Management of Severe Cutaneous Adverse Reactions: Supportive Care, Monitoring, and Immunomodulatory Therapy

Conclusions

• Early recognition of severe cutaneous adverse reactions and immediate withdrawal of the culprit drug remain the foundation of management.
• Intensive supportive care, including wound care, fluids, nutrition, pain control, and infection surveillance, is essential for improving outcomes in SJS/TEN.
• Immune-targeted therapies may help in SJS/TEN, with the best evidence favoring combination approaches such as IVIG plus corticosteroids rather than either alone.
• TNF-alpha inhibitors such as etanercept appear promising for SJS/TEN, with signals for lower mortality, faster healing, fewer infections, and better restoration of immune regulation.
• Prolonged corticosteroid use should be avoided when possible because stage-dependent treatment and earlier tapering may reduce toxicity without sacrificing efficacy.
• JAK inhibitors, especially tofacitinib, are emerging as effective options for refractory SJS/TEN and may shorten skin healing time while reducing inflammatory cytokines and cytotoxic proteins.
• In suspected infection or sepsis complicating SJS/TEN, corticosteroids and cyclosporine should generally be stopped or tapered, IVIG may be preferred, and TNF inhibitors may be relatively safer to continue.
• Bacteremia is a common and clinically important complication in SJS/TEN, particularly during days 5 to 10, so empirical broad-spectrum antibiotics are often warranted when sepsis is suspected.
• Procalcitonin can help predict bacteremia in SJS/TEN, but it has important pitfalls and should not be used alone to rule out infection or replace clinical judgment.
• Disseminated intravascular coagulation is a major poor-prognosis marker in SJS/TEN and requires repeated monitoring because its development substantially worsens survival.
• Granulysin levels in blister fluid and plasma correlate with disease activity and can help guide treatment decisions, including when to taper or stop immunomodulators.
• For wound and mucosal healing, conservative management is preferred over routine surgical debridement, while local measures can help control oral bleeding and promote oral recovery.
• DRESS is generally a Th2/Tc2-driven disease treated with corticosteroids, but several steroid-sparing alternatives are emerging for refractory cases.
• Potent topical corticosteroids may benefit mild-to-moderate DRESS and can reduce the need for systemic steroid exposure.
• Biologic therapies targeting IL-5, IL-4, and related pathways, including mepolizumab and dupilumab, show promise for refractory DRESS.
• GBFDE is distinct from SJS/TEN but shares some cytotoxic pathways, and TNF inhibition may be beneficial in selected cases.
• Overall, management of SCARs is shifting toward tailored immunomodulation guided by disease stage, biomarkers, infection status, and multidisciplinary supportive care.