Waardenburg-Klein syndrome, American paint, autosomal dominant with incomplete penetrance

Overo lethal white foal syndrome, analogous to human Waardenburg type-4 (Hirschsprung’s disease), American Paint horses, autosomal recessive

Albinism, autosomal recessive

Various breeds, dominant and recessive forms reported

Congenital hypotrichosis with anodontia, German Holstein, monogenic X-linked recessive

Congenital hypotrichosis and incisor anodontia, Holstein-Friesian autosomal dominant

Congenital hypotrichosis and partial anodontia, Simmental/Holstein cross, Charolais, Maine-Anjou-Normandy, sex-linked recessive

Dominant congenital hypotrichosis, Hereford and polled Herford, autosomal dominant

Inherited epidermal dysplasia (baldy calf syndrome), Holstein-Friesian, suspect autosomal recessive

Semi-hairlessness, Hereford, polled Hereford, Ayrshire, autosomal recessive

Lethal hypotrichosis, Holstein-Friesian, autosomal recessive

Viable hypotrichosis, Guernsey, Jersey, Holstein, Ayrshire, autosomal recessive

Many breeds, autosomal recessive

Chédiak-Higashi syndrome, Hereford, Brangus and Japanese Black cattle, autosomal recessive

Hereditary zinc deficiency, Friesian, Black Pied Danish, Shorthorn, Angus, and Holstein, autosomal recessive

Congenital hypotrichosis, polled Dorsets, autosomal recessive

Mexican hairless and German swine, presumed autosomal dominant

Other breeds, presumed autosomal recessive

Several breeds, suspect autosomal recessive in some and possible sex linked in others

Landrace pigs, dermatosis vegetans, autosomal recessive trait

Mexican hairless dogs, autosomal dominant

American hairless terrier, autosomal recessive

Ectodermal dysplasia, German shepherd, X-linked recessive

German shorthair pointer, English Springer spaniel, English pointer, suspect autosomal recessive

Collie, autosomal dominant with variable expressivity

Shetland sheepdog, mode of inheritance unknown

Black hair follicular dysplasia, dog, presumed autosomal recessive

Follicular dysplasia, Irish water spaniel, suspect autosomal dominant

Rottweiler, suspect X-linked

Labrador retriever, suspect autosomal recessive

German shepherd, autosomal dominant

Irish terrier, suspect autosomal recessive

Waardenburg-Klein syndrome, Bull terrier, Collie, Dalmatian, Sealyham terrier, and Great Dane, autosomal dominant with incomplete penetrance

Black hair follicular dysplasia, suspect autosomal inherited disorder

Coat color dilution and cerebellar degeneration, Rhodesian ridgeback, autosomal recessive

Albinism, autosomal recessive

Primary seborrhea, West Highland white terrier and others, suspect autosomal recessive

Standard poodle, currently undefined

Akita, possible autosomal recessive component

Lethal acrodermatitis, white bull terriers, autosomal recessive

Zinc-responsive dermatosis, Alaskan malamute, Siberian husky, presumed inherited predisposition

Congenital hypotrichosis, Siamese and Birman, autosomal recessive

Primary seborrhea, Persian cat, autosomal recessive

Waardenburg-Klein syndrome, autosomal dominant with complete penetrance for the loss of pigmentation, and an incomplete penetrance for the inner ear degeneration

Chédiak-Higashi syndrome, Persian cats, autosomal recessive

Maltese coat color dilution, autosomal recessive

1. One of the most detrimental changes occurs when UVB radiation contacts the nucleus and causes the formation of “photoproducts,” which are abnormal covalent or single bonds between two adjacent pyrimidine bases in a strand of DNA. The two major UVB-induced photoproducts are pyrimidine dimers (covalent bonds between two thymine or two cytosine bases) and 6-4 photoproducts (single-bond bridging carbon 4 in one cytosine and carbon 6, either in a cytosine or a thymine). These photoproducts form in keratinocyte DNA (and also in DNA of Langerhans’ cells and dermal dendritic cells). The damage can be easily and accurately repaired before the cell undergoes mitosis by the nucleotide excision repair enzyme system that removes the damaged area and synthesizes a new strand of DNA. However, if the cell undergoes mitosis before the damage is repaired, a gap in the DNA strand is left at the location of the photoproduct. The gap is repaired by a postreplication repair method that is thought to be error-prone and may lead to mutations and the development of neoplasms. Factors that irritate the skin and increase the rate of cell division increase the number of cells repaired by the postreplication repair method and therefore can enhance development of neoplasms.

2. Chronic exposure to UVB radiation also causes damage to DNA in the form of mutations to tumor-suppressor genes, in particular to the p53 gene. Normally, UVR–induced DNA damage causes keratinocyte induction of the p53 gene, which leads to cell cycle arrest, thus allowing the UVR–caused DNA damage to be corrected by the nucleotide excision repair system before the cell undergoes mitosis, and a functional p53 gene also facilitates apoptosis (programmed cell death) of cells with excessive unrepaired damaged DNA so that those defective cells are removed. The p53 gene mutations develop when UVR–induced photoproducts are not repaired before keratinocyte mitosis. The photoproducts form small structural abnormalities in the DNA strand that can result in faulty base paring (i.e., mutations) during replication. The mutations are characterized by the replacement of a cytosine with a thymine (C to T) or double-base changes in which a cytosine dimer is replaced by two nondimerized thymine bases (CC to TT). Although p53 gene mutations occur in a variety of tumors, those mutations caused by UVR (the C to T or CC to TT mutations) are unique and do not occur with other types of DNA damage or in non–UVR-associated tumors, thus are termed signature mutations.

3. UVB causes immunosuppression by depressing host cell-mediated immune reactions that normally serve to eliminate or destroy mutated proliferating cells. A variety of mechanisms contribute and involve UVB-damaged keratinocytes, Langerhans’ cells, dendritic cells, and others. Mechanisms include release of immunosuppressive cytokines such as IL-10 and IL-4, reduction in the number of Langerhans’ cells (antigen-presenting cells), a switch in Langerhans’ cell antigen presentation from T_H1 lymphocytes (involved in immune response against tumors) to T_H2 lymphocytes (release immunosuppressive cytokines), induction of suppressor T lymphocytes, and release of cytokines and other biologic response modifiers that downregulate the immune response.

Molluscum Contagiosum: Equine molluscum contagiosum is a self-limiting cutaneous infection in the horse caused by a poxvirus from the genera Molluscipoxvirus (molluscum contagiosum virus), a virus closely related to, or possibly the same as, the human molluscum contagiosum virus. The equine lesions are small and often incidental, and may be localized to the penis, prepuce, axillary and inguinal areas, and nose. However, the lesions may become widespread, and hundreds of lesions are present over the neck, shoulders, chest, and legs. The pathogenesis of lesion formation is typical of poxvirus infection. Commencing as multiple, circular, smooth-surfaced, gray-white papules 1 to 2 mm in diameter, the lesions become umbilicated and develop a central pore from which a caseous plug is extruded. The microscopic lesions of molluscum contagiosum consist of well-demarcated foci of epidermal hyperplasia and hypertrophy that form invaginated lobules of the epidermis in the superficial dermis. Keratinocytes containing inclusions exfoliate through a pore that forms in the stratum corneum and enlarges into a central crater. The individual keratinocytes are markedly swollen and contain large intracytoplasmic eosinophilic inclusions, known as molluscum bodies, which can be identified histologically and in cytologic preparations. There is usually no dermal reaction. Rarely, molluscum contagiosum has developed in dogs.

Cowpox: Cowpox virus infections occur rarely in cattle in the United Kingdom and other areas of Europe. There is increasing evidence that small wild rodents (i.e., mice, squirrels, voles) serve as a reservoir for infection and that cattle, cats, and rarely other mammals become infected through contact with the wild rodents. Cutaneous infections in cattle usually develop on the teats and udder of cows and on the muzzle of suckling calves. Lesions follow the typical sequence of cutaneous poxviral infections. In cats, poxvirus infection is uncommon and usually occurs in outdoor cats living in rural areas, presumably because these cats hunt and have contact with rodents harboring the poxvirus. Primary cutaneous lesions typically develop on the face, neck, or forelegs and consist of an ulcerated or crusted macule or plaque. Lesions can develop into deep ulcers that heal with granulation tissue or less commonly develop into abscesses or cellulitis. Rarely, oral or mucocutaneous junctional areas are affected. Additional secondary cutaneous lesions can develop within about 2 weeks after viremic distribution to other cutaneous sites and less commonly to the upper or lower respiratory tract. The microscopic lesions are sharply demarcated, often deep ulcers covered by fibrinonecrotic exudate. Intracytoplasmic inclusion bodies in keratinocytes or follicular or sebaceous glandular epithelial cells help establish the diagnosis.

Bovine Papular Stomatitis: Bovine papular stomatitis virus is distributed worldwide, and although it causes disease more commonly in cattle more than 2 years old, it can occur at any age and in any breed. Lesions occur on the muzzle, nostrils, lips, and mouth, and cows with suckling calves can develop teat and udder lesions. The development and appearance of the lesions are similar to pseudocowpox, with resolution of lesions in days to weeks. A chronic form has been described in which exudative necrotic dermatitis involves the trunk, as well as the mouth, and in which the animals died in 4 to 6 weeks. Transmission to humans induces lesions identical to “milker’s nodule” caused by Pseudocowpox virus infection. The histologic appearance of lesions is typical of other poxviral infections.

Capripoxviral Diseases: Capripoxviruses are the cause of sheeppox and goatpox. These viruses cause significant economic losses in countries where they are endemic, and the geographic distribution of these viruses is expanding. Sheeppox and goatpox are present in Africa, Asia, the Middle East, and most of the Indian subcontinent where, despite attempts at vaccination, capripoxvirus is responsible for cycles of epidemic disease followed by periods of endemic maintenance with low morbidity. The disease is exotic to the Americas, Australia, and New Zealand. Although eradication measures eliminated the disease from Britain in the mid-nineteenth century, they have only recently been successful in Eastern European countries. The diseases they cause lead to constraints on international trade of livestock and related products and can prevent the importation of new breeds of sheep or goats into endemic areas because fatality rates can be very high in nonindigenous breeds. Capripoxviruses are highly contagious and spread by the respiratory tract in times of close contact and mechanically by insect vectors and fomites. Virus is shed in saliva, conjunctival secretions, milk, urine, and feces, as well as in skin lesions and scabs. Vaccination of susceptible animals for sheeppox and goatpox provides lifelong immunity. The viruses share a high percentage of homology at the nucleotide and amino acid levels but are distinguishable phylogenetically using PCR-RFLP techniques. These viruses are also considered potential agents of agroterrorism.

Contagious Ecthyma: Contagious ecthyma (contagious pustular dermatitis, orf, sore mouth) is a common localized infection of young sheep and goats caused by a parapoxvirus with worldwide distribution. Less commonly, humans, cattle, wild ungulates, and dogs are infected. Morbidity in lambs is usually great, and although mortality is usually low, it can approach 15% in lambs. Lesions are initiated by abrasions from pasture grasses or forage, begin at the commissures of the mouth, and spread to the lips (Fig. 17-43), oral mucosa, eyelids, and feet. Lambs can transfer the virus to the teats of ewes, and the lesions can spread to the skin of the udder. Contagious ecthyma is economically important as the result of weight loss in lambs that are reluctant to eat because of the pain associated with oral and perioral lesions. Pathogenesis of lesion formation and gross and microscopic features are consistent with the typical poxvirus lesions (see previous discussion and Fig. 17-31), except that the vesicle stage is very brief, the ulcer and crust stage persists and is clinically prominent, and the epidermis is markedly hyperplastic. Inclusion bodies are only briefly detectable histologically at the vesicular stage.

Swinepox: Pox lesions in pigs are caused by the host-specific poxvirus Suipoxvirus (swinepox). Normally, swinepox is transmitted by contact, although transplacental infection has not been ruled out. The sucking louse Haematopinus suis often acts as a mechanical vector and assists infection by causing skin trauma. The virus persists in dried crusts from infected animals. The pathogenesis of lesion formation and morphology of the gross and histologic lesions are consistent with the typical pox infection. The gross lesions typically affect the ventral and lateral abdomen, lateral thorax, and medial foreleg and thigh. Occasionally, lesions on the dorsum predominate. Lesions can be generalized and rarely involve the oral mucosa, pharynx, esophagus, stomach, trachea, and bronchi. The erythematous papules usually transform into umbilicated pustules without a significant vesicular stage (Fig. 17-44). The inflammatory crust eventually sheds to leave a white scar. The disease occurs worldwide and is endemic to areas of intensive swine production. The disease affects young, growing piglets and is mild with very low mortality.

Bovine Herpesvirus 2: Bovine herpesvirus 2, a dermatotropic virus (Allerton virus), can cause generalized disease (pseudo–lumpy skin disease) or as seen in the US, localized infection of the teat called bovine ulcerative mammillitis (bovine herpes mammillitis). Mammillitis is inflammation of the teat or nipple. Localized infection occurs more commonly in lactating dairy cows but can develop in beef cows, pregnant heifers, and suckling calves. Trauma is implicated in the pathogenesis because normal skin is resistant to viral penetration. The pathogenesis of lesion formation was discussed earlier. Bovine ulcerative mammillitis is economically important because of decreased milk production and secondary bacterial mastitis. Lesions develop on the teats and skin of the nearby udder or occasionally the perineum. Suckling calves develop lesions on the muzzle (nose).

Bovine Herpesvirus 4: Bovine herpesvirus 4 (bovine herpes mammary pustular dermatitis) causes a similar but milder disease than the localized form of bovine herpesvirus 2.

Feline Ulcerative Facial Dermatitis and Stomatitis: Feline herpesvirus 1 is an uncommon cause of ulcerative, often persistent, facial dermatitis or stomatitis in cats of various ages and sexes. Glucocorticoid therapy or stresses, such as overcrowding, are thought to play a role in lesion development. Most lesions develop under circumstances suggesting reactivation of latent herpesvirus infection. The pathogenesis is typical of that described for herpesviruses in the previous section. Gross lesions are ulcerative and crusted (see Table 17-3). Histologically, there is extensive necrosis of the epidermal, follicular, and sometimes sebaceous gland epithelium accompanied by prominent mixed dermal inflammation that frequently includes numerous eosinophils. Follicular epithelium can be destroyed, and free keratin in the dermis is associated with eosinophils and foci of eosinophil degranulation bordering collagen fibers and collagen degeneration. Large amphophilic or hyaline intranuclear inclusions are present in the surface and adnexal epithelium. Inclusion bodies are often easily overlooked, variable in number, and sometimes present in small rafts of epithelial cells surrounded by necrotic debris. The lesions are different from those previously reported in domestic cats in that they persist and are limited to the skin of the face or oral mucosa and often have significant eosinophilic inflammation. The inflammation in feline herpesvirus dermatitis overlaps with that of the hypersensitivity reactions, including mosquito bite hypersensitivity, and also with that of eosinophilic ulcers, thus warranting close scrutiny of eosinophilic necrotizing cutaneous lesions for intranuclear inclusion bodies.

Superficial Pustular Dermatitis: Superficial pustular dermatitis, typically caused by staphylococci, encompasses several syndromes including impetigo in a variety of animal species, exudative epidermitis in pigs, and superficial pyoderma in dogs. Pathogenicity may correlate with various proteins and toxins produced by the bacteria and thought to act as virulence factors. One of the factors that has come under recent scrutiny includes the exfoliative toxins. These toxins have been isolated from strains of Staphylococcus aureus in humans with impetigo, an acute contagious superficial bacterial skin infection that usually affects children and is characterized by vesicles and pustules that form yellowish crusts. In addition, similar exfoliative toxins have been identified as a source of another skin condition usually affecting infants and children, termed staphylococcal scalded-skin syndrome. In impetigo and staphylococcal scalded-skin syndrome, it has been shown that virulent forms of S. aureus produce exfoliative toxins that cause the loss of adhesion of keratinocytes in the superficial epidermis. These toxins are glutamate-specific serine proteases that cleave a single peptide bond in desmoglein 1, present in the extracellular protein core of the desmosome. The separation of these superficial keratinocytes results in intraepidermal splitting and initiation of lesion development in these infections. In impetigo, the S. aureus that produce exfoliative toxins can be isolated from the intact pustules. In contrast, in staphylococcal scalded-skin syndrome, there are generalized blisters and superficial exfoliation of the stratum corneum, but cultures from intact vesicles usually are negative for exotoxin producing S. aureus. It appears that the exfoliative toxins are produced in a distant area of infection and reach the skin via the bloodstream (a process called toxemia) where they cause the vesicular and exfoliative lesions. Investigative studies in two domestic species (pigs and dogs) suggest that a similar pathogenic mechanism involving exfoliative toxins may play a role in development of superficial pustular dermatitis caused by staphylococci. For example, it has been shown that Staphylococcus hyicus, which causes exudative epidermitis in piglets, produces an exfoliative toxin that can cleave swine desmoglein 1, and produce cutaneous exfoliation similar to that in pigs with exudative epidermitis. Similarly, an exfoliative toxin isolated from strains of Staphylococcus intermedius (pseudintermedius) from dogs with pyoderma has caused cutaneous exfoliation when injected into the skin of dogs. In addition, the exfoliative toxin gene has been identified in Staphylococcus intermedius and Staphylococcus pseudintermedius isolated from skin, wound, and ear infections in dogs suggesting a role for the toxin in pathogenicity. Although the exfoliative toxins in canine pyoderma have not been fully characterized, these findings suggest that some strains of Staphylococcus sp. in dogs and Staphylococcus hyicus in pigs may cause superficial bacterial infections via a pathologic mechanism involving exfoliative toxins. Further studies are necessary to determine if exfoliative toxins or other virulence factors contribute to the development of superficial pyoderma in other species.

Impetigo: Impetigo is observed most commonly in cows, ewes, does, and dogs and is usually caused by coagulase-positive Staphylococcus sp. Predisposing factors, such as cutaneous abrasions, viral infections, increased moisture, and poor nutrition, may contribute. Lesions of impetigo in cows, does, and ewes, occur predominantly on the ventral abdomen, perineum, medial thigh, vulva, ventral tail, teats, and udder. In dogs, lesions are largely in nonhaired ventral skin. Prepubescent puppies are usually healthy otherwise, but older dogs with impetigo often have underlying disease, including immunosuppression associated with hyperadrenocorticism. Gross lesions consist of nonfollicular pustules that develop into crusts. The microscopic lesion is a nonfollicular neutrophilic subcorneal pustule. In bullous impetigo, a more severe condition occurring in older dogs with underlying disease, the lesions are large interfollicular flaccid pustules (bullae) that when ruptured lead to more extensive loss of the superficial epidermis. Acantholytic cells may be present in the pustules, probably the result of the cleavage of desmoglein 1 by the exfoliative toxin, thus requiring differentiation between impetigo and pemphigus foliaceous (see Fig. 17-15). The presence of coccoid bacteria within intact pustules can help provide support for a bacterial origin of the lesions. Perivascular to interstitial neutrophilic to mixed mononuclear dermal inflammation is present.

Exudative Epidermitis of Pigs (Greasy Pig Disease): Exudative epidermitis, usually caused by Staphylococcus hyicus, is an acute, often fatal, dermatitis of neonatal piglets, but a mild disease in older piglets. Predisposing factors include cutaneous lacerations and poor nutrition. In piglets, brownish exudates develop around the eyes, pinnae, snout, chin, and medial legs and spread to the ventral thorax and abdomen, giving the animal an overall “greasy” appearance (Fig. 17-47). The lesions rapidly coalesce and become generalized, resulting in greasy, malodorous exudates covering an erythematous skin. If piglets survive, the exudate hardens, cracks, and forms fissures. Subacute disease develops gradually in older piglets, and lesions are generally localized to the skin of the face, pinnae, and periocular regions. Grossly, the epidermis is thickened with scaling. The early histopathologic lesion is subcorneal pustular dermatitis, which extends to the hair follicle, resulting in superficial suppurative folliculitis. In the fully developed lesion, the epidermis is hyperplastic and has thick crusts of keratin, microabscesses, and cocci. The term exudative epidermitis is descriptive of this condition as the inflammatory changes largely involve the epidermis, and there is an accumulation of exudates on the surface. The dermis is congested and edematous. In the early stages, the dermatitis is superficial and perivascular with neutrophils and eosinophils, and in the later stages is perivascular and mononuclear.

Canine Superficial Pyoderma (Superficial Spreading Pyoderma): Superficial spreading pyoderma is a common, often pruritic, superficial bacterial infection in dogs caused by Staphylococcus pseudintermedius. Clinical lesions are most frequently recognized in the glabrous ventral thoracic and abdominal skin but can affect the haired skin of the dorsal and lateral trunk as well. Early clinical lesions include erythematous macules, papules, and transient pustules. Older clinical lesions include epidermal collarettes, crusts, alopecia, and hyperpigmentation. Early microscopic lesions are superficial, spongiotic epidermal pustules that rapidly crust and form basophilic debris, often with cocci, on the surface of the epidermis. This basophilic debris can dissect peripherally (laterally) between the epidermis and stratum corneum and is thought to form the rim of scale that clinically represents the epidermal collarette. In this way, the lesions “spread” outwardly from the initial lesion. Occasionally, superficial spreading pyoderma can originate from superficial folliculitis where follicular pustular formation is minor and epidermal collarette formation more prominent. Dermal lesions include superficial perivascular to interstitial accumulations of neutrophils, eosinophils, and mixed mononuclear cells. Some dogs have neutrophilic vasculitis involving superficial venules possibly caused by immune-complex deposition, a feature suggesting a hypersensitivity response to bacterial antigens. Dermal congestion and edema are usually present.

Mucocutaneous Pyoderma: Mucocutaneous pyoderma is a putative bacterial infection of mucocutaneous junctional skin in dogs. Antibiotic responsiveness suggests that bacteria contribute, however, the etiology is likely more complex and may involve immunologic factors as well. A variety of breeds are affected, but the German shepherd breed is thought to be predisposed. The pathogenesis is unknown. Lesions consist of erythema, swelling, and crusting, and in severe cases, ulceration. Depigmentation may develop in chronic cases. Lesions are most common on mucocutaneous skin of the lips, but mucocutaneous skin of prepuce, vulva, and anus can be affected. Histologic lesions include a dense band of lymphoplasmacytic inflammation with variable numbers of neutrophils at the epidermal dermal junction (lichenoid inflammation), typically without basal cell degeneration. Other features include spongiosis and cellular exocytosis into the epidermis, neutrophilic pustular crusts, and folliculitis of adjacent follicles. Over time, pigmentary incontinence develops. Although classic cases are said not to have basal cell degeneration, apoptotic keratinocytes above the basal layer can be present. In addition, there can be interface inflammation obscuring the epidermal-dermal interface. These features prevent definitive histologic differentiation from discoid lupus erythematosus.

Dermatophilosis (Streptothrichosis): Dermatophilosis, caused by Dermatophilus congolensis, is characterized by crusty cutaneous lesions (Fig. 17-48) and occurs in horses, cattle, and sheep more often than goats, pigs, dogs, or cats. The bacterium is transmitted by carrier animals and is more common in tropical and subtropical climates and during wet weather, thus the layman’s term rain rot. Lesions tend to develop on the dorsum of the back and distal extremities and after epidermal irritation from ectoparasites, trauma, or prolonged wetting of the skin, hair, or wool, which allows penetration of the damaged epidermis by the Dermatophilus “zoospore.”

The bacterium grows in the outer root sheath of the hair follicle and superficial epidermis and produces Gram-positive filamentous branches that subdivide longitudinally and transversely (see Fig. 17-48). These bacteria stimulate an acute inflammatory response in which neutrophils migrate from superficial vessels into the dermis and through the epidermis to form intraepidermal microabscesses. The inflammation inhibits further penetration of the bacterium. However, residual bacterial organisms subsequently invade the newly regenerated epidermis. Thus repeated cycles of bacterial growth, inflammation, and epidermal regeneration result in the formation of the multilaminated pustular crusts. Grossly, lesions consist of papules, pustules, and thick crusts that can coalesce and mat the hair or wool (see Fig. 17-48). The microscopic lesions consist of hyperplastic superficial perivascular dermatitis with multilaminated crusts of alternating layers of keratin and neutrophils covering the skin surface. Samples of crusts obtained by biopsy are necessary to identify organisms and make a definitive diagnosis.

Ovine Fleece Rot: Ovine fleece rot is a superficial bacterial dermatitis usually caused by excessive moisture (usually in the form of rain) that penetrates the fleece (wool), wets the skin, and causes proliferation of Pseudomonas spp. Approximately 1 week of continual wetting is usually sufficient to cause marked proliferation of the bacteria on the skin and in the fleece. This is followed by an acute inflammatory response with serum exudation and matting of the fleece. The fleece is also discolored because of production of pigments (chromogens) by the Pseudomonas bacteria and has a rotten odor. Microscopic lesions include epidermal pustular dermatitis and superficial folliculitis. Ovine fleece rot is important economically because the malodor attracts flies, predisposing to myiasis (infestation of tissue by the larvae of dipterous flies), and the value of the affected wool is reduced.

Superficial Bacterial Folliculitis: Staphylococcal folliculitis and furunculosis are discussed with deep bacterial infections in the next section.

Bacterial Folliculitis and Furunculosis (Table 17-8): Infection of the hair follicle can be superficial or deep. Superficial infections involve the follicular infundibulum but can spread to involve the deeper portions of the follicle (the infundibulum and below). Mild-to-moderate folliculitis without furunculosis can resolve completely with appropriate antibiotic therapy. However, untreated or severe folliculitis can progress to involve deeper aspects of the follicle and result in follicular distention with rupture (furunculosis) and release of follicular contents (hair, follicular stratum corneum, and bacteria) into the dermis and sometimes subcutis. The bacteria proliferate in the deep dermis and subcutis and can reach draining lymph nodes. Draining tracts often develop as a foreign body response to extruded follicular contents (e.g., hair and follicular stratum corneum). Thus the infection and severe inflammation spread into the surrounding dermis and subcutis, resulting in the need for intensive long-term treatment and increasing the potential for systemic infection and local scarring.

Numerous bacteria can cause folliculitis and furunculosis, but staphylococcal bacteria are the most commonly involved. Staphylococcal folliculitis and furunculosis develop most commonly in the dog (see Figs. 17-26 and 17-27), frequently affect the horse, sheep, and goat but are uncommon in the cow, pig, and cat.

In horses, lesions develop most commonly in association with tack, especially on the skin of the saddle area, the tail, or the caudal aspect of the pastern (proximal interphalangeal articulation) or fetlock (metacarpophalangeal articulation). When the skin of the pastern or fetlock is involved, the condition is called equine pastern folliculitis (also known as grease heel, scratches). Equine pastern folliculitis is a complex disorder in which secondary staphylococcal folliculitis plays a role. Predisposing factors are numerous and include excessive moisture, trauma, and contact dermatitis. Also, many other conditions affect the pastern skin in horses, including immune-mediated diseases (pemphigus foliaceous, vasculitis, or photosensitization), other infections (dermatophilosis, dermatophytosis), and mite infestation (Chorioptes sp.), necessitating an early thorough clinical evaluation and sometimes microbiologic or histopathologic evaluation to differentiate staphylococcal folliculitis of the skin of the pastern from these other disease processes. In severe chronic lesions, initiating causes may no longer be identifiable.

In adult sheep, lesions develop on the face, especially around the eyes, or on the limbs or teats. In otherwise healthy lambs, mild lesions develop most commonly on the lips and perineum and usually spontaneously regress. In goats, the face, pinnae, distal limbs, and glabrous areas of the udder, ventral abdomen, medial thighs, and perineum are most commonly affected.

In dogs, lesions are localized or generalized and develop on the dorsal nose, pressure points, interdigital areas, and chin. Other cutaneous areas can also be affected, especially if predisposing conditions (e.g., follicular dysplasia, cornification disorders, or demodicosis) are present. Deep pyoderma of adult German shepherd dogs (German shepherd folliculitis, furunculosis, and cellulitis) is a unique deep pyoderma with an apparent genetic predisposition. Lesions are located on the dorsal lumbosacral, ventral abdominal, and thigh areas. Hypersensitivity to the bites of fleas or alterations in immune or neutrophil function have been proposed as predisposing causes, but most of these potential causes have been discounted. Deep folliculitis and furunculosis, especially on the cheek area or neck of some large-breed dogs (golden and Labrador retriever, Saint Bernard, and Newfoundland), can clinically resemble superficial pyotraumatic dermatitis (acute moist dermatitis), belying the deep nature of the lesions.

Postgrooming furunculosis is an uncommon but acute, severe, and painful form of furunculosis in the dog that is believed to be associated with grooming. A variety of bacteria have been cultured from lesions, including Staphylococcus intermedius (pseudintermedius), Pseudomonas aeruginosa, Escherichia coli, and Proteus sp.

Grossly the lesions of superficial folliculitis include papules, crusted papules, pustules, epidermal collarettes, and alopecia. Deep folliculitis can have similar lesions plus hemorrhagic bullae, nodules, and draining tracts. The microscopic patterns include superficial or deep luminal folliculitis, pyogranulomatous furunculosis, draining sinuses, and occasionally, panniculitis. Microscopic lesions include suppurative luminal folliculitis with follicular distention often in conjunction with furunculosis. Pyogranulomatous dermatitis in response to release of follicular contents is often severe, may efface the dermal architecture, extend into the deep dermis and panniculus, and form tracts that drain to the surface. Scarring can lead to loss of adnexal structures and permanent alopecia localized to affected skin.

Subcutaneous Abscesses: Subcutaneous abscesses are localized collections of purulent exudate located within the dermis and subcutis. Abscesses are common in cats because of the frequency of bacterial contamination of puncture wounds. Abscesses also are common in large animals. In addition to puncture wounds, other predisposing causes include foreign bodies, injections, and shearing and clipping wounds. Granulation tissue or mature fibrous connective tissue borders the exudate. Subcutaneous abscesses frequently rupture and drain spontaneously, and heal by scarring. A wide variety of bacteria can cause subcutaneous abscesses. Commonly isolated bacteria include Pasteurella multocida (dog and cat bite wounds), Corynebacterium pseudotuberculosis (horses, sheep, and goats), and Arcanobacterium pyogenes (sheep, goats, cattle, pigs). Other frequently isolated bacteria include β-hemolytic streptococci, Fusobacterium sp., Peptostreptococcus sp., Bacteroides sp., Staphylococcus sp., and Clostridium sp.

Mycobacterial Granulomas: Mycobacterial organisms produce granulomatous to pyogranulomatous dermatitis and panniculitis in many species of animals, particularly cats and less frequently dogs and cattle. The majority of mycobacteria are intracellular pathogens that are able to persist in tissue by entering macrophages. Many are able to survive and replicate within the macrophages by inhibiting fusion with lysosomes. Tissue destruction results from persistence of antigen in the tissue and a cell-mediated inflammatory response. Infection occurs with obligate pathogens that require a vertebrate host to multiply and saprophytes in the environment that occasionally cause opportunistic infections. Infection occurs with the tuberculosis group considered to be obligate pathogens (Mycobacterium tuberculosis, Mycobacterium bovis), the leprosy group considered to be obligate pathogens (Mycobacterium lepraemurium), and the opportunistic group considered to be saprophytes or facultative pathogens (subdivided based on growth rate and pigment production). Rapid-growing opportunistic organisms (Mycobacterium fortuitum, Mycobacterium smegmatis, Mycobacterium chelonae, Mycobacterium abscessus, and Mycobacterium thermoresistible) and slow-growing opportunistic organisms (Mycobacterium avium-intracellulare complex, Mycobacterium kansasii, and Mycobacterium ulcerans) are inhabitants of soil, water, and decomposing vegetation, and infection tends to occur via wound contamination or traumatic implantation. To avoid confusion in terminology, by convention, infections caused by Mycobacterium tuberculosis and Mycobacterium bovis are referred to as tuberculosis. In contrast, infections caused by other mycobacterial agents are referred to as mycobacteriosis, which is sometimes further defined by the group of agents involved (e.g., atypical, opportunistic, or avian).

Mycobacterial infection is more common with the rapidly growing opportunistic mycobacteria (also called atypical mycobacteria), and infections are more common in cats, in which lesions are characterized by recurrent nodules, with draining sinuses frequently located in the dermis and subcutis of the inguinal area. The microscopic lesions are characterized by pyogranulomatous inflammation. Organisms are more often found extracellularly in clear spaces sometimes lined by neutrophils (Fig. 17-49). Infections with the slow-growing, opportunistic mycobacteria are more commonly disseminated (not limited to the skin) and resemble those caused by Mycobacterium tuberculosis.

In cattle, cutaneous infections with opportunistic mycobacterial organisms, historically called skin tuberculosis, occur as single or multiple nodules 1 to 8 cm in diameter in the dermis and subcutis, particularly of the lower legs. But lesions can spread to the thighs, proximal forelimbs, shoulders, and abdomen through skin lymphatics. The skin of the udder is sometimes involved. The lymph nodes are unaffected. The causative organisms are thought to be saprophytic atypical mycobacteria that probably enter through cutaneous abrasions. In most of these infections, the specific mycobacteria have not been identified by culture, but Mycobacterium kansasii has been identified in a few cases. A more appropriate name for this condition is bovine cutaneous opportunistic mycobacteriosis. Clinical lesions are either firm or fluctuant nodules connected by thin cords of tissue that represent inflamed lymphatic channels (lymphangitis). The firm nodules consist of pyogranulomatous inflammation with fibrosis and sometimes mineralization. The fluctuant nodules are thick-walled abscesses that can ulcerate, rupture, and drain thick, tan exudate. Small lesions can spontaneously resolve, but larger lesions are persistent. This disease became apparent during the time of intense tuberculosis eradication efforts because infection with these opportunistic mycobacterial organisms can cause false-positive reactions to bovine tuberculin tests. Bovine cutaneous opportunistic mycobacteriosis is much less commonly identified in current times, partly because the prevalence of and thus testing for bovine tuberculosis has been reduced.

Feline leprosy, caused by Mycobacterium lepraemurium and probably other mycobacterial organisms (see later discussion) develops in cats living in cold, wet areas of the world, including the northwestern US and Canada. Mode of transmission is not known, but bites of cats or rodents, soil contamination of cutaneous wounds, or possible transmission via biting insect vectors may be involved. Mycobacterium lepraemurium does not grow in culture using standard techniques but has been identified by PCR with DNA sequencing. These molecular techniques have resulted in the identification of other, potentially causative, mycobacterial agents (i.e., Mycobacterium visibilis) in cutaneous lesions clinically consistent with feline leprosy. Additional mycobacterial species will likely be identified in lesional tissue in the future. Lesions develop most commonly on the head, neck, and limbs but can occur anywhere (Fig. 17-50). Histologically, two distinct morphologic patterns of inflammation are present. In one, there is diffuse granulomatous inflammation without necrosis and with large numbers of intracellular acid-fast bacilli; some of these infections have been caused by Mycobacterium visibilis. In the other pattern, there are granulomas with central necrosis surrounded by a zone of lymphocytes. Few to moderate numbers of acid-fast bacilli are generally limited to the areas of necrosis. Some of these infections have been caused by Mycobacterium lepraemurium.

Rarely, a nodular granulomatous dermatitis caused by acid-fast bacilli develops on the head, dorsal pinnae, or other distal extremities in dogs, often with short-hair coats (canine leproid granuloma syndrome). Saprophytic mycobacterial organisms transmitted via the bites of flies are thought to be the cause of the syndrome. The dogs are healthy otherwise, and cultures are negative.

Cutaneous infections caused by Mycobacterium tuberculosis and Mycobacterium bovis are rare; alimentary and pulmonary infections are more common, but skin infections can develop alone or in combination with disseminated infection. Tentative diagnosis of mycobacterial infections is made by considering the animal species affected, clinical lesion appearance and location, and cytologic or histopathologic detection of acid-fast bacilli. In the past, culture was required for definitive identification of the organism involved. The acid-fast bacilli can be rare in tissue sections, especially with the saprophytic opportunistic agents, and some organisms, such as those in feline leprosy and canine leproid granuloma syndrome, are exceedingly difficult to grow on culture media; thus diagnosis is challenging. Fortunately the need for cultural identification is being reduced by use of immunohistochemistry and PCR techniques that can identify the organisms or their genetic material in tissue and can be completed within a few days. The use of genetic techniques is enhancing studies of mycobacterial diseases in humans and animals. It is likely that taxonomy of mycobacterial diseases will be refined, based on the use of the genetic techniques.

Bacterial Granulomatous Dermatitis Caused by Other Bacteria: Botryomycosis is a term for a granulomatous dermatitis caused by nonfilamentous bacteria, typically Staphylococcus spp., Streptococcus spp., Pseudomonas aeruginosa, Actinobacillus lignieresii, and Proteus spp. In botryomycosis, these bacteria form small yellow “sulfur” granules, which consist of centrally located bacterial colonies surrounded by radiating club-shaped bodies of homogeneous eosinophilic material termed Splendore-Hoeppli material. This material is considered to be antigen-antibody complexes. Clinically, the lesions are progressive nodular masses located in cutaneous or subcutaneous areas that are composed of granulomatous inflammation with the embedded bacterial colonies bordered by the Splendore-Hoeppli material. Histologic differential diagnoses of botryomycosis include infections with filamentous bacteria that cause similar nodular masses (actinomycotic mycetomas) and nodular masses caused by fungi (eumycotic mycetomas).

Filamentous bacteria also cause bacterial granulomatous dermatitis with granules bordered by Splendore-Hoeppli material and are differentiated from botryomycosis by Gram staining and culture. The bacteria are introduced through traumatic injury; are Gram-positive, filamentous, and branching; and include various species of Nocardia and Actinomyces. Other actinomycetes (e.g., Actinomadura, Streptomyces) can also contribute. The granules contain mycelial filaments that are 1 µm or less in diameter. Nocardia spp. have a limited tendency to clump together; thus they typically do not form granules. The clinical lesions are progressive nodular cutaneous and subcutaneous masses, often with draining sinuses, which can extend into and involve underlying bone. These nodular masses are called actinomycotic mycetomas. Histologic lesions are nodular areas of granulomatous inflammation with abundant fibrosis and embedded bacterial colonies bordered by Splendore-Hoeppli material. Histologic differential diagnoses include botryomycosis and mycetomas caused by fungi (see the discussion of eumycotic mycetomas in the section on Subcutaneous Mycoses). A classic example of actinomycotic mycetoma in cattle is the so-called lumpy jaw, wherein the infection begins via traumatic implantation of Actinomyces bovis into the mandibular mucosa (rather than skin), which progresses to involve mandibular bone (see Chapter 16).

Proliferative Pododermatitis (Canker): Proliferative pododermatitis in horses, also known as canker, is a painful, proliferative, and inflammatory condition of the hoof. The cause of proliferative pododermatitis in the horse is unknown, but the disease appears to be polymicrobial in nature. The condition has been associated with the presence of a variety of Gram-positive and Gram-negative bacteria and, in some cases, with tissue colonization by an as-of-yet unidentified species of spirochetes. Bacteroides sp. and Fusobacterium necrophorum have been isolated in some cases. The pathogenesis of lesion formation is not yet known but moisture and unclean environments often predispose to the condition. It most often affects the rear feet of draft horses but can affect any foot or multiple feet of any breed of horse and even those kept in dry, clean environments. Initial lesions consist of a focal raised pink lesion resembling granulation tissue that bleeds easily and is surrounded by a gray or brown zone located in the frog. This lesion will progress to excessive, soft, white filiform papillomatous-like proliferations emanating from the frog, bars, sole, and sometimes hoof wall of the affected foot. Some cases will be foul smelling and have surface collections of caseous white exudate. Microscopically, areas of marked papillary epidermal hyperplasia associated with hyperkeratosis and neutrophilic infiltrates of the epidermis are present. The outer stratum spinosum may have areas of marked ballooning degeneration. The dermis contains superficial neutrophilic to lymphoplasmacytic infiltrates. A mixed population of Gram-positive and Gram-negative bacteria can be identified on the surface epithelium, but the organisms are not consistently associated with the areas of inflammation. In some cases, spirochetes have been identified within the proliferative epidermis.

Necrotizing Pododermatitis (Thrush): Necrotizing pododermatitis of the horse, commonly known as thrush, is a painful, necrotizing condition of the frog and central and lateral sulci of the hoof. It is caused by the anaerobic bacterium, Fusobacterium necrophorum. Trapping of moist and bacterial-ridden materials such as manure and mud lead to softening of the tissue of the frog and allow colonization by the bacterium. The condition most often affects the hind feet but can affect all hooves. Initial lesions consist of black discoloration and softening of the frog accompanied by a very foul odor. Over time, the black discoloring and softening spread to involve deeper tissues and more areas of the frog. The lesions consist of foul-smelling black exudate and loss of frog tissue. In chronic severe cases, the distal limb can be swollen and the frog becomes spongy and ragged, easily shreds, and can bleed. There can be long-term atrophy of the frog as tissue disintegration occurs. Gross characteristics are usually diagnostic, but microscopic lesions consist of degeneration, necrosis, and suppurative inflammation of the frog epithelium and sometimes of deeper tissues. Bacterial colonization of the tissues is usually present.

Papillomatous Digital Dermatitis: Papillomatous digital dermatitis, also known as foot warts or hairy heel warts, is a painful, contagious dermatitis of the feet of cattle. It occurs worldwide. The cause of papillomatous digital dermatitis is unknown, but the disease appears to be polymicrobial, with spirochetes belonging to the genus Treponema playing a predominant role. The condition is also usually associated with management conditions in which the feet of cattle remain wet for prolonged periods. The pathogenesis of lesion formation is not yet known. Papillomatous digital dermatitis most commonly affects the skin proximal and adjacent to the interdigital space at the caudal (plantar) aspect of the hind feet. Early gross lesions are well-circumscribed, round-to-oval, red plaques up to 6 cm in diameter with a moist granular surface prone to bleeding and with a very strong, pungent odor. Lesions are partially to completely alopecic and can be bordered by hypertrophied hairs two to three times longer than normal. Microscopically, this corresponds to areas of mild epidermal hyperplasia with foci of erosion, necrosis, ballooning degeneration, and microabscesses. The dermis contains minimal perivascular inflammation. Mixed bacteria can be present in the outer necrotic debris, but only spirochetes are present in the deeper viable epidermis. The lesions become progressively more proliferative and less painful with time. Mature lesions are irregular wartlike growths or filamentous papillae that measure 0.5 to 1.0 mm in diameter and 1 mm to 3 cm in length and are pale yellow, gray, or brown. Histologically the older lesions are composed of frondlike projections or plaques of markedly hyperplastic epidermis with parakeratosis and hyperkeratosis. Foci of necrosis and hemorrhage, ballooning degeneration, and aggregates of neutrophils are scattered throughout the hyperplastic epidermis (Fig. 17-52). At this later stage, inflammation is more intense in the dermis and plasma cells can be numerous. Lesions are painful, forcing the animal to shift its weight to the toe of the affected foot, which results in a smooth contour to the toe (clubbing) and atrophy of the bulbs of the heels.

Papillomatous digital dermatitis is economically important because it frequently causes moderate to severe lameness that results in weight loss, decreased milk production, and poor reproductive performance. The vast majority of cases are in dairy cows, but the infection has also been reported in beef cattle. Although the disease occurs in cattle of all ages, the highest incidence appears to be in replacement dairy heifers.

Necrobacillosis of Cattle: Necrobacillosis (foul-in-the-foot) of cattle occurs secondary to trauma to the interdigital skin and is caused by Fusobacterium necrophorum and Bacteroides melaninogenicus. There is lameness with an interdigital dermatitis and cellulitis with fissures and necrosis that may extend into the deeper structures of the foot such as the distal phalanx, distal sesamoid bone, distal interphalangeal joint, and tendons.

Contagious Foot Rot: Contagious foot rot in cattle and sheep develops when predisposing factors, such as moisture and trauma, damage the interdigital epidermis and allow colonization by a variety of microorganisms, including Fusobacterium necrophorum from skin or feces. If the obligate anaerobic bacteria Dichelobacter nodosus is present in interdigital skin, foot rot will develop. Contagious foot rot is a synergistic bacterial infection principally involving D. nodosus (elaborates proteases and growth-enhancing factors, which aid bacterial penetration of the epidermis and bacterial growth) and F. necrophorum (responsible for most of the necrosis and inflammation). Contagious foot rot in sheep occurs in virulent and benign forms, whereas foot rot in cattle occurs in a benign form. The virulent form of foot rot in sheep is caused by more virulent D. nodosus that produces significantly more proteolytic enzymes (proteases including elastase), allowing more bacterial penetration of the epidermis. The proteases in the virulent form also tend to be more heat stable. Virulent foot rot is more persistent (and can last for more than 1 year if not treated), affects a high percentage of sheep, affects more than one foot, and can result in death of sheep because of emaciation as a result of severe pain and reluctance to graze. Early lesions of virulent foot rot begin in the interdigital axial (inner) bulbar notch, affect both digits, and consist of red, moist, and swollen eroded skin. The infection spreads around the bulb of the heel to the epidermal matrix of the hoof and results in a malodorous exudate that separates the horn from the interdigital skin. Lesions progress to the bulb and sole and finally to the axial and abaxial (outer) surfaces of the hoof wall. The germinal epithelium is not destroyed and regeneration is attempted, but the new horn is destroyed. In chronic infections, hooves can become long and misshapen. Benign foot rot in sheep (foot scald) and benign foot rot in cattle are mild, confined to interdigital skin, and can have slight separation of the horn of the heel; also the hoof can overgrow.

Necrobacillosis of Sheep: Necrobacillosis of the foot in sheep includes ovine interdigital dermatitis and foot abscesses. Ovine interdigital dermatitis is an acute necrotizing dermatitis that clinically is similar to benign foot rot. Ovine interdigital dermatitis is differentiated from foot rot by the failure to demonstrate Dichelobacter nodosus in smears or cultures of exudate. Foot abscesses include heel abscesses (infective bulbar necrosis) and toe abscesses (lamellar abscesses). Foot abscesses are more common in wet seasons and in heavy adult sheep. In addition to Fusobacterium necrophorum, Arcanobacterium pyogenes (Actinomyces pyogenes) may be isolated from the lesions.

Contagious Ovine Digital Dermatitis: Contagious ovine digital dermatitis (CODD) is a newly documented and severe infection of the ovine hoof reported in the United Kingdom and rarely in Ireland. The disease is of major animal welfare concern. The cause of this form of digital dermatitis in sheep is not yet completely defined but thought to be polymicrobial, with Dichelobacter nodosus and possible spirochetes belonging to the genus Treponema playing a role. The condition differs from typical contagious foot rot in sheep in that the lesions have an acute onset, are more severe, and are characterized by ulcerative lesions of the coronary band and hoof wall in some cases (contagious foot rot lesions affect the heel and interdigital region). CODD also fails to respond to conventional treatment and is not preventable by vaccines. The pathogenesis of lesion formation is not yet known. Early gross lesions consist of ulcers at the coronary band and progress to loosening, and possible shedding, of the hoof wall. Interdigital lesions are not reported. Microscopic lesions have not been described.

Dermatophytoses: Dermatophytoses are fungal infections of the skin, hair, and claws of animals caused by taxonomically related fungi known as dermatophytes. Pathogenic genera include Epidermophyton, Microsporum, and Trichophyton. Dermatophytosis occurs worldwide, is the most important cutaneous (superficial) mycosis, and is common in humans and animals, especially cats. Superficial and cutaneous mycoses (dermatophytosis) are acquired by contact with infected animals or by contact with scales shed from infected animals. Dermatophytes are able to colonize the cornified structures (hair, claws) and the stratum corneum and cause disease without ever entering living tissue. Clinical disease in a dermatophyte infection is the result of the host’s reaction to the organism and its by-products. Dermatophytes are more contagious than other fungal infections, are more common in hot, humid environments, and young animals are more susceptible than adults. Animals kept in overcrowded, dirty, or damp areas and those with inadequate nutrition are also more susceptible. Fungal species that more commonly infect domestic animals are included in the genera Microsporum and Trichophyton. Epidermophyton is adapted to humans (anthropophilic) and rarely infects animals. Zoophilic dermatophytes (e.g., Microsporum canis) are primary animal pathogens but can infect humans. Microsporum canis is so well adapted, especially in long-haired, purebred cats that inapparent infections occur. Geophilic dermatophytes (e.g., Microsporum gypseum) occur in soil as saprophytes, but under favorable conditions can infect humans and animals if the integrity of the skin is broken or the host immune system is compromised.

Dermatophytes invade cornified tissues (stratum corneum, hair shafts, and claws) by producing proteolytic enzymes, which help them penetrate the surface lipid coat. The fungal hyphae invade the cornified tissue, and the hyphae break into chains of arthrospores. The products elaborated by the dermatophytes cause dermal irritation and damage to the epidermis. The fungal products and cytokines released from damaged keratinocytes result in epidermal hyperplasia (hyperkeratosis, parakeratosis, and acanthosis) and dermal inflammation. Inflammatory cells arrive via the superficial vessels (superficial perivascular dermatitis) and, subsequently, migrate through the epidermal layers (exocytosis) to the invaded keratinized layers, forming intracorneal microabscesses. Exocytosis of inflammatory cells into follicular walls and lumens results in mural and luminal folliculitis and, if the follicular wall is destroyed, in furunculosis. Bacterial infection increases the severity of the folliculitis and furunculosis. Gross and microscopic lesions are highly variable and range from an asymptomatic infection to an eruptive nodular mass (kerion), to deep granulomatous nodular dermal and pannicular masses containing distorted fungal hyphae (pseudomycetoma), to discolored, malformed, friable, broken, or sloughed claws (onychomycosis).

Gross lesions in haired skin are often circular or irregularly shaped, scaly to crusty patches of alopecia (Fig. 17-53), which can coalesce to involve large portions of the body. Fungi tend to die in areas of inflammation in the center of lesions but are viable at the periphery, thus giving rise to the peripheral red ring and the term ringworm. Hair loss is caused by breakage of hair shafts and loss of hair shafts from inflamed follicles. Follicular papules and pustules can be present. In animals with severe furunculosis, the inflammation can extend into the deep dermis and subcutis leading to draining tracts. Microscopic patterns include perifolliculitis, luminal folliculitis, or furunculosis, and epidermal hyperplasia with intracorneal microabscesses. In many lesions, septate hyphae or spores are present in hair shafts and in the stratum corneum of the epidermis or follicles (Fig. 17-53, B).

Candidiasis: Candidiasis is a yeast infection caused by Candida sp., normal inhabitants of the skin and gastrointestinal tract (see Figs. 7-28 and 7-29). Infection occurs when host resistance is compromised. Infections with Candida sp. are rare in domestic animals and usually occur on mucous membranes and at mucocutaneous junctions. Gross lesions consist of exudative and pustular to ulcerative inflammation of the lips (cheilitis), oral mucosa (stomatitis), and external ear canal (otitis externa). Microscopic lesions consist of spongiotic neutrophilic pustular inflammation, parakeratosis, and ulceration with exudation. The yeast organisms are present in the superficial exudates.

Malassezia Dermatitis: Malassezia dermatitis is caused by Malassezia pachydermatis (Pityrosporum canis), a lipophilic yeast isolated from the normal external ear canal and skin. This yeast proliferates and causes clinical disease when the microclimate or host defenses are altered. Lesions can be regional (interdigital, otic, perianal, or intertriginous) or more generalized (Fig. 17-54). Grossly the lesions are erythematous, often hyperpigmented, lichenified, alopecic, and scaly. Microscopic lesions consist of hyperkeratosis, focal parakeratosis, variable spongiotic pustular dermatitis, acanthosis, and the presence of Malassezia pachydermatis within the surface keratin. Because Malassezia organisms can be lost during tissue processing, cytology is often a more reliable method of assessing the number of yeast present. Low numbers in histologic sections with lesions compatible with Malassezia dermatitis are often considered significant, especially with concurrent characteristic gross lesions (see Fig. 17-54).

Eumycotic Mycetomas: Eumycotic mycetomas develop most often in horses and dogs and are rare fungal infections resulting in progressive cutaneous and subcutaneous nodular enlargements of granulomatous inflammation that can have draining sinuses and that resemble botryomycosis and actinomycotic mycetomas. The portal of entry is through traumatic injury into the dermis or subcutis, and most of the fungi involved in these infections are saprophytes. Curvularia geniculata is the most commonly isolated fungus in animals; other fungal genera include Madurella, Acremonium, Pseudoallescheria, and Phaeococcus. Histologic lesions are nodular masses of granulomatous inflammation with fibrosis and exudate in which there are embedded granules composed of masses of septate, branching fungal hyphae measuring 2 to 4 µm in diameter. The granules vary in size, shape, color, and texture and are bordered by Splendore-Hoeppli material. Culture identifies the organism involved.

Dermatophytic Pseudomycetoma: Dermatophytic pseudomycetoma is a rare, deep dermal and subcutaneous infection, usually caused by Microsporum canis, that develops predominantly in Persian cats, suggesting the possibility of a specific genetic deficit in innate or adaptive immunity in this breed. It is presumed that follicles rupture, releasing dermatophytes into the subfollicular dermis. Gross lesions are similar to other subcutaneous mycoses. Microscopic lesions are in the subfollicular dermis or subcutis and consist of a granulomatous inflammatory response and intermixed aggregates of fungal hyphae with irregular dilations. Hair shafts within adjacent follicles contain Microsporum hyphae and spores.

Phaeohyphomycosis: Phaeohyphomycosis is a mycotic infection caused by species of pigmented fungi (dematiaceous) of a variety of genera that have dark-walled, septate hyphae. Genera include Alternaria, Drechslera, Exophiala, Phialophora, and others. These fungi are plant pathogens, soil saprophytes, or in some instances, normal flora that enter the skin at sites of trauma. Most of these infections remain localized to the skin and subcutaneous tissue, but they can spread to other tissue via lymphatic drainage in immunocompromised hosts. Grossly, lesions consist of alopecic or haired cutaneous nodules that can ulcerate and drain (Fig. 17-55). Microscopically, lesions consist of foci of granulomatous, pyogranulomatous, or lymphocyte-rich granulomatous inflammation containing pigmented fungal organisms. Culture is necessary for specific identification of the fungus involved. Subcutaneous phaeohyphomycosis occurs in horses, cattle, cats, and rarely dogs. Hyalohyphomycosis (paecilomycosis) is similar to phaeohyphomycosis except that the fungal hyphae in tissue are nonpigmented (nondematiaceous). Organisms include Pseudoallescheria sp., Acremonium sp., Fusarium sp., Paecilomyces sp., and Geotrichum sp.

Sporotrichosis: Sporotrichosis, caused by Sporothrix schenckii, is an uncommon mycosis that occurs in cutaneous, cutaneolymphatic, and disseminated forms in horses, mules, cattle, cats, and dogs. Sporothrix schenckii is a saprophytic dimorphic fungus found in moist organic debris, and entry into the body is by traumatic implantation. Ulcerated cutaneous nodules and fistulas develop at the site of inoculation and along lymph vessels (lymphangitis), but visceral dissemination is uncommon. Deep dermal to subcutaneous pyogranulomatous inflammation develops. Organisms are ovoid to elongate (cigar-shaped) bodies, which are often sparsely distributed and difficult to find in histologic sections. Immunohistochemistry or culture or both may be required to document infection. The exudate containing organisms is infectious to humans if introduced into cutaneous wounds.

Oomycosis (Pythiosis and Lagenidiosis): Oomycosis refers to dermal and subcutaneous infection by Pythium insidiosum or Lagenidium sp., which are both aquatic dimorphic water molds and members of the Oomycetes in the kingdom Stramenopila. Pythiosis most often affects the skin of the limbs and trunk of horses, cattle, dogs, and cats. Lagenidiosis has only been reported in dogs. Many infections develop in conjunction with exposure to freestanding water. Contamination of minor skin wounds is thought to be necessary for infection to occur. Infections are more common in tropical or subtropical climates, including the Gulf Coast of the US, and are characterized clinically by erythematous, sometimes necrotizing, nodular lesions that ulcerate and drain (Fig. 17-56). There can be extensive tissue destruction by inflammation and necrosis. A unique gross feature of pythiosis in the horse are yellow, friable fragments of necrotic tissue and hyphae, which can be dislodged from the lesions. Pythiosis in the dog is a rapidly progressive, debilitating, and often fatal disease seen most often in young, large-breed dogs. Although cutaneous pythiosis is most common, gastric pythiosis also occurs in dogs of this same signalment. Lagenidiosis in the dog is also a very aggressive disease, and dogs may have lesions in organs other than the skin and lymph nodes. Histologically, hyphae or hyphal-like structures are in areas of eosinophilic to pyogranulomatous dermal or subcutaneous inflammation. Organisms may not be readily visible in H&E-stained sections; thus special stains, such as Gomori’s methenamine silver stain, may be required to identify the organisms. Pythiosis, lagenidiosis, and entomophthoromycosis (see next discussion) cannot be reliably differentiated from one another via examination of histologic sections. PCR assays to detect oomycotic DNA and immunoblot analyses are required to differentiate these diseases from one another. Special collection and culture techniques are also necessary.

Entomophthoromycosis (Zygomycosis): Entomophthoromycosis refers to dermal and subcutaneous infections caused by Basidiobolus sp. and Conidiobolus sp., which are saprophytic fungi that gain entry to the body by inhalation or traumatic implantation by wounds or insects. Most Basidiobolus sp. infections have been seen in the horse. Infections with Conidiobolus sp. have been seen in horses, llamas, sheep, and dogs. Systemic dissemination of Conidiobolus sp. has developed in the sheep and dog. As in oomycosis, infections are more common in tropical or subtropical climates. Clinical and histologic features are similar to those of oomycosis. Differentiation between entomophthoromycosis and oomycosis requires culture and other techniques, such as PCR assays and immunoblot analyses, and is therapeutically important because infections with Zygomycetes (true fungi) can be responsive to antifungal treatment, whereas infections with Oomycetes are not.

Demodicosis: Demodectic mange is rare in the horse. Demodex caballi is commonly present in pilosebaceous units of eyelids and nose, generally without producing lesions. In contrast, Demodex equi is distributed over the body. Clinical lesions are rare, but when present, develop on the face, neck, shoulders, or forelimbs, and consist of localized to diffuse alopecia and scaling or of papules, nodules, and pustules.

Demodicosis in cattle (Demodex bovis, Demodex tauri, and Demodex ghanaensis) and goats (Demodex caprae) is of little clinical significance, but extensive infection can damage hides by development of multifocal nodules in the skin of shoulders, neck, and face or in a more generalized distribution. Nodules correspond to follicular cysts that are filled with mites and keratinaceous material. Rupture of the cysts leads to severe granulomatous dermatitis and damage to the hide.

Sheep have two species of mites. Demodex ovis is located in hair follicles or sebaceous glands distributed over the body and can cause alopecia, erythema, scaling, pustules, and matted fleece. Lesions develop on the face, neck, shoulders, and back, but the ears, limbs, and coronary bands can also be affected. Demodex aries is located in sebaceous glands of the vulva, prepuce, and nostrils and can cause papular, rarely pustular, or nodular lesions.

Demodex phylloides of pigs causes scale-covered papules progressing to nodules that are filled with keratinaceous debris and mites and that damage the hide. Lesions develop in the ventral body skin, eyelids, and snout.

Demodicosis is one of the most common skin disorders of dogs in North America. Several different demodectic mites have been identified in dogs, Demodex canis (most common), Demodex injai (rare), and Demodex cornei (rare), a short-bodied mite. Demodex canis and Demodex injai live in hair follicles and can be found in sebaceous glands. Demodex cornei is found on the skin surface. Mixed infections with Demodex canis and Demodex injai and Demodex canis and Demodex cornei have been reported. Demodex injai has been associated with generalized demodicosis and a clinically greasy hair coat. Demodex cornei has been associated with generalized and localized demodicosis. Most cases of canine demodicosis are caused by Demodex canis, and occur in two clinical forms, localized and generalized, both of which are more common in juvenile dogs. Transmission from mother to offspring occurs via close skin contact, as occurs during suckling. Purebred dogs of many breeds are predisposed to infestation, suggesting an inherited basis for the disease related to a primary deficit in cell-mediated immunity. Research studies suggest the defect is one of T lymphocyte helper dysfunction, resulting in damage by cytotoxic T lymphocytes. Active lesions of demodicosis result in lymphocytic mural folliculitis with lymphocyte-mediated damage to the keratinocytes of the follicular wall. It is speculated that follicular keratinocytes express altered self-antigens or Demodex antigens, which leads to immune-mediated destruction of the follicular wall. Secondary immunodeficiency, caused by T lymphocyte suppression, is also associated with demodicosis, particularly if a secondary Staphylococcus intermedius (pseudintermedius) infection is present. The secondary immunodeficiency improves as the demodicosis resolves. Results of studies conflict as to whether the secondary immunodeficiency is caused by the accompanying bacterial infection or the mite infestation. Demodicosis occurs in adult dogs with underlying metabolic disorders (hypothyroidism, hyperadrenocorticism) or that are given drugs (glucocorticoids or cytotoxic drugs) that can compromise the immune system. Idiopathic cases also occur.

Gross lesions of localized demodicosis in the dog consist of one to several small scaly, erythematous, alopecic, areas on the face or forelegs (see Fig. 17-25). Canine generalized demodicosis usually involves large areas of the body; lesions consist of larger coalescing patches of erythema, alopecia, comedones, scales, and crusts. The early microscopic lesions include epidermal hyperkeratosis, perifolliculitis, and lymphocytic interface mural folliculitis, including mild degeneration of follicular basal cells, follicular pigmentary incontinence, and intraluminal mites (see Fig. 17-25). Follicles can become plugged with large numbers of mites, keratin, and sebum. Secondary bacterial infection leads to neutrophilic folliculitis that in conjunction with mite proliferation and follicular hyperkeratosis, progresses to follicular rupture. Mites, bacteria, keratin, and sebum spill into the dermis, stimulating a granulomatous to pyogranulomatous dermatitis. Perifollicular granulomas with portions of mites are often seen. Gross lesions in dogs with severe secondary bacterial infection include papules, pustules, edema, and draining tracts. In severe demodicosis, inflammation and organisms spread into the subcutis, and lymphadenitis and septicemia can develop. Severe chronic lesions consist of dermal fibrosis with effacement of adnexal structures.

In cats, demodicosis is rare and is caused by two species of mites, one (Demodex cati) lives in follicles and sebaceous glands, and the other (Demodex gatoi) resides on the skin surface within the stratum corneum. Unless the immune response is compromised, lesions associated with Demodex cati are usually localized to the chin, eyelids, head, or neck. When the immune response is compromised, as in feline retroviral infections, generalized lesions of erythema, scaling, alopecia, pustules, and crusts develop. Histologically, cats with Demodex cati have epidermal and follicular hyperkeratosis and follicular atrophy. Inflammation is minimal. The most common sign associated with the presence of Demodex gatoi is pruritus, resulting in excessive grooming and symmetric alopecia. Demodex gatoi is contagious between cats, and there is an asymptomatic carrier state.

Scabies: Scabies is caused by Sarcoptes scabiei. This highly contagious and zoonotic mite is the most important ectoparasite of pigs, is common in dogs, and is uncommon to rare in horses, cattle, sheep, goats, and cats. The mites burrow in tunnels in the stratum corneum and cause intense pruritus principally as a result of hypersensitivity reactions, although irritation from secretions also plays a role. Lesions begin on the external ears, head, and neck and can become generalized. Early gross lesions include erythematous macules, papules, crusts, and excoriations. Chronic lesions are scaly, lichenified, and hairless (Fig. 17-57). Microscopically, early lesions consist of superficial perivascular dermatitis with eosinophils, mast cells, and lymphocytes. Mild focal spongiosis can be seen. Small parakeratotic crusts can develop as spongiotic lesions age. Chronic lesions are associated with epidermal acanthosis with marked rete ridge formation, compact hyperkeratosis, parakeratosis, crusting, and perivascular dermatitis with eosinophils, mast cells, and lymphocytes. In areas of excoriation, neutrophils—and with time, dermal scarring—may be evident. Mites, mite eggs, or feces may be found in tunnels in the stratum corneum (see Fig. 17-57, B) but are not commonly seen in tissue sections because of small numbers of mites.