Stevens-Johnson Syndrome and Erythema Multiforme

Stevens-Johnson Syndrome

Overview

Stevens - Johnson Syndrome (SJS) is an idiosyncratic, delayed hypersensitivity reaction involving necrosis and sloughing of the skin and mucous membranes. TEN (toxic epidermal necrolysis) has greater than 30% epidermal involvement (skin sloughing).  SJS/TEN overlap has 10-30% epidermal involvement and Stevens-Johnson has less than 10% epidermal involvement.  Typically SJS occurs in individuals between 25 and 47 years of age and TEN occurs in individuals between 46 and 63 years of age.  There are about 2 to 7 cases per 1 million people per year. 

Causes

SJS is most commonly caused by medications (between 30-50% of cases) and antibiotics are the most common medication causing SJS.  Of the antibiotics, sulfonamides are the most likely to cause SJS.  Penicillins and cephalosporins are common causes as well.  Other medications include anti-gout agents (allopurinol), anti-psychotics, anti-epileptics (carbamazepine, phenytoin, lamotrigine, phenobarbital), analgesics and anti-inflammatory agents, commonly piroxicam.  The second most common cause of SJS is infection, which includes a variety of viral and bacterial causes. 

Signs/symptoms

Patients may have a prodrome of fever, sore throat, productive cough, headache, and malaise about 1 to 14 days prior to onset of the rash.  The mucocutaneous lesions tend to be non-pruritic, burning blisters with epidermal detachment and have a positive nikolsky’s sign (extension of area of superficial sloughing by pressure on the surface of the skin apparently not involved).  Facial edema and tongue swelling may also be present.  Mucous membrane involvement as well as ocular involvement is common. 

Treatment

Stop all unnecessary medications as they may be the trigger. If medications that may be potentially triggering SJS are stopped early, prognosis improves.  Patients are typically transferred to burn units for management.  Supportive care is the mainstay of treatment and involves wound care, fluid/electrolyte management, nutrition, ocular care and pain control.  Corticosteroids may be considered for adult patients with SJS, not for patients with TEN, due to increased risk of sepsis.  IVIG may also be considered for severe SJS or TEN. 

Mortality

Mortality rate varies widely depending on the source, but generally for SJS is about 5% and for TEN can be between 25 and 30%. 

Erythema Multiforme (EM)

EM is a delayed hypersensitivity reaction with appearance of target-like lesions of the skin which are self-limited and resolve in weeks.  The annual incidence is less than 1% and tends to occur in adults between the ages of 20 and 40.  There are two types, EM major which has mucosal involvement and EM minor which does not involve mucous membranes.  Fifty percent of the cases of EM are idiopathic but infectious causes, both viral and bacterial, are the most common causes.  HSV is a common cause of EM minor.  Medications are the cause for less than 10% of cases. 

Signs/symptoms

With EM minor, an abrupt onset of rash, usually within 3 days of exposure to the causative agent occurs.  A prodrome of symptoms is usually absent or minor.  EM major typically has prodromal symptoms 1 to 14 days prior to the rash and includes fever, cough and sore throat.  The rash tends to be in the appearance of a target (hallmark of EM), occurs in an acral distribution, and may involve the genitalia.  Dyspnea secondary to tracheobronchial epithelial involvement may be present as well. 

Treatment

Similar to SJS, all unnecessary medications need to be stopped.  Prior to the development of a rash, antivirals may be helpful if the cause is HSV.  Supportive care including a short course of glucocorticoid therapy if there is extensive mucosal involvement, ocular care, fluid/electrolyte management and control of pain and pruritus if there is mild disease is the mainstay of treatment. 

Mortality

Mortality is much less with EM than with SJS.  EM minor is not life threatening and EM major has a mortality of less than five percent. 

 

	Stevens-Johnson/TEN	Erythema  Multiforme
Type of lesion	Macules (erythematous/nonpruritic) +nikolsky sign	Papules/target lesion, pruritus
Distribution of lesion	Generalized (trunk & face)	Acral (head and peripheral ext)
Most common cause	Medications	Idiopathic/infectious (HSV)

 

Sources:

1)      Rosen’s Emergency Medicine, seventh edition, 2009.

2)      Uptodate, Stevens-Johnson syndrome and toxic epidermal necrolysis : Management, prognosis and long-term sequelae by Whitney High MD and Milton Nirken MD.

3)      Uptodate, Stevens-Johnson syndrome and toxic epidermal necrolysis: Clinical manifestations; pathogenesis; and diagnosis by Whitney High MD and Milton Nirken MD.

4)      Uptodate, Pathogenesis, clinical features and diagnosis of Erythema Multiforme by David Wetter MD.

5)      Uptodate, Treatment of Erythema Multiforme  by David Wetter MD.

 

from Dr. Radha Shah