JPC SYSTEMIC PATHOLOGY

INTEGUMENTARY SYSTEM

September 2016

I-M29

Signalment (JPC 2017927):  4-year-old dog   

HISTORY:  The dog was treated for vomiting and diarrhea with trimethoprim-sulfa and prednisolone, and developed sudden onset erythema and sloughing of the epidermis 48 hours after treatment began.

HISTOPATHOLOGIC DESCRIPTION:  Haired skin:  Multifocally within all layers of the epidermis and follicular epithelium, are many individualized and occasionally clustered apoptotic keratinocytes that are shrunken with brightly eosinophilic cytoplasm and pyknotic nuclei, admixed with many viable and degenerate neutrophils and fewer lymphocytes (intraepidermal pustules) that are often clustered around apoptotic keratinocytes (satellitosis). Remaining keratinocytes often exhibit hydropic degeneration. There is rare vacuolation of the basement membrane zone (subepidermal vacuolar alteration) and multifocally the epidermis is separated from the dermis immediately subadjacent to the basal cell layer, forming subbasilar clefts that contain erythrocytes, small amounts of fibrin, and few viable and degenerate neutrophils.  Multifocally infiltrating the superficial dermis, obscuring the dermoepidermal interface and surrounding superficial dermal blood vessels and adnexa, are numerous neutrophils, macrophages, and fewer lymphocytes (interface dermatitis). Dermal fibroblasts are often hypertrophied (reactive), and vessels in affected areas are lined by hypertrophied endothelial cells. Multifocally there is mild epidermal and follicular hyperplasia with thickening of the stratum spinosum (acanthosis), rete ridge formation, intercellular edema (spongiosis) and mild orthrokeratotic hyperkeratosis. 

MORPHOLOGIC DIAGNOSIS:  Haired skin:  Keratinocyte apoptosis, transepidermal and follicular, multifocal, with hydropic degeneration, subepidermal clefting, satellitosis, and neutrophilic and lymphohistiocytic interface dermatitis, breed not specified, canine.

ETIOLOGIC DIAGNOSIS:  Drug-induced dermatosis (historically)

CONDITION:  Erythema multiforme (EM)

GENERAL DISCUSSION: 

PATHOGENESIS: 

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

DIFFERENTIAL DIAGNOSIS

Histologically:

 Condition

 Location

Depth of Necrosis

 Inflammation

 SJS/TEN

Mucosa and cutaneous; extensive

full epidermal with +/- subepidermal bullae, does not affect dermis

none or minimal except when ulcerated

 EM

Glabrous skin of groin and axillae, mucocutaneous, oral mucosa, pinnae, foot pad

full epidermal with numerous apoptotic keratinocytes and +/- subepidermal bullae

lymphohistiocytic, perivascular and interface

 Burns

Variable

coagulative necrosis extends into dermis depending on degree

peripheral neutrophils and macrophages

COMPARATIVE PATHOLOGY:

REFERENCES:

  1. Ackermann AL, Frank LA, McEntee MF, May ER. Erythema multiforme associated with zonisamide in a dog. Vet Dermatol. 2015;26(5):391-392.
  2. Banovic F, Dunston S, Linder KE, Rakich P, Olivry T. Apoptosis as a mechanism for keratinocyte death in canine toxic epidermal necrolysis. Vet Pathol. Epub 2016 Aug 31.
  3. Banovic F, et al. Clinical and microscopic characteristics of canine toxic epidermal necrolysis. Vet Pathol. 2015; 52(2): 321-330.
  4. Fisher PG. Erythema multiforme in a ferret (Mustela putorius furo).  Vet Clin North Am Exot Anim Pract. 2013;16:599-609.
  5. Goodale EC, White SD, Outerbridge CA, Everett AD, Affolter VK. A retrospective review of hyperaesthetic leucotrichia in horses in the USA. Vet Dermatol. 2016; 27(4):294-e72.
  6. Gross TL, Ihrke PJ, Walder EJ, Affolter VK. Skin Diseases of the Dog and Cat, 2nd ed. Ames, IA: Blackwell Publishing Professional; 2005: 61-63, 65-68, 75-86, 94-98.
  7. Hargis AM, Ginn PE. The integument. In: McGavin DM, Zachary JF eds. Pathologic Basis of Veterinary Disease. 5th St. Louis, MO: Mosby Elsevier: 2012:984-985,1056-1057.
  8. Herder V, Barsnick R, et al. Equid herpesvirus 5-associated dermatitis in a horse – resembling herpes-associated erythema multiforme.  Vet Microbiol. 2012;155(2-4):420-4.
  9. Maudlin EA, Peters-Kennedy J. Integumentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016: 609-610.  
  10. Miller WH, Griffin CE, Campbell GA. Muller & Kirk’s Small Animal Dermatology. 7th ed. Philadelphia, PA: WB Saunders Co.; 2013: 472-477.
  11. Nemec A, Zavodovskaya R, Affolter VK, Verstraete FJM. Erythema multiforme and epitheliotropic T-cell lymphoma in the oral cavity of dogs 1989-2009. J Small Anim Pract. 2012;53:445-452.
  12. Scott DW, Miller WH. Equine Dermatology. 2nd ed. St. Louis, MO:Elsevier; 2011:341-344.
  13. Senturk S1, et al. Toxic epidermal necrolysis associated with Mycoplasma bovis in calves. Vet Rec. 2012;170:566.
  14. Woldemeskel M, Liggett A, Ilha M, Saliki JT, Johnson LP. Canine parvovirus-2b-associated erythema multiforme in a litter of English setter dogs.  J Vet Diagn Invest. 2011;23:576.
  15. Yager JA. Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis: a comparative review. Vet Dermatol. 2014; 25(5):406-e64.


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