Clinical and Microscopic Characteristics of Canine Toxic Epidermal Necrolysis

Abstract

Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug reaction, traditionally has been described as full-thickness devitalization of the epidermis with minimal dermal inflammation; however, few reports detail the histologic findings. We characterize the clinical features and histologic variations of 3 canine TEN patients. Clinically, irregular erythematous and purpuric macules evolved into widespread and severely painful erosions. The number of eroded mucosae varied; however, periocular and perilabial mucocutaneous junctions frequently were affected. Thirteen of 17 biopsies were evaluated. Apoptosis at multiple epidermal levels was the most common pattern of epidermal necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis was present less often (7/13 biopsies, 52%). Lymphocytic interface dermatitis was the predominant inflammatory pattern, and intraepidermal lymphocytes, along with fewer histiocytes, were present to some degree in all samples along with lymphocytic satellitosis of apoptotic keratinocytes. The sequence of changes points to lymphocyte-mediated keratinocyte apoptosis as an early step in lesion development with subsequent variation in progression to coagulation necrosis among patients. Histopathologic changes overlapped with those reported for erythema multiforme, in contrast to traditional histologic descriptions of canine TEN. A specific algorithm for assessment of drug causality in epidermal necrolysis (ALDEN) was applied for each patient; carprofen was associated with a probable score for causality in 1 dog. Clinicians should be encouraged to take multiple biopsies in TEN suspect cases as nearly 25% of all biopsies lacked epithelium and were not diagnostic.

Presumed phenobarbital-induced Stevens–Johnson syndrome in a 4-year-old female Great Dane

“…In this case, the clinical lesions were flat, evolved into ulcers and had a positive Nikolskiy sign, as would be expected with SJS. Notably, SJS lesions can blister in the center, as was seen in this case, and this does not denote raised lesions (Banovic et al 2015). Indeed, epidermal detachment, as seen in this case is a hallmark of SJS.…”

“…Indeed, epidermal detachment, as seen in this case is a hallmark of SJS. The extent of the epidermal detachment on the body surface is the main criterium to differentiate SJS from TEN (Yager 2014;Banovic et al 2015). SJS typically has epidermal detachment of less than 10% of the body surface, whilst TEN presents with epidermal detachment of more than 30% of the body surface.…”

Erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis: a comparative review

“…The lesions progress from single cell necrosis to clusters of dying cells to full‐thickness confluent necrosis (Figure a,b). There may be significant keratinocyte cell swelling in outer spinous and granulosum layers . In dogs and cats, the follicular infundibular epithelium is usually affected concurrently.…”

Stevens–Johnson syndrome/toxic epidermal necrolysis caused by cefadroxil in a cat

“…4 In veterinary medicine, ALDEN has been recently applied to a series of canine TEN cases, and a ‘probable’ causality for carprofen in a dog was established. 5 …”

“…Multiple epidermal levels apoptosis was recently reported as the most common pattern of TEN in dogs. 5 …”