JPC SYSTEMIC PATHOLOGY
INTEGUMENTARY SYSTEM
September 2022
I-M35

Signalment (JPC #3070330):  One-year-old neutered male Chihuahua

HISTORY:  Focal alopecia in the right scapular area at the site of a rabies vaccination that was given 12 weeks previously.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin and subcutis: Effacing and replacing over 80% of adipocytes within the panniculus adiposus there is an inflammatory infiltrate surrounded by abundant pale, “smudgy” collagen exhibiting diminished fiber detail and decreased birefringence (degeneration), admixed with fibrin, edema, and necrotic debris. The inflammatory infiltrate is composed of numerous macrophages with abundant microvacuolated cytoplasm, few neutrophils, and numerous lymphocytes and plasma cells that often form dense perivascular nodular aggregates and efface vessel walls (vasculitis). Multifocally, there is a moderate amount of amphophilic granular material both within macrophages and free in the extracellular matrix (vaccine product).  Within the overlying dermis, hair follicles and adnexa are small (atrophic) and superficial (telogenization) with fragmented hair shafts and globular deposits of melanin within hair shafts and the external root sheaths, and are surrounded by similar pale, “smudgy” collagen. The superficial dermis is multifocally infiltrated by low numbers of macrophages, lymphocytes, and neutrophils. The overlying epidermis is minimally hyperplastic and focally eroded with replacement by degenerate neutrophils, serum, and fibrin. Previously described inflammatory cells multifocally infiltrate the panniculus carnosus, and skeletal muscle fibers are occasionally degenerate with pale eosinophilic sarcoplasm and loss of cross-striations or necrotic with hypereosinophilic fragmented sarcoplasm.

MORPHOLOGIC DIAGNOSIS:  Haired skin and subcutis:  Panniculitis, granulomatous, diffuse, marked, with follicular atrophy and telogenization, extracellular and intrahistiocytic vaccine material, follicular melanin clumping, and lymphoplasmacytic perivascular dermatitis, Chihuahua, canine.

CONDITION:  Post-rabies vaccination panniculitis

SYNONYMS:  Poodle patch, vaccine-associated ischemic dermatopathy

GENERAL DISCUSSION:

• An ischemic dermatopathy leading to alopecic, hyperpigmented patches of atrophic skin that is associated with subcutaneous administration of rabies vaccines in dogs
• All breeds are affected; Poodles, Yorkshire Terriers, and Silky Terriers are most commonly affected (long anagen-phase hairs)
• 2 clinical presentations – localized form and generalized form
  • Generalized form is similar in appearance to canine familial dermatomyositis
  • Localized form develops several months after injection

PATHOGENESIS:

• The lesion is a focal, cell-poor vasculitis with subsequent ischemic necrosis of the adjacent panniculus and overlying dermis with follicular atrophy
• Rabies virus antigen has been identified in the walls of affected vessels and in the follicular epithelium
• Pathogenesis unknown, but type III hypersensitivity has been proposed with immune mediated vasculitis

CLINICAL FINDINGS:

• Lesions are usually asymptomatic
• Hyperpigmentation may be an occasional sequela, especially in black miniature poodles or other breeds that tend to accumulate pigment in response to inflammation

TYPICAL GROSS FINDINGS:

• Visually distinctive: 2-10 cm alopecic, depressed, hyperpigmented patch or macule/plaque at site of prior subcutaneous rabies vaccination, usually at vaccine site, i.e. caudal lateral thigh, withers or in neck or shoulder region near scapula, but gravitational shift can lead to lesions on the lateral or ventral thorax
• Inflammation is generally not visible grossly

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Mild chronic lymphocytic vasculitis
• Cell-poor interface dermatitis, vacuolation in basal cell layer, pigmentary incontinence, and mural folliculitis
• Amorphous blue-to-gray granules (vaccine material) may be present within macrophages or free in the extracellular matrix
• Atrophy and hyalinization of the dermis with mucin
• Marked atrophy and pale staining of hair follicle

ADDITIONAL DIAGNOSTIC TESTS:

• The lesion is visually distinctive, but biopsy for histopathologic evaluation should be obtained from affected skin and subcutis at the outer margin of the lesion

DIFFERENTIAL DIAGNOSIS:

There are five subtypes of ischemic dermatopathies in dogs including post-rabies vaccination panniculitis (vaccine-associated ischemic dermatopathy). The other four are:

• canine familial dermatomyositis (Collies and Shelties)
• juvenile-onset ischemic dermatopathy (similar to canine familial dermatomyositis but without breed predisposition)
• generalized vaccine-induced ischemic dermatopathy
• adult-onset non–vaccine-induced generalized ischemic dermatopathy

For gross findings:

• Focal demodicosis, dermatophytosis, alopecia areata (spot baldness), cicatricial alopecia (scarring alopecia) and erythema ab igne (chronic radiant heat dermatitis), lupus profundus (mild variant of cutaneous lupus erythematosus), traction alopecia (low grade ischemia), idiopathic vasculopathy, Familial cutaneous vasculopathy of German shepherd dogs (includes pawpad swelling), sterile granulomatous panniculitis
• Sterile abscess of repositol injection: "drip configuration" of solitary pannicular nodule composed of uniformly degenerate neutrophils, frank necrosis, no recognizable adipocytes and a thin fibrous capsule; overlying skin is normal
• Post-injection panniculitis: Often forms a discrete granuloma/pyogranuloma +/- vaccine material; the overlying dermis and hair follicles are normal
• Canine subcutaneous panniculitis-like T-cell lymphoma (Noland, Vet Pahol. 2018)

For generalized condition:

• Dermatomyositis: idiopathic inflammatory condition involving skin and muscle, causing crusting and alopecia, most commonly on head and over bony prominences; skin changes are variable but follicular atrophy and perifolliculitis are most consistent

COMPARATIVE PATHOLOGY:

• Cats: Post-injection panniculitis is common in the cat but rare in the dog; it is a combined foreign-body and hypersensitivity reaction purportedly caused by vaccines, antibiotics, or potassium bromide injections; overlying skin is usually normal; panniculus contains a discrete granuloma or pyogranuloma with a necrotic center which often contains injected material and, occasionally, intrahistiocytic lipid-rich material; epithelioid macrophages are surrounded by dense zones, or follicles, of lymphocytes, +/- eosinophils
• May progress to vaccine-associated sarcoma
• Horses: After prolonged exposure to flood waters, 5 horses exhibited ischemic perivascular dermatitis with vasculitis and coagulative necrosis (ischemia) (Taylor, Vet Pathol. 2020)
• Sheep: SQ granulomas associated with aluminum adjuvant vaccines: Aluminum adjuvant vaccines generated persistent sterile granulomas with macrophages carrying aluminum to LNs/systemically. (Asin, Vet Pathol. 2019)

REFERENCES:

1. Asín J, Molín J, Pérez M, et al. Granulomas Following Subcutaneous Injection With Aluminum Adjuvant-Containing Products in Sheep. Vet Pathol. 2019;56(3):418-428.
2. Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat: Clinical and Histopathologic Diagnosis. Oxford, UK: Blackwell Science; 2005: 49-52, 538-558.
3. Mauldin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Saunders Elsevier; 2016: 528-529, 541-542.
4. Miller WH, Griffin CE, Campbell KL. Small Animal Dermatology. 7th ed., St. Louis, MO: Elsevier Mosby; 2013: 480, 485-488, 561-563, 804-806.
5. Noland EL, Keller SM, Kiupel M. Subcutaneous Panniculitis-Like T-cell Lymphoma in Dogs: Morphologic and Immunohistochemical Classification. Vet Pathol. 2018;55(6):802-808.
6. Rosa FB, Older CE, Meason-Smith C, et al. Analysis of Bacterial and Fungal Nucleic Acid in Canine Sterile Granulomatous and Pyogranulomatous Dermatitis and Panniculitis. Vet Pathol. 2018;55(1):124-132.
7. Taylor BM, Chaffin MK, Hoffmann AR, Edwards JF, Arenas-Gamboa AM. Immersion Foot Syndrome in 6 Equids Exposed to Hurricane Floodwaters. Vet Pathol. 2020;57(2):290-295.
8. Welle MM, Linder KE. The Integument. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1244-1245.

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