Skin inflammatory (nontumor)
Vesiculobullous and acantholytic reaction patterns
Stevens-Johnson syndrome


Topic Completed: 1 February 2015

Revised: 28 March 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Stevens-Johnson syndrome [title] skin "loattrfree full text"[sb]

Erin M. Carlquist, M.D.
Lauren N. Stuart, M.D., M.B.A.
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Cite this page: Carlquist EM, Stuart LN Stevens-Johnson syndrome. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skinnontumorstevensjohnsonsyndrome.html. Accessed October 16th, 2019.
Definition / general
  • Historically there has been controversy as to whether Stevens-Johnson syndrome (SJS) is a distinct entity or at the center of the disease spectrum that includes erythema multiforme (EM) and toxic epidermal necrolysis (TEN)
  • Currently, there is an increasing trend for SJS and TEN as representing the ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions (Orphanet J Rare Dis 2010;5:39)
Terminology
  • SJS: keratinocyte necrosis; epidermal detachment < 10% body surface area; the beginning of the spectrum (Orphanet J Rare Dis 2010;5:39)
  • SJS / TEN: considered point of overlap of two diseases in patients with 10 - 30% body surface area epidermal detachment (N Engl J Med 1994;331:1272)
  • TEN: severe disease state and the end of a spectrum of epidermolytic adverse cutaneous drug reactions; full thickness epidermal necrosis; epidermal detachment > 30% body surface area (Orphanet J Rare Dis 2010;5:39)
  • Atypical SJS: referred to by some as severe mucositis with Mycoplasma pneumoniae infection but without skin lesions (Pediatrics 2007;119:e1002), while others argue that the classification of SJS requires cutaneous involvement (Pediatr Dermatol 2006;23:546)
Epidemiology
Sites
  • Lesions usually begin on trunk and spread centrifugally
Pathophysiology
  • Mechanism unknown, but appears to be CD8+ T cell mediated immune reaction (J Allergy Clin Immunol 2011;127:S74)
  • Granulysin, a mitochondrial protein, is most important factor in epidermal destruction; is found in blister fluid in increasing concentrations with increased severity of disease (Nat Med 2008;14:1343)
Etiology
  • Cases in children are usually associated with infection, especially Mycoplasma pneumonia and herpes simplex virus

  • In adults, most cases are due to medications, including:
  • ALDEN (algorithm for assessment of drug causality in SJS and TEN) provides a structured approach to determine the responsible drug (Clin Pharmacol Ther 2010;88:60), although no identifiable cause in some cases (Orphanet J Rare Dis 2010;5:39)
Diagrams / tables

Images hosted on other servers:

SJS vs. SJS / TEN overlap vs. TEN

SCORTEN severity of illness score

Clinical features
  • Drug-associated cases typically present one to three weeks following initiation of therapy with the offending drug; occurs more rapidly with re-challenge (N Engl J Med 1994;331:1272)
  • Fever, malaise, cutaneous and mucosal eruption
  • Cutaneous and mucosal lesions are tender
  • Nikolsky sign positive for epidermal detachment with application of tangential mechanical pressure (Orphanet J Rare Dis 2010;5:39)
  • Eruption consists of either "flat atypical target" lesions or erythematous to purpuric macules, many with central epidermal necrosis or blister formation
  • Epidermal detachment < 10% body surface area
  • Variable GI and respiratory tract involvement (Orphanet J Rare Dis 2010;5:39)
  • Potentially fatal, a medical emergency
Diagnosis
  • Based on clinical picture plus confirmatory skin biopsy showing vacuolar interface alteration, often with epidermal necrolysis (Orphanet J Rare Dis 2010;5:39)
Prognostic factors
Case reports
Treatment
Clinical images

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Cutaneous and mucosal lesions

Widespread macules

Maculopapular distribution

Gross description
  • Cutaneous and mucosal lesions
  • Eruption consists of either "flat atypical target" lesions or erythematous to purpuric macules, many with central epidermal necrosis or blister formation
Frozen section description
  • Helpful to confirm diagnosis of Stevens-Johnson syndrome
  • Patient below had toxic epidermal necrolysis with extensive body surface and mucosal involvement
Frozen section images

Contributed by Hillary Rose Elwood, M.D.

Detached and necrotic epidermis

Microscopic (histologic) description
  • Early lesions: apoptotic keratinocytes scattered in basal epidermis
  • Later lesions: numerous necrotic keratinocytes, full thickness epidermal necrosis and subepidermal bullae
  • Epidermal changes are often accompanied by a moderate or dense lymphocyte predominant dermal infiltrate
  • Less commonly, neutrophils and eosinophils are present (Mayo Clin Proc 2010;85:131)
  • Less common findings are red blood cell extravasation, pigment incontinence, regenerating epidermis, parakeratosis and necrosis of hair follicle (Mayo Clin Proc 2010;85:131)
  • Clinical correlation is essential to distinguish erythema multiforme, SJS and TEN, as they may look nearly identical histologically
    • Cannot reliably distinguish based on full thickness epidermal necrosis / necrolysis, because EM may have it and SJS / TEN may not, depending on the site of the biopsy
Microscopic (histologic) images

Contributed by Hillary Rose Elwood, M.D.

Detached epidermis with full thickness necrosis and dyskeratotic cells



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Basal cell vacuolar change

Full-thickness necrosis of epidermis

Differential diagnosis
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