Epidermal necrolysis refers to severe cutaneous reactions that cause extensive necrosis of tissue and detachment of the epidermis. It encompasses three conditions which are on a continuum of severity and how much of the body’s surface area is affected:

  • Stevens-Johnson syndrome (SJS): Less than 10% of BSA is detached
  • Toxic epidermal necrolysis (TEN) – More than 30% of BSA is detached
  • SJS/TEN overlap: Between 10 and 30% of BSA is detached

Epidermal necrolysis is a rare and painful condition that causes areas of the skin and mucus membranes to blister, peel, and detach. Much like a burn, this causes significant fluid losses and puts the individual at high risk for infection and other life-threatening complications. It affects five to six individuals per million per year in the United States.

Epidermal necrolysis pathophysiology and risk factors

Epidermal necrolysis is thought to occur when keratinocytes undergo apoptosis triggered by an inappropriate immune response that is often related to medications. Apoptosis leads to the death of the affected tissue and sloughing of the skin. While many medications can cause SJS or TEN, high risk medications include monoclonal antibodies used to treat cancer such as atezolizumab and ipilimumab. Patients taking these medications are four times more likely to develop SJS/TEN and the overall mortality rate is 37%. Other high-risk medications include allopurinol, anti-seizure medications, medications used to treat HIV, oxicams (a class of NSAIDs) and sulfonamides. 

In some cases, epidermal necrolysis is a result of infection, vaccination, and it may even be idiopathic, meaning it has no clear underlying trigger. It may also be associated with an autoimmune condition such as systemic lupus erythematosus.

Epidermal necrolysis typically develops a few weeks after taking the triggering medication. It begins with prodromal symptoms that usually last two to three days before the skin becomes affected.

Individuals most at risk for SJS/TEN include: 

  • Studies show that individuals with cancer develop SJS or TEN at a rate 30 to 60 times higher than the general population.
  • Individuals with connective tissue disease have a twofold increased risk of developing SJS or TEN.
  • Individuals with HIV have a higher risk for SJS or TENS due to immune system dysregulation and the high-risk medications used to treat both HIV and associated opportunistic infections such as tuberculosis.
  • While SJS and TEN can occur at any age, older adults are more likely to develop the condition.
  • Certain individuals and ethnicities are at higher risk for SJS or TEN due to genetic mutations that make these individuals more likely to have strong reactions to medication or reduced ability to breakdown and clear medications. This includes ethnicities with a higher incidence of a specific HLA allele such as those from Southeast Asia, Kora, Japan and Europe.
  • Individuals taking allopurinol who have impaired renal function (and thus reduced clearance of the medication) and those on higher doses are at increased risk of developing allopurinol-induced SJS or TEN.
  • Those with a prior incidence of SJS or TEN or a first-degree relative who has developed epidermal necrolysis are at increased risk as well.

Factors that increase an individual’s risk of dying from epidermal necrolysis include older age, sepsis, greater BSA affected, delayed transfer to a specialty center, and granulocytopenia (a decrease in a specific type of white blood cell). In general, the mortality rate of TEN is 25 to 30%, while SJS has a mortality rate of 1 to 5%.

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What are the complications of this condition?

Mucosal involvement – Complications of epidermal necrolysis are numerous and can involve extracutaneous tissue including mucus membranes. Mucosal involvement most often involves the oral cavity, but can also involve the upper airway, putting the individual at higher risk for pulmonary complications. 

Ocular involvement – When the eyes are affected, complications include reduced visual acuity, chronically dry eyes, sensitivity to light, and scarring of the cornea among others. 

Genital involvement is present in up to 70% of cases leading to severe pain, difficulty urinating, urinary retention, and UTI. Females can experience ulcerative vaginitis and other complications which can lead to adhesions and long-term genitourinary dysfunction.

Infection – Infection occurs in up to 50% of patients with SJS or TEN, which brings with it a significantly higher mortality risk. In most cases, patients with epidermal necrolysis who develop infection die from sepsis or septic shock. The most common infections are staphylococcal and pseudomonas infections.

Other organs – Organ involvement can affect the liver, kidneys, lungs and GI tract. Liver injury has been shown to occur in up to 30% of individuals with SJS or TEN and those with diabetes, underlying liver disease, and hyperlipidemia are most at risk. Acute kidney injury is common in epidermal necrolysis, and some patients will even require temporary dialysis and be at significantly higher risk for death. Respiratory complications include lung injury due to sloughing of the bronchial epithelium, atelectasis, pulmonary edema and pneumonia. Approximately 25% of individuals who experience respiratory complications require mechanical ventilation. Complications of the GI tract include rectal bleeding, diarrhea, abdominal pain and esophageal ulceration.

Hematologic complications – Disseminated intravascular coagulation and other hematologic abnormalities occur in over 20% of patients with SJS or TEN. Click here to learn more about DIC.

Skin – The skin can also be affected long-term with some patients experiencing alopecia, hyperhidrosis and abnormal pigmentation.

Now that you have some background knowledge about epidermal necrolysis, next you’ll learn the nursing implications utilizing the Straight A Nursing LATTE framework

L: How does the patient LOOK?

The patient’s signs and symptoms will vary depending on the phase of the illness and the presence of any specific complications. In the prodromal phase, signs and symptoms are flu-like and include fever, chills, body aches, red eyes and headache. This phase lasts two to three days and precedes any visible skin involvement.

The condition progresses to involve cutaneous and possibly also extracutaneous symptoms somewhere between 4 and 28 days after exposure to the triggering agent. The initial cutaneous symptom of epidermal necrolysis is a rash of painful pink to dark-red spots (macules) that typically appear on the face, torse, and proximal arms and legs. These macules spread as the condition progresses and commonly affect the palms and soles of the feet. As the condition progresses, the macules develop into fluid-filled blisters, extensive sheet-like detachment and erosions. 

The patient will also be in significant pain and can exhibit a wide range of complications depending on which areas of the body are affected. In addition to the skin, commonly affected areas are the lips, oral cavity, eyes and genitals, though other organs such as the GI tract and lungs may be involved. Specific symptoms could include difficulty swallowing, diarrhea, painful urination, vision problems, shortness of breath or hemoptysis.

Another manifestation of epidermal necrolysis is the Nikolsky sign, which is a finding in which the top layers of the skin slip away from the layers underneath when lateral pressure is applied. It was named after Dr. Nikolsky in 1896.

A: How do you ASSESS the patient with SJS or TEN?

  • Head-to-toe skin assessment – Examine all of the patient’s skin to determine which areas are affected and to determine TBSA, which determines the condition’s severity. Consider utilizing a skin diagram to designate which areas of the skin are affected and follow up daily to monitor progression. A Lund-Browder diagram may be utilized to determine the percentage of TBSA affected.
  • Pain – Epidermal necrolysis can cause significant pain, whether the patient has SJS or TEN. Perform a thorough pain assessment with your head-to-toe and follow up with a focused pain assessment at regular intervals or with any intervention.
  • Airway patency – Sloughing of the lining of the oral cavity and airway can lead to airway compromise. Additionally, involvement of the oral cavity can lead to difficulty swallowing, which increases aspiration risk and could also compromise the patient’s airway. Coughing, shortness of breath, hemoptysis, and increased oral secretions could all be signs of airway involvement.This patient requires further respiratory evaluation and close monitoring.
  • Urine output – A complication of SJS/TEN is dysuria which can lead to urinary retention. Utilize a bladder scanner to determine if the patient is retaining urine. Additionally, patients can lose a significant amount of fluid when large areas of the skin are involved, so keep careful track of I/O.
  • Temperature – Heat loss can occur through affected areas, which puts patients (especially those with more severe forms of TEN) at high risk for hypothermia. Additionally, these patients are at risk for infection, so keep a watchful eye for elevated temps.

T: What TESTS are conducted for a patient with SJS/TEN?

Both SJS and TEN are diagnosed through visual inspection and presence of an underlying risk factor. If necessary, a skin biopsy may be performed and will show necrotic tissue and/or detachment of the epidermis from the dermis.

Lab tests will be utilized to evaluate and monitor the patient:

  • CBC with differential – to monitor for infection
  • Coagulation studies – patients with SJS/TEN are at risk for hematologic complications such as DIC
  • Electrolytes – just like a patient with burn injury, these patients are at risk for electrolyte imbalances
  • BUN/Cr – acute kidney injury is a complication of SJS/TEN
  • LFTs – liver function tests will be utilized to monitor for hepatic impairment
  • CRP and ESR – C-reactive protein and erythrocyte sedimentation rate will be elevated in inflammatory states
  • Procalcitonin – may be utilized as an early indicator of bacteremia, especially in conjunction with hypothermia
  • Wound cultures – patients with SJS/TEN are at high risk for infection, so the recommendation is for cultures to be obtained at frequent intervals during the acute phase
  • Mycoplasma serology – if an obvious culprit cannot be identified, the condition may be related to mycoplasma pneumonia infection
  • Chest X-ray or chest CT – imaging studies may be ordered if the patient has respiratory complications

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T: What TREATMENTS are provided for a patient with SJS/TEN?

In addition to identifying and stopping the triggering medication, treatment for the acute phase of SJS and TEN includes replenishing fluids, maintaining electrolyte balance, preventing hypothermia, providing comfort, preventing infection, caring for wounds, optimizing nutrition, and addressing organ dysfunction as needed. It is recommended that patients with greater than 10% TBSA involvement or worsening organ function be treated in a specialty unit such as a burn center.

Fluids and electrolytes –  The damaged skin is unable to retain fluids and fluid losses can be significant, especially with larger areas of the body affected. Fluid requirements in the first 24 hours are estimated to be 2 ml per kg per BSA percentage. Ongoing fluid replacement is generally titrated to achieve optimal urine output of 0.5 to 1 ml/kg/hr. Additionally, electrolyte imbalances occur along with fluid loss, so these will be replaced as needed.

Prevent hypothermia – Heat loss occurs through open wounds and can be significant when large areas of the skin are involved. Room temperatures are recommended to be kept between 82.4 to 89.6-degrees F (28 to 32 degrees C). External heating devices may also be utilized.

Comfort – Pain management is essential as SJS/TEN are extremely painful, and opioids are commonly utilized. Note that additional doses may be necessary during dressing changes and mobilization. In addition, take care to position the patient off affected areas whenever possible.

Wound care – Meticulous wound care is vital for patients with SJS/TEN and may involve surgical debridement, manual scrubbing of the affected skin, or hydrotherapy which helps clean wounds while removing dead tissue. Other wound care methods utilized include skin grafts and biosynthetic dressings, which are applied after surgical debridement.

In some cases, a more conservative approach to wound care may be utilized where the affected epidermis is not debrided but instead left in place. Non-adhesive dressings such as petrolatum-impregnated gauze, biosynthetic dressings or a dressing containing silver are utilized to protect the skin and promote healing. The skin is gently cleansed with each dressing change.  

Prevent and treat infection – The evidence shows that up to 50% of individuals with SJS/TEN develop an infection, with sepsis being the most common cause of death. Infection prevention is a vital component of your plan of care and includes use of sterile gloves and supplies, PPE, reverse isolation, antiseptic cleansing solutions and silver-imbued gauze materials. It is also recommended that cultures of wounds, blood, indwelling catheters be obtained regularly such as every 48 hours. Antibiotics are utilized to treat bacterial infections as needed.

Optimize nutrition – Nutrition should be started as early as possible to support the healing process. If eating is difficult or painful due to mucosal involvement, enteral feeding is utilized. 

Support elimination – Many patients with SJS/TEN develop dysuria and urinary retention due to erosions and adhesions of the urogenital area. Treatments utilized to prevent adhesions and promote healing include barrier creams, nonadhesive dressings, and topical corticosteroids. Female patients may benefit from sitz baths and suppression of menstruation, which reduces the risk for endometriosis and vaginal adenosis. Urinary catheters may be needed to promote elimination, but note the use of an indwelling catheter greatly increases the risk for infection. 

Patients with GI tract involvement may have diarrhea, which can lead to infection of wounds on the buttocks of perineum. It is imperative that patients be kept clean and dry, especially if intubated with reduced mobility. 

Respiratory support – A significant number of patients with SJS/TEN develop acute respiratory complications which can include pulmonary edema, atelectasis, pneumonia, and bronchial erosions. Up to 38% experience acute respiratory failure and require mechanical ventilation. Note that the mortality rate for ventilated patients increases to over 50%. Bronchoscopy may be utilized to evaluate the lining of the airways, remove sloughed epithelium, and diagnose pulmonary infections. Careful oropharyngeal suctioning may also be utilized to maintain airway patency.

Ophthalmic treatments – Treatments to support the eyes when ocular involvement is present includes lubricants, saline rinses, topical antibiotics and topical corticosteroids. In some cases, adhesions may need to be separated and patients with extensive sloughing may undergo amniotic membrane transplantation (AMT), which acts as a graft and provides a substrate for the growth of epithelial cells. 

Address DIC – If disseminated intravascular coagulation (DIC) develops, patients may be administered blood products such as fresh frozen plasma (FFP), red blood cells and cryoprecipitate. Learn more about DIC here

Plasmapheresis – In this procedure, blood is removed from the body and the plasma is separated from other components. The plasma is run through a filter or centrifuge and returned to the patient without the autoantibodies or triggering agent associated with the autoimmune response.

Pharmacologic treatments – Currently there is no standardized pharmacologic treatment for SJS/TEN. Some medications utilized include: 

  • Immune globulin (IVIG) has been utilized for SJS/TEN, but the evidence shows there may be no significant benefit.
  • Immunosuppressants may be utilized to keep the body’s immune system from attacking its own tissues.
  • Corticosteroids such as prednisolone, methylprednisolone and dexamethasone may be used but their efficacy has not at this time been definitively proven.
  • Anti-tumor necrosis factor (TNF) inhibitors such as etanercept and infliximab have shown promising results and additional studies are needed to confirm efficacy.
  • Cyclosporine has been shown to reduce mortality, especially when used within 24 to 48 hours of symptom onset.

E: How do you EDUCATE the patient and family?

A key factor to educate patients about is the triggering agent, if one can be identified, so the patient knows to avoid it in the future. You’ll also be teaching patients and caregivers how to treat wounds and change dressings if the patient is not hospitalized and is caring for wounds at home. It’s also important to let the patient know that having SJS/TEN puts them at higher risk for developing it in the future, so they need to be able to recognize the early signs of the condition. Additionally, teach all patients to inform their health care providers that they’ve had SJS/TEN, since this may affect which medications are prescribed. 

Take this topic on the go by tuning in to episode 319 of the Straight A Nursing podcast. Listen from any podcast platform, or straight from the website here.

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