evidence of disease in organ systems other than the skin. Does the animal appear thin and mal­nourished, suggesting a pigmentary change secondary to a dietary deficiency or toxicity?

b. If the patient's problem is hypopigmentation, examine the coat closely to determine if leukoderma, leukotrichia, or both are present.

c. Look for evidence of other cutaneous lesions (inflam­mation, ulceration) that could result in postinflammatory pigmentary changes.

3. Microfilarial preparation

4. Biopsy for routine histopathologic examination (affected, unaffected, and marginally affected areas should all be biopsied and labeled appropriately for histologic comparison).

REFERENCES

The complete list of references can be found at www.expertconsult.com.

REFERENCES

1. Evans AE, Stannard AA: Diagnostic approach to equine skin disease, Compend Cont Educ Pract Vet 8:652, 1986.

2. Frank: LA, Kania SA, Weyant E: RT-qPCR for the diagnosis of derma - tophilosis in horses, Vt Dermatol 27:431, 2016.

3. Tartor YH, El Damaty HM, Mahmmod YS: Diagnostic performance of molecular and conventional methods for identification of dermatophyte species from clinically infected Arabian horses in Egypt, Vt Dermatol 27:401, 2016.

4. Das A, Deng MY, Babiuk S, et al: Modification of two capripoxvirus quantitative real-time PCR assays to improve diagnostic sensitivity and include beta-actin as an internal positive control, J Vet Diagn Invest 29:351, 2017.

5. Das A, Ward G, Lowe A, et al: Development and validation of a highly sensitive real-time PCR assay for rapid detection of parapoxviruses, J Vet Diagn Invest 29:499, 2017.

6. Shanley KJ: Pathophysiology of pruritus, Vt Clin North Am Small Anim Pract 18:971, 1988.

7. Scott DW, Miller WH, Jr: Equine dermatology, ed 2, St Louis, MO, 2011, Saunders.

8. Gnirs K, Prelaud P: Cutaneous manifestations of neurological diseases: review of neuropathophysiology and diseases causing pruritus, Vet Dermatol 16:137, 2005.

9. Scott DW: Large animal dermatology, Philadelphia, PA, 1988, Saunders.

10. Stannard AA: Stannard’s illustrated equine dermatology, Vt Dermatol 11:163, 2000.

11. Scott DW: Color atlas of farm animal dermatology, Ames, IA, 2007, Wiley Blackwell.