STEVENS-JOHNSON SYNDROME
Skin and mucosal lesions of Stevens-Johnson syndrome
Introduction
Erythema multiforme, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are thought to have a common auto-immunological mechanism, 1and so are thought to be manifestations of the same disease process.
There is disagreement and confusion in the literature about the interrelationships of these 3 conditions.
Current general consensus is that they represent a spectrum of a common disease process that ranges in severity from mild to severe as follows:
●Erythema multiforme,relatively benign (most common).
●Severe erythema multiforme with mucosal involvement and systemic features (SJS), which may be life threatening (uncommon).
●TEN, the most life threatening manifestation, (rare).
These guidelines describe the Stevens-Johnson syndrome
The hallmark of the Stevens-Johnson syndrome is mucosal and systemic involvement.
Treatment of Stevens-Johnson syndrome is complex, not well defined and controversial and so consultation with a specialist dermatologist is therefore mandatory.
Pathophysiology
Stevens-Johnson syndrome (SJS) is considered to be an immune-complex mediated hypersensitivity reaction and is a severe expression of erythema multiforme.
SJS is a serious systemic disorder with the potential for severe morbidity and even death.
Causes
Causes fall into 4 groups:
1.Drugs are the most common cause:
A large range of drugs have been implicated in Stevens-Johnson syndrome, including in particular:
Antimicrobials:
●Sulfonamide antimicrobials (including sulfamethoxazole and dapsone), aminopenicillins, quinolones, cephalosporins, trimethoprim.
Anticonvulsants:
●Phenytoin, carbamazepine, phenobarbitone and lamotrigine.
Anti-Rheumatologic agents:
●NSAIDs (especially oxicam derivatives, piroxicam), allopurinol, gold.
Other less common associations include:
2.Malignancies.
3.Infections:
●Mycoplasma in particular, but alsoherpes simplex virus, influenza virus, mumps, and coxsackievirus have been implicated.
4.Idiopathic:
●A number of cases have no specific etiology ever identified.
Drugs and malignancies are most often implicated as the etiology in adults and the elderly.
Pediatric cases are related more often to infectious causes than to malignancy or drugrelated causes.
Clinical Features
Somewhat arbitrarily, Stevens-Johnson syndrome is distinguished from Erythema multiforme by the presence of significant systemic and mucosal surface involvement.
Stevens-Johnson syndrome is then distinguished from TEN, according to its severity of extent.
SJS, leads to <10% full-thickness epidermal death and shedding, (whilst TEN has >30% of full-thickness epidermal death and shedding)
Clinical manifestations may include:
1.Prodrome:
Significant systemic flu-like symptoms may precede the skin manifestations
●Fever
●Sore throat and tender cervical lymphadenopathy may be seen.
2.Constitutional symptoms:
●Anorexia, lethargy, malaise.
3.Skin manifestations:
●Within 24-48 hours skin blistering and mucosal ulceration occur.
●The change from a previously itchy exanthematic eruption to skin pain, or the sudden appearance of dusky purpuric tender skin changes, warn that epidermal destruction has begun and blistering and/or areas of confluent epidermal shedding will follow. Exanthematic drug eruptions with any of these associated symptoms or signs can rapidly evolve into SJS or TEN.
●Occasionally SJS has classic target lesions similar to erythema multiforme.
●Hypertrophic and pigmented scarring may occur long term.
Widespread skin involvement can lead to important secondary complications, including:
●Fluid and electrolyte losses.
●Hypothermia
●Secondary bacterial infection.
●Loss of protein albumin
●High output cardiac failure, (in elderly).
4.Mucosal involvement:
Mucosal changes are unrelated to severity or extent of skin involvement.
Mucosal involvement may include erythema, edema, sloughing, blistering, ulceration, and necrosis.
Ocular:
●Early ocular symptoms include itchy/gritty eyes and photophobia.
●Ocular complications can be severe, ranging from persistently dry, irritated eyes to corneal scarring, ulceration and even blindness.
ENT:
●Rhinorrhoea and ear pain may occur.
GIT:
●Involvement of oral and/or mucous membranes may be severe enough that patients may not be able to eat or drink.
●Gut involvement may progress to necrosis with perforation and haemorrhage.
Respiratory:
●May lead to hypoxia and respiratory failure.
Genito-urinary:
●Phimosis or vaginal adhesions can result.
Renal:
●Renal impairment may occur, but is uncommon.
5.Mortality:
●Mortality from widespread skin involvement or systemic complications can reach 5%.
Investigations
Blood tests
●FBE
●CRP
●U&Es and glucose.
CXR
●If infection or malignancy is suspected
Biopsy
●Biopsy of skin lesions is the only definitive diagnostic investigation.
Other tests are done as clinically indicated.
Management
Principles of management include:
1.Immediate cessation of any possible implicating drug.
2.Supportive, the mainstay of treatment.
3.Immunosuppressive agents.
4.Specialist referral as clinically indicated.
Cessation of offending agent:
●Any possible offending drug agent must be immediately ceased.
●Stopping drugs early has been shown to reduce mortality and morbidity.
●Patient must be warned of the offending agent as recurrences may occur.
Supportive care:
1.Oxygen therapy, as indicated.
2.IV fluid resuscitation.
3.Treat any secondary bacterial infections.
4.Protect from hypothermia.
Immunosuppressive agents:
Two agents have been advocated for SJS/TEN and if given at time of diagnosis and during period of disease extension and tissue destruction may be of benefit, however they are not proven treatments:1
●Normal human immunoglobulin
●Cyclosporin
See Dermatology Therapeutic Guidelines for full prescribing details.
The role of oral corticosteroids is controversial but if used they need to be started early, in high doses and for a short period (ie less than 1 week).
Referrals:
Urgent hospital admission and specialist advice are essential.
1.Dermatologist:
●Treatment of Stevens-Johnson syndrome is complex, not well defined and controversial and so consultation with a specialist dermatologist is therefore mandatory.
2.Ophthalmologist:
●Ophthalmology consultation is mandatory for those with ocular involvement.
3.Skin lesions are treated similar to burns:
●Referral to a burns unit may be required, although this is more usually the case with TEN
References
1.Dermatology Therapeutic Guidelines, 2004.
Dr J Hayes
Reviewed 2May 2008.