As in any controversial subject, it is essential to sort out areas of consensus versus disagreement. Most dermatologists would recommend managing Stevens-Johnson syndrome/Toxic Epidermolysis Necrolysis (SJS/TEN) by eliminating the culprit drug, monitoring fluid and electrolytes, being vigilant for secondary infection, and adhering to strict wound care, possibly in a burn unit. As far as treating SJS/TEN is concerned, opinions vary, due to the lack of randomized, controlled clinical trials.
A survey was sent to members of the Medical Dermatology Society, dermatology residency programs, and burn units questioning their preferred approach to patients with SJ/TEN. The authors classified the responses between providers who had seen 10 or fewer patients and those who had seen more than 10 patients in the last 5 years. The survey revealed that the majority of providers in both subsets do not use systemic steroids for patients in any classification of SJS or TEN. Both provider subsets preferred IVIG in SJS/TEN overlap and TEN (statistically significant); however, providers in the subset who cared for fewer than 10 patients overwhelmingly did not use IVIG in SJS cases. Cyclosporine was the most frequently used alternative therapy for all classifications (1). Etanercept, which has recently been reported as a successful treatment for TEN (2) was not included in the survey. Personally, I have never used cyclosporine or etanercept for SJS/TEN (although I have recommended them). My experience with IVIg has yielded mixed outcomes. I have prescribed systemic steroids, if the diagnosis was considered very early in the course when the skin was red, tender, and had not begun to desquamate. I am confident that this has aborted several cases of SJS/TEN – if there was no apparent improvement within 48 hours, I recommended discontinuing steroids.
In a retrospective chart review of 71 patients for SJS/TEN, of which 64 cases were included in the data analysis, the predicted severity-of-illness score for TEN mortality was compared with actual mortality for patients treated with either cyclosporine or IVIg. A relative mortality benefit using cyclosporine in the treatment of SJS/TEN with a standardized mortality ratio of 0.43, over the use of IVIg with a standardized mortality ratio of 1.43, was demonstrated. The authors concluded that the use of cyclosporine over IVIg may offer a greater mortality benefit in the treatment of SJS/TEN (3).
At a single center, a comparative analysis was made on mortality outcomes with patients treated with cyclosporine versus what was expected based on SCORTEN. Forty-four patients were assessed; 24 patients received cyclosporine and the remaining 20 patients were treated supportively. SCORTEN predicted 7.2 deaths in the group treated with cyclosporine and 3 were observed. In the group treated supportively, SCORTEN predicted 5.9 deaths and 6 deaths were observed. The standardized mortality ratio of SJS/TEN treated with cyclosporine was 0.42 (95% confidence interval 0.09-1.22). Despite the limitations of the small sample size, retrospective design, and referral bias, the authors concluded that utilizing cyclosporine may improve mortality in SJS/TEN and that this needs to be validated in controlled studies (4).
According to Harris et al “the pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand. Currently, granulysin is accepted as the most important mediator of T cell proliferation.” (5).
The morbidity of TEN can be devastating, affecting the eyes, mucous membranes, and skin. The mortality rate is usually considered 20 to 35% (6). Whenever I am consulted on a case of SJS/TEN, I always note these grim complications and statistics. I also state that there is no accepted therapy in the literature (other than the previously mentioned consensus approach), and offer a rationale for my recommendations. At least annually, I receive a call from an attorney asking me to review a case of SJS/TEN. My heart goes out to the patient, but also to the physicians. Unless there was incredible neglect, there may be an undesired outcome despite everyone’s best efforts. I know that I could easily be the defendant. Dermatologists know what may go wrong in patients with SJS/TEN. I hope that cyclosporine (or other agents) improves the dynamic.
On New Year’s Eve 2015, our group was consulted on a case of TEN. Last night, New Year’s Eve 2016, I was in the emergency room with my resident, assessing a patient for possible SJS/TEN (the actual diagnosis was a bullous fixed drug eruption to trimethorprim/sulfamethoxazole). My New Year’s resolution this year is simple – to try either cyclosporine or etanercept the next time I see a case of SJ/TEN. Hopefully it does not need to be prescribed as we enter 2018!
- Curtis JA, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis treatments: An internet survey. J Am Acad Dermatol 2016; 74: 379-80.
- Didona D, et al. Successful use of etanercept in a case of toxic epidermal necrolysis induced by rituximab. J Eur Acad Dermatol Venereol 2016; 30: e83-4.
- Kirchorf MG, et al. Retrospective review of Stevens-Johnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. J Am Acad Dermatol 2014; 71: 941-7.
- Lee HY, et al. Cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis: Retrospective analysis of a cohort treated in a specialized referral center. J Am Acad Dermatol 2017; 76: 106-13.
- Harris V, et al. Review of toxic epidermal necrolysis. Int J Mol Sci 2016 Dec 18; 17(12).
- Kinoshita Y, Saeki H. A review of toxic epidermal necrolysis management in Japan. Allergol Int 2016 Jul 8 [Epub ahead of print].
*image from myDermPath