Erythema Multiforme Stevens Johnson Syndrom

 There has been controversy in the literature regarding the clinical definitions of EM, SJS, and TEN and whether they are distinct entities or represent a spectrum of one disease process. While EM major and SJS were once considered synonymous, many now consider EM and SJS to be separate diseases . SJS and TEN are widely but not universally regarded as a continuum.

EM, as classically described by von Hebra, is a benign, self-limited condition with symmetric, fixed lesions, some of which evolve into typical targets composed of three concentric rings. The lesions are located primarily on the extremities (Fig. 9-26A). Bullous EM is a more severe form, which was defined by an international consensus group in 1993 as having typical targets or raised atypical targets with <10% of body surface area detachment .

Patients with SJS often present with fever and malaise and develop a cutaneous eruption consisting of "flat atypical targets," or erythematous or purpuric macules, many with central epidermal necrosis or blister formation. The lesions usually start on the trunk and spread centrifugally. Again, epidermal detachment is <10% of the body surface area .

TEN, also referred to as Lyell's syndrome, is characterized by widespread, full-thickness epidermal necrosis involving >30% of the body surface area . These patients also have systemic symptoms and may initially present with diffuse erythema and skin tenderness, followed by the development of large, flaccid bullae and detachment of the epidermis in sheets . SJSfTEN overlap is used to refer to patients with epidermal detachment between 10% and 30% of the body surface area . TEN has a high mortality rate because offluid loss and sepsis.

Mucosal involvement (oral, ocular, and/or genital) is common in all of these severe acute bullous diseases and is a serious cause of morbidity. Mycoplasma pneumoniae infection has been associated with severe mucositis without skin lesions, which has been referred to by some as atypical SJS , while others argue that the classification of SJS requires cutaneous involvement .

EM, which may be recurrent, is most commonly associated with herpes simplex infection . Other infections, (Epstein-Barr virus , cytomegalovirus , and Lyme disease ), and rarely drugs, have been implicated in EM. SJS is most commonly drug-induced , except in

children where the majority of cases have been associated with infection, notably M. pneumoniae ). Immunizations are another etiology to consider. TEN is almost always attributed to drugs, and only rare cases have been thought to have an infectious etiology . The most commonly implicated drugs include NSAIDs, sulfonamides and other antibiotics, anticonvulsants, antiretrovirals, and allopurinol .

Histopathology. EM is considered the prototype of the vacuolar form of interface dermatitis . The early changes include vacuolization of the basal cell layer; tagging of lymphocytes along the dermal-epidermal junction; and a sparse, superficial, perivascular lymphoid infiltrate . Necrosis of individual keratinocytes in the basal unit occurs, which is the hallmark of EM. Because of its acute nature, there is an orthokeratotic stratum corneum. Mild spongiosis, papillary dermal edema, and extravasation of red blood cells are seen. As the lesion becomes more developed, there is a moderate lichenoid infiltrate of Iymphohistiocytes at the dermal-epidermal junction with exocytosis. More apoptotic keratinocytes within and above the basal epidermal layer are present. The

intensity of epidermal necrosis varies from vacuolated individual keratinocytes surrounded by lymphocytes (satellite cell necrosis) at the basal unit to confluent necrosis in association with intraepidermal and subepidermal vesicles. The dermal infiltrate comprises lymphocytes and histiocytes. Eosinophils may also be present. Although one study has noted a significant number of eosinophils in drug-induced EM, this has not been noted by others. In the authors' estimation, a generous number of eosinophils exclude EM. One study has found that an acrosyringium concentration of apoptotic keratinocytes in EM is a clue to a drug etiology .

In early lesions of SJSITEN, apoptotic keratinocytes are observed scattered in the basal layer of the epidermis. In established lesions, there are numerous necrotic keratinocytes, even full-thickness epidermal necrosis, and a subepidermal bulla. The dermal inflammatory infiltrate is sparser in TEN than in EM (Fig. 9-278). Extravasated erythrocytes are commonly found within the blister cavity. Melanophages within the papillary dermis occur in late lesions. Eccrine epithelium shows a variety of changes from basal cell apoptosis to necrosis of the duct.