Erythema Multiforme
Erythema Multiforme: Excerpt from The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter
Melissa B. Black
Approach
Erythema multiforme (EM) is a clinical syndrome, not a diagnosis. It is thought to be a hypersensitivity reaction to an antigenic stimulus, commonly a drug or infection. It occurs in males more often than in females; and 50% of cases occur in those aged less than 20 years, with most of the remaining cases occurring in those aged 20 to 30 years (1). The spectrum of symptoms allow categorization into:
A. EM minor— an eruption usually with little to no mucous membrane involvement or systemic symptoms and causing little or no complications.
B. EM major
1. Stevens–Johnson syndrome presents with bullae or vesicles with more systemic symptoms. Significant complications, including keratitis and visual impairment or damage to upper airways, can occur with this syndrome.
2. Toxic epidermal necrolysis (TEN) is a life-threatening condition with widespread cutaneous damage with a prognosis similar to that of a second degree burn. Death can occur in up to 50% of cases (2).
History
A. Were there any prodromal symptoms?
1. Prodromal symptoms occur in one-third of cases, usually in the form of an upper respiratory illness (3).
2. A prodrome is unusual in EM minor, but fever, malaise, and myalgias can precede the more severe varieties (Chapters 2.6 and 13.6).
B. Characteristics of the rash
1. What was the time course of onset and the duration of lesions?
a. An acute onset with enlargement of papules over 24 to 48 hours is typical of EM. New lesions can develop over 10 days or more with a usual duration of 1 to 6 weeks from onset to healing (3). Be aware of late onset lesions as they may also be a recurrence.
2. Where are the lesions?
a. EM lesions usually start on the hands and feet, including palms and soles, and can spread proximally to become generalized.
b. The mouth and lips are involved up to 99% of the time. More extensive mucosal involvement is seen in the more severe cases. Mouth lesions are usually tender.
c. The rash is symmetric.
3. Skin symptoms
a. Are the lesions painful or pruritic? Oral lesions are usually tender. The patient may complain of itching, swelling, and tenderness of the hands and feet.
C. Recent exposures
1. Has the patient been exposed to any drugs 1 to 3 weeks prior to onset (4)? These most often include sulfonamides, penicillin, anticonvulsants, and nonsteroidal antiinflammatory drugs. Drugs often lead to extensive mucosal erosions with large bullae.
2. Has the patient recently been ill?
a. The percent of EM cases precipitated by herpes simplex virus (HSV) is likely greater than 50% (3). HSV usually presents as EM minor, and it is recurrent in one-third of cases.
b. Another well-documented factor is infection with mycoplasma pneumonia (2). In this case, EM generally presents in bullous form or as Stevens–Johnson syndrome (Chapter 13.8).
c. Other bacterial and viral causes have been suggested, including tuberculosis (TB), β-hemolytic streptococci, staphylococcal infections, and the bacillus Calmette-Guérin vaccine.
d. Other factors such as radiation therapy, collagen vascular diseases, pregnancy, and carcinomas have been implicated.
Physical examination
A. Description of lesions
1. The rash begins as a round erythematous papule, which enlarges up to 1 to 2 cm over 24 to 48 hours. The periphery of the lesion is erythematous and raised or edematous. The center becomes more cyanotic looking and can be white/yellow or gray. This is the pathognomonic “target lesion,” but it may not be present in all cases. If a blister forms in the middle, the term “iris lesion” is more appropriate.
2. Lesions are generally symmetrical, with acral to central spread including extensor surfaces, face, palms, and soles. Mucosal lesions indicate a more severe type; bullae with sloughing in large sheets suggests TEN.
B. Systemic signs
1. Systemic signs are present in the more serious Stevens–Johnson syndrome and TEN.
2. Systemic signs include high fever, involvement of eyes with corneal ulceration, pulmonary findings, widespread cutaneous involvement, or pneumonia, indicating higher morbidity and mortality.
Testing
A. Biopsy. The history and physical examination will be most helpful in making the diagnosis; however, biopsy of an early lesion helps to confirm it and exclude others. The differential diagnosis would include urticaria, vasculitis, fixed drug eruptions, and bullous pemphigoid.
B. Other tests. If underlying infection is suspected, laboratory tests including a complete blood count, throat culture, antistreptolysin-O titer, slide test for infectious mononucleosis, and hepatitis screen may be indicated. A chest x-ray study may be needed if Mycoplasma pneumoniae, histoplasmosis, coccidiomycosis, or TB is suspected. Skin tests or serum complement fixation titers for infectious agents may be needed.
Diagnostic assessment
A. If the history and physical examination are consistent with the diagnosis of EM, a symmetric, fixed, discrete, round, erythematous rash is seen, which lasts 1 to 6 weeks from onset to healing, which is self-limited, acute, or episodic in nature. If biopsy supports the diagnosis, then the clinical criteria for EM have been met.
B. Cause. Then, determine the most likely cause in order to remove the antigenic stimulus, whether this means stopping a drug, treating an infection, or invoking preventative measures such as avoiding a drug or providing prophylaxis for recurrent HSV.
C. Determining which subtype of EM is present helps dictate treatment and anticipate prognosis.
References
1. Fitzpatrick TB, Johnson RA, Polano MK, Suurmond D, Wolff K. Color atlas and synopsis of clinical dermatology, 2nd ed. New York: McGraw-Hill, 1992:474–477.
2. Goldberg GN. Erythema multiforme controversies and recent advances. Adv Dermatol 1987;2:73–90.
3. Huff JC. Erythema multiforme. In: Sams WM, Lynch PJ, eds. Principles and practice of dermatology, 2nd ed. New York: Churchill Livingstone, 1996:483–490.
4. Stampien TM, Schwartz RA. Erythema multiforme. Am Fam Physician 1992;46(4):
1171–1176.
Book Source Details
- Book Title: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter
- Author(s): Robert B. Taylor (editor)
- Year of Publication: 2000
- Copyright Details: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, Copyright © 2000 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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