**11. Management of Severe Cutaneous Adverse Reactions**

#### **11.1 Treatment of SJS/TEN**

#### *11.1.1 General management/supportive care*

Correct identification of the causative drug and immediate withdrawal of potentially causative drugs. May use the ALDEN algorithm to determine the culprit drug. Supportive management of skin wounds with anti-shear dressings, nutrition status, electrolyte balance, renal and airway function, and adequate pain control, prevent or treat the wound infections. Refer to the specialized unit/burn center for supportive care, silver wraps, apply emollients, air fluidized beds, and prevent infections. Fluid balance is very important to prevent end-organ hypo perfusion with daily monitoring of urine output (maintain 0.5–1.0 ml/kg/hr) or intra-arterial hemodynamic monitoring. Adequate nutrition supplement for protein loss- 20-25 kcal/kg/day in the early phase and 25–30 kcal/kg/day in the recovery phase is recommended either through oral intake or nasogastric feed. Analgesic care with acetaminophen in mild cases or opiod-based analgesics based on the severity of pain [38, 39].

#### *11.1.2 Specific treatment for SJS/TEN*

*Corticosteroids-* Systemic corticosteroids have shown non-inferiority when compared with supportive care in treating patients with SJS. However, in cases of TEN, many studies have shown survival benefits to the patient but some studies have also shown a lack of efficacy and also an increase in mortality. High doses of systemic steroids have shown to be more effective in TEN patients as recommended by Japanese experts. Araki *et al* have successfully used corticosteroid pulse therapy (methylprednisolone 500 mg/day for 3 days in 5 patients of TEN and all survived also supported by one recent published meta-analysis suggesting systemic corticosteroids as promising immunomodulating therapies for SJS/TEN [40].

*Intravenous Immunoglobulin-* some studies have shown the survival benefit of Intravenous immunoglobulins (IVIG) with a dose of 2.8 g/kg up to 4 g/kg [41, 42]. Those studies with no survival benefit used doses mostly up to 2 g/kg or lower [43]. Huang et al. performed the first meta-analysis on the efficacy of IVIg for the treatment of TEN showing the benefit of the use of high dose IVIG over low dose IVIG [44]. But recent published reviews and meta-analyses showed no differences in mortality with IVIG compared with only supportive care [45, 46].

*Cyclosporine-* Inhibits CD8+ cytotoxic T cells with anti-apoptotic effect by inhibition of Fas ligand. Cyclosporine 3 mg/kg for 10 days with gradual tapering over 1 month revealed less skin detachment and a lower mortality rate in one of the pilot studies recruiting 29 patients of SJS/TEN. Chen *et al* in a meta-analysis found significantly lower mortality than calculated as per SCORTEN score in patients receiving cyclosporine (OR: 0.42, 95% CI- 0.19-0.95) [47, 48]. Zimmermann et al. metaanalysis also showed a better reduction in mortality with the use of cyclosporine when compared with just supportive care. However large-scale randomized controlled studies are required to confirm these findings [49].

*Anti-TNF alpha agents:* Increase in TNF-alpha in skin specimens, skin blister fluids, and in serum of SJS/TEN patients have been observed and hence the role of anti-TNF alpha agents may prove effective. Infliximab and Etanercept use have shown to be effective as published in many case reports and case series with better survival outcomes. Only one trial by Wolkenstein *et al* that used Thalidomide for treatment of SJS/TEN was prematurely terminated in view of the increase in mortality observed in patients [50, 51].

*Plasmapheresis***:** Plasmapheresis is known to filter the harmful mediators in blood and have shown dramatic improvement in a patient with SJS/TEN. Narira *et al* study demonstrated that the use of plasmapheresis in patients refractory to conventional therapy treatment reduced the interleukin levels (IL-6, 8, and TNF-alpha) and is recommended for use by Japanese experts in TEN patients refractory to high dose corticosteroids [52].
