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

Stevens-Johnson syndrome in Child

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) represents an acute, severe drug hypersensitivity reaction with mucositis and desquamative skin lesions. Historically, terminology surrounding this entity has been imprecise, and terms such as erythema multiforme major and mycoplasma pneumonia-associated SJS have been used to embody a heterogenous group of mucositides resulting from a variety of drug and infectious exposures. Recently, there has been a movement toward reclassification of this entity into three separate entities:

SJS / toxic epidermal necrolysis (TEN) spectrum drug hypersensitivity:
  • Induced strictly by medication exposure (sulfamethoxazole / trimethoprim, NSAIDs, allopurinol, antiepileptics, etc)
  • SJS when <10% body surface area (BSA) is involved, SJS/TEN overlap when 10%-30% BSA is involved, TEN when >30% BSA is involved
  • Dusky macules (so-called "targetoid" with 2 zones of color) evolving into flaccid bullae and skin desquamation
  • Skin lesions favor truncal sites
  • Oral, ocular, and genitourinary mucositis
  • Nikolsky sign and Asboe-Hansen sign positive
  • Skin pain is a sign alerting to this diagnosis
Erythema multiforme (EM):
  • Secondary to infection, typically herpes simplex virus, or medications
  • Presents with typical, true target lesions (3 zones of color as opposed to 2 zones of color in SJS/TEN)
  • Lesions predominate on acral locations, particularly palms and soles
  • Lesions may or may not be vesiculated but do not desquamate or result in widespread erosions as seen in SJS/TEN
  • Mucositis may be entirely absent or limited to a single mucosal site, skin findings are more prominent than mucositis
  • Nikolsky sign is negative
Mycoplasma pneumoniae-induced rash and mucositis (MIRM):
  • Secondary to mycoplasma infection as evidenced by clinical pneumonia, imaging studies, and/or mycoplasma titers
  • Pronounced oral and ocular mucositis with absent, spare, or mild cutaneous involvement
  • Cutaneous lesions are most often tense and vesiculobullous, with or without target or targetoid lesions
  • 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
These entities all represent a hypersensitivity response presenting with varying degrees of mucositis and skin lesions as a result of infectious or pharmacologic exposure. Given the degree of overlap between these entities, each patient presenting with these findings should be evaluated for each possible diagnosis.

In SJS/TEN, common drug precipitants include sulfonamides, phenytoin, lamotrigine and other anticonvulsants, allopurinol, penicillins, and nonsteroidal anti-inflammatory drugs. 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.

SJS/TEN runs an unpredictable clinical course. It is typically preceded with nonspecific prodromal symptoms followed by characteristic skin and mucosal lesions.

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

Cutaneous lesions may begin as a more typical exanthematous eruption which 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, underlying 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.
  • Erythema multiforme (EM) – Histologic features may not differentiate EM from SJS/TEN. Clinically, however, 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 (typically herpes simplex virus) but may include medications. Lesions may be papular or vesicular but do not result in widespread desquamation. Note that EM is not considered within the same disease spectrum as SJS/TEN and confers no risk in progressing to TEN. Nikolsky sign is negative. Other implicated infections include influenza, hepatitis, Epstein-Barr viruses, Yersinia, tuberculosis, histoplasmosis, and coccidioidomycosis.
  • Mycoplasma pneumonia-induced rash and mucositis (MIRM) – Mucositis accompanied by no or mild cutaneous involvement, usually of vesicles or tense bullae secondary to mycoplasma infection. Oral and usually ocular mucositis is pronounced relative to skin findings.
  • Staphylococcal scalded skin syndrome – Usually occurs in newborns, infants, and young children; mucous membranes 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.
  • Purpura fulminans / disseminated intravascular coagulation (DIC) – 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.
  • Generalized fixed drug eruption – Look for erythematous plaques that develop on the lips, face, distal extremities, and genitalia 1-2 weeks after drug ingestions. Oral mucosa can be involved. Histology will differentiate fixed drug eruptions from SJS/TEN.
  • Bullous dermatosis of childhood – Look for tense blisters; histology will help differentiate linear IgA from SJS/TEN. Direct immunofluorescence (DIF) will demonstrate linear IgA deposition. DIF is negative in SJS/TEN.
  • Drug hypersensitivity syndrome (DRESS) – Look for facial edema (hallmark of DRESS), eosinophilia, hepatitis, and other viscera.
  • Bullous pemphigoid – Rare in children and presents with tense bullae arising within urticarial plaques. If necessary, immunofluorescence studies help confirm this diagnosis.
  • Pemphigus vulgaris is extremely rare in children and presents with flaccid blisters and erosions. If necessary, immunofluorescence studies help confirm this diagnosis.
  • Paraneoplastic pemphigus is extremely rare in children and presents with extensive, severe mucosal lesions. Like other autoimmune blistering diseases, characteristic immunofluorescence findings help confirm the diagnosis.
  • SJS/TEN-like variant of chikungunya

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: 05/14/2019
Copyright © 2019 VisualDx®. All rights reserved.
Potentially life-threatening emergency
Stevens-Johnson syndrome in Child
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
Erosions and hemorrhagic crusting on and around the lips, and some erosions on the tongue, in a case of SJS induced by an anticonvulsant.
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