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Pages 45-53 (January 2010)Volume 62, Issue 1

Recurrent erythema multiforme:

Clinical characteristics, etiologic associations, and treatment in a series of 48 patients at Mayo Clinic, 2000 to 2007
Accepted 10 June 2009. published online 10 August 2009.

Recurrent erythema multiforme (EM) is a condition of substantial morbidity.

Our efforts toward the etiologic attribution and treatment of recurrent EM have been less fruitful than those previously described.


We sought to further characterize clinical characteristics, etiologic associations, and treatment of recurrent EM.


We conducted a retrospective review of patients with recurrent EM seen between 2000 and 2007.


Of 48 patients (mean age at disease onset, 36.4 years), 28 (58%) were female (mean duration of recurrent EM, 6 years).

Thirty (63%) patients had oral involvement. Herpes simplex virus caused recurrent EM in 11 (23%) patients, and the cause remained unknown in 28 (58%).

In all, 37 (77%) patients received systemic corticosteroids, 33 (69%) received continuous antiviral treatment, and 23 (48%) used immunosuppressive or anti-inflammatory agents.

Sixteen of 33 patients receiving continuous antiviral treatment had either partial or complete disease suppression. Patients had varied responses to immunosuppressants, with mycophenolate mofetil providing partial or complete response in 6 of 8 patients.

Features of recalcitrant cases included clinicians' inability to identify a specific cause, lack of improvement with continuous antiviral therapy, severe oral
involvement, extensive corticosteroid therapy, and immunosuppressive therapy (two or more agents).


and W. TERESA HSU, M.D., PH.D., Drexel University College of Medicine, Philadelphia, Pennsylvania

Erythema multiforme is an acute, self-limited, and sometimes recurring skin condition considered
to be a hypersensitivity reaction associated with certain infections and medications

(Table 11,2).2,3

Previously, the condition was thought to be part of a clinical spectrum of disease that included erythema minor, erythema major (often equated with Stevens-Johnson syndrome [SJS]), and toxic epidermal necrolysis (TEN), with erythema minor being the most mild and TEN the most severe.4 An often-cited study from 1993 proposed a useful clinical classification of erythema multiforme, SJS, and TEN based on the pattern of individual skin lesions and the estimation of body surface area with detachment of the epidermis (i.e., blisters, denuded areas, or erosions) at the worst stage of the disease

(Table 21,2,5,6).5 Although SJS and TEN may represent the same process with differing severity,6 erythema multiforme, with its minimal mucous membrane involvement and less than 10 percent epidermal detachment, now is accepted as a distinct condition.

The remainder of this article will focus on erythema multiforme.

Etiology and Pathophysiology
Erythema multiforme usually occurs in adults 20 to 40 years of age,6 although it can occur
in patients of all ages.1 Herpes simplex virus (HSV) is the most commonly identified etiology of this hypersensitivity reaction, accounting for more than 50 percent of cases.1,3,7-10

Mycoplasma pneumoniae is another commonly reported etiology, especially in children,
as is fungal infection.1,11,12 The medications most often associated with erythema multiforme are barbiturates, hydantoins, nonsteroidal anti-inflammatory drugs, penicillins, phenothiazines, and sulfonamides.2 In addition, there have been reports of erythema multiforme associated with vaccines

Erythema multiforme is a skin condition considered to be a hypersensitivity reaction to infections or drugs. It consists of a polymorphous eruption of macules,
papules, and characteristic “target” lesions that are symmetrically distributed with a propensity for the distal extremities. There is minimal mucosal involvement.
Management involves treating the existing infectious agent or discontinuing the causal drug. Mild cases resolve without sequelae and do not require treatment.
Recurrent cases have been prevented with continuous acyclovir. Patients who have no response to acyclovir may have a response to valacyclovir or famciclovir,
which have greater oral bioavailability and more convenient dosing. Patients with recurrent erythema multiforme despite suppressive antiviral therapy
should be referred to a dermatologist for further treatment.

(Am Fam Physician 2006;74:
1883-8. Copyright © 2006 American Academy of Family Physicians.)


What is erythema multiforme?

Erythema multiforme is a skin disorder characterized by symmetrical, red, raised skin areas all over the body. These patches often look like "targets" (dark circles with purple-grey centers). The skin condition may be chronic and usually lasts for two to four weeks each time.

Most often, this disorder is caused by the herpes simplex virus. Other causes may include the following:

  • An interaction with a certain medication

  • Other infectious diseases

  • Certain vaccines

What are the symptoms of erythema multiforme?

The following are the most common symptoms of erythema multiforme:

  • Sudden, red patches and blisters, usually on the palms of hands, soles of feet, and face

  • Flat, round red "targets" (dark circles with purple-grey centers)

  • Itching

  • Cold sores

  • Fatigue

  • Joint pains

  • Fever

The symptoms of erythema multiforme may resemble other skin conditions. Always consult your physician for a diagnosis.

Treatment for erythema multiforme

Specific treatment for erythema multiforme will be determined by your physician based on:

  • Your age, overall health, and medical history

  • Severity of the condition

  • Stage of the condition

  • Your tolerance of specific medications, procedures, or therapies

  • Expectations for the course of the condition

  • Your opinion or preference

Erythema multiforme minor is not very serious and usually clears up on its own. However, if a person develops a more severe form of erythema multiforme (erythema multiforme major), the condition can become fatal. Erythema multiforme major is also known as Stevens-Johnson syndrome, and is usually caused by a medication reaction rather than an infection.

Treatment may include:

  • Treating the infectious disease causing the disorder

  • Eliminating any medication causing the disorder

  • Cool compresses

  • Corticosteroids

  • Antibiotics

It is recommended that if you have symptoms of erythema multiforme, go to your emergency room or call 911. If a large area of skin is involved, it is an emergency situation. 

ERYTHEMA MULTIFORME and Stevens-Johnson syndrome are morphologically characterized by the iris or target lesion. Erythema multiforme ranges in severity from mild to severe. In the mild form, erythema multiforme is minor, the lesions are predominantly seen in the extremities and are strikingly symmetrical; these patients are usually not systemically ill.

In the severe form, the skin disease is more generalized and vesicles are sometimes seen. When mucosal membrane involvement is present this is Stevens-Johnson syndrome, and patients are usually febrile and frequently feel ill. The most common causes of erythema multiforme are drugs and infection. The most commonly associated drugs are sulfonamides, penicillins, barbiturates, phenytoin, thiazides, and NSAIDs...

Treatment is based on elimination of the causative drug, and treatment of the causative infectious agents. In Stevens-Johnson syndrome, systemic steroid therapy is still controversial. Nevertheless, systemic corticosteroid administration should be initiated at the early stage of the reaction. The initial dose ranges from 100-250 mg/day of prednisone, and it should be tapered very cautiously. Supportive measures are also important in patients with severe Stevens-Johnson syndrome...

TOXIC EPIDERMAL NECROLYSIS (TEN) is the most devastating drug eruption of all. The monality rate has been reported to be 30-50%. The skin eruption is characterized by generalized erythema and denudation of the skin. Patients usually experience a prodrome of skin tenderness, fever, malaise, and arthralgia. This phase is quickly followed by a generalized maculopapular rash which rapidly progresses to confluent diffuse erythema. A positive Nickolsky sign may be elicited. ...

Treatment can be quite complex. TEN patients should be treated as burn patients. When the extent of denudation of the skin is severe, the patient is best managed and monitored in a burn unit. Patients should be monitored closely for fluid and electrolyte imbalance, thermal regulation, and infection. The use of systemic steroids in TEN is controversial.

Use of steroids for erythema multiforme in children

Use of steroids for erythema multiforme major is debatable because no randomized studies clearly indicate which children will benefit from this treatment. ... -

Diagnosis, classification, and management of erythema multiforme ...

Kakourou T, Klontza D, Soteropoulou F, Kattamis C. Corticosteroid treatment of erythema
multiforme major
(Stevens-Johnson syndrome) in children. ... -


Pathophysiology of Disease: An Introduction to Clinical Medicine -

by William Francis Ganong, Stephen J. McPhee - 2005 - Medical - 784 pages
Many examples of erythema multiforme major also display severe, widespread cutaneous involvement. Erythema multiforme major encompasses Stevens-Johnson ...


Erythema multiforme major following use of diclofenac

Erythema multiforme major following use of diclofenac. Brian A.P. Morris and
Suleman S. Remtulla. Full text. Full text is available as a scanned copy of the ... -


Erythema multiforme major following docetaxel.

OBJECTIVE: The objective was to report a severe skin reaction, erythema multiforme major, following .


Diagnosis, classification, and management of erythema multiforme ...

No 11, M15Labial herpesNoneHerpes (3) 8 daysNoYesNo Erythema multiforme
12, M 4orfAcyclovir (1) orf10 daysNoNoNo 13, M 6Bronchoendoscopy
Ampicillin (3) -

Erythema Multiforme and Toxic Epidermal Necrolysis

Many authors use the designation erythema multiforme minor and major, with EM
minor meaning skin lesions only, and EM major being synonymous with ... - 25k -


Increased Risk of Erythema Multiforme Major

Erythema multiforme major (EMM; Stevens-Johnson syndrome) is a cutaneous disorder associated with a wide variety of factors including ingestion of drugs ... -


Stevens-Johnson syndrome from Online Medical Dictionary

erythema multiforme major -->. Stevens-Johnson syndrome ... syndrome is considered
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