History
A 2.5-year-old neutered male Bichon Frise crossbred dog was evaluated because of a sparsely haired, nonpruritic area on the left side of its neck. The lesion had been present for approximately 5 months and first appeared as 2 small areas that subsequently enlarged and coalesced. The dog reportedly had been injected with a killed rabies virus vaccinea and a combination vaccineb against distemper, hepatitis, leptospirosis, and diseases associated with parainfluenza virus and parvovirus by another veterinarian 1 month before the lesion appeared.
Clinical Findings
On initial evaluation, an alopecic patch (13 × 5 cm) with hyperpigmentation and lichenification was evident on the left side of the dog's neck (Figure 1). The physical examination findings were otherwise unremarkable. No bacteria or yeast organisms were detected cytologically in an impression smear of the epidermis. Results of a microscopic examination of a skin scraping were negative for parasites. Serum thyroxine and thyroid-stimulating hormone concentrations were apparently normal (2.35 μg/dL [reference range, 1.3 to 4.0 μg/dL] and 0.007 ng/mL [reference range, 0.00 to 0.65 ng/mL], respectively). Punch biopsy specimens of skin were collected for bacteriologic and histologic evaluation. Bacterial culture of the skin specimens yielded no growth.
Photographs illustrating an area of nonpruritic alopecia that developed on the left side of the neck of a Bichon Frise crossbred dog 1 month after vaccination. A—The lesion had been present for approximately 5 months and had first appeared as 2 small areas that enlarged and coalesced into an alopecic and pigmented patch on the left side of the neck. B—In close-up view, notice the hyper-pigmentation and lichenification within the alopecic region.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photographs illustrating an area of nonpruritic alopecia that developed on the left side of the neck of a Bichon Frise crossbred dog 1 month after vaccination. A—The lesion had been present for approximately 5 months and had first appeared as 2 small areas that enlarged and coalesced into an alopecic and pigmented patch on the left side of the neck. B—In close-up view, notice the hyper-pigmentation and lichenification within the alopecic region.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photographs illustrating an area of nonpruritic alopecia that developed on the left side of the neck of a Bichon Frise crossbred dog 1 month after vaccination. A—The lesion had been present for approximately 5 months and had first appeared as 2 small areas that enlarged and coalesced into an alopecic and pigmented patch on the left side of the neck. B—In close-up view, notice the hyper-pigmentation and lichenification within the alopecic region.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histologic Findings
The most severe histologic changes were evident in the biopsy specimens collected from the center of the lesion. Histologic features of diagnostic importance included follicular atrophy, edema, and panniculitis (Figure 2). The epidermis was thin (generally approx 2 cell layers in thickness) with loose orthokeratotic hyperkeratosis that also distended follicular infundibula. Sebaceous glands were small but present in most follicular units. Hair follicles were in the telogen stage, generally lacked a hair shaft in the plane of section, and were severely atrophied (Figure 3). The superficial dermis and the connective tissue around the external root sheath of hair follicles had a pale washed-out or rarefied appearance attributable to decreased eosin uptake and loss of definition of collagen fibers. Melanophages and a few lymphocytes were scattered through the superficial dermis; elsewhere, dermatitis was mild, perivascular to perifollicular, and predominantly lymphocytic. Inflammation was concentrated in the subcutis where coalescing nodules (up to 2 mm in diameter) of lymphocytes and plasma cells were organized around small vessels (Figure 4). Some vessels had disrupted endothelium with light mural infiltration by lymphocytes.
Photomicrograph of a section of affected haired skin from the center of the lesion on the neck of the dog in Figure 1. Notice the epidermal hyperkeratosis (top of image), marked follicular atrophy (arrows), areas of pallor in the dermis and subcutis, and coalescing nodules (asterisks) of leukocytic infiltration around vessels in the subcutis. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of affected haired skin from the center of the lesion on the neck of the dog in Figure 1. Notice the epidermal hyperkeratosis (top of image), marked follicular atrophy (arrows), areas of pallor in the dermis and subcutis, and coalescing nodules (asterisks) of leukocytic infiltration around vessels in the subcutis. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of affected haired skin from the center of the lesion on the neck of the dog in Figure 1. Notice the epidermal hyperkeratosis (top of image), marked follicular atrophy (arrows), areas of pallor in the dermis and subcutis, and coalescing nodules (asterisks) of leukocytic infiltration around vessels in the subcutis. H&E stain; bar = 500 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of affected dermis from the lesion on the neck of the dog in Figure 1. Hair follicles (arrows) are in telogen stage and severely atrophied. Notice the pallor and blurring of dermal collagen fibers (open arrows), especially those around the external root sheath. Leukocytic infiltration (predominantly lymphocytic) is concentrated around vessels and apocrine sweat glands. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of affected dermis from the lesion on the neck of the dog in Figure 1. Hair follicles (arrows) are in telogen stage and severely atrophied. Notice the pallor and blurring of dermal collagen fibers (open arrows), especially those around the external root sheath. Leukocytic infiltration (predominantly lymphocytic) is concentrated around vessels and apocrine sweat glands. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of affected dermis from the lesion on the neck of the dog in Figure 1. Hair follicles (arrows) are in telogen stage and severely atrophied. Notice the pallor and blurring of dermal collagen fibers (open arrows), especially those around the external root sheath. Leukocytic infiltration (predominantly lymphocytic) is concentrated around vessels and apocrine sweat glands. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of subcutis from the lesion on the neck of the dog in Figure 1. Dense accumulations of lymphocytes and plasma cells form nodules around subcutaneous vessels (asterisks). A few lymphocytes infiltrate the vascular wall. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of subcutis from the lesion on the neck of the dog in Figure 1. Dense accumulations of lymphocytes and plasma cells form nodules around subcutaneous vessels (asterisks). A few lymphocytes infiltrate the vascular wall. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Photomicrograph of a section of subcutis from the lesion on the neck of the dog in Figure 1. Dense accumulations of lymphocytes and plasma cells form nodules around subcutaneous vessels (asterisks). A few lymphocytes infiltrate the vascular wall. H&E stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 238, 9; 10.2460/javma.238.9.1115
Morphologic Diagnosis
Lymphoplasmacytic panniculitis with vasculitis, follicular atrophy, and perivascular lymphocytic dermatitis with edema and smudged collagen fibers.
Comments
For the dog of this report, the initial clinical differential diagnoses included injection-site reaction, bacterial infection or dermatophytosis, insect-bite hypersensitivity, and alopecia areata. An injection-site reaction was considered the most likely cause of the lesion because of its clinical appearance, location, and development after vaccination. The bacterial culture results and cytologic findings helped to rule out bacterial infection and dermatophytosis. An arthropod-bite reaction of this size might be expected to be a palpable nodule rather than a macule. Alopecia areata typically affects facial skin but could not be ruled out clinically in this case. Histologically, the paucity of neutrophils or eosinophils at any level of the skin and the lack of folliculitis helped to rule out all differential diagnoses except injection-site reaction. The histologic findings of lymphoplasmacytic panniculitis with vasculitis, follicular atrophy, dermal edema, and pallor and loss of definition (smudging) of collagen fibers were considered typical of ischemic dermatopathy associated with rabies virus vaccination.1
Post–rabies vaccination panniculitis is detected most commonly in Toy and Miniature Poodles and in Bichon Frises.1,2 The presence of rabies viral antigen in the walls of cutaneous vessels is the cause of the vasculitis that develops in this condition.2 Clinically, the reaction is typified by a variably sized area of alopecia with irregular margins that develops at the injection site 2 to 4 months after vaccination. The lesion is initially thickened, plaque-like, and erythematous and subsequently becomes scaly and hyperpigmented.3 The follicular atrophy and alopecia as well as the dermal edema and smudging of collagen fibers are attributed to ischemia secondary to cutaneous vasculitis; hence, the condition is known as ischemic dermatopathy. Rarely, ischemic dermatopathy may become generalized or vasculitis may develop in tissues other than skin.4
Topical treatment of the dog with 0.1% tacrolimus ointmentc was recommended for 30 days, but the owner declined to undertake that treatment. Tacrolimus ointment has local immunomodulatory effects. It is a macrolide lactone, produced by the fungus Streptomyces tsukubaensis, that inhibits T-lymphocyte activation by inhibiting the phosphatase activity of calcineurin with resultant decreased production of interleukin-2. It also downregulates cytokine expression in mast cells, basophils, eosinophils, keratinocytes, and Langerhans cells. The most common adverse effect of topical application of this drug is cutaneous irritation and erythema at the treatment site.5 Pentoxifylline (100 mg, PO, q 12 h) was prescribed for the dog. Pentoxifylline is a synthetic methylxanthine derivative that increases erythrocytic and leukocytic deformability, inhibits adhesion of leukocytes to endothelium, decreases platelet aggregation, decreases cytokine production, and inhibits lymphocyte activation.6,7 The mechanisms of action are not fully understood, but the drug probably increases erythrocyte deformability by inhibiting erythrocyte phosphodiesterase and decreases coagulability by reducing plasma fibrinogen concentration and increasing fibrinolytic activity.7 In 1 report,4 skin disease was improved in 3 dogs with vaccine-induced ischemic dermatopathy after oral treatment with pentoxifylline and vitamin E.
Post–rabies vaccination panniculitis is typically clinically inapparent,1 and treatment may not be necessary. Spontaneous hair regrowth may occur but can take up to 1 year and may be associated with altered pigmentation.3 If alopecia is permanent, surgical excision is an option.3 Dogs that develop post–rabies vaccination panniculitis may react to subsequent vaccinations. Thus, in previously affected dogs, it is advisable to use rabies virus vaccines that require administration every 3 years, avoid administration of multiple vaccines at 1 time, and inject the vaccines IM.3 In the dog of this report, the response to treatment could not be evaluated because of poor owner compliance and loss of the patient to follow-up. Because of the expense, the owner did not treat the dog topically with tacrolimus ointment and only administered pentoxifylline for 1 month.
Rabvac 1, Fort Dodge Animal Health, Fort Dodge, Iowa.
Duramune Max 5/4L, Fort Dodge Animal Health, Fort Dodge, Iowa.
ProTopic, Astellas Pharma US Inc, Deerfield, Ill.
References
- 1.↑
Gross TLIhrke PJWalder EJ, et al. Diseases of the panniculus. In: Skin diseases of the dog and cat. 2nd ed. Ames, Iowa: Blackwell, 2005;538–558.
- 2.↑
Wilcock BPYager JA. Focal cutaneous vasculitis and alopecia at sites of rabies vaccination in dogs. J Am Vet Med Assoc 1986; 188:1174–1177.
- 3.↑
Medleau LHnilica KA. Cutaneous vasculitis. In: Small animal dermatology: a color atlas and therapeutic guide. 2nd ed. Philadelphia: WB Saunders Co, 2001;216–217.
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Vitale CBGross TLMagro CM. Vaccine-induced ischemic dermatopathy in the dog. Vet Dermatol 1999; 10:131–142.
- 5.↑
Wolters Kluwer Health. Dermatologic agents. In: Drug facts and comparisons. St Louis: Drug Facts and Comparisons Publishing Group, 2009;1660d.
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Samlaska CPWinfield EA. Pentoxifylline. J Am Acad Dermatol 1994; 30:603–621.
- 7.↑
Plumb DC. Pentoxifylline. In: Veterinary drug handbook. 6th ed. Ames, Iowa: Blackwell Publishing, 2008;714–715.
