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toxic (bullous) epidermal necrolysis (Lyell syndrome, TEN)

Etiology: 1) allergic reaction, almost always to a drug 2) pharmaceutical agents (~90%) [3] a) antibiotics: (21%) [10], 32% [11] - antibacterial agents - sulfonamides (trimethoprim sulfamethoxazole), fluoroquinolones, aminopenicillins (ampicillin, amoxicillin), cephalosporins, macrolides, minocycline, nalidixic acid - antiretroviral agents - nevirapine, abacavir b) anticonvulsants: (19%) [10] - carbamazepine, phenytoin, fosphenytoin, lamotrigine oxcarbazine, phenobarbital c) NSAIDs: (11%) [10] - meloxicam, piroxicam, tenoxicam - diclofenac, indomethacin, ionazolac, etodolac, aceclofenac, sulindac, ketorolac, phenylbutazone d) other: - allopurinol (11%) [10], sertraline, pantoprozole, bromides, iodides, chlormezanone, sulfasalazine e) see pharmaceutical agents causing SCARs 3) less common causes: - infection (4%) [3] - radiation, malignancy, vaccination, graft vs. host Epidemiology: 1) all age groups affected; uncommon in children 2) female predominance (1.5-2:1) 3) high incidence in HIV+ patients (1/1000/year) Pathology: - acute epidermal necrosis Genetics: - drug-induced TEN (carbamazepine, phenytoin) linked to HLA-B*1502 in Han Chinese (Asians, South Asian Indians) Clinical manifestations: 1) prodrome of malaise, anorexia, arthralgias, fever & upper respiratory tract infection 1-3 days before appearance of skin lesions 2) skin & mucous membrane manifestations a) initially, warm, diffuse erythema, spreading from face & genitalia to trunk & extremities b) later, generalized tender erythema, often with bullae formation c) dusky patches with imminent blistering - suggests incipient skin necrosis & detachment d) >= 30% of body surface involved e) Nikolsky's sign f) early blistering, eroding oral-labial lesions (90%) g) sloughing & necrosis of entire epidermis h) purulent conjunctivitis (75%) * images [5,6] Laboratory: 1) blood cultures 2) complete blood count (CBC) a) anemia b) leukocytosis c) eosinophilia 3) basic metabolic panel - serum electrolytes, serum urea nitrogen, serum creatinine serum glucose 4) liver function tests 5) erythrocyte sedimentation rate may be elevated 6) urinalysis a) proteinuria b) hematuria 7) skin biopsy to ensure appropriate diagnosis [3] - full-thickness epidermal necrosis [8] 8) do not screen for SJS or TEN with HLA-B*1502 & HLA-B*5801 [3] Differential diagnosis: - Stevens-Johnson syndrome (SJS) & toxic epidermal necrolysis (TEN) represent a continuum of a single disorder - TEN is a severe form of SJS - in SJS, skin detachment involves < 10% of body area - in TEN, skin detachment involves > 30% of body area - in SJS-TEN overlap syndrome, 10-30% of body area involved - see Stevens-Johnson syndrome for more broad differential diagnosis Complications: 1) death generally occurs from sepsis that results from epidermal & mucosal necrosis (25-39%) [3] 2) GI hemorrhage 3) pulmonary embolism 4) long-term sequella SJS/TEN [9] - post-inflammatory dsypigmentation: hyperpigmentation, hypopigmentation, or a combination - hypertrophic or keloidal scars - nail changes: onycholysis or onychomadesis, onychorrhexis, onychoschizia, koilonychia, erythronychia, oil-drop sign - nail loss may be permanent (20%) - hair changes: telogen effluvium is common - eruptive nevi & atypical nevi - other cutaneous manifestations: pruritus, hyperhidrosis, photosensitivity, heterotopic ossification, ectopic sebaceous glands Management: 1) treat like a burn 2) hospitalize in intensive care or burn unit 3) discontinue offending agent(s) 4) rehydrate & correct electrolyte imbalances 5) aggressive treatment of suspected infections a) Staphylococcus b) Pseudomonas c) no role for prophylactic antibiotics [3] 6) use of glucocorticoids is controversial 7) intravenous immune globulins used [3] 8) cyclosporine has been used [10] Prognosis: 1) overall mortality is 30% (10%-70%, 20% [10]) 2) poorer prognosis with advanced age, extensive surface area involved & azotemia 3) see SCORTEN severity index score

Related

pharmaceutical agents causing severe cutaneous adverse reactions (SCARs) SCORTEN severity index score Stevens-Johnson syndrome (SJS)

General

severe cutaneous adverse reaction (SCAR)

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
  2. H. Quinny Cheng, USSF Fresno lecture, Oct 21, 1998
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018.
  4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 94
  5. Cohen V, Bronze MS (images) Medscape: Toxic Epidermal Necrolysis http://emedicine.medscape.com/article/229698-overview
  6. DermNet NZ. Toxic epidermal necrolysis (images) http://dermnetnz.org/doctors/emergencies/ten.html
  7. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol 2013 Aug; 69:173.e1. PMID: 23866878 - Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol 2013 Aug; 69:187.e1 PMID: 23866879
  8. NEJM Knowledge+ Question of the Week. Nov 8, 2016 http://knowledgeplus.nejm.org/question-of-week/1452/
  9. Heymann E Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis: The Aftermath. AAD Reading Room Content MedPage Today. June 22, 2021 https://www.medpagetoday.com/reading-room/aad/general-dermatology/93214
  10. Kridin K, Bruggen MC, Chua SL et al Assessment of Treatment Approaches and Outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Insights From a Pan-European Multicenter Study. JAMA Dermatol. Published online August 25, 2021. PMID: 34431984 https://jamanetwork.com/journals/jamadermatology/fullarticle/2783034
  11. Lee EU, Knox C, Phillips EJ Worldwide Prevalence of Antibiotic-Associated Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis. JAMA Dermatol. Published online February 15, 2023. PMID: 36790777 https://jamanetwork.com/journals/jamadermatology/fullarticle/2801093
  12. Noe MH, Micheletti RG. Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis. Clin Dermatol. 2020;38:607-12. PMID: 33341195
  13. Charlton OA, Harris V, Phan K, et al. Toxic epidermal necrolysis and Steven-Johnson syndrome: A comprehensive review. Adv Wound Care (New Rochelle). 2020;9:426-439. PMID: 32520664