INTRODUCTION

Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN) are mucocutaneous drug-induced or idiopathic reaction patterns characterized by skin tenderness and erythema o skin and mucosa! ollo"ed by extensive cutaneous and mucosal epidermal necrosis and sloughing# They are potentially li e-threatening due to multisystem involvement# $t a ecting approximately %or &'%!(((!((( annually! and are considered medical emergencies as they are potentially atal# They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions! erythema and more or less severe epidermal detachment presenting as blisters and areas o denuded skin## %!& The $mmunological basis o Stevens-Johnson syndrome is )ypersensitivity Type $$$ * $+#, -enetic actors associated "ith drug hypersensitivity are a complex issue that has been studied in di erent populations and a variety o ethnic backgrounds# . uni/ue and strong association bet"een )uman 0eukocyte .ntigen ()0.)! drug hypersensitivity and ethnic background# # 1ost commonly implicated drugs are anti-convulsants! antibiotics (such as sul a! penicillin and cephalosporin) and anti-in lammatory medications# &!2 Table %# 3rugs .ssociated "ith Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Drugs Most Frequently Associated* Sul adoxine Sul adiazine Sul asalazine 4o-trimoxazole )ydantoins 4arbamazepine 7arbiturates 7enoxapro en 8henylbutazone Drugs Also Associated 4ephalosporins 5luoro/uinolones +ancomycin 6i ampin Ethambutol 5enbu en Tenoxicam Tiapro enic acid 3iclo enac

&

$soxicam 8iroxicam 4hlormezanone .llopurinol .mithiozone .minopenicillins

:

Sulindac $bupro en 9etopro en Naproxen Thiabendazole

Together these drugs account or approximately t"o-thirds o the cases attributed to

drugs in large series in 5rance! -ermany! and the ;nited States# % 8athogenesis o SJS-TEN is only partially understood# $t is vie"ed as a cytotoxic immune reaction aimed at the destruction o keratinocytes expressing oreign (drug-related) antigens# Epidermal in<ury is based on the induction o apoptosis# 3rug-speci ic activation o T cells has been sho"n in vitro on peripheral blood mononuclear cells o patients "ith drug eruptions# The nature o the antigens that drive the cytotoxic cellular immune reaction is not "ell understood# 3rugs or their metabolites act as haptens and render keratinocytes antigenic by binding to their sur aces# 4utaneous drug eruptions have been linked to a de ect o the detoxi ication systems o liver and skin! "hich results in direct toxicity or alteration o antigenic properties o keratinocytes# 4ytokines produced by activated mononuclear cells and keratinocytes probably contribute to local cell death! ever! and malaise# % Table# & 4linical 1ani estations o SJS * TEN 4linical 1ani estation 3istribution $nitial erythema on ace! extremities! becoming con luent over a e" hours or days# Epidermal sloughing may be generalized! resulting in large denuded areas# Scalp! palms! soles may be less severely involved or spared! and "idely distributed "ith prominent involvement o trunk and ace# =(> o patients have mucosal lesions! i#e#! erythema! pain ul erosions? lips! buccal mucosa! con<unctiva! genital and anal skin# @A> have con<unctival lesions? hyperemia! pseudo membrane ormationB synechiae bet"een eyelids and con<unctivaB keratitis! corneal erosions#

1ucous 1embranes Eyes

Table# , 0aboratory 5inding o SJS 0aboratory 5inding )ematology .nemia! lymphopeniaB eosino-philia uncommon# Neutropenia correlates "ith poor prognosis# Early? +acuolization'necrosis o basal keratinocytes and 3ermatopathology individual cell necrosis throughout the epidermis# 0ate? 5ull-thickness epidermal necrosis and detachment "ith ormation o subepidermal split above basement membrane# 0ittle or no in lammatory in iltrate in dermis# $mmuno luorescence studies unremarkable! ruling out other blistering disorders# Time rom irst drug exposure to onset o symptoms? % to , "eeks# Cccurs more rapidly "ith rechallenge# Cccurs a ter days o ingestion o the drugB ne"ly added drug is most suspect# 8rodromes? ever! in luenza-like symptoms % to , days prior to mucocutaneous lesions# 1ild to moderate skin tenderness! con<unctival burning or itching! then skin pain! burning sensation! tenderness! paresthesia# 1outh lesions are pain ul! tender# $mpaired alimentation! photophobia! pain ul micturition! anxiety# %!& .ll suspected cases o SJS should be con irmed by skin biopsy or histologic and immuno luorescence examinations# 0ater lesion sho"s ull-thickness epidermal necrosis and separation o epidermis rom dermis## A SJS-TEN is an acute! sel -limited disease! "ith high morbidity! that is potentially li e-threatening# Epidermal detachment may be extensive! to the entire skin sur ace# .s in severe burns! luid losses are massive! producing electrolyte imbalance# 1ucous membrane involvement (oropharynx! eyes! genitalia and anus) re/uire attentive nursing care# .ge! percentage o denuded skin! neutropenia! serum urea nitrogen level! and visceral involvement are prognostic actors# . ter healing! altered pigmentation and corneal lesions are the main long-term complications#D The diagnosis relies on the one hand on clinical symptoms and on the other hand on histological eatures# Typical clinical signs initially include areas o

erythematous and livid macules on the skin! on "hich a positive Nikolsky sign can be induced by mechanical pressure on the skin! ollo"ed "ithin minutes to hours by the onset o epidermal detachment characterized by the development o blisters# & SJS and TEN are li e threatening conditions that need intensive care "ith experienced physicians and specialist nurses and multidisciplinary team "ork# The rame"ork o the management is depicted chart belo"# A