Abstract
Purpose: :
Ocular complications including conjunctival cicatrisation related to Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. Whilst little is known about the ocular surface inflammatory process, keratinocyte death in cutaneous SJS-TEN is induced by blister fluid granulysin secreted by CD8+ cytotoxic T cells and CD56+ Natural Killer cells. The aim of this study was to characterise infiltrative cellular profiles within the conjunctival epithelium during acute and chronic SJS-TEN.
Methods: :
Impression cytology with sterile Supor filters was used to collect superficial conjunctival cells from consecutive patients presenting with SJS-TEN to a tertiary ocular surface diseases clinic over a 12 month period. Cells were recovered and stained with fluorochrome-conjugated antibodies identifying T cells and other leukocytes by two 9-colour panels analysed with flow cytometry. Comparisons were made with a cohort of healthy, age-matched controls (n=21) using the worst affected eye.
Results: :
Of 10 patients (median age 44 [range 18-67 years], 8 females), four presented with acute [<6 weeks after disease onset]) disease and four with chronic [>12 months after disease onset]) disease. Five patients were categorised as TEN and all but one patient had a SCORTEN of 1. Drugs were the most common causative agent (n=7) and conjunctival inflammation was gauged as absent/mild in 9/10 patients (18/20 eyes). Objective evidence of fornix shrinkage using a Fornix Depth Measurer was seen in 9/10 subjects, and this inversely correlated with duration of disease (p<0.05). Although there was no change in the total number of conjunctival epithelial leukocytes in SJS-TEN compared with controls, there was a reduction in the percentage (80% vs. 57%;p<0.01), but not the number of TCRαβ+CD3+CD8αβ+ T cells. These changes were due to a corresponding increase in the number and percentage of CD11b+CD16+ neutrophils (186 vs. 3.4, p<0.01;31% vs. 0.8%, p<0.001) which inversely correlated with disease duration.
Conclusions: :
These data highlight that in ocular SJS-TEN, an inflammatory infiltrate with CD11b+CD16+ neutrophils is present even in mildly involved or clinically quiescent conjunctival mucosa. This results in a reduction in the percentage of CD8αβ+ cells in the superficial conjunctival epithelium during acute and chronic disease.
Keywords: conjunctiva • inflammation • flow cytometry