JPC SYSTEMIC PATHOLOGY

INTEGUMENT SYSTEM

September 2016

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:  Disrupting 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 (necrosis), 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 obscure vessel walls.  Multifocally, there are moderate amounts of vaccine product, characterized by amphophilic granular material, both within macrophages and free in the extracellular matrix.  Within the overlying dermis, hair follicles and adnexa are small and superficial (atrophic) with fragmented hair shafts and are surrounded by similar pale, “smudgy” collagen.  The superficial dermis is multifocally infiltrated by low numbers of macrophages, lymphocytes, and neutrophils, and there is rare pigmentary incontinence.  There multifocal globular deposits of excess melanin pigment within hair shafts and epithelium of the external root sheaths.  The overlying epidermis is multifocally minimally hyperplastic and focally eroded with replacement by a serocellular crust composed of degenerate neutrophils, hemorrhage, serum and fibrin.  Previously described inflammatory cells multifocally infiltrate the panniculus carnosus and skeletal muscle fibers are occasionally degenerate or necrotic.

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

CONDITION:  Post-rabies vaccination panniculitis

SYNONYMS:  Poodle patch

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, but miniature or toy poodles, bichon frises, Yorkshire terriers, and silky terriers are predisposed; this may be due to the long anagen hair growth cycle in these breeds
• Panniculitis is inflammation of subcutaneous fat
• Usually develops 2-3 months after subcutaneous inoculation with a rabies vaccine, but may take longer
• Does not resemble post-injection panniculitis of cats
• Gross et al., have noted exacerbation of previous lesions as well as development of new lesions after repeated rabies vaccinations
• No age or gender predilection have been noted

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
• A few dogs may be lethargic and febrile and rarely have elevated liver enzymes
• Rarely, some dogs develop chronic rear limb pitting edema and swelling believed to be associated with a rabies vaccine administered in that limb
• Hyperpigmentation may be an occasional sequela, especially in black miniature poodles or other breeds that tend to accumulate pigment in response to inflammation
• A subset of dogs develop "generalized vaccine-induced ischemic dermatopathy" with severe, widespread alopecia and skin lesions in conjunction with lethargy and depression that can mimic familial canine dermatomyositis

TYPICAL GROSS FINDINGS:

• 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 or 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:

• Lesions are highly characteristic: Follicular atrophy with diffuse pallor and smudging of the dermal and pannicular collagen (due to ischemia) accompanied by a very mild cell-poor lymphocytic vasculitis which may not be present in all cases
• Nodular accumulations of lymphocytes, fewer macrophages, and occasional plasma cells are in the deep dermis and panniculus at the site of vaccination in the subcutis, often around vessels
• Amorphous blue-to-gray granules (vaccine material) may be present within macrophages or free in the extracellular matrix
• Cell-poor vasculitis of small vessels is common but may be subtle; vessels may have thick walls infiltrated by lymphocytes, and the endothelium may be reactive
• A cell-poor interface dermatitis is occasionally present with vacuolar change in the basal epithelial layer, pigmentary incontinence and mural folliculitis
• Edema and/or mucin may be prominent
• Subtle satellite lesions may be present
• In cases of chronic rear leg swelling, the panniculitis is more extensive with severe diffuse edema
• Eosinophils are not observed in lesions associated with rabies vaccination sites, although they are often present in reactions to other vaccine products

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:

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
• 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
• 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 variable but follicular atrophy and perifolliculitis 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

REFERENCES:

1. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Infectious nodular and diffuse granulomatous and pyogranulomatous diseases of the dermis. In: Skin Diseases of the Dog and Cat, Clinical and Histopathological Diagnosis. 2nd ed. Ames, IA: Blackwell; 2005: 538-542.
2. 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: 542, 612-614.
3. Miller WH, Griffin CE, Campbell KL. Small Animal Dermatology. 7th ed., St. Louis, MO: Elsevier Mosby; 2013:483, 561-563. 

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