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

Abstract

BackgroundHuman erythema multiforme (EM) and Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are separate conditions. There is no consensus on classification criteria for the eponymous diseases in animals.ResultsAnimalEMis very different from 90% of humanEM, which is herpes virus associated (HAEM). Animals lack acrally distributed, typical raised targets. Unlike canine parvovirus ‘EM’,HAEMis not an active infection. AnimalEMis often attributed to drugs, but this is rarely proved. Conversely, human and animalSJS/TENare almost identical, life‐threatening disorders of epidermal necrosis and detachment, typically triggered by drugs (occasionally by infectious agents). BothEMandSJS/TENare mediated by cytotoxic lymphocyte responses against altered keratinocytes (infectious agents or drugs). Apoptosis results from direct cytotoxicity or through soluble mediators, namely Fas ligand, granzymes, perforin and granulysin. Diagnosis in humans is clinicopathological, with emphasis on clinical lesions; histopathology confirms the pathological process as interface (cytotoxic) dermatitis. HumanEMis self‐limiting; only recurrent and rare persistent cases require antiviral/immunosuppressive therapies. Drug‐inducedEMresponds to drug withdrawal. Idiopathic canineEM(>40%) is usually chronic, refractory to treatment and may represent heterogeneous conditions. Early identification and removal of the causative drug and high‐quality supportive care are critical inSJS/TEN. Mortality rate is nevertheless high.Conclusions and clinical importance(1) Histopathological lesions do not reliably differentiateEM,SJSandTEN. (2) A multicentre study to develop a consensus set of clinical criteria forEMandSJS/TENin animals is overdue. (3) No adjunctive therapies, including intravenous immunoglobulin and ciclosporin, have met evidence‐based standards.