Definition and Etiology

The term pemphigus is derived from the Greek word for “blister” and is used to describe a group of autoimmune vesiculobullous disorders characterized histologically by intraepidermal acantholysis and immunologically by intercellular deposition of immunoglobulin. Pemphigus foliaceus is the most common of this group of autoimmune diseases; in large animals it has been reported in horses,^1,2 goats,^3,4 and a donkey.⁵ In small animals, pemphigus foliaceus has been putatively associated with drugs,⁶ but this has not been identified in large animals. The factors precipitating the development of pemphigus foliaceus in large animals are unknown. The clinical lesions recognized in horses and goats are primarily scaling and crusting.

Pathophysiology

Pemphigus foliaceus is characterized by the production of autoantibodies. In humans and dogs, these are directed against transmembrane proteins (desmoglein 1 in humans and a minority of dogs). The pemphigus autoantibody binds to the transmembrane protein, resulting in the release or activation of one or more proteolytic enzymes. These enzymes destroy the attachments between adjoining epidermal cells. The result is acantholysis; the epidermal cells assume a rounded shape and separate from one another, leading to the formation of intraepidermal clefts and vesicles.⁷

Clinical Signs

Pemphigus foliaceus is characterized clinically as a generalized exfoliative dermatitis (Fig. 40-1). Ventral or peripheral limb edema and crusts are the most common clinical signs.¹ In one recent study, no age, breed, or gender predilection was noted, although (80%) of affected horses first exhibited signs between September and February.¹ In the horse, lesions are usually first noted on the head, limbs, or ventrum. Initial lesions also may be associated with fever, depression, or rarely urticaria. The disease usually progresses to involve the entire body over days to weeks. The primary lesion is a pustule, but these are fragile and transient lesions. Pustules rupture soon after formation, resulting in erosions, epidermal collarettes (rings of exfoliating superficial epidermis), scale, and crust. The lesions may or may not be associated with pruritus or pain.^1,2*

Fig 40-1 Pemphigus foliaceus in a horse; note generalized crusts.

In the goat, pemphigus foliaceus also presents as a generalized exfoliative dermatitis. In the limited number of cases described, lesions were initially noted on the limbs, perineal region, and ventrum. The lesions consisted of crusting and scaling resulting from rupture of vesicles and bullae. Pruritus and malaise appear to be variable findings.³

Diagnosis

Diagnosis of pemphigus foliaceus in large animals is typically based on biopsy of lesions submitted for routine histopathology. Characteristic histologic findings include intragranular to subcorneal cleft and vesicle formation associated with acantholysis. Both follicular and surface epithelia are frequently involved. Neutrophils tend to predominate in the inflammatory infiltrate, although eosinophils may also be present.^1-3 Because certain strains of Trichophyton species of dermatophytes may also cause acantholysis, any histology suggestive of pemphigus foliaceus must be stained for fungi.⁸ Direct immunofluorescence or immunohistochemistry as an aid in the diagnosis of pemphigus foliaceus in horses and goats has also been reported but is somewhat limited to research and academic institutions.^3,7,9 Indirect immunofluorescence testing (for pemphigus antibodies in serum) is reported to be unreliable for the diagnosis of pemphigus foliaceus in horses.^7,10

Therapy

Treatment is corticosteroids at immunosuppressive doses, such as prednisolone at 1 mg/kg every 24 hours (q12h) or dexamethasone at 0.08 to 0.1 mg/kg q24h, then tapering. Oral prednisolone is preferred to prednisone because some horses are unable to metabolize prednisone into the active metabolite of prednisolone.¹¹ Injectable gold (Solganal, Schering) was also used successfully, but this product is no longer available. There are anecdotal reports of benefits using another gold salt, aurothiomalate (Myochrysine, Rhône-Poulenc Rorer), 1 mg/kg intramuscularly (IM) every 7 days. Gold salts take 1 to 3 months to reach effectiveness, when dosage frequency can be tapered to every 14 to 30 days. Adverse reactions of gold salts, although rare in the horse, include thrombocytopenia and glomerulonephropathy.

There are also reports of azathioprine (1 to 3 mg/kg q24-48h) being used for various autoimmune skin diseases in horses.^12,13 A potential side effect is thrombocytopenia because horses have low levels of the enzyme thiopurine methyltransferase (TPMT),¹⁴ which is responsible for the metabolization of azathioprine in other species, including humans. However, I have administered azathioprine (1 to 3 mg/kg for 1month, then q48h) to eight healthy horses with no deleterious effects.¹⁵ Azathioprine is used as a steroid-sparing drug with corticosteroids, eventually to decrease the steroid needed. Approximate cost in a 500-kg horse for daily azathioprine is $300/month.

Goats have also been treated successfully with corticosteroids (dexamethasone, prednisolone) and aurothioglucose.^3,4,9 Dosages approximate those for the horse.

Prognosis

The response to treatment in equine pemphigus foliaceus varies from patient to patient. Many horses require lifelong administration of medication to control the clinical signs; others may be gradually weaned from medication without further relapse. In one study in which follow-up information was available for 13 horses, four were euthanized because of complications from the disease or its treatment. The reported cases of caprine pemphigus foliaceus are insufficient in number to establish a prognosis reliably.

Definition and Etiology

Atopic dermatitis may be defined as an abnormal immunologic response to environmental allergens, such as pollens, barn dust, and molds. It is increasingly being recognized as a cause of pruritus in horses. The disease may be seasonal or nonseasonal, depending on the allergen(s) involved. Age, breed, and gender predilections have not been extensively reported. A familial predisposition may be present.¹⁷

The presumed etiology is a type I (immediate) hypersensitivity response, mediated by immunoglobulin E (IgE). Although evidence indicates that atopic horses do produce allergen-specific IgE,¹⁸ etiology is largely extrapolated from other species. The IgE is presumed to be directed against specific allergens. When that allergen is bound to two or more IgE antibodies on the surface of a mast cell, the mast cell releases granules containing various substances that cause erythema, vascular leaking, and pruritus.

Clinical Signs

Pruritus, often affecting the face, distal legs, or trunk, is the most common clinical sign. Alopecia, erythema, urticaria, and papules may all be present. Urticarial lesions may be severe but nonpruritic. Horses may have a secondary pyoderma, typified by excess scaling, small epidermal collarettes, or encrusted papules (“miliary dermatitis”). Diagnosis of atopic dermatitis is based on clinical signs and the exclusion of other diagnoses, especially parasite (Culicoides) allergy.

Diagnosis

Diagnosis is based on clinical signs and exclusion of other pruritic skin disease. Confirmation to formulate allergen-specific immunotherapy (ASIT, “hyposensitization”) is based on either intradermal testing (IDT) or serum allergy tests. The IDT involves a series of intradermal injections of aqueous allergen extracts along with a positive (histamine) and negative (saline) control. The injections are usually performed over the lateral cervical or thoracic region. The injection sites are then observed for 30 minutes to 24 to 48 hours for evidence of wheal formation associated with the injection site. A positive reaction does not necessarily mean that the horse’s clinical signs are caused by the reacting allergen, but rather that the horse has antibodies to the allergen that, on intradermal exposure, trigger those clinical signs. False-negative IDT reactions may occur, the most important cause of which is the use of corticosteroids, antihistamines, or phenothiazine tranquilizers before testing.

Thus, although horses with atopic dermatitis generally have a higher incidence of positive reactions than healthy horses, the diagnosis (as in other species) cannot be solely made on the basis of the IDT or serologic test alone; rather, these tests should be interpreted in light of the history of the disease; for example, a horse with seasonal signs is more likely to have an allergic response to seasonal allergens (pollens in summer, barn dust in winter). This interpretation thus will help the clinician determine which allergens might be relevant in hyposensitization, should the owners choose that treatment.^18-21

There is continuing controversy in the horse (and other domestic species) in regard to IDT versus the serologic tests available. These tests look for the allergen-specific IgE in the animal’s blood.²² I have used serologic tests as the basis for determining the allergens to be used for hyposensitization when the owner did not want the horse shaved for the IDT or the horse was receiving antihistamines. Preferentially, IDT and/or serologic testing is performed on horses with atopic dermatitis and with owners who are interested in pursuing hyposensitization. It should be remembered that in regard to food allergy, neither serologic testing nor IDT likely has any relation to reality. Clinical research is ongoing to determine the most important allergens, their testing dilutions, and effective control substances.^23,24

Therapy

Corticosteroid treatment is usually effective in the control of pruritus or urticaria resulting from atopic dermatitis. The usual oral medication used is prednisolone (1 mg/kg q24h), although dexamethasone (0.05 mg/kg q 24h) may also be used. The injectable dexamethasone solution may be used orally, although the clinician should remember that the bioavailability is 60% to 70% of the injectable route.

Corticosteroids in horses may cause various adverse effects, including steroid hepatopathy, laminitis, and iatrogenic hyperadrenocorticism. Therefore, other modalities of treatment may be used, such as the antihistamines hydroxyzine pamoate (200 to 400 mg/500 kg q12h), or cetirizine (0.2 mg/kg q12h), doxepin (a tricyclic antidepressant with antihistaminic effects; 300 to 600 mg/500 kg q12h), or diethylcarbamazine syrup (6 to 12 mg/kg q24h). Hydroxyzine, cetirizine, and doxepin may cause either drowsiness or nervousness, although these adverse effects are uncommon. Some clinicians have noted improvement when an essential fatty acid (EFA) product is added to the feed; Platinum Performance has been used successfully in some atopic horses as an adjunctive treatment.*

In general, hyposensitization injections for any manifestation of atopic dermatitis in the horse should be evaluated for efficacy for at least 12 months. The veterinarian should maintain consistent communication with the client to monitor the progress of treatment and encourage the owner to continue with the injections for the full year. If hyposensitization is successful, it is thought that, as in other domestic species, most horses will need to be maintained on the injections for life, although sometimes at a reduced frequency (one to three times monthly). Approximately 70% of the owners of atopic horses at the Veterinary Teaching Hospital, School of Veterinary Medicine, University of California, Davis (UCD), that have had IDT or serologic testing have elected to try hyposensitization. In general, I find that approximately 60% to 70% of atopic horses improve with hyposensitization²⁵; other researchers have reported even better results, but in a noncontrolled study.²⁶

Definition and Etiology

Urticaria is characterized by transient focal swellings in the skin or mucous membranes called wheals, which represent localized areas of dermal edema. Angioedema is essentially identical but involves the subcutaneous tissues. The swelling of angioedema is diffuse, often involving the entire face and neck of the animal.

Urticaria is more frequently recognized in the horse than in ruminants. Allergic urticaria is usually caused by atopic dermatitis (environmental allergens such as pollens),^17,20,21,27 drug eruptions (especially antibiotics and nonsteroidal antiinflammatory drugs), contact allergies, and food allergies (rarely).⁷

Physical urticarias are less common and involve a nonimmunologic pathogenesis. The three most important categories include mechanically induced, such as dermatographism, essentially a “pressure” urticaria; cold urticaria; and exercise-induced urticaria. Miscellaneous diseases that can cause urticaria include dermatophytosis (initial lesions),²⁸ pemphigus foliaceus, “stress” (sometimes seen in racehorses immediately before a race), and vasculitis (Box 40-1). Urticaria is a recognized manifestation of milk allergy in cattle.²⁹

Pathophysiology

The wheals result from vasodilation and transudation of fluid from capillaries and small blood vessels. Both immunologic and nonimmunologic factors can trigger the release of mediators from mast cells and blood basophils that will ultimately produce the characteristic wheals (Fig. 40-2). The most frequently cited immunologic mechanism of urticaria is a type I hypersensitivity (IgE). Non-IgE-dependent, immune-mediated urticaria may be induced by either type II (cytotoxic, involving antibody and complement) or type III (immune complex) hypersensitivity reactions. Complement-activated urticaria may involve either immunologic or nonimmunologic mechanisms and may occur through either the classic or the alternative pathway. Urticariogenic materials can induce wheal formation without involving immunologic mechanisms by being ingested, injected, or contacting the animal. Physical agents, including mechanical injury, thermal changes, and solar radiation, may induce urticaria. An example of mechanically induced urticaria is dermatographism (whealing after blunt scratch injury to the skin). Local or generalized exposure to heat or cold may induce urticarial lesions in certain individuals.

Fig 40-2 Flow of pathophysiologic events in the development of urticaria.

Clinical Signs and Differential Diagnosis

Wheals range from 1 to 10 cm (0.4 to 4 inches) in diameter and tend to involve the cervical and craniolateral thorax (Fig. 40-3). The animal may or may not be pruritic. Alopecia is not usually a feature of urticaria. The most important factor in distinguishing urticaria from other nodular diseases is that the individual lesions pit with pressure. This is easily demonstrated in the early stages of wheal formation, when the lesions consist primarily of dermal edema. In the later stages, when there is cellular infiltration into the dermis, the pitting is less apparent.

Fig 40-3 Acute urticaria in a horse caused by an adverse drug reaction.

Diagnosis

Urticaria is usually a clinical diagnosis; the diagnostic dilemma is to determine the cause of the urticarial eruption. A skin biopsy not only will lend support to the clinical diagnosis of urticaria, but also may show evidence of pemphigus foliaceus, dermatophytosis, or vasculitis, Initiation of ectoparasite control, IDT or serologic tests for atopic dermatitis, and feed trials may all be used to determine the underlying disease.²⁷

Therapy

Avoiding the allergen/initiating factor or treating the underlying disease is the best therapy. When this is not possible or when the allergens cannot be identified, medical therapy should be used, as described under Atopic Dermatitis.

Definition and Etiology

Contact dermatitis is recognized in both horses and ruminants and can be subdivided into irritant and allergic contact dermatitis. Irritant contact dermatitis occurs more often and is defined as a cutaneous reaction to an irritating concentration of an offending agent. The substance chemically damages the skin without immunologic mediation. The reaction may occur after a single contact with a strong irritant or after repeated contacts with a milder irritant. Allergic contact dermatitis represents a cutaneous reaction in a sensitized animal to a nonirritating concentration of the offending agent. Tissue damage is immunologically mediated by delayed-type hypersensitivity (type IV); thus prior exposure is required to sensitize the skin to the material eliciting the dermatitis.^7,29 It may be difficult to differentiate between the two types of contact dermatitis, and it may not be clinically important. In my experience the vast majority of contact dermatitis cases are iatrogenic, caused by topical products placed on the skin by veterinarians or owners.

Clinical Signs

The clinical lesions associated with allergic and irritant contact dermatitis are very similar. Predisposed areas include the muzzle, the extremities, and the areas contacted by tack. Early lesions include erythema, edema, and vesiculation, which progress to erosions, ulcerations, and crusting and ultimately to lichenification and hyperpigmentation. A gravity-induced drip pattern may be evident when the irritant is a liquid.³⁷

Diagnosis

Patch testing is possible but usually impractical. Provocative exposure is the most useful test for diagnosis of contact dermatitis, although it does not reliably distinguish between allergic and irritant contact dermatitis. Provocative exposure requires avoiding contact with all suspected agents for 7 to 10 days to permit clearing of the skin lesions. The patient is then reexposed to these agents on an individual basis at 7- to 10-day intervals while being observed for recurrence of the dermatitis. When a positive reaction is observed, challenge with the suspected agent should be repeated to confirm the diagnosis. The process is time-consuming, requiring patience and cooperation from the owner.

Therapy

An animal with a suspected or confirmed diagnosis of acute or irritant contact dermatitis should be placed in an environment where there is negligible chance of exposure to agents that might have produced the dermatitis. Symptomatic treatment pending spontaneous resolution includes gently washing the affected regions with water. Pentoxifylline at the dose noted earlier for vasculitis may be helpful in horses.

Definition and Etiology

Dermatophilosis is caused by an actinomycete bacterium, Dermatophilus congolensis. The organism is a gram-positive, non-acid-fast, branching, filamentous, aerobic bacteria that divides longitudinally and then transversely to form parallel rows of coccoid zoospores. Dermatophilosis affects horses, cattle, sheep, and goats, as well as a wide host range of other mammals.^38-41

Three conditions must be present for Dermatophilus to manifest itself: a carrier animal, moisture, and skin abrasions. Chronically affected animals are the primary source of infection; however, they become a serious source of infection only when their lesions are moistened, which results in the release of zoospores, the infective stage of the organism. Mechanical transmission of the disease occurs by both biting and nonbiting flies, ticks, and possibly fomites. Because normal healthy skin is quite impervious to infection with D. congolensis, some predisposing factor that results in decreased resistance of the skin is necessary for infection to occur, especially prolonged wetting of the skin by rain. The organism has only recently been isolated from the environment of affected animals. Although the distribution is worldwide, the frequency of occurrence of dermatophilosis varies with geographic location. There is no apparent age, breed, or gender predilection.

Clinical Signs

Dermatophilosis is usually seen during the fall and winter months, with the dorsal surface of the animal most often affected (Fig. 40-7). In horses, this association with the wetter months of the year has led to the term “rain scald.” Occasionally the lesions involve the lower extremities when animals are kept in wet pastures (“dew poisoning”) or if horses are left in the stall while the stall is cleaned with high-pressure water hoses. In the early stages of disease the lesions can be felt easier than they can be seen. Thick crusts can be palpated under the hair coat. Removing the crusts and attached hair exposes a pink, moist skin surface, with both the removed hair and the exposed skin assuming a paintbrush shape. The undersurface of the crusts are usually concave, with the roots of the hairs protruding. In cattle and goats the older term “cutaneous streptothricosis” is sometimes used. In sheep the condition is referred to as “lumpy wool” or “mycotic dermatitis” when wooled areas are affected and “strawberry foot rot” when the distal extremities are involved.

Fig 40-7 Dermatophilosis (Dermatophilus congolensis). A, Horse with suppurative crusts and matted hair on the back. B, Scaling and crusting over withers and neck of a bovine.

Body areas predisposed to infection include those that are most susceptible to maceration and trauma. The distal extremities, muzzle, and entire length of the dorsum are frequently the initial sites of infection. Nonpigmented skin is also reported to be more susceptible to infection. Horses develop lesions in areas rubbed by tack, and cattle often have involvement of the udder and scrotum. Goat kids reportedly have a tendency to develop lesions on the pinnae and under the surface of the tail. Sheep may develop a form of dermatophilosis that begins as an encrusted, proliferative dermatitis at the coronet region; removal of the external crusts reveals a pink-red granulation bed that resembles the surface of a strawberry. Lesions can extend from the hoof to the hock, and with loss of the crusts, ulceration occurs. Under appropriate conditions, dermatophilosis can become generalized.

Diagnosis

Diagnosis is made by demonstrating the “railroad track” cocci on impression smears. A portion of one of the crusts should be minced and mixed with a few drops of sterile water on a glass slide, Gram stained, and examined microscopically. Alternatively, bacterial culture or histopathology may be used for diagnosis, particularly in chronic cases. A thick crust composed of alternating layers of parakeratotic stratum corneum, dried serum, and degenerating neutrophils is the most characteristic change. A superficial folliculitis may be a prominent feature of the disease.³⁸ In Gram-stained sections the branching, filamentous organisms can be observed in the crusts and in the follicles.

Therapy

The animal should be removed from the wet environment, if possible. Careful removal of possibly painful crusts, washing with iodophors or lime sulfur, and administration of antibiotics (for horses, 22,000 mg/kg procaine penicillin G intramuscularly twice daily, or 30 mg/kg trimethoprim-sulfa orally twice daily) for 7 to 10 days.⁴¹ Long-acting oxytetracycline given as a single 20-mg/kg intramuscular dose has been reported to be effective for bovine and ovine dermatophilosis. The crusts are important in contagion, so these should be disposed of rather than brushed to the ground.

Definition and Etiology

Bacterial folliculitis (superficial pyoderma) is defined as inflammation of the hair follicles secondary to a bacterial infection. Furunculosis is the term used to describe a follicular infection that breaks through the follicular wall (“boil”). Bacterial infection that causes subcorneal pustules but does not involve the hair follicles is called impetigo. Folliculitis and furunculosis are often seen in horses^28,38,41 and goats⁴⁰ but are an uncommon problem in cattle and sheep. Impetigo is relatively common in cattle and goats.

Bacterial folliculitis is usually caused by a coagulase-positive Staphylococcus species. Both S. aureus and S. intermedius have been isolated.^28,42 In one study in horses, S. aureus accounted for twice as many isolates as S. intermedius; the same study isolated some strains of S. hyicus as well.⁴³ Many isolates are resistant to penicillin G.⁴³ Occurrence of pyoderma has been linked to poor nutrition and husbandry in some cases.⁴⁴

Clinical Signs

Clinical signs of staphylococcal pyoderma are most often crusts, usually in a circular pattern suggestive of dermatophytosis (this may be the reason that equine pyoderma is underdiagnosed), epidermal collarettes (circular skin lesions with an exfoliative border as seen in dogs with superficial pyoderma), or encrusted papules similar to the miliary dermatitis reaction pattern in cats.²⁸ These infections tend to vary in intensity of pruritus. Histology often shows folliculitis and furunculosis, but bacterial colonies are not always seen. A truncal form of bacterial folliculitis (contagious acne, contagious pustular dermatitis, Canadian horsepox) is often associated with poor grooming and trauma from tack and saddle, warm wet weather, and heavy work. It is painful and interferes with working and riding. It is usually caused by a coagulase-positive Staphylococcus species but may also result from Corynebacterium pseudotuberculosis⁴⁵ (more often a cause of deep pyoderma, as discussed later). In horses, folliculitis often develops in the saddle and lumbar region, particularly in the summer. The affected area initially may be swollen and sensitive, followed by formation of follicular papules and pustules. These may become confluent or may rupture, forming plaques and crusts. Deep pyoderma followed by ulceration may develop over large areas of the body, especially the neck, sides of the thorax, inner surface of the thighs, and prepuce.

A pastern bacterial infection (pastern folliculitis) is often seen. Again, the causative agent is usually a coagulase-positive Staphylococcus species. As with most “primary pyodermas,” the mechanism by which the organism gains its foothold is unknown; it is not contagion or poor sanitary conditions. The lesions are usually limited to the posterior aspect of the pastern and fetlock regions; one or more limbs may be involved. The initial lesions consist of papules and pustules. If left untreated, the lesions coalesce and may produce large areas of ulceration and suppuration, which may be quite painful. The disease is usually not associated with systemic signs, and the general health of the horse is not affected.

A relatively uncommon nodular disease termed botryomycosis mimics actinomycosis or a deep fungal infection but is most often caused by Staphylococcus species in the horse. These may require surgical excision as well as long-term antibiotics.

Public Health Considerations

In a 2000 study, methicillin-resistant, coagulase-negative staphylococcal species were cultured from healthy horses in Japan; the authors concluded, “These organisms must be considered a potential threat to horses and veterinarians who care for them.”⁴⁶ In a 2006 study from the Netherlands, methicillin-resistant coagulase-negative staphylococci were found frequently.⁴⁷ The organism was usually Staphylococcus sciuri, as opposed to S. epidermidis, which was found in the humans in close contact with these horses. No methicillin-resistant Staphylococcus aureus (MRSA) was found in healthy horses.

In contrast, a single strain of MRSA was isolated from both humans (13%) and horses (4.7%) on horse farms in Canada and New York state.⁴⁸ In looking at horses admitted to a university teaching hospital (Ontario Veterinary College), MRSA was isolated from 120 (5.3%) of 2283 horses. Of these 120 horses, 50.8% were positive at admission, and clinical infections attributable to MRSA were present or developed in 14 animals. Horses colonized at admission were more likely to develop clinical MRSA infection. Administration of ceftiofur or aminoglycosides during hospitalization was the only risk factor associated with nosocomial MRSA colonization. Another strain of MRSA was isolated from a small number of horses at the Veterinary University, Vienna, Austria.⁴⁹

Of most concern is the finding of humans reporting skin lesions after contact with a community MRSA-positive affected foal, despite short-term contact with standard protective barriers. The isolates from the foal were indistinguishable from those affecting humans.⁵⁰

Therapy

The antibiotic usually used for bacterial skin infections in the horse is trimethoprim-sulfamethoxazole (TMS) orally (PO, 30 mg/kg q12h for 2 to 6 weeks, longer for deep infections).^7,28 Interestingly, dosing intervals for intravenous (IV) administration of TMS in horses may not be appropriate for use in donkeys or mules. Donkeys eliminate the drugs rapidly compared with horses.⁵¹ In cases of staphylococcal resistance to TMS, enrofloxacin or doxycycline may be used. Doxycycline is less expensive, but is associated with a higher incidence of colic. Dosage is usually 10mg/kg q12h. Off-label use of oral enrofloxacin formulations for poultry, ruminants, or swine has been suggested; a dose for the poultry formulation has been suggested as 7.5 mg/kg PO once daily. The formulation for poultry may be used; the dose is 7.5 mg/kg PO once daily. Use of enrofloxacin in young horses (<2 years old) should be avoided because of concerns about damage to the articular cartilage.⁵² A recent report of the usage of an oral gel formulation of enrofloxacin (100 mg/mL of gel) showed good clinical efficacy for infections in several organs; however, almost one-third of the horses had some diarrhea, and 10% had oral lesions.⁵³ The authors believed that this latter side effect could be overcome with a tap water rinse of the oral cavity after administration. Interestingly, enrofloxacin binds to melanin in equine hair, although the clinical implication is unknown.⁵⁴ Ceftiofur sodium 2.2 mg/kg, q12-24h, IM or IV, may also be used for pyoderma in horses, although its usefulness over a long period is limited by its parenteral route. In one report of 15 horses, vancomycin was used, alone or in combination with an aminoglycoside, to treat MRSA and enterococcal infections. The average vancomycin dosage was 7.5 mg/kg q8h IV over 30 minutes. The antibiotic, alone or in combination with an aminoglycoside, was safe and effective. Because of the problems with emerging resistance, the authors recommended vancomycin use in horses be limited to cases in which culture and susceptibility indicate effectiveness and no reasonable alternative treatment exists.⁵⁵

For localized lesions, mupirocin ointment 2% or silver sulfadiazine cream (Silvadene) may be effective. As shampoos, ethyl lactate (Etiderm, VIRBAC, Fort Worth, Texas) or chlorhexidine (2% to 4%) are helpful.

Pyoderma in ruminants has not been studied as much as in horses. In goats, lesions (often pustules that progress to crusts) usually begin on the udder and spread to the abdomen, thigh, perineum, and face. Pruritus is variable. Stress from parturition is also an important predisposing factor in goats. In sheep a generalized, staphylococcal, scalded skin—like disease has been reported in lambs.⁵⁶ In addition, staphylococcal infections in association with Psoroptes ovis infestation have been noted.^57,58

In cattle, furunculosis caused by C. pseudotuberculosis manifests as a locally extensive, raised, raw lesion that is frequently hemorrhagic. The lesions are almost constantly covered with a serosanguineous exudate, and palpation of the lesions usually elicits a pain response. Treatment is similar to treatment of dermatophilosis, taking into consideration culture and susceptibility results, as well as withdrawal times for food animals.

Clinical Signs

About 80% of PDD lesions occur on the plantar aspect of the hindfoot, immediately proximal to the heel bulbs and adjacent to or extending into the interdigital space.⁶⁵ Less common sites for lesions are the plantar aspect of a forefoot and the dorsal aspect of any foot. Multiple lesions may exist on a single animal, even on a single foot, but lesions are confined to the digital skin and have not been reported to occur above the level of the dewclaws.⁶⁵

The gross appearance of the lesions and the predilection for hindlimbs and skin-horn junctions, especially those bordering the heel bulbs and interdigital space, distinguish this disease from other bovine dermatitides. Lesions are most often 2 to 6 cm (0.8 to 2.4 inches) across at their greatest dimension, are circular or oval, and have clearly demarcated, raised borders.^65,67 Lesion borders are often surrounded by hairs that are two to three times normal length. Lesion surfaces may have filiform papillae varying in length from 1 mm to 3 cm (1.2 inches) and 0.5 to 1 mm in diameter, thus the name “hairy foot warts.” Lesions lacking the filiform papillae (“hairs”) may have a granular surface. Lesions vary in color and appearance. Washed surfaces are generally very painful and either red and granular or composites of white, yellow, gray, brown, or black papillary areas with red, granular areas interspersed.⁶⁵ The lesions bleed easily if traumatized. When PDD lesions develop in the interdigital space, they frequently occur on a preexisting fibroma.

The lesions slowly enlarge and become raised (papillomatous) masses 2 to 6 cm in diameter that are red, gray, or black and oval, spherical, or U shaped. Proliferative or papillomatous lesions are seen less often in Europe than in the United States and are less common on dairies with a consistent treatment and control program.

A foul odor may be present and appears to be caused by secondary bacterial growth in the exudate covering the PDD lesion. Swelling of the pastern and fetlock regions is not present in uncomplicated cases. Lameness is a herd characteristic on dairies where PDD has a high prevalence but is an inconsistent finding on individual infected cattle and is not consistently related to lesion size or maturity.⁶⁸ If PDD lesions remain untreated, the claws of feet with plantar or palmar lesions may develop a clubbed appearance because the cow prefers to bear weight on (and wear down) the toes.⁶⁵

Differential Diagnoses

Differential diagnoses for an individual case of PDD include interdigital necrobacillosis (foot rot, “foul in the foot,” or interdigital phlegmon), interdigital hyperplasia (corns or interdigital fibroma), interdigital dermatitis, and traumatic injury with granulation tissue. For herd problems of lameness localized to the digit, differential diagnoses should include PDD, interdigital necrobacillosis, interdigital dermatitis, laminitis, excessive sole wear from caustic or abrasive flooring, and improper claw trimming. If signs of polysystemic disease exist, coronitis from viral diseases (e.g., bovine viral diarrhea) should also be considered.

Epidemiology

Once introduced into a herd, PDD spreads rapidly within adult cows, often affecting the majority of adults within the first year of infection.⁶⁵ When established in a herd, lameness is most often seen in first- and second-lactation cows.^65,67 Lesions are typically present in a proportion of older cows, but lameness is less apparent than in the younger cows. Bulls and yearling heifers may also be affected but usually comprise a small fraction of clinical cases. In California the disease appears to be most severe during the spring and summer months,⁶⁵ whereas in Europe it is most severe in the winter months. Free-stall herds are more often affected than stanchion (tie-stall) herds, probably because of better foot hygiene in the stanchions. Cattle confined to pasture are rarely affected,⁶⁹ but the disease is emerging in some South American countries with wet pastures during part of the year. PDD is almost exclusively seen in dairy cattle, with Holsteins more likely to be affected than Jersey or dual-purpose breeds.^69,70 Eradication of PDD from an endemically infected herd is unlikely.

Retrospective epidemiologic studies indicated that two risk factors are significant in high-prevalence herds: muddy or wet conditions and purchasing replacement cattle from off premises.^69,71,72 Other risk factors identified were the use of outside hoof trimmers and not washing hoof-trimming equipment between cows.⁷²

Attempts to transmit the disease experimentally were successful when scrapings from active lesions were applied to the feet of calves subjected to constant moisture and low oxygen tension. Constant moisture and low oxygen tension are present on confinement dairies if manure management and hygiene are not adequate. Poor free-stall or bedding area management will exacerbate the problem by forcing cows to stand in manure slurry for longer periods and will not allow the feet of cattle to dry out periodically.

Pathogenesis

Numerous obligate anaerobic organisms have been associated with PDD.⁷³ Spirochetes from the genus Treponema have been identified most consistently.^74-78 During experimental transmission studies, Treponema species are the first organisms to appear, comprise the bulk of the colonizing bacterial mat found on active lesions, and are the organisms that invade the epidermis and dermis.⁷⁶ These spirochetes also produce a humoral response in cows with active lesions.^65,78 PDD lesions show gross and histologic similarities to viral papillomas; however, bovine papillomavirus has not been found.⁶⁵

Current evidence indicates that PDD is multifactorial, involving environmental, microbial, host, and management factors. Factors such as rough flooring; poor drainage; accumulation of feces and urine on floors; dirty, wet, or uncomfortable bedding areas; and overcrowding have an adverse effect on digital skin health and could increase the risk of PDD. The mode of transmission between cows and between herds is currently unclear, although one study found concurrent spirochetal infection of feet and colon in cattle.⁷⁹ Clinically and subclinically affected cows and fomites such as foot-trimming instruments, livestock trailers, and farm equipment may be sources of infection for naive herds.

A California study found that antibodies against two antigenically distinct spirochetes were increased on dairies with PDD compared with PDD-free dairies.⁷⁸ Also, cattle with PDD on a high-prevalence dairy were much more likely to have antibodies to the spirochetes than were cattle without lesions on the same dairy.⁷⁸ There was no cross-reactivity between the two spirochetes or to other spirochetal diseases of cattle.⁷⁸ The concentration of clinical disease in the younger animals of an endemically infected herd suggests that some degree of immunity may develop in older cows. Nonetheless, chronic and recurrent cases in otherwise healthy adult cattle have been reported, and immunity to PDD, if it does develop, may be incomplete or temporary. One study found high recurrence or new lesions 7 to 12 weeks after successful treatment.⁶⁵ Spontaneous regression of lesions and resolution of lameness have also been observed but appear to be rare.

Pathologic Findings

Histopathologic criteria to establish a diagnosis of PDD are as follows⁶⁵:

If performed, biopsies should be full-thickness 6-mm punch biopsies, washed off with sterile saline, and placed in buffered formalin. Histopathology is helpful to confirm a diagnosis of PDD but is not necessary because lesions have such a characteristic appearance and location.

Preliminary results of a biopsy study on treatment and recurrence of PDD indicate that the gross visual and histopathologic diagnoses were in agreement for active lesions before treatment. Histopathology on day 28 after treatment with lincomycin or oxytetracycline, however, found a high percentage (55%) of lesions that visually appeared to be healed but still had microscopic evidence of infection.⁸⁰ It could not be determined if lesions were incompletely healed or recurrent infections.

Treatment and Prevention

The most common treatments for PDD involve the use of topical antibiotics.^68,81 There are limited reports of nonantibiotic products being efficacious, although research and development continue. Currently, no antibiotics are labeled for treatment of PDD in the United States; therefore, adherence to extralabel drug use regulations is imperative.

The most common treatment for PDD in the United States is topical oxytetracycline or lincomycin used as a spray or applied with a bandage. For topical spray treatments, oxytetracycline or lincomycin are mixed with deionized or distilled water in a 2- to 4-L agricultural sprayer (25 g/L oxytetracycline, 8 g/L lincomycin) and applied directly to the heels of PDD-affected cattle once daily for 5 to 10 days. Recurrence is sufficiently common that topical treatments need to be repeated every 45 to 60 days on affected cattle to control the disease. No antibiotic residue violations have been reported resulting from topical application of antibiotics.⁸² Efficacy from parenteral antibiotics has been inconsistent.

Footbaths are often used on dairies to control PDD and other infectious causes of lameness, although most footbath products have not been rigorously evaluated.⁶⁸ Products used include antibiotics, copper or zinc sulfate (5%), formalin (5%), and various proprietary products. On large dairies, footbaths may be more effective at controlling PDD when the disease is at a low prevalence (<10%). When the disease has a high prevalence, individual topical treatment is probably more efficacious at reducing the prevalence. The efficacy of footbaths is reduced if feces and debris are allowed to accumulate in the treatment solution. This problem can be limited by placing two footbaths in tandem, with the first containing water or a mild detergent solution for cleaning the feet and the second containing the antiseptic solution. The footbath solution should be changed every 150 to 300 cow passages, depending on soiling. Footbaths should be a minimum of 8 feet long and 2 to 3 feet wide, with a depth of 5 to 6 inches so that cows have to place all four feet in the solution as they walk through. The baths should be covered to limit dilution by rain and should be located in an exit alley off of the milking parlor to avoid splash contamination of the teat ends before milking. Additional footbaths can be placed in other locations to treat bulls, dry cows, and heifers. Treatments should occur every 2 to 7 days depending on response on the individual dairy. Laws regarding the use and disposal of certain chemicals, as well as where on the dairy such medications can be used, often vary among locales. Consultation with local regulatory agencies is prudent before initiation of a control program on a dairy.

The efficacious use of footbaths on dairies signals major husbandry problems on dairies because the environmental and hygiene problems are often not addressed.⁸³ Improvement of stall, corral, and alley hygiene; provision of dry and comfortable bedding; reduction of stocking rate; and improved ventilation to allow drying of stalls and alleys may result in reduction of the incidence or severity of clinical cases. Claw-trimming equipment, mobile tilt tables, and livestock trailers should be thoroughly cleaned and disinfected to prevent potential transmission of the agent(s) of PDD between dairies.

A Treponema bacterin was developed, tested, and licensed for use in the United States. A blind field study where half the lactating cows were vaccinated and half received a placebo vaccine (no Treponema) did not find a prophylactic or therapeutic effect of the vaccine.⁸⁴

Definition and Etiology

Cutaneous papillomas or warts occur (in decreasing order of frequency) in cattle, horses, goats, and sheep.^85-88 The growths usually occur in young animals,⁸⁸ as well as on teats of mature cattle and goats, and are white, tan, or gray, firm protruding masses with a dry, horny surface. They vary in size from 1 to 500 mm and may be single or multiple. Species-specific papillomaviruses (subgroup of papovavirus) are responsible for causing warts. It is now accepted that parts of the bovine papillomavirus (BPV) genome are found in naturally occurring equine sarcoids.⁸⁹ There are at least 10 BPV strains, designated BPV-1 through BPV-10 (Table 40-1),⁹⁰ and there are probably more. Only one strain of virus is currently recognized in horses, goats, and sheep, but little research on papillomas has been done in these species, and two horse and two goat strains are likely.

Table 40-1 Distribution and Appearance of Bovine Warts by Type of Virus

Clinical Signs

Warts are usually small, benign growths that appear on young animals under 2 years of age, persist for 3 to 12 months, and then spontaneously regress without causing clinical signs (other than a blemish). In cattle, warts on the teats, penis, or interdigital skin⁹¹ or in the alimentary tract may produce clinical signs of pain or occlusion. Warts usually develop in the ears of young cattle after tagging or tattooing, especially if instruments are not disinfected between individuals; these are not age related. Teat warts also predispose to environmental mastitis. Occasionally, individuals with (presumed) defective cellular immunity may develop multiple, extremely large warts that may result in weight loss.

In horses, warts on the face are rather common but rarely cause a significant problem (Fig. 40-8). The previously reported congenital wart in young horses has now been more properly termed a hamartomatous lesion (epidermal nevus) and has been shown not to be virus induced.⁹²

Fig 40-8 Typical warts (papillomas) on the nose of a yearling horse.

Warts are relatively rare in goats. They occur mainly on teats and may spread throughout the herd. A 1936 report described a herd outbreak involving the head, neck, shoulders, and forelegs in milking goats.⁹³ Does without adequate pigmentation on the udder develop persistent mammary gland warts that may undergo transformation to become squamous cell carcinomas.⁹⁴ There are probably at least two different strains of goat papilloma virus (head/neck and mammary).

Warts are rare in sheep but may occur on the face or legs. Differential diagnosis in sheep and goats includes contagious ecthyma (orf), ulcerative dermatosis, dermatophilosis, and sheeppox and goatpox.

Treatment and Control

Small warts can be crushed, pinched off, or surgically removed. Cryosurgery can be used on larger warts. Many regress spontaneously within a few months, even without treatment.

When show animals are involved or when animals have multiple large papillomas, tissue can be removed and made into crude autogenous vaccine (2 mL intradermally three times weekly) by homogenizing, grinding, freeze-thawing twice, filtering, and killing virus with 0.5% formalin. Autogenous wart vaccines are variable in their efficacy, as are commercial vaccines.^95-97 The latter rarely seem to result in effective regression of existing warts, but may prevent the development of new lesions if the same BPV strain is involved. Autogenous vaccines are capable of preventing new lesions caused by the same BPV strain in a herd. There is no indication that cattle vaccines have any efficacy in other species. No wart vaccines for horses, sheep, or goats are currently marketed.

Because the viruses can be directly or fomite transmitted, prevention involves isolation, preventing animals from rubbing on each other, and not sharing halters, brushes, and other equipment. Dipping of dehorning, tagging, and tattooing instruments in a viricidal solution between animals will also slow spread of the virus.

Etiology and Pathogenesis

The most common equine dermatophyte species isolated from horses are Trichophyton equinum, Microsporum equinum, Trichophyton mentagrophytes, and Trichophyton verrucosum.^7,28,104 T. verrucosum infections in humans caused by transmission from horses have been reported.¹⁰⁵ In ruminants the majority of dermatophytosis lesions are caused by T. verrucosum and to a lesser extent by T. mentagrophytes. The transmission of the disease is usually from animal by direct contact or indirectly through fomites such as grooming instruments, tack, housing, fencing, or feed bunks. The incubation period may range from 1 to 6 weeks.

Several factors may influence the susceptibility of an animal to dermatophyte infection. Age is probably most important, with younger animals more susceptible to infection. The susceptibility of young animals is most likely related to lack of prior exposure/infection and thus no immunity, as well as crowding of young animals and conditions that decrease resistance to infection (e.g., poor nutrition). Environmental factors such as warmth and humidity also may play a role. Calves kept indoors or exposed to foggy weather with little or no sunlight have an increased incidence.

Under normal circumstances, dermatophytes only invade fully keratinized, nonliving tissues.⁷ This results in weakened hair shafts, leading to alopecia.

In many cases, dermatophytosis is theorized to be a self-limiting disease, with the duration of infection ranging from 1 to 4 months. The spontaneous regression is at least partly related to the development of immunity, of which cell-mediated immunity is the more important. The immunity that develops is probably not complete, and its duration is unknown.

Clinical Signs

The lesions are often circular and usually appear first on the face or in the axillary/girth area and may spread over the trunk, rump, neck, head, and limbs (Fig. 40-10). Occasionally in the horse, dermatophytoses may be limited to the pastern region. Rarely, dermatophytes may be a cause of coronary band disease in horses. The mane and tail are rarely involved. Cattle and goats are frequently affected around the eyes and face (Fig. 40-11).

Fig 40-10 Ringworm lesion in flank area of a horse (Trichophyton species).

Fig 40-11 Ringworm lesions around the eye of a calf, caused by Trichophyton verrucosum.

Lesions may be superficial or deep. Superficial infections are much more common and manifest with the development of thick crusts or more generally a diffuse moth-eaten appearance with desquamation and alopecia, sometimes in a ring pattern. A small crust may form over the follicle, and the hair is lost. Occasionally the initial lesions may be urticarial, progressing to multifocal, sharply demarcated areas of alopecia and scaling. The degree of pruritus varies but is usually mild or absent. Erythema is usually absent or obscured by pigmented skin. The lesions in cattle are usually characterized by excessive crusting, taking on an almost wartlike appearance.

Dermatophytosis must be considered in the differential diagnosis of any dermatoses characterized by multifocal alopecia or scaling and crusting. For a solitary lesion in horses, the occult sarcoid is the primary differential diagnosis. The two most important differential diagnoses of more extensive lesions are dermatophilosis and pemphigus foliaceus.

Diagnosis

Direct microscopic examination of infected hairs is of value, but in general the most common and reliable method of diagnosing dermatophytosis is fungal culture (see Chapter 11). Broken hairs at the periphery of lesions are most satisfactory for this purpose. Large crusts and areas of separation should be avoided. The use of specialized indicator media is preferred. On occasion, dermatophytosis is diagnosed histopathologically. Interestingly, Trichophyton species occasionally may cause acantholysis, mimicking pemphigus foliaceus on histopathology.¹⁰⁶

Therapy

Although 50% captan (2 tablespoons powder in 1 gallon water) has been recommended in the past and is certainly safe for tack, its effectiveness has been questioned. Lime Sulfur (LymDyp, IVX Animal Health, St. Joseph, MO), 1 cup to 1 gallon of water, and bleach 1:10 with water are both effective, but messy, odiferous, and staining. Miconazole shampoos are becoming more widely used and may be as effective. In Europe and Canada an enilconazole rinse (Imaveral, Jaansen), approved for horses and cattle, is highly effective.

Systemic treatment is occasionally needed. The efficacy and proper dose of griseofulvin in horses has not been thoroughly researched. However, a dosage of 100 mg/kg daily for 7 to 10 days has been advocated and has been used with good success on a small number of horses by the author. Griseofulvin is a teratogen and should not be used in pregnant mares. Alternatively, 20% sodium iodine (NaI) may be given IV (250 mL/500-kg horse once or twice every 7 days) but also is contraindicated in pregnant mares because it may cause abortion.²⁸

Vaccinating cattle against T. verrucosum has long been successful in Eastern Europe and Scandinavia. Effective control of ringworm in cattle has been achieved in regions implementing systematic vaccination.¹⁰⁷ Vaccination against T. equinum in horses may reduce the incidence of new infections and protect a high percentage (>80%) of vaccinates from infection. These data are based on results with an inactivated vaccine containing both conidia and mycelial elements.¹⁰⁸ In cattle, newer vaccines consisting of recombinant protein and deoxyribonucleic acid (DNA) derived from heat-shock protein 60 of T. mentagrophytes have shown success experimentally.¹⁰⁹ Such vaccines are not yet available in the United States.

Psoroptic Mange

Psoroptic mange has been recognized in horses, cattle, sheep, and goats (and rabbits). The host specificity of Psoroptes equi, P. ovis, P. natalensis, and P. cuniculi is controversial; two recent reports state that the mites are all genetically homogenous with little or no host specificity,^122,124 whereas another report documents an inability to transfer Psoroptes ovis to goats.¹²⁵ The mites do not affect people. Psoroptic mange is common in cattle but has been eradicated from horses and sheep in the United States; it is still a concern for sheep production in the United Kingdom and elsewhere in the world. The mites have a 2-week life cycle on their host but can live away from the host for up to 3 weeks. Psoroptes mites live on the surface of the epidermis and do not burrow. Symptomatic infestation tends to be more prevalent during the cooler months.

The hallmark of infestation in all species is pruritus. In cattle, crusted papular lesions are typically first apparent on the withers but then generalize, resulting in weight loss, secondary infections, and decreased production.¹²⁶ Horses develop papules, crusts, and alopecia most often at the base of the mane, tail, ears, and intermandibular area, with subsequent spreading to the trunk.¹²² An otitis externa may be present, seemingly with Psoroptes cuniculi.¹²² In sheep, typical lesions include papules and crusts in wooled areas, and secondary infection with Staphylococcus aureus may occur.¹²⁷ The intense pruritus can be debilitating. Certain sheep breeds (e.g., merino) are more susceptible to infestation than others.¹²⁵ The immune response in sheep has been extensively studied, with early innate and longer-term adaptive cutaneous immunoinflammatory responses as well as mite antigen—directed IgE being reported.¹²⁶ Goats usually have lesions restricted to the ears, although infestation and symptoms may spread to the neck and body.²⁹

Diagnosis is based on demonstrating mites in skin scrapings and ear swabs from affected animals. Psoroptic mites are recognized by their round bodies and long, segmented pedicles.²⁹

A number of topical insecticides have been recommended for treatment and should be applied to all affected and contact animals according to the manufacturer’s guidelines. These include deltamethrin, coumaphos, diazinon, malathion, toxaphene, and lime sulfur.^29,123,128 The contaminated environment should also be treated. Ivermectin, doramectin, and moxidectin have been used for Psoroptes species in large animals at 0.2 mg/kg subcutaneously (SC),^123,129,130 but treatment does not eliminate live mites from all animals. It has been recommended that P. ovis–infested cattle be isolated for a minimum of 14 days after treatment to prevent transmission to susceptible contact cattle.¹³⁰ Psoroptes-infested ears in horses should not be treated topically because of the resulting discomfort; reliance is on systemic treatment. Psoroptic mange is a reportable disease in the United States.

Chorioptic Mange

Chorioptic mange, also known as leg mange, is common in cattle and sheep, uncommon in goats, and seen with variable frequency in horses depending on geographic area. Draft horses may be more susceptible than other breeds. Chorioptes species are relatively host specific and include C. bovis, C. texanus, C. ovis, C. equi, and C. capre.^29,123,131 The mites do not penetrate the epidermis¹²³ and do not affect humans.¹³⁰ They have a life cycle that spans 2 to 3 weeks and can live off the host for only a few days.²⁹

This disease is variably pruritic, more so in ruminants than horses, and less so than infestations with Psoroptes or Sarcoptes mites. Lesions consisting of papules, erythema, scaling, crusting, ulceration, and alopecia result from self-trauma. In cattle the lower aspects of the hindlimbs, the perineum (particularly the perianal fossa), tail, and scrotum are usually affected. Sheep typically demonstrate involvement of the lower limbs and scrotum. Goats have involvement of the lower limbs. Horses typically have lesions on the pasterns, although the ventral abdomen may become involved in severe cases. In all species, infestation can become generalized.^122,123,130

Mites are often numerous and readily demonstrated with skin scrapings. Cattle may be asymptomatic.¹³⁰ Chorioptic mange will respond to treatments described for psoroptic mange, although ivermectin and related compounds are more effective in ruminants than horses; in horses, lime sulfur or fipronil applied once weekly for at least 1 month is recommended.^122,132,133 A recent study in horses showed efficacy using a single dose of moxidectin 2% oral gel (Equest, Fort Dodge, IA) at the manufacturer's recommended therapeutic dose of 0.4 mg/kg body weight.^133a Chorioptic mange is a reportable disease in the United States.

Sarcoptic Mange

Sarcoptic mange is an uncommon, contagious disease of horses, cattle, sheep, and goats. The etiologic agent is Sarcoptes scabiei; several subspecies are relatively host specific but can be transmitted to humans. The mite burrows into the epidermis, where the egg is deposited, and its life cycle is complete in 10 to 17 days. Transmission is usually by direct contact, but the mite has a variable survival time off the host; therefore, environmental and fomite transmission is possible.^122,123

The clinical signs are all referable to the severe pruritus caused by the mite. Lesions include papules, scaling, crusting, ulceration, and alopecia. The head (especially the ears) and neck are usually the initial areas of involvement, although lesions become generalized.^29,122,123 Horses in areas frequented by infected wild foxes may have lesions affecting the legs and the ventral abdomen.¹²² Dairy cattle may have an associated udder cleft dermatitis.¹³⁴ Sheep tend to have initial involvement of the nonwool areas. The ears should always be scraped for mites; the mite is identified by its rounded body, terminal anus, short legs, and long unsegmented pedicles.^29,122,123

Because mites may be present only in small numbers, negative skin scrapings do not rule out the disease. Diagnosis should be based on clinical suspicion and response to therapy.^7,29,122,123

Topical acaricides have been recommended for treatment and are applied to all affected and contact animals at 10- to 14-day intervals for four to six treatments. These include lindane, coumaphos, diazinon, malathion, toxaphene, and lime sulfur.^29,122,123 Ivermectin, 0.2 mg/kg at 2-week intervals for two to four injections (ruminants) or orally (horses), has been shown to be effective, as has injectable moxidectin and topical doramectin. The contaminated environment should also be treated. It is recommended that the state regulatory agency for livestock disease control be consulted for methods of treatment and products to use because sarcoptic mange is a reportable disease.

Demodectic Mange

Demodectic mange is a rare disorder, although it has been recognized in all the large domestic species. The mites live in the hair follicles and in the sebaceous and sweat glands and are host specific. They are not contagious between members of the same species, but Demodex species are presumably transmitted from mother to offspring during the first few days of life by direct contact with the dam. Little else is known regarding the life cycle of the mite.^122,123 Two species of Demodex are recognized in the horse.^7,122 Demodex caballi is a normal inhabitant of the pilosebaceous apparatus of the eyelids and muzzle and may be found in skin scrapings of these areas on horses in the absence of skin lesions. Demodex equi inhabits the pilosebaceous apparatus of the remainder of the body and is the species found on horses that has been associated with disease. The species found on cattle, sheep, and goats are Demodex bovis, D. ovis, and D. caprae, respectively.^{29,122,123,130}

Clinical signs are variable, depending on the species affected. The disease is quite rare in horses, which may develop alopecia of the head and trunk; I have seen one case of concurrent demodicosis and chorioptic mange on the legs of a draft horse. Underlying pituitary dysfunction of the pars intermedia has been seen in some horses.¹²² Pruritus and secondary pyoderma are variable. Goats and cattle usually develop nodular lesions that involve the face, shoulder, and neck.^135,136 In goats the nodular contents are white and caseous; microscopic examination for mites differentiates the lesions from Corynebacterium pseudotuberculosis.¹³⁶ Sheep tend to develop periocular nodular lesions.

Diagnosis is based on recognizing mites with microscopic examination of skin scrapings or exudates obtained from nodular lesions. The mites are elongated and have short, stubby legs.^29,122,123

No treatment has proved to be consistently effective in large animals, although relatively few case reports exist in the literature. Amitraz has not been successful in the treatment of caprine demodicosis.¹³⁶ Horses sprayed with 0.025% amitraz developed somnolence, depression, ataxia, muscular weakness, and progressive large intestinal impaction, suggesting that amitraz is contraindicated in equids.¹³⁷ Daily ivermectin has been suggested as a successful treatment for equine demodicosis, but dosages have not been codified. Oral ivermectin (0.67 mg/kg once weekly for 12 weeks) and pour-on eprinomectin (0.5 mg/kg) each successfully treated one goat with generalized demodicosis.¹³⁸

Definition and Etiology

Cutaneous onchocerciasis in horses is a common filarial dermatitis with a worldwide distribution. Its incidence in the United States has decreased dramatically since the introduction of ivermectin for routine deworming. In a recent report from South America, Onchocerca cervicalis microfilariae were detected in midventral skin biopsy samples in 215 (17.9%) of 1200 horses examined, and the adult worms were recovered from 200 (16.6%) ligamentum nuchae from the same animals.¹⁵⁷

The disease is caused by the microfilaria of O. cervicalis and is seen primarily in adult horses.^158,159 Adults typically are found coiled in the funicular part of the ligamentum nuchae, where they produce calcified nodules. Viviparous females may live for up to 5 years and produce large numbers of microfilariae that migrate through connective tissues to the superficial layers of the dermis. Preferential areas of microfilarial localization include the ventral midline, lower eyelid, and lateral limbus of the eye.¹⁵⁸ The infection is transmitted by Culicoides, which act as an intermediate host. The larvae are ingested by the vector and undergo development into the third-stage larvae (L₃) in approximately 2 weeks. The L₃ larvae enter the animal host through lesions created by the feeding vector.³³ Many horses are infected with the parasite without demonstrating clinical disease.^33,158

Pathophysiology

Pathogenesis is believed to involve a hypersensitivity reaction to antigens released by dying microfilariae.^33,158 This theory has support because not all infected horses demonstrate disease, neither the presence nor the severity of the dermatitis is correlated with the number of organisms present, and treatment with filaricides often causes a temporary exacerbation of clinical signs.

Clinical Signs

Clinical signs occur most often in older horses and can include both ocular and cutaneous lesions.^33,158 Ocular lesions include uveitis, conjunctivitis, keratitis, and depigmentation of the lateral limbus.¹⁶⁰ Cutaneous lesions include diffuse or patchy alopecia, erythema, and scaling. Focal cutaneous depigmentation is common. Lesions tend to occur in regions where microfilariae are typically present in highest concentrations, such as the ventral midline, face (Fig. 40-13), base of the mane, anteromedial proximal forelimbs, and anterior pectoral region. An inflammatory, alopecic, or hyperpigmented area in the center of the forehead is highly suggestive of the disorder.³³ The dermatitis is generally reported as being nonseasonal and nonpruritic.^33,161

Fig 40-13 Cutaneous onchocerciasis in a horse.

Diagnosis and Histopathology

Because many normal horses have microfilariae without disease, the finding of microfilariae does not prove that they are the cause of the cutaneous lesions. In addition, because microfilariae tend to “nest” in the dermis, there is a tremendous difference in the number of microfilariae recovered from adjacent skin samples.^158,162 Thus, although the absence of microfilariae makes cutaneous onchocerciasis unlikely, it does not definitively exclude it as a diagnosis. Differential diagnoses should include ventral midline dermatitis caused by the horn fly Haematobia irritans, hypersensitivity reaction to Culicoides, dermatophytosis, and infestation with mange mites.

Ultimately, diagnosis should be based on history, supportive clinical findings, exclusion of other differential diagnoses, and most importantly, response to treatment.

A positive Onchocerca microfilarial saline preparation demonstrates slender, delicate microfilariae that are approximately 8 × 220 μm. Typical histopathologic changes include an eosinophilic and lymphocytic perivascular dermatitis, a finding that is nonspecific and common to many other equine parasitic dermatoses (see Chapter 11). Aggregations of microfilariae may be found in the superficial dermis or perifollicular region.^33,158,162

Therapy

Ivermectin or moxidectin are the treatments of choice and are administered at 0.2 mg/kg PO.^163,164 Most horses improve within 2 to 3 weeks. Minor adverse reactions, including fever and swelling of the periorbital, facial, and ventral midline regions, may occur in up to 25% of infected horses treated with ivermectin; moxidectin did not cause posttreatment dermal reactions in one study.¹⁶⁴ Severe reactions may benefit from treatment with corticosteroids, but most reactions resolve within 24 to 72 hours. Because there is no effective adulticide, recurrence may be noted as soon as 2 months after therapy. Most animals remain free of clinical signs for 6 to 12 months.^161,163 Re-treatment is recommended at 4-month intervals.

In cattle, onchocerciasis has been caused by the microfilariae of Onchocerca gutturosa and Onchocerca lienalis and in Africa, Onchocerca ochengi.^165,166 Flies of Simuliidae are the vectors. The disease causes nodules and crust on the skin, including the teats; adult worms surrounded by neutrophils were detected free in the teat canal.¹⁶⁶ Ivermectin and moxidectin are effective treatments.¹⁶⁵

Definition and Etiology

Infestation with the larvae of Hypoderma species is a common and serious economic problem in cattle and is recognized sporadically in horses that are pastured near cattle. Occurrences have also been reported in sheep, goats, and humans.¹⁷¹ Warble flies are present in the Northern Hemisphere between 25 and 60 degrees latitude in more than 50 countries of North America, Europe, Africa, and Asia. Hypoderma species are not established south of the equator.^152,171 The U.S. cattle industry loses millions of dollars annually because of cattle grubs.

Two species of Hypoderma parasitize cattle: H. bovis and H. lineatum. The latter prefers warmer climates and is the only Hypoderma species present in the southern United States. Each of the species occurs in the northern United States and in Canada.¹⁵² H. lineatum and H. bovis have very similar life cycles, but the stages of H. lineatum tend to occur 3 to 8 weeks earlier than those of H. bovis. Timing of the life cycle also varies with local geographic and climatic factors.^152,171

The adult flies are beelike in appearance, covered with dense chin bristles (hair), 12 to 188 mm in length, and have nonfunctional mouthparts.¹⁷² They have a short lifespan, only 1 week. Adult flies are active in the spring to early summer, with H. lineatum appearing 3 to 4 weeks before H. bovis. Female H. lineatum flies deposit eggs on the hairs of the legs or lower body, whereas H. bovis tends to deposit eggs on the rump or upper parts of the hindlimbs. Total egg production by a single female has been estimated to range from 500 to 800.¹⁷² The eggs hatch in 3 to 7 days, after which the larvae penetrate the skin and begin their migration through the connective tissues. H. lineatum larvae migrate to the subcutaneous connective tissues of the esophageal wall, whereas H. bovis larvae migrate toward the spinal canal. The first-stage (L₁) larvae remain in this location for 2 to 4 months, during autumn and early winter. Between January and February the larvae begin a final migration through the connective tissues to the subdermal tissue of the back of the host, where they form a breathing hole through the skin. Cysts (warbles) develop around L₁ larvae. Within the cyst the larvae undergo two molts over a 4- to 6-week period. The L₃ larvae (grub) emerge from the breathing pore, fall to the ground, and pupate. Adult flies emerge from the pupae in 1 to 3 months, and emergent adults are ready to mate almost immediately.^172,156 The life cycle is complete in 1 year. Most larvae fail to reach normal size and complete their life cycle in the horse.^171,172

Clinical signs

Therapy

When small numbers of cattle are affected with just a few grubs, manual removal of the grubs is possible by simply enlarging the breathing pore. This is usually the preferred treatment in horses as well, if only one or two lesions are present. Care must be taken to remove the larvae in their entirety because breaking the larvae and rupturing the cyst during removal can result in a severe systemic reaction.^152,171

Systemic insecticides are the only means of eliminating the migrating larvae. Organophosphates or the macrocyclic lactones (doramectin, eprinomectin, ivermectin, moxidectin) have been used for this purpose and are applied on the midline of the back.^171,174 Administration of insecticides should be timed to provide treatment in early autumn after all eggs have hatched and larvae are in the early stages of their connective tissue migration. Third-stage larvae are less susceptible to insecticides, and destruction of larvae in later stages of migration increases the risk of serious secondary illness. It is advisable not to administer systemic insecticides later than 8 to 12 weeks before the anticipated first appearance of grubs along the back.^152,171 In the northern United States and Canada, treatment of cattle with systemic insecticides is not recommended from October 1 to March 1 because this is when H. bovis larvae are located in the epidural space and H. lineatum larvae reside in the esophagus.¹⁵²