Erythema multiforme
Picture 1. Target lesion of erythema multiforme
Picture 2. Raised atypical targets and arcuate lesions
Picture 3. Hemorrhagic crusts on the lips
Background: Erythema multiforme (EM) is an acute mucocutaneous hypersensitivity reaction of variable severity characterized by a symmetrically distributed skin eruption, with or without mucous membrane lesions.
The more common mild form, EM minor, consists of skin lesions with involvement of no more than one mucosal surface.
EM major, or Stevens-Johnson syndrome, is more severe, involving 2 or more mucous membranes with more variable skin involvement. It may involve internal organs and typically is associated with systemic symptoms.
Some authorities consider toxic epidermal necrolysis (TEN) to be a severe manifestation of EM, while most experts currently regard it as a discrete disease.
Pathophysiology: Pathophysiology of EM is not completely understood but appears to involve a hypersensitivity reaction that can be triggered by a variety of stimuli, particularly bacterial, viral, or chemical products. Histopathologic characteristics include a lymphocytic infiltrate at the dermal-epidermal junction and around dermal blood vessels, dermal edema, epidermal keratinocyte necrosis, and subepidermal bullae formation. Immune complex deposition is variable and nonspecific. In severe cases, fibrinoid necrosis can occur in the stomach, spleen, trachea, and bronchi.
Frequency:
- In the US : Incidence of EM minor is unknown, but the condition may account for as many as 1% of dermatological outpatient visits and is more common in spring and fall. Incidence of EM major is 0.8-6.0 per million per year.
- Internationally: Similar to US incidence
Mortality/Morbidity:
- EM minor is associated with minimal morbidity. Most cases are self-limited and resolve without sequelae in 2-4 weeks.
- EM major results in significant morbidity and a mortality rate from 5-15%. Morbidity and mortality are attributable to complications of EM major, which are described below. Uncomplicated EM major usually resolves spontaneously in 2-4 weeks.
Sex:
- EM affects males more often than females, with a male-to-female ratio ranging from 3:2 to 2:1. Incidence of drug-related cases of EM major is equal in males and females.
Age:
- All ages are affected, with a peak incidence in the second through fourth decades of life; the condition rarely occurs in persons younger than 3 years or older than 50 years.
History: In addition to characterizing skin and mucous membrane lesions of EM, a complete history should document recent constitutional symptoms, prior history of herpes simplex infection, and use of prescription and over-the-counter medications.
- Erythema multiforme minor
- Sudden onset of rapidly progressive, symmetrical, mucocutaneous lesions, with concentric color changes in some or all lesions
- Burning sensation in affected areas
- Pruritus generally absent
- Nonspecific prodromal symptoms in some cases
- Erythema multiforme major (Stevens-Johnson syndrome)
- Prodromal symptoms suggestive of a viral syndrome in at least 50% of cases, usually 1-14 days before skin lesions develop
- May include symptoms of fever, malaise, myalgias, arthralgias, headache, sore throat, cough, nausea, vomiting, and diarrhea
- Prominent mucosal involvement
- Mucosal lesions, which may appear before or with skin lesions
- Oral pain, which may be severe enough to result in difficulty eating, drinking, or opening the mouth
- Eye pain, edema, and drainage
- Breathing difficulty resulting from tracheobronchial involvement
- Skin involvement similar to EM minor but may be more severe
Physical:
- Erythema multiforme minor
- Symmetrically distributed, erythematous, expanding macules or papules evolve into classic iris or target lesions, with bright red borders and central petechiae, vesicles, or purpura.
- Lesions may coalesce and become generalized.
- Vesiculobullous lesions develop within preexisting macules, papules, or wheals.
- Rash favors palms and soles, dorsum of the hands, and extensor surfaces of extremities and face.
- Resolution usually occurs over 7-10 days.
- Postinflammatory hyperpigmentation or hypopigmentation may occur.
- Mucous membrane blistering occurs in about 25% of cases of EM minor, usually is mild, and typically involves oral cavity.
- Erythema multiforme major (Stevens-Johnson syndrome)
- Skin findings may be similar to EM minor but often are more variable and severe. Inflammatory vesiculobullous lesions, often with hemorrhage and necrosis, are typical. Fixed macules and target lesions may be larger and more confluent than in EM minor.
- Skin tenderness usually is not present.
- Mucous membranes are strongly affected, most commonly mouth, lips, and bulbar conjunctivae; less often, anogenital mucosae are affected. A minimum of 2 mucosal surfaces must be involved; 3 mucosal surfaces are involved in about 40% of cases.
- Lips may be edematous, bloody, or crusted.
- Bullae and shallow ulcers resembling aphthous ulcers are common. When bullae rupture, mucosal lesions become deeply erythematous erosions, often covered by gray pseudomembranous exudates.
- Salivation often is increased.
- Nasopharynx, respiratory tract, GI tract, and genitourinary (GU) tract are sometimes affected.
- Genital involvement consists of hemorrhagic, bullous inflammation; urinary retention and phimosis may occur.
- Eye involvement occurs in approximately 70% of cases of EM major and 10% of cases of EM minor, and usually takes the form of bilateral purulent conjunctivitis with increased lacrimation. Ocular complications may include corneal ulceration, anterior uveitis, panophthalmitis, corneal opacities, symblepharon formation, and blindness.
Causes: Many potential triggers have been implicated as possible causes of EM. Infectious causes are more common in children and are implicated more commonly in EM minor. Drugs are the major culprits in adults and in EM major. Herpes simplex infection is the most common cause in young adults and is strongly associated with recurrent EM minor. The most prevalent bacterial precipitant is Mycoplasma pneumoniae . Approximately 50% of cases are idiopathic, with no precipitating cause identified.
- Viral
- Herpes simplex I & II
- Adenovirus
- Coxsackievirus B5
- Echoviruses
- Enteroviruses
- Epstein-Barr
- Hepatitis A
- Hepatitis B
- Measles
- Vaccinia
- Varicella
- Influenza
- Mumps
- Poliovirus
- Bacterial
- Mycoplasma pneumoniae
- Proteus species
- Salmonella species
- Tuberculosis
- Vibrio parahaemolyticus
- Psittacosis
- Catscratch disease
- Brucella species
- Tularemia
- Gonorrhea
- Typhoid fever
- Diphtheria
- Lymphogranuloma venereum
- Cholera
- Yersinia enterocolitica
- Fungal
- Histoplasmosis
- Coccidioides species
- Postvaccination
- Bacille Calmette-Guйrin (BCG)
- Oral polio vaccine
- Vaccinia
- Tetanus/diphtheria
- Sulfonamides, including hypoglycemics
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Pyrazolones
- Phenylbutazone, oxyphenbutazone, and phenazone
- Collagen vascular disease
- Risk factors
- Previous history of EM
- Male sex
Lab Studies:
- No specific laboratory tests are indicated.
- In severe cases of EM major, laboratory testing should be guided by clinical picture.
- CBC usually reveals moderate leukocytosis. Higher white blood cell counts indicate infection. Mild anemia may be present.
- Electrolytes values may be abnormal with severe skin and mucous membrane involvement. These values are useful to guide fluid and electrolyte therapy.
- BUN and creatinine tests are indicated to screen for renal involvement and dehydration in cases of EM major requiring hospitalization.
- Sedimentation rate is elevated but nonspecific.
- Cultures are indicated in severe cases of EM major and should be obtained from blood, sputum, and mucosal lesions.
Imaging Studies:
- No specific imaging studies are necessary in most cases.
- Chest x-ray may be useful in cases with respiratory symptoms or signs, particularly if an underlying pulmonary infection is suspected.
Procedures:
- Skin biopsy may be performed in equivocal cases when diagnosis is in doubt, particularly in absence of target lesions.
- Pathological findings include a predominantly inflammatory pattern characterized by a lichenoid infiltrate, which is high density and rich in T cells, and epidermal necrosis that mainly affects basal layer.
Prehospital Care: In severe cases of EM major, prehospital personnel may need to treat respiratory complications and fluid imbalances aggressively, in the same manner as thermal burns.
Emergency Department Care: Mild cases of EM require only symptomatic treatment, which may include analgesics or NSAIDs such as aspirin, cold compresses with saline or Burow solution, topical steroids and soothing oral treatments like saline gargles, viscous lidocaine, and diphenhydramine elixir. Severe cases of EM major can be life threatening and should be treated in a manner similar to thermal burns.
- Aggressive monitoring and replacement of fluids and electrolytes are of paramount importance.
- Provide supportive respiratory care, including suctioning and postural drainage, as needed.
- Administer empiric antibiotics if clinical evidence of secondary infection exists. Most authorities advise against routine use of prophylactic antibiotics.
- Use analgesics as needed to control pain, which may be severe.
- Avoid systemic corticosteroids in minor cases. In severe cases, their use is controversial because they do not improve prognosis and may increase risk of complications.
- Treatment of underlying cause
- Withdrawal of any causative drugs
- Symptomatic treatment for mild cases
- For more severe cases, meticulous wound care and use of Burow or Domeboro solution dressings may be necessary.
- Oral lesions: Use mouthwash with warm saline or a solution of diphenhydramine, Xylocaine, and Kaopectate for symptomatic relief.
Consultations:
- A dermatological physician may be helpful with diagnosis, able to perform skin biopsies when indicated, and may assist with care in all admitted patients.
- Ophthalmological consultation should be obtained whenever eyes are involved.
- Internists, critical care specialists, or pediatricians should be consulted for patients requiring admission.
Further Inpatient Care:
- Hospitalization for fluid and electrolyte management is indicated when severe mucous membrane involvement is present or with impaired oral intake, dehydration, or secondary infection.
- Implement barrier isolation to decrease risk of infection.
- IV antibiotics may be necessary to treat secondary infections.
- Areas of denuded skin should be managed like thermal burns, although debridement is best avoided while lesions are still progressing.
- Eroded areas may be bathed q1-2d with saline or Burow solution and dressed with nonadherent dressings.
Further Outpatient Care:
- Provide symptomatic relief.
- Discontinue use of potentially contributing drugs.
In/Out Patient Meds:
- Avoid use of systemic corticosteroids in EM minor; their use in EM major is controversial.
- Topical corticosteroids are useful for outpatient treatment of patients with limited disease.
- Prophylactic oral acyclovir is effective in decreasing frequency and severity of recurrent herpes and herpes-associated EM.
- Consider use when recurrences are more frequent than 5 per year.
Transfer:
- Severe cases of EM major may require treatment in an intensive care unit or burn unit. Transference to such a facility may be necessary.
Deterrence/Prevention:
- Avoid known or suspected predisposing medications.
- Acyclovir may be helpful in reducing recurrence of EM caused by herpes.
- Tamoxifen may prevent premenstrual EM.
Complications:
- Hypopigmentation or hyperpigmentation
- Dehydration and electrolyte disturbances
- Secondary bacterial infections/sepsis
- Ocular complications, including corneal ulceration, anterior uveitis, panophthalmitis, corneal opacities, symblepharon formation, and blindness
- Esophageal, bronchial, urethral, vaginal, and anal strictures (rare)
- Possible GI hemorrhage, renal failure, and respiratory failure in severe cases
Prognosis:
- Most cases are self-limited, with lesions evolving over 1-2 weeks and subsequently resolving within 2-3 weeks. EM major may require 3-6 weeks to resolve.
- Scarring is rare but may follow Stevens-Johnson syndrome and is more common after resolution of mucosal lesions.
- Hypopigmentation or hyperpigmentation may follow resolution of lesions.
- Recurrence is common in EM minor (up to one third of cases) but is not common in EM major.
- Stevens-Johnson syndrome may have a fulminant course complicated by severe secondary infection, fluid and electrolyte imbalances, and death in 5-15% of cases.
Patient Education:
- Educate patients in appropriate symptomatic treatment.
- Provide reassurance that disease is self-limited.
- Advise of significant risk of recurrence, especially in EM minor.
- Emphasize avoidance of any identified etiologic agent.
|
Medical online consultation with qualified doctors
Copyright © 2004-2005