EN is a life-threatening disease that requires optimal management: early recognition and withdrawal of the offending drug(s) and supportive care in an appropriate hospital setting.
Prompt withdrawal of offending agent(s) is associated with an increased rate of survival in patients with EN induced by drugs with short elimination half-lives.81 On the other hand, it is preferable to continue every important and nonsuspected medication. That will avoid reluctance on the part of the patient's physicians to prescribe them in the future. In case of doubt, all nonlife-sustaining drugs should be stopped, and particularly those administered within the previous 8 weeks.
Only patients with limited skin involvement, a SCORTEN score of 0 or 1, and a disease that is not rapidly progressing can be treated in nonspecialized wards. Others should be transferred to intensive care units or burn centers.82 There is no “specific” treatment of demonstrated efficacy and supportive measures are the most important.5 Supportive care consists of maintaining hemodynamic equilibrium and preventing life-threatening complications. The aims are basically the same as for extensive burns.
EN is associated with significant fluid loss from erosions, which results in hypovolemia and electrolyte imbalance. Fluid replacement must be started as soon as possible and adjusted daily. Volumes of infusions are usually less than for burns of similar extent, because interstitial edema is absent. Peripheral venous lines are preferred when possible, because the sites of insertion of central lines are often involved in detachment of epidermis and prone to infection. The environmental temperature should be raised to 28°C to 30°C (82.4°F to 86°F). The use of an air-fluidized bed improves patient comfort.
Early nutritional support is preferentially provided by nasogastric tube to promote healing and to decrease the risk of bacterial translocation from the gastrointestinal tract. To reduce the risk of infection, aseptic and careful handing is required. Skin, blood, and urine specimens should be cultured for bacteria and fungi at frequent intervals. Prophylactic antibiotics are not indicated. Patients should receive antibiotics when clinical infection is suspected. Prophylactic anticoagulation is provided during hospitalization.
We do not recommend extensive and aggressive debridement of necrotic epidermis in EN because the superficial necrosis is not an obstacle to reepithelialization, and might even accelerate the proliferation of stem cells due to the inflammatory cytokines. This is the single noticeable divergence between authors of this chapter and the recommendations of US Burn centers.5 A few recent series suggest that debridement is necessary neither in superficial burns81 nor in EN. 84,85 There is no standard policy on wound dressings and the use of antiseptics. It is a matter of experience for each center. Skillfulness on the part of specialized nurses, careful manipulation, and an aggressive protocol of prevention and treatment of pain are essential.
Eyes should be examined daily by an ophthalmologist. Preservative-free emollients, antibiotic or antiseptic eye drops, and vitamin A are often used every 2 hours in the acute phase, and mechanical disruption of early synechiae is indicated. Early graft of cryopreserved amniotic membrane has been proposed as capable to decrease the rate of severe eye sequelae.64
The mouth should be rinsed several times a day with antiseptic or antifungal solution.
Specific Treatment in Acute Stage
Because of the importance of immunologic and cytotoxic mechanisms, a large number of immunosuppressive and/or anti-inflammatory therapies have been tried to halt the progression of the disease. None has clearly proved its efficacy. The low prevalence of the disease makes randomized clinical trials hard to perform.
The use of systemic corticosteroids is still controversial. Some studies found that such therapy could prevent the extension of the disease when administered during the early phase, especially as intravenous pulses for a few days.86 Other studies concluded that steroids did not stop the progression of the disease and were even associated with increased mortality and adverse effects, particularly sepsis. Thus, systemic corticosteroids cannot be recommended as the mainstay treatment of EN,5 but a large cohort study has suggested a possible benefit that should be explored by a prospective study.87
The proposal to use high-dose intravenous Ig was based on the hypothesis that Fas-mediated cell death can be abrogated by the anti-Fas activity present in commercial batches of normal human Ig.45 Benefits have been claimed by several studies and case reports,45,88–90 but refuted by several others.16,87,91,92 Thus, intravenous Ig cannot be considered the standard of care,5 especially after recent findings that the Fas-L/Fas pathway was not, or only marginally, involved in the mechanisms of EN.50 If used, a minimal precaution is to avoid preparations that are potentially nephrotoxic.
Cyclosporine is a powerful immunosuppressive agent associated with biologic effects that may theoretically be useful in treatment of EN: activation of T helper 2 cytokines, inhibition of CD8+ cytotoxic mechanisms, and antiapoptotic effect through inhibition of Fas-L, nuclear factor-κB, and TNF-α. Several case reports and series suggested some efficacy of cyclosporine A in halting the progression of EN without worrisome side effects when administered early.93,94
Plasmapheresis or Hemodialysis
The rationale for using plasmapheresis or hemodialysis is to prompt the removal of the offending medication, its metabolites, or inflammatory mediators such as cytokines. A small series reported their efficacy and safety in treating EN.95–98 However, considering the absence of evidence and the risks associated with intravascular catheters, these treatments cannot be recommended.
Antitumor Necrosis Factor Agents
Anti-TNF monoclonal antibodies have been successfully used to treat a few patients. Because a prior randomized controlled trial of thalidomide, an anti-TNF agent, had to be interrupted due to significantly increased mortality,99 extreme caution is suggested in the use of anti-TNF agents to treat EN.
Very promising treatments have now been developed for the ocular sequelae of EN, including gas permeable scleral lenses100,101 and grafting of autologous stem cells from contralateral limbus or mouth mucosa.102,103 With the exception of ocular sequelae, the literature contains only case reports related to treating sequelae. Photoprotection and cosmetic lasers may help resolve the pigmentation changes on the skin.