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Stevens-Johnson syndrome (SJS)

Etiology: 1) hypersensitivity (most likely) a) possibly immunologic b) drugs & infection most likely triggers 2) pharmaceutical agents (~70-80%) [2,10,12] a) antibiotics 32% [13] - antibacterial agents (21%) - sulfonamides (trimethoprim sulfamethoxazole), fluoroquinolones, aminopenicillins (ampicillin, amoxicillin), cephalosporins, macrolides, minocycline, nalidixic acid - antiretroviral agents - nevirapine, abacavir b) anticonvulsants (19%) [12] - carbamazepine, phenytoin, fosphenytoin, lamotrigine oxcarbazine, phenobarbital c) NSAIDs (12%) [12] - meloxicam, piroxicam, tenoxicam - diclofenac, indomethacin, ionazolac, etodolac, aceclofenac, sulindac, ketorolac d) others - allopurinol (11%) [12], sertraline, pantoprozole, sulfasalazine - carbonic anhydrase inhibitors used in ophthalmic agents to treat glaucoma - brinzolamide, dorzolamide [10] e) see pharmaceutical agents causing SCARs 3) infections (26%) [2] a) Herpes simplex b) Mycoplasma Epidemiology: 1) most common in young adults 2) male:female ratio 2:1 Pathology: - acute epidermal necrosis (full thickness) - involvement of mucous membranes - potentially fatal due to secondary infection, transcutaneous fluid loss, respiratory complications * histopathology image [6] Genetics: - drug-induced SJS (carbamazepine, phenytoin, allopurinol) linked to HLA-B*1502 in Han Chinese (Asians, South Asian Indians) Clinical manifestations: 1) prodrome of fever, malaise, arthralgia, headache, respiratory symptoms, vomiting &/or diarrhea 1-14 days before appearance of skin lesions 2) skin & mucous membrane manifestations a) diffuse pruritus or burning may occur in the prodromal phase b) early lesions are pink, edematous papules c) these then evolve into dull, red macules with central cyanosis or into vesicles (atypical 'target lesions') d) lesions can coalesce & progress to flaccid bullae with sloughing - positive Nikolsky sign [14] e) lesions are most prominent on extremities, palms & soles - trunk may also be involved - up to 10% of body surface involved [2] f) erosive lesions may occur on mucous membranes - oral mucosa, conjunctiva, genitourinary - mucosa alone may be affected - hemorrhagic crusting of oral mucosa is characteristic [2] 3) systemic manifestations a) arthralgia b) hepatitis c) myocarditis d) nephritis e) pneumonia 4) time course: 4-6 weeks * images [6,7] Laboratory: 1) blood cultures 2) complete blood count (CBC) a) anemia b) leukocytosis c) eosinophilia 3) serum electrolytes, serum urea nitrogen, serum creatinine 4) liver function tests 5) erythrocyte sedimentation rate may be elevated 6) urinalysis a) proteinuria b) hematuria 7) skin biopsy if diagnosis uncertain - full-thickness epidermal necrosis [9] 8) do not screen for SJS or TEN with HLA-B*1502 & HLA-B*5801 [2] Differential diagnosis: - erythema multiforme - target lesions - DRESS syndrome (lymphadenopathy) - often delayed onset 2-6 weeks - morbilliform exanthem, facial edema & redness - generalized exanthematous pustulosis - rapid onset of a pustular rash after a medication exposure - erythroderma - diffuse erythema covering 80% to 90% body surface area - pruritus, peripheral edema, erosions, scaling, & lymphadenopathy - toxic epidermal necrolysis (TEN) is a severe form of SJS - Stevens-Johnson syndrome (SJS) & toxic epidermal necrolysis (TEN) represent a continuum of a single disorder - 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 Complications: - epidermal necrosis resulting in infection, sepsis - mortality is 1-5% (5-13% [2]) - long-term sequella SJS/TEN [11] - 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) hospitalize; admit to intensive care unit (burn unit) 2) identify & eliminate triggering agent 3) mild disease (erythema multiforme minor) a) outpatient treatment with topical steroids b) dermatology follow-up 4) severe disease (Stevens-Johnson syndrome) a) a short course of high intensity glucocorticoid treatment may be of benefit b) intravenous immune globulin controversial [2] c) cyclosporine has been used [12] d) treat secondary infections e) no role for prophylactic antibiotics [2] 5) ophthalmology consult for eye involvement 6) prognosis: mortality 10% generally due to infection

Related

erythema multiforme pharmaceutical agents causing severe cutaneous adverse reactions (SCARs) toxic (bullous) epidermal necrolysis (Lyell syndrome, TEN)

General

severe cutaneous adverse reaction (SCAR) syndrome

References

  1. H. Quinny Cheng, UCSF Fresno lecture, Oct 21, 1998
  2. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
  3. Carr DR et al Approach to the acute, generalized, blistering patient. Semin Cutan Med Surg. 2007 Sep;26(3):139-46. Review. PMID: 18070680
  4. Cotliar J. Approach to the patient with a suspected drug eruption. Semin Cutan Med Surg. 2007 Sep;26(3):147-54. Review. PMID: 18070681
  5. Wetter DA, Camilleri MJ. Clinical, etiologic, and histopathologic features of Stevens- Johnson syndrome during an 8-year period at Mayo Clinic. Mayo Clin Proc. 2010 Feb;85(2):131-8 PMID: 20118388
  6. Foster CS, Roy H (images) Medscape: Stevens-Johnson Syndrome http://emedicine.medscape.com/article/1197450-overview
  7. DermNet NZ. (images) Stevens Johnson Syndrome & Toxic Epidermal Necrolysis http://www.dermnetnz.org/reactions/sjs-ten.html
  8. Fein JD, Hamann KL. Images in clinical medicine. Stevens-Johnson syndrome. N Engl J Med 2005 Apr 22; 352:1696 PMID: 15843672 Free full text http://www.nejm.org/doi/full/10.1056/NEJMicm031127
  9. NEJM Knowledge+ Question of the Week. Nov 8, 2016 http://knowledgeplus.nejm.org/question-of-week/1452/
  10. Yang MS, Lee JY, Kim J et al Searching for the culprit drugs for Stevens-Johnson syndrome and toxic epidermal necrolysis from a nationwide claim database in Korea. J Allergy Clin Immunol Pract 2020 Feb; 8:690 PMID: 31614216 https://www.sciencedirect.com/science/article/abs/pii/S221321981930858X
  11. 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
  12. 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
  13. 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
  14. NEJM Knowledge+ Dermatology - 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(2):173.e1-13; PMID: 23866878 Review. - 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(2):187.e1-16; PMID: 23866879 Review.
  15. Noe MH, Micheletti RG. Diagnosis and management of Stevens-Johnson syndrome/toxic epidermal necrolysis. Clin Dermatol. 2020;38:607-12. PMID: 33341195
  16. 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