Long term ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in children Asim Ali, MD, FRCSC Kamiar Mireskandari, MD, PhD Caroline Catt, MBBS, FRANZCO No financial disclosures to report

SJS and TEN SJS SJS/TEN overlap TEN <10% BSA Adult mortality 1-3% Mean age ~25 years SJS/TEN overlap 10-30% BSA Intermediate form TEN >30% BSA Adult mortality 10-70% Mean age ~53 years Rare but severe mucocutaneous blistering diseases COMMONLY INVOLVING THE OCULAR SURFACE The clinical entity between these 2 ends of the spectrum is designated Overlap Syndrome.

SJS and TEN in children Compared to adults Lower incidence Better survival Acute ocular involvement in ~80% Ocular manifestations in the acute and long term, and visual acuity outcomes not well reported An important disease for us to understand in children. Although it has a lower incidence, survival is better, so there is potentially a greater disease burden, long-term, in this population with a long life ahead of them. Mortality of 0-17% in TEN in children cf adults in which it is ~30%

METHODS Retrospective cohort review Inclusion criteria: Demographics Admission details Ophthalmic findings and treatment At every inpatient and subsequent outpatient review Inclusion criteria: Admitted to Hospital for Sick Children, Toronto, Canada from 2001 - 2011 Diagnosis according to Bastuji-Garin1 consensus definition We undertook an REB approved.. 1. Bastuji-Garin S, Rzany B, Stern RS, et al. Clinical classification of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol 1993;129;92-6

RESULTS - Demographic Information Patient Characteristics Mean value (range) Total Male Female 36 22 (61%) 14 (39%) Age 8.8 (0.67 – 15) years Admitted to ICU 11 (31%) Mean duration of admission 15 (2 – 87) days Mean duration of follow-up 13 months (day 0 – 9 years) Diagnosis: SJS SJS/TEN TEN 20 (56%) 9 (25%) 7 (19%)

Severity of acute ocular involvement Severity criteria published by Power et al (1995) We classified the severity of ocular involvement…. 81% had ocular involvement acutely. Mild involvement was defined as ocular signs requiring routine eye care, which completely resolved before discharge from hospital (eg. lid edema, conjunctival injection, requiring prophylactic antibiotics or lubricants); Moderate involvement included specific ocular complications requiring specific treatment, normal vision and near complete resolution of ocular disease prior to discharge (eg. conjunctival membranes, corneal epithelial loss of more than 30%), and; Severe involvement included sight-threatening disease with the need for ongoing specific ophthalmic treatment after discharge (eg. symblepharon, active corneal disease at the time of discharge). Where there was asymmetry between the two eyes, the more severe category was recorded.

Conjunctival manifestations Clinical Sign Number of patients affected (%) Mean time of onset after admission (range) Conjunctivitis 28 (77.8%) 1 day (0-9) Conjunctival membranes 10 (27.8%) 1 day (0-5) Bulbar conjunctival ulceration 14 (38.9%) 4 days (0-18) Subconjunctival hemorrhage 12 (33.3%) 4 days (0-30) Tarsal conjunctival ulceration 6 days (0-20) Symblepharon 44 days (1-207) Sub-conjunctival scarring 5 (13.9%) 3.8 months (0.6-11) Ankyloblepharon 4 (11.1%) 5 months (0.4-18)

Eyelid manifestations Clinical Sign Number of patients affected (%) Mean time of onset after admission (range) Lid margin ulceration 9 (25%) 6 days (0-26) Lid edema 14 (38.9%) 8 days (0-44) Trichiasis 3 (8.3%) 24 days (10-31) Blepharitis 2 (5.6%) 30 days (22-37) Meibomian gland disease 5.4 months (0.5-12) Lid margin keratinisation 8 (22.2%) 4.8 months (0.5-21) Entropion 5.7 months (1-13) Distichiasis 4 (11.1%) 9.5 months (3-24) Punctal auto-occlusion 10.8 months (1-30) Changes in the eyelids also occurred with high frequencies and onset over a large time period ranging between…

Corneal manifestations Clinical Sign Number of patients affected (%) Mean time of onset after admission (range) SPEE 18 (50%) 3 days (0-9) Corneal epithelial defect 9 (25%) 30 days (0-242) Corneal opacification 4 (11.1%) 3.5 months (1.3-5) Dry eye 10 (27.8%) 6.7 months (2-17) Corneal vascularisation 3 (8.3%) 12.3 months (3.8-22) Limbal stem cell failure 16 months (4 months-3 years)

Long term follow-up group: chronic manifestations All patients with at least one review after discharge were analyzed separately 17 met these criteria (6 SJS, 6 SJS/TENS and 5 TENS) Complications in this group Corneal opacification (23.5%), Corneal neovascularization (17.6%) Limbal stem cell failure (17.6%) New symblephara (35.3%)

Long term follow-up group: visual acuity outcome + interventions VA>20/40 VA <= 20/50 VA<20/200 Better eye 17 (100) Worse eye 14 (82.4%) 2 (11.8%) 1 (5.9%) Mean follow-up 26.9 mo 4 patients required a PROSE device (Boston Foundation for Sight, Needham, MA) 1 patient required eyelid repair for entropion

CONCLUSIONS Ocular manifestations are acutely present in 81% of children, and 100% of those with TEN 11% of all patients required surgical intervention for their ophthalmic sequelae Prolonged follow-up is indicated to identify late ocular complications Despite high frequency of vision threatening complications, most children maintain good vision Ocular manifestations are acutely present in 81% of children, and 100% of those with TENS – securing a role for the ophthalmologist in the care of these children in the acute care setting