Apoptosis as a Mechanism for Keratinocyte Death in Canine Toxic Epidermal Necrolysis

Abstract

In humans and dogs, toxic epidermal necrolysis (TEN) is a life-threatening dermatosis characterized by sudden epidermal death resulting in extensive skin detachment. There is little information on the pathogenesis of keratinocyte cell death in canine TEN. We studied the occurrence of apoptosis in skin lesions of dogs with TEN to determine if apoptosis contributes to the pathogenesis of this disease. Immunostaining with antibodies to activated caspase-3 and the terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique revealed positive apoptotic keratinocytes in basal and suprabasal epidermal compartments in 17 biopsy specimens collected from 3 dogs with TEN and 16 from 3 dogs with erythema multiforme (EM). There was no significant difference in the number of positively stained epidermal cells between TEN and EM. These results suggest that apoptosis of epidermal keratinocytes and lymphocytic satellitosis represent one of the early steps in the pathogenesis of canine TEN, as in the human disease counterpart.

Cutaneous lupus erythematosus in dogs: a comprehensive review

“…The prominence of basal apoptosis and intrabasal epidermal vesiculation, when present, supports the histological diagnosis of VCLE over that of other variants of CCLE, but this distinction is difficult for more chronic lesions and is best done clinically, as for all forms of canine CLE. Occasionally superficial epidermal apoptosis with lymphocytic satellitosis might erroneously suggest the diagnosis of erythema multiforme and its morphologically related conditions [ 29 ]. Neutrophilic inflammation is common in lesions that progress to ulcers and support the development of secondary bacterial infection.…”

Case Report: Positive Outcome of a Suspected Drug-Associated (Immune Mediated) Reaction in a 4-Year-Old Male French Bulldog

“…Antibiotic drugs, especially sulfonamides, penicillins, and cephalosporins are most often incriminated ( 4 , 10 , 17 , 18 ). The pathomechanism is presumed to be immune-mediated, involving a cytotoxic CD8+ T-cell and natural killer (NK) cell activation against altered keratinocytes ( 7 , 19 ). Soluble mediators including Fas-ligand, tumor necrosis factor-α (TNF-α), perforin, granzym, and mainly granulysin lead to confluent cell death ( 1 , 20 ).…”

“…Interface dermatitis with extensive full-thickness epidermal necrosis and minor dermal inflammation are characteristic histological features although not pathognomonic for SJS/TEN ( 2 , 3 , 7 , 19 ). However, in some occasions, this feature is not observed but rather a cytotoxic dermatitis with apoptosis of individual keratinocytes and satellitosis in multiples layers of the epidermis, signs that overlap histologically with erythema multiforme (EM) ( 2 ).…”

Responsiveness to i.v. immunoglobulin therapy in patients with toxic epidermal necrolysis: A novel pharmaco‐immunogenetic concept

“…23 Annexin A1 triggers its effects through binding to a specific receptor, the formyl peptide receptor 1 (FPR1), which is expressed mainly in mammalian leukocytes. 24 Necroptosis involves the formation of a "necrosome", 25 a specific complex containing receptor interacting proteins 1 and 3 26 with subsequent recruitment and phosphorylation of mixed-lineage kinase domain-like protein. The entire complex forms oligomers, creating pores in the cell membrane of the keratinocyte.…”