Publish date: Posted on
Last updated: October 23, 2023
Keywords #
drug-induced
medication
reaction
erosion
detachment
Stevens-Johnson Syndrome
SJS
Toxic Epidermolysis Necrosis
TEN
bullae
sloughing
Diagnosis #
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are variants of the same rare, severe drug reaction distinguished by severity. They are defined by skin pain, mucosal erosions, and detachmentith or without systemic involvement and is most commonly triggered by medications. TEN displays denudation of the epidermis in the acute phase, while SJS shows confluent purpuric macules or atypical flat targetoid lesions with bullae and erosions covering <10% body surface area (BSA), 10-30% BSA for SJS/TEN overlap, and >30% BSA for TEN.[1] SJS and TEN are thought to be due to a cytotoxic host T cell response to a drug or its metabolites that leads to keratinocyte apoptosis.[1,2] As it may be life-threatening, it requires immediate evaluation and carries a high morbidity and mortality risk.[1]
Key Concepts #
- SJS and TEN are dermatologic emergencies.
- It is caused by a cell-mediated host immune response to an offending drug.
- Skin pain, detachment, and mucosal erosions are present with possible systemic symptoms.
- SJS has a 1-5% mortality risk and TEN has a 25-35% mortality risk.
- Rapid identification and withdrawal of the offending drug and transfer to a burn unit with aggressive supportive care are the most critical steps in management.
Epidemiology #
SJS/TEN can affect patients of any race or ethnicity, though several studies have shown association with nonwhite race, particularly Asian origin. There is a slight female predominance and incidence is higher with increasing age, though it can affect both younger and older patients. Certain HLA haplotypes and CYP450 polymorphisms have been associated with higher risk of SJS/TEN after specific drug exposures; prevalence of certain haplotypes among different races may at least in part explain the incidence variation by race. Patients with HIV infection have been shown to have a 1000-fold increased risk for SJS/TEN.[3,4]
Clinical Features #
- TEN displays denudation of the epidermis in the acute phase, while SJS shows confluent purpuric macules or atypical flat targetoid lesions with bullae and erosions covering <10% body surface area (BSA), 10-30% BSA for SJS/TEN overlap, and >30% BSA for TEN.[1]
- SJS/TEN most often begins with a prodrome of fever, malaise, anorexia, pharyngitis, headache, and rash, which may be morbilliform or consist of atypical targetoid macules.
- Flaccid bullae, skin erosions, and painful mucosal ulceration are the major signs, which can develop anywhere from 1 day to 2 weeks later.
- The skin is often tender to palpation, and Nikolsky sign (sloughing of the epidermis with gentle external pressure) is positive.
- Once blister arrest occurs, re-epithelialization in TEN begins within days, though mucosal sites and areas which are exposed to pressure or superinfected are slower to heal.[1,2]
- SJS and TEN are associated with sloughing of both internal and external mucocutaneous membranes; erosion, necrosis, and severe dysfunction of the ocular, pulmonary, cardiovascular, gastrointestinal, and renal systems, as well as hematopoietic disturbances can be observed.[2,4]Secondary infection and respiratory compromise are largely responsible for fatality.
Differential Diagnoses #
- Erythema multiforme (EM) major
- Staphylococcal scalded skin syndrome
- Drug-induced linear immunoglobulin A dermatosis
- Acute graft-versus-host disease
- Acute generalized exanthematous pustulosis
- Drug reaction with eosinophilia and systemic symptoms (DRESS) or Drug-induced hypersensitivity syndrome (DIHS)
- Generalized morbilliform drug eruption
- Mycoplasma induced rash and mucositis (MIRM)
Diagnostic Workup #
The diagnosis of SJS/TEN is made on the basis of both clinical findings mentioned above in addition to histologic findings. SJS/TEN can resemble nonspecific drug reactions characterized by a morbilliform eruption; however, skin biopsy will reveal epidermal necrosis on frozen sections, which has a high sensitivity and low specificity for diagnosing SJS/TEN. It is effective in distinguishing SJS/TEN from other bullous disease. Important steps in evaluation including ruling out alternative diagnoses and specialist consultation for ocular and visceral involvement. [2]
Treatment #
Removal of all potential offending medications is the most important step in treatment. Then, the primary goals are to provide fluid and nutritional support, pain control, and infection surveillance. Intensive care level or burn unit level care is usually required. While the evidence for immunosuppression is controversial, corticosteroids and other immunosuppressants are theoretically most beneficial in the acute inflammatory stage. However, once desquamation stops, wound healing and secondary infection prevention may be impeded by long courses of immunosuppression.[2] Cyclosporine 3-5 mg/kg divided twice daily has shown efficacy in case series. IVIg, usually dosed at 0.8 g/kg/day for 3-4 days, also has mixed data supporting its use. Etanercept has been described as useful in small numbers of patients.[2,5-7]
Prognosis is aided by a severity-of-illness score that estimates mortality in SJS/TEN (SCORTEN) with the following factors: age >40, HR > 120 bpm, malignancy, involved BSA >10%, BUN > 10 mEq/L, serum bicarbonate < 20 mEq/L, blood glucose > 252 mg/dL. Higher number of criteria met is associated with higher mortality estimate.[8]
Slide Viewer #
https://utahderm.med.utah.edu/image-viewer/References #
- 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;69:173.e1-13; quiz 85-6.
- Schwartz RA, McDonough PH , Lee BW. Toxic epidermal necrolysis: Part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol 2013;69:187.e1-16; quiz 203-4.
- Hsu DY, Brieva J, Silverberg NB , Silverberg JI. Morbidity and Mortality of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in United States Adults. J Invest Dermatol 2016;136:1387-97.
- Valeyrie-Allanore L , Roujeau J. Epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis). In: K. S. Goldsmith LA, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s Dermatology in General Medicine. New York: McGraw-Hill; 2012. p. 439-48.
- Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D , Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol 2014;71:278-83.
- Zimmermann S, Sekula P, Venhoff M, Motschall E, Knaus J, Schumacher M et al. Systemic Immunomodulating Therapies for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Systematic Review and Meta-analysis. JAMA Dermatol 2017;153:514-22.
- Lee HY, Fook-Chong S, Koh HY, Thirumoorthy T , Pang SM. Cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis: Retrospective analysis of a cohort treated in a specialized referral center. J Am Acad Dermatol 2017;76:106-13.
- Guegan S, Bastuji-Garin S, Poszepczynska-Guigne E, Roujeau JC , Revuz J. Performance of the SCORTEN during the first five days of hospitalization to predict the prognosis of epidermal necrolysis. J Invest Dermatol 2006;126:272-6.
