JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

August 2025

I-M04

Signalment (JPC# 1908364): 3-year-old rabbit

HISTORY: Tissue from the rear leg of a pet rabbit found dead in its outdoor hutch.

HISTOPATHOLOGIC DESCRIPTION: Haired skin and subcutis: There is focally extensive full-thickness loss of the epidermis (ulceration) and dermis, with replacement by abundant eosinophilic cellular and karyorrhectic debris (lytic necrosis) and an overlying serocellular crust composed of necrotic heterophils, necrotic cellular debris, foreign material, hemorrhage, eosinophilic fibrillar material (fibrin), and numerous colonies of 1-2 um diameter basophilic coccobacilli. The adjacent epidermal and adnexal epithelium is characterized by a loss of differential staining with retention of tissue architecture (coagulative necrosis). Subjacent to previously describe necrosis blood vessels are lined by reactive endothelium and lumens contain organized, eosinophilic, finely fibrillar material with enmeshed degenerate inflammatory cells (fibrin thrombi). Infiltrating the remaining adjacent viable superficial and deep dermis, surrounding adnexa, and extending into the subcutis and panniculus carnosus are numerous heterophils, macrophages, fewer lymphocytes, plasma cells, and reactive fibroblasts with multifocal hemorrhage. Multifocal myocytes within the panniculus carnosus are characterized by swollen, pale, vacuolated sarcoplasm (degeneration) or are shrunken with hypereosinophilic sarcoplasm, loss of cross-striations, and pyknotic nuclei (necrosis). Multifocally, dermal lymphatics are mildly ectatic (edema).

MORPHOLOGIC DIAGNOSIS: Haired skin and subcutis: Epidermal and dermal necrosis, subacute, focally extensive, severe with heterophilic, and granulomatous dermatitis and myositis, fibrin thrombi, and superficial bacterial colonies, rabbit, lagomorph.

CONDITION: Full‑thickness thermal or chemical burn

GENERAL DISCUSSION:

• Burn classification according to depth of injury:
  • First degree: Involves epidermis only, no vesicles
  • Second degree: Epidermis and part of the dermis are damaged; also known as partial-thickness burns
  • Third degree: Full thickness damage to the dermis and epidermis; epidermis is often completely lost
    • Includes connective tissue, blood vessels, and adnexa
  • Fourth degree – penetrates to and beyond the subcutis, muscle and even bone
  • Irritant contact dermatitis
• Agents of thermal injury: Boiling fluid (70° C water burns in 1 second); steam; fire; heating pads (administration of subcutaneous fluids may allow burning at very low heating pad settings); drying cages; X‑rays; ultraviolet rays or microwaves; electricity (wire chewing and lightning strike); mechanical injury (rope burn)Agents of chemical burns: Medications (flea powder); cleaning and carpet chemicals; acids, alkalis, kerosene, turpentine, antiseptics
• Full extent of burn may not be apparent for 48-72 hours (fire, hot metal) and up to 7 days (chemical, solar, electric, microwave)
• Differentiation between thermal and chemical burns may be impossible without visible chemical residue or history
• Thermal injury usually occurs where hair inadequately protects the skin
• Chemical burns are usually present on footpads (interdigital spaces), ventral abdomen, perianal area
• Rarely neoplasia (usually squamous cell carcinoma) may develop at the burn site years later
• Black skin absorbs approximately 50% more solar radiation than white skin

PATHOGENESIS:

• Heat > capillaries leak > marked loss of fluids and electrolytes > necrotic tissue > bacterial growth > damage to vasculature prevents leukocytes from migrating to the site of infection > initial gram-positive bacterial population is replaced within five days by gram-negative bacteria (usually Pseudomonas aeruginosa) > sepsis > death
• Dry heat causes desiccation and carbonization of skin
  • Sources of dry heat: flames of open fires (candles, fireplaces), hot items, hot air or radiant heat (heat lamps, oven) with conversion of infrared light into thermal heat at the skin surface; contact with electrical wires or lightning strike
• Moist heat induces coagulation of tissue
• Extent of thermal and chemical injury depends on duration and intensity of noxious stimulus
• Longer exposure to lower temperatures is more damaging than shorter exposure at high temperature
• Re‑epithelialization depends on migration of epidermal cells from the edges of the burns or from perifollicular epithelium
• First- and second-degree burns may re-epithelialize because tissue damage does not involve the adnexa
• In deep burns that extend past the adnexa, scarring is prominent
• Microcirculation is restored within 48 hours to areas of partial‑thickness injury
• Systemic manifestations (e.g. septicemia, shock, renal failure, anemia, and respiratory failure) occur with burns covering more than 25% of the body
• Thermal damage continues after removal of the heat source; burns do not progress after 5 days
• Radiant heat dermatitis (moderate heat dermatitis): prolonged repetitive exposure to moderate heat; caused by heating pads, heated kennel mats, electric blankets, etc.

TYPICAL CLINICAL FINDINGS:

• Pain
• Hypovolemia and hemoconcentration due to fluid loss
• Hypoproteinemia

TYPICAL GROSS FINDINGS:

• First degree: well demarcated erythema and edema, possible surface desquamation after several days
• Second degree: marked dermal edema; vesicles and bullae containing serum or debris at the dermal-epidermal junction (burn blister)
• Third degree: outer epidermis is desiccated and charred, underlying connective tissues are swollen and necrotic; sloughing of the necrotic tissue leads to healing by second intention
• Fourth degree: similar to third but extend through/beyond subcutaneous fascia
• Alternatively, first- and second-degree burns may be referred to as “partial-thickness” and third and fourth degree burns as “full-thickness”
• Radiant heat dermatitis (moderate heat dermatitis) – hair loss; irregular areas of erythema and ulceration in drip-like formation; superficial dermal mucinosis; and peripherally hyperpigmented and centrally scaly and depigmented
  • Lateral or sternal recumbency
  • Similar to erythema ab igne in humans
• Lightning strike – jagged line of singed hair more easily visible when hair is moistened, linear or punctate burns, keraunographic markings; may have
• Electrocution – Loss of elasticity of skin which easily tears, separation of skin from underlying tissue, underlying musculature appears dry and discolored (resembling cooked meat)
• Takes 2 – 4 days
• Chemical burns – marked erythema, swelling and a transient popular-vesicular stage that leads to ulceration and sloughing of affected skin
  • Common to occur on glabrous skin of abdomen, axilla, medial thigh, perianal and perineal areas, footpads, ventral tail, chin and inner aspect of ear in dogs and cats
  • Muzzle, lower limbs and in areas of contact with the riding tack in horses

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• First degree: edema, acute coagulation necrosis of the superficial epidermis only
• Second degree: hypereosinophilic epithelial cell cytoplasm, shrunken or karyorrhectic nuclei, marked dermal spongiosis; vesicles (at the dermoepidermal junction) may contain granular debris or leukocytes
• Third degree: coagulation necrosis involving connective tissues, vasculature and adnexa; secondary bacterial infection may attract many neutrophils; vasculitis and thrombosis
• Fourth degree: extends beyond the subcutaneous tissues; there is no sharp demarcation between vital and damaged tissue, the injury dissipates gradually with increasing tissue depth
• Adnexa more severely affected than surrounding dermis due to “wicking effect”
• Moderate heat dermatitis - keratinocyte karyomegaly, atypia,
• and degeneration
  • endothelial degeneration (vasculopathy), dermal edema, focal hemorrhage, variable number of wavy, strongly eosinophilic elastic fibers and mixed dermal mononuclear inflammation, including accumulation of melanophages and hemosiderophages
  • adnexal atrophy due to the vasculopathy
  • can have changes of normal thermal burns as well
• Electric burns: elongated cytoplasmic processes extending into the vesicular space from the detached basal cells with elongation of basal and epithelial cell nuclei; smudging of dermal collagen; loss of differential staining; damaged keratin glows orange-red when observed through red filter and exposed to 530-560nm light
• Chemical burns: superficial, perivascular dermatitis
  • Early lesions consist of epidermal edema and spongiotic vesicles and neutrophils or epidermal necrosis with separation from the dermis
  • Chronic lesions include mild acanthosis with compact parakeratosis in the presence of a granular layer

DIFFERENTIAL DIAGNOSIS:

• Gross:
  • Pemphigus vulgaris – acanthosis and pustular dermatitis
  • Bullous pemphigoid – immunohistochemically detected antibody to bullous pemphigoid antigen in the basement membrane
  • Malassezia dermatitis – impressions of skin show yeast
  • Early scabies – skin scraping or histology show Sarcoptes scabei
  • Hypersensitivity reaction – eosinophils and mast cells without necrosis
• Microscopic:
  • Allergic contact dermatitis – differentiation based on history
  • Erythema multiforme – no vasculitis, inflammation is lymphohistiocytic
  • Toxic epidermal necrolysis – generalized process with minimal inflammation
  • Dermatopathy/nephropathy syndrome of swine
  • Superficial necrolytic dermatitis-like lesion in rhinos
  • Microwave burns – unique in that there is a sharp line of demarcation between damaged and vital tissue, degree of injury is uniform throughout the tissue and there is minimal inflammation

COMPARATIVE PATHOLOGY:

• In horses, chemical burns are most frequent on muzzle, extremities and areas of contact with tack or the perineum from diarrhea
• In swine, tiamulin administration causes toxic metabolites to be excreted in the urine and feces leading to full-thickness epidermal necrosis in areas in contact with excreta
  • Fatal necrolytic dermatitis: full thickness epidermal necrosis, intraepidermal pustules, serocellular crusting
• In grazing animals, lightning strikes occur regularly; may have no lesions, or may have linear or punctate burns, keraunographic markings (regarded as pathognomonic lightning skin lesions in humans), exit burns on soles of hooves or coronary bands
• Pteropodid bats: Collision with power lines; patagium most commonly affected, often associated with heat lamps, hot packs, and/or heating pads
• Chelonians, captive lizards, and snakes: Iatrogenic thermal burns associated with husbandry, such as inappropriately managed hot rocks and heating lamps
• Pet birds: Burns often secondary to feeding overheated food; lesions are in the cranioventral crop

REFERENCES:

1. Abee CR, Mansfield K, Tardif S, Morris T. Nonhuman Primates in Biomedical Research: Volume 2: Diseases. 2nd ed. San Diego, CA: Elsevier; 2012:576, 578.
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3. Kumar, Vinay, et al. Robbins & Cotran Pathologic Basis of Disease. 10th ed., Elsevier, 2020;9:427-433
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8. Rodriguez CE, Duque AMH, Steinberg J, Woodburn DB. Chelonia. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018:836.
9. Sidor I. Gastrointestinal System and Pancreas. In: Schmidt R, Struthers JD, Phalen DN, eds. Pathology of Pet and Aviary Birds. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2024:155.
10. Viner TC, Kagan RA. Forensic Wildlife Pathology. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018:23.
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