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Potentially life-threatening emergency
Stevens-Johnson syndrome in Adult
See also in: External and Internal Eye,Oral Mucosal Lesion
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Potentially life-threatening emergency

Stevens-Johnson syndrome in Adult

See also in: External and Internal Eye,Oral Mucosal Lesion
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Contributors: Andrew Walls MD, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two rare, severe drug reactions that are characterized by mucosal erosions with skin pain and detachment most commonly triggered by medications. SJS and TEN should be considered the same disease along a spectrum but, importantly, are conceptualized as distinct entities from erythema multiforme (EM) and mycoplasma pneumoniae-induced rash and mucositis (MIRM), which are both infection-related entities (see Differential Diagnosis section).

SJS is characterized by involvement of detached and detachable skin that is less than 10% of body surface area (BSA), while TEN involves greater than 30% BSA. SJS-TEN overlap occurs when 10%-30% BSA is involved. Note that SJS can rapidly evolve into TEN, and both can have an unpredictable clinical course.

Investigations over the past decade have provided strong evidence that SJS and TEN are secondary to the host's inability to detoxify the culprit drug and its metabolites. This results in a cell-mediated immune response that activates cytotoxic T-cells and induces keratinocyte apoptosis via cell surface death receptor signaling. The primary medications most frequently implicated include allopurinol, NSAIDs, antibiotics, and anticonvulsants. Additional causes, albeit rare, include immunizations and infections.

SJS/TEN can affect all ages and races, with a slight preponderance seen in women (1.5:1) and an increasing incidence with age. Studies have linked certain HLA haplotypes and genetic p450 polymorphisms to increased risk of SJS/TEN when exposed to specific medications. AIDS is associated with 1000-fold increase risk of SJS/TEN.

The onset of SJS/TEN occurs 1-3 weeks, and sometimes as long as 8 weeks, after the ingestion of the culprit medication. It is typically preceded by nonspecific prodromal symptoms followed by characteristic skin and mucosal lesions.

Prodromal symptoms include fevers, malaise, arthralgias / myalgias, ocular irritation, and oropharyngeal pain. They may precede skin / mucosal findings by 1-3 days.

Cutaneous lesions may begin as a more typical exanthematous eruption that evolves to dusky, irregular, ill-defined coalescing macules with purpuric or detached centers. Lesions typically appear first on the central trunk, palms, and soles and then spread to involve the face and proximal extremities. As the disease progresses, large areas of serous blistering and sloughing may occur. Skin is typically painful and tender.

Mucosal lesions: Oral mucosal sloughing and crusting is present in >90% of cases and ocular involvement in >80%. Urogenital and, more rarely, respiratory and gastrointestinal (GI) mucosa may also be involved.

With severe involvement of the eyes, ulceration, scarring, visual impairment, and ultimately blindness may result. An estimated 50%-90% of patients will experience chronic ocular sequelae that may develop as long as 8 years following acute SJS/TEN.

Esophageal, anal, vaginal, and urethral meatal stenosis may be seen. GI bleeding, hepatitis, urinary retention, nephritis, anuria from dehydration and genitourinary injury, myocarditis, pneumothorax, obtundation, and seizures are rare complications. Other involvement includes GI lesions with diarrhea, cystitis, splenic inflammation, arthritis, pneumonitis, otitis media, paronychia, and nail shedding.

Prognosis:
SJS carries a 1%-5% mortality risk, may or may not have systemic symptoms, and involves the trunk and face with many isolated lesions. TEN carries a 25%-35% mortality risk, invariably has systemic symptoms, and the lesions on the trunk and face are largely coalesced. Secondary infection of denuded skin plays a significant role in mortality, as does respiratory compromise from mucositis.

Risk factors that confer a worse prognosis include extent of BSA involved, older age, malignancy, number of medications, leukopenias, and elevated serum urea, glucose, and creatinine levels.

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.

Long-term ocular and genitourinary follow-up is vital in mitigating complications.

Codes

ICD10CM:
L51.1 – Stevens-Johnson syndrome

SNOMEDCT:
73442001 – Stevens-Johnson syndrome

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Toxic epidermal necrolysis (TEN) – Same disease but more severe clinical phenotype with more widespread involvement.
  • Erythema multiforme (EM) – EM has characteristic target lesions (3 concentric colors that are round and well-demarcated) that occur on the extremities more often than the trunk. Precipitating factors are usually infectious (herpes simplex virus, mycoplasma, etc) and not drug-induced. Lesions may be papular or centrally bullous. Note that EM is not considered within the same disease spectrum as SJS/TEN and confers no risk in progressing to TEN. Nikolsky sign negative. Mucosal involvement with EM is termed EM major. Mucosal involvement may resemble that of SJS/TEN.
  • Mycoplasma pneumonia-induced rash and mucositis (MIRM) – Occurs secondary to mycoplasma infection as evidenced by clinical pneumonia, imaging studies, and/or mycoplasma serologies. There is pronounced oral and ocular mucositis with absent, spare, or mild cutaneous involvement. Cutaneous lesions are most often tense vesiculobullae. Target or targetoid lesions may be present. Cutaneous lesions do not erode or desquamate as seen in SJS/TEN (Note: erosion is seen in the genital and perianal skin, which are considered akin to mucosal surfaces). Nikolsky sign is negative. Acute and convalescent mycoplasma titers may be employed to help to establish this diagnosis in the correct clinical scenario.
  • Staphylococcal scalded skin syndrome – Usually occurs in newborns, infants, and young children; mucous membranes and palms / soles are spared. The exfoliated skin is more superficial (subcorneal versus epidermal-dermal). Also look for purulent discharge from the nose. Histologically, very different from SJS/TEN. Nikolsky sign can be positive. Mucosal surfaces are spared.
  • Purpura fulminans / disseminated intravascular coagulation – Can present with sudden superficial desquamation that may be easily misdiagnosed as SJS/TEN. Look for dusky macules or retiform purpura underlying denuded skin. Areas of retiform purpura and necrosis of the digits or face suggest this diagnosis.
  • Toxic shock syndrome and toxic-shock-like syndrome – Fever >38.9°C, hypotension, diffuse sunburn-like erythroderma (commonly affects palms and soles), and involvement of at least three organ systems. Ocular hyperemia and oral mucosal redness may be features. Delayed desquamation of the hands occurs (development of desquamation may be delayed). Severe cases have noted bullae.
  • Acute graft-versus-host disease – Clinically and histopathologically indistinguishable from TEN. Look for history of bone marrow transplant.
  • Acute generalized exanthematous pustulosis (AGEP) – Look for neutrophilia, eosinophilia, almost confluent erythema with overlying nonfollicular pustules. Nikolsky sign can be positive. Histology will clearly differentiate AGEP from SJS/TEN.
  • Drug hypersensitivity syndrome (DRESS) – Look for facial edema (hallmark of DRESS), eosinophilia, hepatitis, and other viscera.
  • Generalized fixed drug eruption – Look for dusky, violaceous, fixed plaques that develop on the lips, face, distal extremities, and genitalia 1-2 weeks after drug ingestions. Oral mucosa can be involved. Fixed drug eruptions should typically demonstrate round lesions of different sizes that do not progress to bullae or desquamation.
  • Pemphigus vulgaris – May present with widespread desquamation and oral lesions. Histology can differentiate the two.
  • Paraneoplastic pemphigus – Significant involvement of the oral mucosa including vermillion border. Usually has underlying associated malignancy. Erosions develop on skin but usually not with any preceding dusky macule or other skin lesion. Histology can differentiate.
  • Linear IgA dermatosis – Look for tense blisters, often annular; histology will help differentiate linear IgA from SJS/TEN. Direct immunofluorescence (DIF) will demonstrate linear IgA deposition. DIF is negative in SJS/TEN.
  • Bullous pemphigoid – Widespread tense bullae arising on urticarial plaques, usually in older patients. Pruritus is a common feature. Oral mucosa rarely involved, ocular mucosa virtually never.
Differential diagnosis of hemorrhagic crusting of both lips:

Best Tests

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Management Pearls

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Therapy

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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References

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Last Reviewed: 01/05/2017
Last Updated: 09/08/2017
Copyright © 2019 VisualDx®. All rights reserved.
Potentially life-threatening emergency
Stevens-Johnson syndrome in Adult
See also in: External and Internal Eye,Oral Mucosal Lesion
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Stevens-Johnson syndrome : Bullae, Eyelids, Lip mucosa hemorrhagic crust, Lips, Patient appears ill, Widespread, Conjunctival injection, Vesicles
Clinical image of Stevens-Johnson syndrome
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