History

• 3-year-old boy presented four days after development of new, worsening rash
• Past medical history of myoclonic epilepsy on valproic acid for six months and lamotrigine for two weeks

Exam Findings

Differential Diagnosis

• Stevens-Johnson syndrome/toxic epidermal necrolysis
• Erythema multiforme
• Drug-induced pemphigoid
• Drug-induced pemphigus
• Staphylococcal scalded skin syndrome
• Coxsackie virus

Additional Investigations

• Skin biopsy: keratinocyte necrosis, full thickness epidermal/epithelial necrosis, minimal inflammation in dermis

Diagnosis

• Stevens-Johnson syndrome/toxic epidermal necrolysis

Pathophysiology

• Hypersensitivity complex against skin and mucous membranes
• Synthesis of genetic and innate immune mechanisms leading to apoptotic keratinocyte cell death and secondary epidermal necrosis
• Causes include pharmacologic, vaccinations, infections, chemical exposures, natural/herbal medicines

Treatment

• Aggressive topical lubrication
• Discontinue offending agent
• Topical steroids
• Topical antibiotics
• PROKERA
• Amniotic membrane graft

Prognosis and Future Directions

• The three main goals of management in acute Stevens-Johnson syndrome/toxic epidermal necrolysis are to:
  1. Control acute inflammatory reaction
  2. Restore intact ocular surface
  3. Prevent long-term sequelae
• If the acute phase is treated aggressively and early, progression to the chronic phase can be prevented or limited. Compared to the acute phase, the management tools for the chronic phase are much less efficacious.
• One of the mainstays for management in the aggressive phase is use of amniotic membranes. Recently, the first randomized controlled trial on amniotic membrane transplantation with medical therapy vs. medical therapy alone was conducted and showed significant relative improvement with use of amniotic membrane. (Sharma et al. Adjuvant Role of Amniotic Membrane Transplantation in Acute Ocular Stevens-Johnson Syndrome: A Randomized Control Trial. Ophthalmology. 2016 Mar;123(3):484-91.)

References

• Chang YS, Huang FC, Tseng SH, et al. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management. Cornea 2007 Feb;26(2):123-129.
• Sekula P, Dunant A, Mockenhaupt M, et al. Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol 2013 May;133(5):1197-1204.
• Kim KH, Park SW, Kim MK, Wee WR. Effect of age and early intervention with a systemic steroid, intravenous immunoglobulin or amniotic membrane transplantation on the ocular outcomes of patients with Stevens-Johnson syndrome. Korean J Ophthalmol 2013 Oct;27(5):331-340.
• Raucci U, Rossi R, Da Cas R, et al. Stevens-Johnson syndrome associated with drugs and vaccines in children: a case-control study. PLoS One. 2013 Jul 16;8(7):e68231.
• Sotozono C, Ueta M, Koizumi N, et al. Diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications. Ophthalmology 2009;116:685-690.
• Solomon A, Ellies P, Anderson DF, et al. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency. Ophthalmology. 2002 Jun;109(6):1159-1166.
• Sharma N, Thenarasun SA, Kaur M, et al. Adjuvant Role of Amniotic Membrane Transplantation in Acute Ocular Stevens-Johnson Syndrome: A Randomized Control Trial. Ophthalmology. 2016 Mar;123(3):484-91.

Contact

• Charles Flowers, Jr., MD, Associate Professor of Clinical Ophthalmology, charles.flowers@med.usc.edu
• Ramon Lee, MD, PGY-2 Ophthalmology Resident, ramon.lee@med.usc.edu

Section Editors

• Vivek Patel, MD, Associate Professor of Clinical Ophthalmology, Program Director, vivek.patel@med.usc.edu
• Jesse Berry, MD, Assistant Professor of Clinical Ophthalmology, Associate Program Director, jesse.berry@med.usc.edu

Produced by: Monica Chavez, John Daniel, Joseph Yim and Dr. Vivek Patel