Etiology

Papillomas are the most common tumors in dairy cattle; fortunately most papillomas are benign and self-limiting. Animals between 6 and 24 months seem most at risk for warts, and previous incidence of the tumors gives an individual a degree of immunity. Papillomas are well documented to be caused by bovine papilloma virus (BPV) types 1 through 6. These viruses have some common antigenic components but do not have good immunologic cross-reactivity. BPV1 and especially BPV2 cause typical warts on the head, neck, trunk, and legs of young cattle (Figure 7-1). A “typical” wart means that a true fibropapilloma exists histopathologically. These masses usually are cauliflower-like, rough, or crusty-surfaced skin lesions that are colored white to gray. Some appear flatter, gray, and have a broad-based skin attachment. Others have a pedunculated base. The virus infects the basal cells of the epithelium, and as these cells eventually reach the surface, large quantities of virus are available to contaminate fomites and the environment. Therefore warts tend to become endemic rather than occur sporadically. Stanchions, feed bunks, neck straps, brushes, halters, pens, and back rubs all become coated with virus. Abrasion of the skin caused by mild trauma from sharp objects (e.g., nails, splintered wood, barbed wire, and bolt ends) allows inoculation of the virus into skin and will increase the incidence in a group of calves. Epidemic and endemic situations also have been associated with dehorning (Figure 7-2), ear tagging, and the use of tattooing devices or emasculatomes when disinfection of a common instrument has not been performed. This is especially true when laypeople perform the aforementioned procedures. Insects also have been suspected of spreading or inoculating the virus into skin, but this remains difficult to prove.

Figure 7-1 Multiple small fibropapillomas on the eyelids, masseter region, and a large fibropapilloma originating at the dehorning site.

Figure 7-2 Large bilateral fibropapillomas in a Jersey calf representative of an epidemic occurrence following dehorning by a layperson.

Cattle with large multiple warts that do not regress probably have concurrent deficient cell-mediated immunity (Figure 7-3) or some other immunodeficiency such as persistent infection with bovine virus diarrhea virus (BVDV) or bovine leukocyte adhesion deficiency (BLAD). Genital fibropapillomas caused by BPV1 are commonly found on the penis of young bulls, on the teats, and occasionally in the vagina of heifers.

Figure 7-3 Multiple large warts that failed to regress over a 6-month period in a heifer.

Atypical warts that tend to persist for years have been associated with BPV3 infections. Young and mature animals may be affected, and the lesions are multiple low, flat, and annular, with fingerlike or frondlike projections that are papillomas with epithelial proliferation but lack dermal fibrosis. These lesions are not raised as noticeably as BPV1 or BPV2 warts and may simply be interspersed with normal-haired skin.

Alimentary warts involving the esophagus, forestomach, and oral cavity are thought to be associated with BPV4. Although cattle with alimentary fibropapillomas are asymptomatic, occasionally fibropapillomas interfere with effective eructation, resulting in signs associated with vagal indigestion. Malignant transformation of BPV4-induced alimentary lesions to carcinomas is also possible and is a much greater risk when carcinogens such as bracken fern compose a major portion of the diet.

BPV4, as well as BPV1 and BPV2, may contribute to urinary bladder tumors in cattle consuming bracken fern at pasture. This condition, known as enzootic hematuria, can be life threatening to affected cattle.

BPV5 causes so-called “rice-grain” teat fibropapillomas, probably the most common form of teat wart seen in dairy cattle in the United States. (This virus is discussed further in Chapter 8). It is spread by milking procedures and machines that predispose to teat chapping or minor teat abrasions. Similarly BPV6 has been shown to cause papillomatous frondlike lesions on the skin of the udder.

Signs

Signs usually are obvious for skin papillomas, but flat wide-based gray warts occasionally may be misdiagnosed as crusty ringworm lesions. Lesions tend to be multiple and mainly occur in facial, neck, shoulder, and trunk locations. Lesions limited to a common anatomic area in most infected animals may help identify the cause of infection. This is especially easy for eartag and dehorning wounds, for example. Fly irritation, myiasis, and bleeding are common problems associated with large cauliflower-like warts during warm weather. Hemorrhage may be life threatening in those rare cattle with huge, multiple warts over a large portion of the body.

Penile warts in young bulls may interfere with breeding and can spread the virus to cows naturally serviced or to other bulls from artificial vaginas that are not routinely disinfected. Bleeding from the penis or sheath following collection or service is the usual owner complaint concerning affected bulls. Heifers with vaginal fibropapillomas frequently go undetected unless the mass becomes large.

Alimentary warts seldom are observed clinically except during oral examination, esophageal endoscopy, or rumenotomy. The lesions commonly are observed during gross postmortem examination.

Enzootic hematuria leads to obvious hematuria and dysuria or stranguria in affected cattle on pastures containing bracken fern.

Although teat lesions of fibropapillomas (BPV1, BPV2), rice-grain lesions (BPV5), or papilloma (BPV6) may be observed in individual cattle, they frequently become endemic in a herd. Warts may interfere with effective milking or be irritated by milking but seldom cause serious problems unless they occur at the teat end. Interference with effective milkout and mastitis are risks for cattle having teat end warts.

Diagnosis

Clinical signs are sufficient for diagnosis in most instances. Atypical lesions may require biopsy and histopathologic study. Gross sectioning of surgically excised fibropapillomas also is suggestive because epidermal proliferation over dermal fibroplasia is obvious on cut sections.

Treatment

Because skin warts usually are self-limiting within 1 to 12 months, treatment seldom is necessary. However, the variable duration of warts (up to 12 months) before self-cure causes owners to request treatment, particularly in young show cattle. In addition, various treatments, vaccines, and quack medications have gained acceptance because owners attribute eventual resolution of warts to treatment with these products, rather than to a spontaneous cure. Commercial or autogenous vaccines have been used extensively. Unfortunately they suffer from some major deficiencies:

Vaccination may be helpful when used as a preventive measure to decrease the risk of penile warts for bull calves assembled in bull studs or in herds with a high incidence of warts.

“Emergency treatment” is a frequent owner request during the summer months when heifers are to be shown in cattle shows. This frustrating situation results from regulations forbidding animals with warts to be shown for fear of contagion. Veterinarians are pressured into doing “something” to resolve lesions quickly, and this may be impossible.

Many treatments, such as surgical removal or crushing of individual warts, have been tried in an effort to stimulate the cell-mediated immunity that is most important to eventual resolution of the problem. In addition, autogenous bacterins injected intradermally or subcutaneously (SQ), levamisole, and other products have been tried. The success of these techniques is not known. Cryosurgery on selected tumors may be used both to destroy the tumor and to stimulate cell-mediated immunity to cause rejection of other tumors in the same animal. I have found this technique most useful in severe epidemics of warts following dehorning by laypeople in which each affected heifer has bilateral warts overlying the skin of the dehorning wounds.

Prevention is the best form of treatment and includes identification of likely fomites and contaminated or sharp structural devices that can be removed or corrected. In addition, surgical instruments, tattooing implements, and dehorners should be sterilized or disinfected with virucidal solutions between uses.

Penile fibropapillomas in bulls require careful surgical dissection followed by cryosurgery of the base of the wart. A double freeze-thaw-freeze gives the best results. Although the tumor base should be frozen to at least 230.0° C, it is difficult to use thermocouples to monitor temperature in this tissue, so subjective ensurance of adequate freezing by viewing the ice ball may be necessary. Pedunculated penile warts are much easier to treat and less likely to recur than those with a broad base. Vaginal fibropapillomas requiring treatment are rare. When necessary, excision at the base or cryosurgery may be successful. Vaginal warts may have extremely vascular stalks, and ligatures are sometimes necessary to prevent severe hemorrhage during removal.

Flat or rice-grain teat warts seldom are removed, but raised fibropapillomas or papillomas on the teat or teat end that mechanically interfere with milking may have to be removed flush with the skin by scissors.

Individual cattle with large multiple warts that persist indefinitely probably have deficient cell-mediated immunity. This may be a genetic fault or be associated with medical problems such as persistent infection with BVDV or previously bovine leukocyte adhesion deficiency (BLAD). This problem, when unrelated to either persistent infection with BVDV or BLAD, seems more common in beef cattle (especially Herefords) than in the dairy breeds.

Etiology

Dermatophytosis or ringworm is extremely common in dairy calves and may occur in adult cows as well. Trichophyton verrucosum is the most common pathogen, with lesser instances of Trichophyton mentagrophytes and other dermatophytes. Calves over 2 months of age through yearling stage are most commonly affected. This coincides with the ages of young dairy animals that are grouped rather than managed individually. The causative organisms are extremely hardy and survive on inanimate objects, bedding, and soil for months after cattle have been removed. Concentration or grouping of young cattle—especially during the winter months—leads to an increased incidence in herds having the problem. It is not unusual to find yearly epidemics in heifers on farms that have had ringworm in the past. Conversely, herds that do not have clinical ringworm seem to remain free of the problem unless new animals that are infected are introduced. Adult cattle may experience severe infections as well. These outbreaks tend to occur during the winter months and frequently follow infected freshening heifers being introduced into the milking herd. Although adult cows that had ringworm when calves have been assumed to be “immune for life,” the existence of outbreaks in adult cattle raise serious questions as to the longevity of immunity following natural exposure.

Dermatophytes affect the keratinized layers of skin thanks to toxins and allergens with resultant exudation, crusting, and alopecia. Fungal organisms themselves do not invade tissue and survive best when they provoke little host inflammatory reaction. Lesions tend to be oval or circular and are often multifocal. Incubation requires 1 to 4 weeks, and lesions persist for 1 to 3 months in most circumstances. Infection by contact is accelerated by mechanical irritation of the skin by contaminated objects. Stanchions, neck straps, halters, milking straps for old-fashioned bucket milking machines, brushes or curry combs, chutes, and other devices may spread infection through a group of cattle. Chronically ill, unthrifty, poorly nourished, or acutely ill cattle will show diffuse or rapidly progressive lesions compared with herdmates. This may imply either cellular or humoral factors that contribute toward worsening of dermatophytosis. Calves persistently infected with BVDV and calves with BLAD are examples of animals that frequently have severe ringworm lesions, whereas healthy herdmates remain either unaffected or have only mild lesions. Adult cows or heifers with typical ringworm lesions may progress to diffuse lesions when stressed by acute severe infections such as pneumonia or peritonitis. Exogenous corticosteroids will worsen existing ringworm lesions.

Lack of sunlight also has been proposed as a contributing cause because animals penned indoors seem to have a higher incidence. This theory also led many veterinarians to administer vitamins A and D as a treatment. However, the appearance of ringworm in both calves and adult cows during the summer months seems to diminish the importance of sunlight in prevention or cure.

Signs

Round or oval areas of crusting and alopecia that range from 1.0 to 5.0 cm in diameter are typical for ringworm in calves. Early lesions may appear raised because of serum oozing or secondary bacterial pyoderma underlying the crust (Figure 7-4). In calves, the periocular region, ears, muzzle, neck, and trunk are most usually affected, but lesions may occur anywhere (Figures 7-5 and 7-6). Head and neck lesions are common because lock-ins, stanchions, or neck straps become contaminated and help spread the disease. Posts or beams that are used for scratching may provide an area that infects the trunk in a group of heifers. The escutcheon is another area that frequently is affected with one or more lesions. Skin lesions may be painful but are rarely pruritic.

Figure 7-4 Raised, crusted lesions of ringworm involving the facial and periocular region of a Holstein calf.

Figure 7-5 Multifocal ringworm lesions that appear as dry, crusted areas of alopecia of the head, neck, and shoulders in a Holstein heifer.

Figure 7-6 Epidemic ringworm in a group of Holstein yearlings.

(Photo courtesy Dr. Pam Powers.)

In adult cattle, the lesions may be anywhere on the body but often appear on the trunk and neck, with fewer cows showing the typical facial lesions found in calves. In addition to oval and circular lesions, larger geographic lesions of ringworm occasionally appear in adult cattle.

During ringworm outbreaks in adult cattle, individual cows that experience unassociated systemic illness may show dramatic worsening of their ringworm lesions. Ketotic cattle treated with corticosteroids also will show worsening of the ringworm condition. Adult cattle also may have lesions on the udder, skin of the flank, or hind limbs that increase the risk of zoonotic disease because these lesions occur where milkers come into contact with the animals. Lesions of ringworm in milkers or handlers of infected cattle are a common occurrence. Ringworm is the most common example of a zoonosis in cattle practice.

Diagnosis

Cultures of hair from the peripheral zone of a lesion on selective media such as dermatophyte test medium, scrapings of lesions for mineral oil or potassium hydroxide preps, or skin biopsies can be used to confirm the diagnosis, but clinical signs usually suffice. Early lesions may be sufficiently raised in appearance to mimic warts or other lesions, but careful examination will differentiate them.

Treatment

Although hundreds of products have been used to treat ringworm in cattle, few have been shown to be efficacious. The self-limiting nature of ringworm infection in most cattle that are otherwise healthy makes it difficult to assess how much, if at all, the treatment helped natural healing. Controlled studies are essential for any product to be proven as efficacious against ringworm.

Treatment often is requested because of zoonotic potential or because an affected heifer or cow has been selected to go to a show or a sale. Animals with ringworm, as with warts, are ineligible for admission to shows or sales. This latter situation often leads to the sudden “emergency” status of ringworm even though it has been present on the animals for months.

Before discussing various treatments, one must realize the magnitude of the labor required to treat hundreds of ringworm lesions in a group of calves, heifers, or cows. The failure of treatment and lack of owner interest in it are simply based on the sometimes impossible task of catching, restraining, and treating groups of heifers. Treatment more often involves selected animals that need to be “cured” so they can enter a fair or a show. Owners who are willing to treat their calves also should be educated about disinfection and prevention.

Topical treatments that probably are efficacious are:

Numbers 1 through 3 are applied as a spray or dip daily for 5 days, then once weekly until cured.

Topical treatments that may be effective for limited lesions or selective treatment of a few animals:

Systemic treatment that probably is efficacious:

Systemic treatments that may be efficacious:

For best results, animals that are treated with any of the aforementioned products should first have their lesions scraped or brushed to remove the infective crusts. Clipping also may be helpful but risks spread of the infection. Remember that brushes, curry combs, and clippers used on infected animals should be cleaned and disinfected. Workers handling the cattle should wear gloves or wash thoroughly following handling of the animals with an iodophor or tincture of green soap.

Disinfection of premises and fomites offers the best opportunity to avoid future outbreaks. Physical cleansing and pressure spraying can be followed with lime sulfur or Clorox disinfection. Premises should be allowed to dry and supplied with new bedding. Only animals without detectable lesions should be reintroduced.

Vaccines have been developed in some parts of the world and have been reported to be efficacious; however, they are not available in the United States.

Etiology

Dermatophilosis, also called Streptothricosis or rain scald, is a common skin infection of cattle and other large animals caused by Dermatophilus congolensis. Moist environmental conditions and long hair coats predispose to contagious infection by D. congolensis. Rain and snow that wet hair coats and cause matting present the greatest opportunity for infection. In addition to moisture and long hair, physical damage to the skin seems to be necessary because D. congolensis is thought not to be able to invade healthy skin. Depending on the region and time of year, external parasites such as flies and lice may sufficiently injure skin and also help spread the infection. Other sources of skin injury include abrasions from scratching, rubbing, or licking and moist dermatitis that develops under wet matted hair.

D. congolensis probably is part of the normal skin flora in some cattle and is known to proliferate in a moist environment. Cattle that are highly stressed by illness, transient or long-standing alterations of their immune status, or treated with corticosteroids may develop severe lesions.

Heifers that are housed outside and some herds of adult cattle that have access to outdoor environments each day are most at risk for dermatophilosis.

Signs

In animals housed outdoors, a crusty dermatitis along the topline represents the classical distribution of dermatophilosis. Animals with short hair coats may have a folliculitis with mild raised crusts and tufts of hair, whereas more classical cases with long hair coats have thick tufts of matted hair and crusts that can be plucked off to expose a thick, yellow-green pus on the skin and attachment areas of crust. Pink areas of dermis may be apparent after removal of crusted tufts of hair (Figure 7-7).

Figure 7-7 A crusted tuft of hair being removed from a cow infected with dermatophilosis. Although the underside of this tuft appears somewhat dry, more typical cases will have a thick pus evident.

Cattle that have access to farm ponds, deep mud, or lush wet pastures may develop lesions on the lower limbs and muzzle rather than the classical dorsal distribution. Bulls may develop the lesions on the skin of the scrotum, and occasionally cows develop lesions on the udder and/or teats (see Chapter 8).

Dermatophilosis that becomes widespread or covers more than 50% of the body surface may be fatal. Fortunately severe dermatophilosis is rare in the United States but remains a serious cause of cattle mortality in tropical climates, where greater heat and humidity coupled with more profound insect loads exist (Figure 7-8). Death may occur in severe cases as a result of debility, discomfort, protein loss, and septicemia.

Figure 7-8 Unusually severe dermatophilosis in a single Holstein cow from a New York herd. A heavy summer fly load apparently contributed to the diffuse spread of the organism in this cow. That no other herdmates were affected and that the disease occurred during July both were unusual in this case.

Animals with long hair coats, crusts of matted hair with underlying pus, and a dorsal distribution, especially over the gluteals, loin, and withers, are easily diagnosed by physical examination. Animals with short hair coats that have signs of folliculitis or lesions on the extremities may present a difficult differential diagnosis that includes staphylococcal folliculitis, viral infections, zinc-responsive dermatoses, dermatophytosis, and immune-mediated dermatoses.

Diagnosis

When pus can be found underneath plucked tufts of hair or on the bottom of the detached tuft, it provides an excellent diagnostic specimen for direct microscopic examination. Smears may be examined with Gram stain, new methylene blue, or Diff-Quik (Baxter Healthcare) to look for chains of branching and multiseptate coccoid bacteria resembling hyphae and clumps of gram-positive coccoid cells arranged in characteristic parallel rows (“railroad tracks”). When pus cannot be found, diagnosis is made more difficult. Crusts may be ground up and made into smears for microscopic examination, but the most helpful techniques remain skin biopsy and culture. Histopathology may show folliculitis, intracellular edema of keratinocytes, and surface crusts with alternating layers of keratin and leukocytic debris (palisading crust); the organisms may be observed in crusts or other locations. Gram stain used on sections may highlight the organisms more so than standard hematoxylin and eosin.

Treatment

Treatment is difficult and time consuming. In wet or damp, cold environments, the thought of bathing large numbers of cows to treat the condition is dismissed quickly by most owners. Infections often resolve spontaneously over several weeks if affected animals can be kept dry. In addition to keeping the animals dry, it is helpful to remove tufts of crusted hair or to clip matted hair to reduce the numbers of organisms present. Whenever possible, combining grooming with an iodine or chlorhexidine shampoo is an excellent treatment. Unlike ringworm, dermatophilosis lesions seldom are focal enough to be treated individually. Therefore overall grooming or clipping usually is necessary. Clippers, combs, and other grooming equipment must be thoroughly disinfected before reuse with chlorhexidine, iodophors, or bleach to prevent cross-contamination. The rational treatment of the disease also is complicated by the fact that in the winter animals may need as much hair as possible to survive outdoors. Unless there is an opportunity for indoor housing, owners are reluctant to clip hair. Systemic therapy with penicillin or oxytetracycline is highly efficacious and can be life saving for animals with diffuse disease. Therefore standard treatment recommendations include:

Human infections with D. congolensis are possible, and veterinarians should advise handlers to wear gloves and wash themselves with iodophor soaps after handling or treating affected cattle.

Etiology

Lymphosarcoma may involve the skin in the classic “skin form” of lymphosarcoma, wherein affected cattle usually are serologically negative for antibodies against the bovine leukemia virus (BLV), or as sporadic skin tumors associated with lymphadenopathy and other organ involvement with the adult form of lymphosarcoma that occurs in BLV-positive animals.

The skin form of lymphosarcoma usually occurs in cattle 6 to 24 months of age and is a progressive disease causing multifocal skin tumors. Lymphadenopathy may accompany the skin lesions. The skin form of lymphosarcoma is observed in all breeds but is most common in Holsteins. This may simply reflect the number of Holsteins in the United States. Genetic predisposition has not been demonstrated, and association with BLV has not been confirmed. Skin tumors caused by lymphosarcoma in adult cattle are uncommon compared with tumors in more typical target organs (e.g., abomasum, heart, uterus, retrobulbar area, and lymph nodes) but may reach sizeable proportions in some affected cattle.

Signs

Diffuse nodular skin masses (1.0 to 10.0 cm in diameter) develop over the neck and trunk of young cattle with the skin form of lymphosarcoma. Lesions are initially dermal or subcutaneous, and the overlying skin appears normal. However, alopecia, crusting, hyperkeratosis, and ulceration develop with time. The tumors may become numerous enough to obliterate any normal skin spaces between them (Figure 7-9). Tumors may occur on the skin over any portion of the body. Peripheral lymph nodes are usually enlarged. The heifer or young cow seems otherwise healthy at the onset. However, over a period of 6 to 12 months, affected animals become uncomfortable because of the tumor burden, and visceral masses may develop. Fly and other insect irritation can be intense during warm weather, causing bleeding from the enlarging nodular tumors, which may have become alopecic (Figure 7-10). Most cases are BLV negative.

Figure 7-9 The skin form of lymphosarcoma in an 18-month-old Holstein heifer.

Figure 7-10 A 4-year-old Holstein with the cutaneous form of lymphosarcoma involving the udder.

In adult cattle with lymphosarcoma, singular or multiple skin tumors may appear along with typical signs of lymph node enlargement and target organ lesions. Skin tumors in this form are larger, often plaquelike, and may be on the neck, chest or trunk, or eyelids. Physical examination usually identifies other lesions or locations of lymphosarcoma.

Fine needle aspirates or skin biopsies are the best means of definitive diagnosis for lymphosarcoma. Although advanced cases of the skin form are unlikely to require diagnostics, early cases with fewer lesions may require differentiation from other neoplasms and diseases such as urticaria and infectious or sterile granulomas.

Treatment

Although corticosteroids may reduce the size of tumors or result in short-term remission, it is impractical to treat cattle with lymphosarcoma because the tumors can never be fully controlled, and the animal will suffer a prolonged course or complications as a result of the medication.

Signs

Clinical signs of a pink, cobblestone, raised or ulcerated mass arising from a depigmented area of skin are pathognomonic for squamous cell carcinoma (Figure 7-12). Frequently a white or yellow “cake frosting” of necrotic material covers the pink, highly vascular tumor surface, and an anaerobic or necrotic odor is detectable. Heavy purulent discharges make the tumors greatly attractive to flies and maggots. Biopsies are preferable to cytology for definitive diagnosis.

Figure 7-12 Squamous cell carcinoma of the nictitans in a Holstein cow.

Treatment

Treatment may be easy or may be impossible based on the size of the tumor, its anatomic location, and the lack or presence of obvious metastases to regional lymph nodes.

Small squamous cell carcinomas are amenable to many treatment modes such as cryosurgery, radiofrequency hyperthermia, radiation, immunotherapy, or even sharp surgery. Each tumor must be evaluated by anatomic location, how much tissue may be destroyed without loss of tissue function (e.g., an eyelid), and expense of treatment. Treatment is addressed in detail in Chapter 13. In general, cryosurgery, radiofrequency hyperthermia, and radiation are the best treatments for small tumors and allow preservation of critical normal structures. Immunotherapy, especially with intratumor injections of Bacillus Calmette Guérin (BCG) or other mycobacterial cell wall products, will risk future tuberculosis tests being positive but may be helpful in large tumors. Other topical or intralesional treatments that are used in horses for sarcoids could be beneficial but no reports are available. Regional lymph nodes should be palpated and biopsied if they appear enlarged or firm, thus possibly indicating metastasis. Metastases have been reported to occur in about 10% of squamous cell carcinomas, but clinically, obviously neglected or large tumors are more likely to metastasize than early or small lesions.

Etiology

Urticaria, angioedema, and anaphylaxis are the most obvious clinical consequences of hypersensitivity reactions or “allergic” reactions. Urticaria (hives) appears as skin wheals or mucous membrane swellings as a result of dermal edema (Figure 7-13). Angioedema tends to imply larger swelling or plaques of edema that involve subcutaneous tissue. Anaphylaxis is the life-threatening extreme manifestation of these hypersensitivity reactions, and its rapid onset causes severe respiratory and cardiovascular signs resulting from smooth muscle contraction and vascular alteration. Anaphylaxis usually is fatal unless attended immediately and may or may not have urticaria and angioedema associated with it. A plethora of drugs, feeds, and other stimuli may evoke hypersensitivity reactions in calves and adult cattle. The exact immunologic phenomenon or type of hypersensitivity reaction (types I through IV) is sometimes difficult to determine, but most probably represent type I and type III hypersensitivity reactions. Type I hypersensitivities are IgE mediated, whereas type III are associated with immune complexes. Type I hypersensitivities cause mast cell and basophil degranulation with subsequent release of histamine, leukotrienes, prostaglandins, and other mediators. Type I reactions probably provoke most ruminant causes of urticaria, angioedema, and anaphylaxis. Type III reactions may include some drug-induced causes, but this conclusion is largely speculative.

Figure 7-13 Urticaria on the thorax and flank of an adult Holstein cow. Raised tufts of hair appear over painful areas of dermal edema. These lesions appeared within 20 minutes following an IM injection of ampicillin.

In dairy cattle, most cases of urticaria, angioedema, and anaphylaxis result from injections of various products, including antibiotics, vaccines, whole blood, lidocaine, and IV fluids. Insect bites occasionally cause urticaria and angioedema but seldom anaphylaxis. Milk allergy is another important cause of urticaria, angioedema, and anaphylaxis that ranges from mild to severe in individual patients. Milk allergy is observed in cattle (any breed but more commonly Channel Islands breeds) at drying off or when delays in milking occur either accidentally or intentionally when showing or selling cattle. Alpha-casein appears to be the milk protein that causes type I hypersensitivity in these cows.

Virtually any antibiotic can cause sporadic hypersensitivity reactions. Penicillin, tetracycline, ampicillin, various sulfonamides, and streptomycin have been incriminated. It is important to differentiate procaine reactions from true hypersensitivity to penicillin when procaine penicillin has been given. Many owners and veterinarians interpret the relatively common procaine reactions as penicillin hypersensitivity, and this is wrong. Cattle with procaine reactions may still be safely given penicillin.

Vaccines are the most common cause of anaphylaxis. Although serum origin products are used less frequently, many “antisera” are still available on the market, and these are especially dangerous as causes of both immediate and delayed hypersensitivity reactions. Polyvaccines have gained favor in the cattle industry, and it is not unusual to give a single shot that contains antigens of four viruses, five serotypes of leptospirosis, and a vehicle. Reactions to such polyvaccines make determining the causative antigen difficult. Strain 19 Brucella vaccine occasionally has caused either immediate or delayed hypersensitivity reactions. A rare reaction involves the larynx, causing severe laryngeal edema within 24 hours of strain 19 vaccine. Although some vaccines are more notorious than others as causes of anaphylaxis, any vaccine may cause occasional reaction. Various gram-negative bacterins containing slight amounts of bacterial-origin endotoxin can induce reactions that mimic anaphylaxis through a genetic sensitivity—especially in Holsteins. This theory may explain why reactions are seen in some herds but not in others.

Whole blood or plasma may cause skin hypersensitivity reactions when administered IV. Transfusion reactions are possible because of genetic blood types or too rapid administration. IV fluids, especially formulated fluids, occasionally cause hives and angioedema. This is most likely a result of contaminants, cleaning chemicals incompletely rinsed from large fluid jugs, or endotoxin.

Hypoderma larvae that are killed in situ have caused anaphylactic reactions or reactions to toxins that mimic anaphylactic reactions. Feeds certainly may cause hypersensitivity reactions in individual cattle.