1. No significant difference in mortality rates between inpatients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) who received either plasmapheresis or immunoglobulin (IVIG) therapy first after ineffective systemic corticosteroid therapy.
2. Patients with SJS and TEN who received plasmapheresis over IVIG therapy first after ineffective systemic corticosteroid therapy faced longer hospital stays and higher medical costs.
Evidence Rating Level: 2 (Good)
Study Rundown: Medications can cause severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Both of these conditions can be accompanied by organ failure, lung injury, infection, and/or occasionally death. Although SJS and TEN have morality rates of approximately 10% and 30%, respectively, there are no established treatments due to their rarity. Therefore, this Japan-based retrospective cohort study aimed to investigate the efficacy of plasmapheresis vs. immunoglobulin (IVIG) therapy for patients with SJS or TEN who had previous ineffective systemic corticosteroid therapy. Plasmapheresis was investigated for its ability to clear drug metabolites and cytotoxic mediators, whereas IVIG was considered for its ability to inhibit Fas-mediated widespread apoptosis of keratinocytes. No significant difference in inpatient mortality rates was found between the two therapies; however, plasmapheresis-first patients faced longer hospital stays and higher medical costs. Overlap weighting was used to adjust for potential confounding factors; however, factors such as the percentage of skin detachment, pulse rate, and other laboratory data may have impacted the results. Furthermore, patients who received both plasmapheresis and IVIG therapy at the same time were placed into the plasmapheresis-first group, which could have led to residual confounding. Additionally, the diagnoses of SJS and TEN were based on ICD-10, which has not been directly validated for these conditions. However, it is reasonable to consider the diagnosis accurate as the inclusion criteria combined the diagnostic and procedure codes which are well-validated and accurate for SJS and TEN. Lastly, this study lacks generalizability as it was conducted in one country and predominately compares individuals of Japanese origin without considering long-term life prognosis, functional prognosis, and patient quality of life.
Click to read the study in JAMA Dermatology
Relevant Reading: U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016
In-Depth [retrospective cohort]: This retrospective cohort study was reviewed and approved by the institutional review board of the University of Tokyo. Routinely collected data from the Diagnosis Procedure Combination inpatient database of more than 200 acute care hospitals across Japan was used for data extraction. The inclusion criteria included being over 18 years of age, being hospitalized with diagnosed SJS or TEN between July 2010 and March 2019 as per the ICD-10 guidelines, and having received at least 1000 mg/d of methylprednisolone equivalent systemic corticosteroids within 3 days of hospitalization. Exclusion criteria consisted of patients who had received IVIG or plasmapheresis therapy before the systemic corticosteroid initiation date/index date and patients who did not receive IVIG or plasmapheresis within 5 days of the index date. In total, 266 patients (mean [SD] age, 56.7 [20.2] years; 152 [57.1%] women) were included in the study, with 213 patients who received IVIG first/alone being placed into the IVIG-first group and 53 patients who received plasmapheresis first/alone being placed into the plasmapheresis-first group. Patients who received both treatments on the same day were placed into the plasmapheresis-first group. This decision was based on the rationale the plasmapheresis eliminates most of the antibodies delivered by IVIG. The main outcomes were in-hospital mortality, length of hospital stay, and medical costs. Furthermore, all data were analyzed between October 2020 and May 2021. No significant difference in inpatient mortality rates was found through propensity-score overlap weighting between the plasmapheresis- and IVIG-first groups (18.3% vs 19.5%; odds ratio, 0.93; 95% CI, 0.38–2.23; P = .86). However, the plasmapheresis-first group had a longer hospital stay (45.3 vs 32.8 days; difference, 12.5 days; 95% CI, 0.4–24.5 d; P = .04) and higher medical costs (US $34 262 vs $23 054; difference, US $11 207; 95% CI, $2789–$19 626; P = .009) when compared to the IVIG-first group. Overall, no significant benefit to administering plasmapheresis therapy first after ineffective systemic corticosteroid therapy, rather than IVIG, for SJS or TEN, was found.
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