Lessons from Blister Juice

The biological mechanisms underlying Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS-TEN) — arguably the most compelling and toxic skin reaction — remain largely unknown. Researchers in Taiwan recently investigated the molecular basis for this condition and hit upon a potential therapeutic insight.

The group found that fluid from blisters of SJS-TEN, but not from blisters of thermal burns, killed keratinocytes in culture when added to the medium. When B cells in blister fluid from a carbamazepine-exposed SJS-TEN patient were isolated, these B cells triggered apoptosis in autologous B cells immortalized by Epstein-Barr virus. The researchers were able to compare blister B cells and peripheral blood B cells from the same individuals in a group of five SJS-TEN patients. An expression microarray showed that the cytotoxic protein granulysin was selectively and highly expressed in the blister B cells. The investigators then methodically showed that granulysin was expressed in the skin lesions of SJS-TEN, that the level of granulysin protein in the blister correlated with disease severity, and that pure granulysin was, in fact, cytotoxic to keratinocytes in vitro. The investigators finally injected pure granulysin into the skin of mice and observed TEN develop within 5 hours.