Toxic epidermal necrolysis L51.2

Severe maximum variant of a drug reaction characterized by extensive detachment of the skin and mucous membranes, severe systemic concomitant symptoms and high mortality (20-50%). The risk of TEN is highest between the 4th and 28th day after initiation of drug therapy. The disease is considered a maximum variant of SJS syndrome ( Stevens-Johnson syndrome) with a minimum infestation of > 30% of the body surface.

• Incidence: About 0.15-0.18/100,000 inhabitants/year.
• More common in patients with manifest AIDS (incidence is 100/100,000 per year for those infected with HIV).

• The pathogenesis is unknown. Clinical and histological similarities to severe cutaneous graft-versus-host reactions suggest a common pathogenesis. Evidence suggests that various drugs such as cotrimoxazole and other sulfonamides, antiepileptic drugs, allopurinol (probably the most common cause!), oxicam (nonsteroidal anti-inflammatory drug), psychotropic drugs, anticonvulsants (e.g. phenytoin and phenobarbital), serotonin reuptake inhibitors (e.g. fluoxetine) trigger TEN.
• No evidence of increased risk has been demonstrated for widely used medications such as beta-blockers, ACE inhibitors, calcium channel blockers, thiazides, furosemide, sulfonylureas, and insulin.
• Vaccinations ( measles, mumps, rubella) were occasionally described in the literature as a trigger. For specific concomitant diseases such as HIV, collagenosis, tumor diseases, radiation therapy and acute infections within the last 4 weeks a significant risk could be calculated.

• Predominantly women are affected (up to 10 times more frequently than men).
• The average age is 60-70 LJ.
• Children and young people are very rarely affected.

• Initially finely spotted, later confluent, large-area initially macular, subsequently maculopapular and finally vesicular exanthema. Furthermore: extensive epidermal detachment (epidermal necrolysis) with skin that can be removed like a towel.
• Early involvement of upper and lower eyelids with hemorrhagic encrusting erosions.
• Conjunctivitis with tendency to symblepharon formation.
• Mouth and genital mucosa: Inflammatory redness, erosions, ulcerations, haemorrhagic encrustation, possible adhesions.
• General: High fever, possibly somnolence, fatigue
• Frequently rapid intensive duty!

• Extensive necrolysis of the epidermis with intra- and subepidermal blister formation. Bladder contents are mostly hemorrhagic. Oedematized dermis, epitheliotropic round cell infiltrates and vasodilatation are also observed.
• Cryostat section: For a quick diagnosis a biopsy with a fresh blister cover, which is formed by the entire epidermis, is necessary.

• Staphylococcal Scalded Skin Syndrome: here, intraepidermal blister formation and therefore significantly reduced blister thickness. Typical is the absence of mucosal involvement.
• Erythema exsudativum multiforme (major forms)
• Paraneoplastic pemphigus.

• Skin: scarring, pigmentation disorders, nail growth disorders ( Beau-Reilsche transverse furrows of the nails, nail loss). Diffuse toxic alopecia (usually reversible) (see Alopecia). Bacterial or viral infections of the skin. Risk of sepsis with development of shock and multiorgan failure (most frequent cause of death). Changes in the mucous membrane of the oropharynx, genitals or anal region.
• Eyes: initial mucopurulent inflammation, conjunctival necrosis (destruction of goblet cells, cornification), corneal ulcers. Later consequences are scarring with trichiasis, keratoconjunctivitis sicca or synechia.
• Kidneys: Tubular necrosis.
• Lungs: respiratory failure.
• Gastrointestinal tract: Bleeding.
• Blood: Leukopenia
• Loss of fluid, electrolytes and protein.

• Intensive care in appropriately equipped therapy units.
• Discontinuation of the medication in question.
• Isolation/protection against infection (set up airlock).
• Aseptic protective clothing: protective gowns, mouthguards, gloves for medical and nursing staff.
• Sufficient heat supply (exact temperature control).
• Ensure sufficient moisture content of the room air.
• Use special bed for decubitus prophylaxis and store on metal foil.
• If necessary, place a bladder catheter, urine and fluid balancing.
• Documentation of the collected findings (extent, severity on intensive care treatment sheets).
• If necessary, take swabs of the wound surfaces (culture with resistance behaviour; danger from Pseudomonas colonisation and other superinfections).
• Therapy of complications (sepsis, bleeding).

Glucocorticoids: The use of systemic glucocorticoids is controversially discussed. Some studies indicate a worse prognosis with high-dose glucocorticoid medication. Nevertheless, a short-term shock therapy is still recommended (1000-250-100-20 mg prednisolone on day 1 to 4 i.v.). Ulcer prophylaxis with ranitidine (e.g. Zantic) 150 mg/day.

Ciclosporin A: Controversially discussed so far, a large Spanish study (n=26 patients) demonstrated a significant reduction of the mortality risk compared to a group not treated with Ciclosporin A (IVIG therapy) (Gonzales-Herrada C et al. (2017).

IVIG: Initial 1.0 g/kg bw for 4 days and maintenance therapy of 0.5 g/kg bw (4-weekly rhythm) over several months in case of resistance to therapy of other regimes. Data: The efficiency of IVIG therapy is controversially discussed on the basis of evidence level IIA studies.

Antibiotics (only in case of superinfection): Antibiotic coverage with cephalosporins such as cefotaxime (e.g. claforan) 2 times/day 2 g i.v., if necessary in combination with gentamicin (e.g. refobacin) 240 mg/day i.v. daily i.v. Swabs taken on the wound surfaces and if necessary conversion of the antibiotic treatment according to the antibiogram.

Pain therapy: Morphine (e.g. MST Tbl.) 10-30 mg every 8 hours or opioids such as tramadol (Tramal) 100 mg every 4-6 hours (max. 400 mg/day).

• Fluid balancing: In case of severe courses, initiate fluid balancing and parenteral nutrition. Dosage scheme per day:
  • Colloidal solution 1 ml/kg KG x KO.
  • Electrolyte solution (physiological saline solution) 1 ml/kg KO.
    On stabilization: transition to high-calorific liquid food (e.g. meritene). Later diet with passed food; no spices, no fruit acids.

• Notice! Check intravenous accesses regularly (high risk of contamination)!

• Remember! With glucocorticoid administration and therapy with Ciclosporin A, a bacterial cause of TEN (Staphylogenes Lyell Syndrome) must be excluded!

Remember! Report to the Documentation Centre of Severe Skin Reactions, Dermatological Clinic of the University of Freiburg, Hauptstr. 7, 79104 Freiburg. Web: http://www.ukl.uni-freiburg.de/haut/dzh/homede.htm

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