A meta-analysis of cyclosporine treatment for Stevens–Johnson syndrome/toxic epidermal necrolysis

Figures & data

Table 1 Characteristics of all studies included in this review

Study	Study design	Study sample (N)	Country	Total BSA and SCORTEN	Treatment regimen (n)			Conclusion
Arévalo et al, 2000^Citation17	Retrospective case series	17	Spain	Mean total BSA 83±17%; SCORTEN not specified	• CsA 3 mg/kg/d enterally every 12 hours, for 2 weeks and then tapered gradually (11) • Cyclophosphamide (150 mg IV every 12 hours) and different doses of corticosteroids (≥1 mg/kg/d of 6-methyl-prednisolone) (6)			CsA is safe and is associated with rapid re-epithelization and a lower rate of multi-organ failure, severe leukopenia, and death than treatment with cyclophosphamide and corticosteroids in patients with severe TEN
Firoz et al, 2012^Citation18	Prospective	82*	USA	Mean total BSA 34.8±26.1%; mean SCORTEN 2.17	• CsA (regimen not specified) only used in patients with low BSA and SCORTEN of 0–1 (8) • IVIg 4 g/kg divided over 3 days if patients presented within 72 hours of blistering (23) • Supportive care for patients who presented ≥3 days of blistering (51)			No significant difference in survival among all three treatment options (P=0.15, log-rank test). IVIg did not significantly alter mortality
Giudice et al, 2017^Citation19	Retrospective case series	12	Italy	Mean total BSA 76.7±12.3%;mean SCORTEN 4.3		Standardized treatment protocol: CsA IV 250 mg/d or 4 mg/kg/d in pediatric patients on day one, at day three, daptomycin and plasmapheresis were introduced. CsA continued for 15 days, daptomycin for 10 days, plasmapheresis consisted of 7 cycles spaced by 2 days each (12)	Standardized treatment protocol consisting of CsA and plasmapheresis is safe and efficacious in patients with severe TEN
González-Herrada et al, 2017^Citation20	Retrospective and prospective cases	42	Spain	Mean total BSA 43.5±26.9%; mean SCORTEN 2.39		• CsA 3 mg/kg/d until complete re-epithelialization and then gradual taper (26) • IVIg 0.75 g/kg/d for 4 days (11) • Prednisone-equivalent 37.5–100 mg/d for 9–12 days (2) • Supportive care (3)	CsA offers mortality benefit for SJS/TEN patients
Kirchhof et al, 2014^Citation10	Retrospective case series	64	Canada	Mean total BSA 28.7±26.6%; mean SCORTEN 1.65		• Supportive care (12) • IVIg 1 g/kg/d for 3 days (35) • CsA 3–5 mg/kg/d orally or IV for an average of 7 days (15) • IVIg and CsA (2)	Relative mortality benefit of CsA (SMR 0.42) over IVIg (SMR 1.43) in patients with SJS/TEN
Lee et al, 2017^Citation21	Retrospective case series	44	Singapore	Mean total BSA 29±25%; mean SCORTEN 2.5		• CsA 3 mg/kg/d for 10 days, then 2 mg/kg/d for 10 days, and finally 1 mg/kg/d for 10 days (24) • Supportive care (20)	Relative mortality benefit of CsA (SMR 0.42) over supportive care (SMR 1.02)
Mohanty et al, 2017^Citation22	Retrospective case series	28	India	Mean total BSA 35.95±20.33%; mean SCORTEN 2.05		• CsA 5 mg/kg/d in three divided doses for 10 days, along with supportivecare (19) • Supportive care (9)	SMR of CsA group (0.32) nearly 3.3 times lower than the only supportive treatment group (1.06)
Rajaratnam et al, 2010^Citation23	Retrospective case series	21	UK	Mean total BSA 44%; mean SCORTEN 3.1		• CsA IV 2.5–4 mg/kg/d for 3–5 days (3) • IVIg 0.4–1.0 g/kg/d for 3–7 days (14) • Cyclophosphamide IV 2.5 mg/kg/for 3 days (2)	Corticosteroids did not appear beneficial compared to IVIg or CsA
Reese et al, 2011^Citation9	Retrospective case series	4	USA	Mean total BSA 35.8%; mean SCORTEN 1.25		• CsA 5 mg/kg/d in two divided doses for 5 days to a month (4)	CsA is efficacious with rapid response and re-epithelization. Short-term use of CsA did not have adverse reactions or increased infections
Singh et al, 2013^Citation11	Retrospective case series	11	India	Mean total BSA 23.4±16.3%; mean SCORTEN 1.45		• CsA 3 mg/kg/d in three divided doses for 7 days, then 2 mg/kg/d in two divided doses for another 7 days (11)	Faster re-epithelization, shorter hospital stay and relative mortality benefit of CsA over corticosteroids. CsA was also well tolerated by all the patients
Szepietowski et al, 1997^Citation24	Retrospective case series	3	Poland	Not specified		• CsA 8–10 mg/kg/d for 10–21 days and corticosteroids (3)	Combined and monotherapy with CsA appear superior to monotherapy with corticosteroids. CsA is beneficial for TEN patients
Valeyrie-Allanore et al, 2010^Citation25	Open, Phase II trial	29	France	Mean total BSA 12.2±8.2%; mean SCORTEN 1.27		• CsA orally through NG tube, 1.5 mg/kg twice daily for 10 days, then 1 mg/kg twice daily for 10 days, and finally 0.5 mg/kg twice daily for 10 days (29)	CsA was well tolerated; 26 out of 29 patients completed the 1-month treatment. Lower than expected mortality and disease progression observed

Note:

* Expression of concern by journal editor and staff over possible data irregularities.

Abbreviations: BSA, body surface area; CsA, cyclosporine; IV, intravenous; IVIg, intravenous immunoglobulin; NG, nasogastric; SCORTEN, SCORe of toxic epidermal necrosis; SJS, Stevens–Johnson syndrome; SMR, standardized mortality ratio; TEN, toxic epidermal necrolysis.

Figure 1 PRISMA flowchart showing the studies identified during the literature search and abstraction process.

Abbreviations: SJS, Stevens–Johnson syndrome; TEN, toxic epidermal necrolysis; SCORTEN, SCORe of toxic epidermal necrosis; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2 Funnel plot (with pseudo 95% confidence limits) to assess publication bias; Egger test for publication bias=0.751, 95% CI=0.0146–1.488, P=0.0467.

Figure 3 Forest plot showing the standardized mortality ratio and 95% CI of studies on cyclosporine therapy.

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