Toxic Epidermal Necrolysis Treated with Intravenous High-Dose Immunoglobulins: Our Experience

Abstract

Background: Toxic epidermal necrolysis (TEN) is a rare severe acute exfoliative drug-induced skin disorder which has recently been ascribed to alterations in the control of keratinocyte apoptosis, mediated by an interaction between the cell surface death receptor Fas and its respective ligand. A therapeutic approach with intravenous immunoglobulins (IVIG) associated with pulse methylprednisolone, based on the inhibition of Fas-mediated keratinocyte death by naturally occurring Fas-blocking antibodies included in human immunoglobulin preparations, has produced good preliminary results. Objective: To analyse the efficacy of IVIG in the treatment of TEN. Patients: Nine patients with erythematous body surface area ranging from 38 to 85% and dermo-epidermal detachment from 4 to 37% were treated. Results: Eight patients were healed and 1 died of septic shock and multiple organ failure. Interruption of further epidermal detachment occurred after an average of 4.8 days from the onset of IVIG therapy. Complete wound healing occurred after an average of 12 days. Concerning complications, 3 out of 8 surviving patients had acute respiratory failure requiring mechanical ventilation and 1 acute renal failure was treated with dialysis. Late sequelae were limited to dyschromia and nail dystrophies. No hypertrophic scars were observed. Conclusion: IVIG therapy represents a safe and valid approach for TEN.

High-dose intravenous immunoglobulin in the treatment of toxic epidermal necrolysis: a study of ocular benefits

“…4 The rationale for the use of IVIG is based on the inhibition of Fas-mediated keratinocyte apoptosis in TEN by naturally occurring Fas-blocking antibodies within the IVIG. 5 Studies on the use of IVIG in TEN [5][6][7][8][9] have so far focused on cutaneous outcomes, including some reports of reduction in mortality rates, with none reporting specifically on the effects on ocular outcomes. In SJS, the severity of systemic involvement is reported to be a factor that determines late ocular complications.…”

Nimesulide induced Stevens Johnson syndrome (SJS); managed successfully with combined approach of steroids, intravenous immunoglobulin and placentrex gel: A case report

“…IVIg is a safe and useful method of treatment in children by blocking Fas antibodies in vitro and preventing apoptosis by the formation of Fas -Fas ligand compounds [12]. The effective drug dosages of IVIg range from 0.2 to 2g/kg/day [13,14]. In this context, combination therapy seems an attractive option as they have a synergistic action targeting different pathways of apoptosis active in TEN/SJS [15].…”

Analytical quantification of the inflammatory cell infiltrate and CD95R expression during treatment of drug-induced toxic epidermal necrolysis

“…Although T lymphocytes are the main target of CsA, the drug could also somewhat prevent keratinocyte apoptosis in TEN [15]. Some TEN patients have also been treated with intravenous human immunoglobulins (IVIg) [2,10,14,19,20,24,[28][29][30]. The rationale for this treatment was to block CD95R on keratinocytes.…”

“…High IVIg dosages were recently used to treat some TEN patients [2,10,14,19,20,24,[28][29][30]. The rationale for this treatment relied on the in vitro inhibition of FasRFasL interaction and keratinocytes apoptosis by Ig.…”

“…This observation points to the difficulties in standardizing IVIg treatment of TEN. Preliminary clinical results about this treatment remain controversial so far, showing either improvement [10,14,19,20,24,[28][29][30] or worsening [2] in TEN morbidity and mortality. All the clinical non comparative studies reported so far were not supported by histological examination.…”