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Erythema Multiforme - Causes and Treatment

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Erythema multiforme is a skin condition that may be caused by an infection or an adverse response to medication. Read the article below to learn more.

Medically reviewed by

Dr. Filza Hafeez

Published At October 11, 2022
Reviewed AtJanuary 22, 2024

What Is Erythema Multiforme?

Erythema multiforme (EM) is a self-contained immune-driven mucocutaneous illness with distinctive target lesions. Erythema multiforme major can be distinguished from erythema multiforme minor by significant mucosal involvement. Episodes may be singular, repeated, or persistent. Herpes simplex virus (HSV) infection is the most common cause of erythema multiforme; other potential triggers include various infections, drugs, and immunizations. The fingers and toes do seem to have a greater obvious appearance of these lesions. Traditional target lesions may or may not involve mucosal membranes. They manifest as symmetrically developing concentric rings of color variation. The skin condition may happen repeatedly and usually lasts two to four weeks. Toxic epidermal necrolysis (TEN) and Steven Johnson syndrome (SJS) are not the same as erythema multiforme. Both toxic epidermal necrolysis and Steven Johnson syndrome are severe skin diseases caused by an adverse reaction to drugs or an infection.

How Common Is Erythema Multiforme?

There are EM reports from all around the world, regardless of ethnicity. Though more common in young adults, it can happen to anyone at any age. The typical age range ranges from 20 to 30 years, while 20 percent of instances include youngsters. It is more prevalent in men. Although the prevalence is unknown, it seems to be far lower than one percent. Individuals with weakened immune systems, lupus, corticosteroid use, HIV, or a history of bone marrow transplant are more likely to get EM.

How Does Erythema Multiforme Occur?

The primary causes of erythema multiforme include herpes simplex virus (HSV) type 1 and 2 infections. The other causes may include the following:

  • Antibiotics include Penicillins, cephalosporins, macrolides, sulfonamides, anti-tuberculosis agents, and antipyretics.

  • In some people, contact with heavy metals, herbal agents, topical therapies, and poison ivy can also trigger erythema multiforme.

  • Fungal infections can also cause erythema multiforme.

What Are the Symptoms of Erythema Multiforme?

The symptoms of erythema multiforme include:

  • Red spots (macules and papules) and blisters, usually on the palms of hands and soles of feet.

  • Round, erythematous papules are the initial manifestation of the lesions, which eventually turn into target lesions.

  • Three concentric bands of varying colors make up the target lesions:

    • A dark, central region of epidermal necrosis.

    • Encircled by a region of less edema.

    • Has an erythematous border on the periphery.

  • Common lesions can coexist with atypical lesions. Atypical lesions are elevated, have lesser color-variation zones, and lack clearly defined borders.

  • Eye pain, itching, or burning.

  • Malaise.

  • Cold sores.

  • Fatigue.

  • Joint pains (arthralgia).

  • Fever.

What Are the Stages of Erythema Multiforme?

The two stages are:

  • Erythema Multiforme Minor: Erythema multiforme minor (EMm) is a skin condition characterized by symmetrical acral (affecting a distal location, such as the nose, penis, ear, finger, toe, or nipple) distribution and characteristic lesions. Mucosal involvement is uncommon; when it does occur, it usually affects only one mucosa, the mouth.

  • Erythema Multiforme Major: The skin lesions in erythema multiforme major (EMM) are larger but only make up ten percent of the body's surface area. There are typical target lesions. The oral mucosa is usually impacted by severe mucosal involvement, which affects at least two distinct mucosal sites.

Some disorders may have symptoms similar to erythema multiforme:

  • For example, Stevens-Johnson syndrome (SJS) affects up to 10 percent of the body surface area, larger than in erythema multiforme. The target-like lesions are asymmetrical and made of two concentric zones. The mucosal involvement is similar; however, the skin involvement differs from erythema multiforme by the absence of typical targets.

  • Urticaria symptoms resemble erythema multiforme, but both differ in the duration of the individual lesions. The lesions in erythema multiforme cases last for seven days, while in urticaria, lesions often resolve within one day.

  • Erythema nodosum is an inflammatory skin disease presented by red spots (nodules) that mostly appear on the shins but occasionally involve the arms or other areas.

  • Bullous pemphigoid is a skin disorder most commonly seen in older individuals.

  • Dermatitis herpetiformis (Duhring disease) is a skin condition characterized by clusters of itchy blisters, elevated spots (papules), and urticaria-like lesions.

  • Pemphigus is an uncommon hereditary severe skin disease-causing blister (bullae) in the topmost layer (epidermis) of healthy skin and mucous membranes.

What Are the Diagnostic Methods for Erythema Multiforme?

  • Clinically, erythema multiforme is diagnosed based on the patient's history and physical examination. It is essential to inquire about recent infection symptoms. Most cases of erythema multiforme do not require further diagnostic tests.

  • Skin biopsies and laboratory tests may exclude other diagnoses. Direct immunofluorescence differentiates between erythema multiforme and blistering autoimmune diseases.

  • Herpes simplex virus testing should be performed on all individuals with recurrent erythema multiforme, including smear samples of skin or mucosal lesions. If there is no obvious cause for recurrent or persistent erythema multiforme, workup for major organ or blood-related malignancies should be considered.

How to Treat Erythema Multiforme?

  • Treatment of the Acute Erythema Multiforme:

    • Topical treatment includes antiseptics for bullous lesions, antiseptic mouthwashes, and anesthetic. Healing is promoted by applying petroleum jelly on the lips and vitamin A ointment on the eyes.

    • If an individual is unable to manage their discomfort, eat, or stay hydrated, they must be admitted to the hospital. If the lesions are large, daily observation is required.

    • When a cause (or, in some cases, a likely cause) is discovered, etiological treatment must begin. Azithromycin treatment for three days is warranted for Mycoplasma pneumoniae infection, even without waiting for the findings of bacteriological testing.

  • Treatment for Recurrent Infection:

    • The most frequent reason is herpes. Prolongation of treatment with Acyclovir or Valacyclovir ought to be suggested, even in cases where specimens have not demonstrated the evidence.

    • Valacyclovir treatment prevents herpes simplex virus-induced erythema multiforme outbreaks.

    • In the long run, alternative treatments such as Hydroxychloroquine, Dapsone, or early systemic corticosteroid treatment for sprouts may be suggested if the etiology is not detected.

  • Treatment for Severe Cases:

    • Severe erythema multiforme requires hospital admission to manage complications, dehydration, and infection.

    • All offending drugs should be immediately discontinued. Nutrition support is vital.

What Are the Complications of Erythema Multiforme?

  • The mucosal lesions heal completely; the skin lesions may result in scars.

  • Urinary retention, phimosis (inability to retract the foreskin covering the head (glans) of the penis), and hematocolpos (vagina filled with menstrual blood) were also reported.

  • Eye complications can result in uveitis (inflammation of the uvea), conjunctivitis (inflammation of the conjunctiva), scarring, panophthalmitis (a complete purulent inflammation and dissolving of the eyeball's membranes and tissues), and permanent blindness.

  • Many people develop dry eye syndrome and corneal scarring.

What Is the Prognosis of Erythema Multiforme?

  • The mucosal lesions take a longer time to heal. For the erythema multiforme minor, the healing generally occurs within two to three weeks, while it takes four to six weeks to heal erythema multiforme major.

  • Recurrences were seen in less than five percent of the cases, mainly in those caused by herpes infection.

  • The main long-term risk is the formation of synechiae (adhesions formed between adjacent structures within the eye, usually due to inflammation) in case of mucosal involvement.

  • Severe ocular consequences may result in blindness.

  • At the genital level, synechiae can produce functional sequels.

  • During the acute phase, proper vigilance is helpful to prevent these sequels.

  • Some patients may get persistent, treatment-unresponsive erythema multiforme. For instance, reactivation of the Epstein-Barr virus (EBV), occult renal cell carcinoma, inflammatory bowel illness, and herpes simplex virus infection can all cause this.


Erythema multiforme is a skin disorder triggered by an allergic reaction to medicine or an infection. It has also been associated with many factors. Most often, this disorder is caused by the herpes simplex virus infection. The management of erythema multiforme involves symptomatic treatment with topical steroids or antihistamines. Severe mucosal erythema multiforme can require hospitalization for intravenous fluids and depleting electrolytes. Recurrent cases associated with the herpes simplex virus should be treated with prophylactic antiviral therapy.

Frequently Asked Questions


What Is the Treatment of Erythema Multiforme Major?

To lessen itching, use antihistamines and moisturizing cream (emollients). Painkillers for any pain, steroid cream to minimize inflammation and swelling. Antiviral medications if a viral infection is an underlying reason.


How Does a Person Get Erythema Multiforme?

A viral infection, frequently the herpes simplex (cold sore) virus, is to blame for most instances. Viruses remain inactive in the body after the first infection; the virus can occasionally reactivate in the body. As a result, some people develop a cold sore a few days before the onset of the rash.


What Are the Causes of Erythema Multiforme?

The herpes simplex virus typically brings on this disorder. It has also been linked to fungus infections and Mycoplasma pneumonia. These additional factors might be to blame, a reaction to a particular drug.


How Is Erythema Multiforme Associated With Autoimmune Disease?

HAEM (herpes simplex virus-associated erythema multiforme) is a viral disease with an autoimmune component caused by the herpes simplex virus (HSV). It is considered to be a hypersensitive reaction associated with certain medications and infections.


Can Erythema Multiforme Revert Back?

In particular, if the herpes simplex virus carries the disease, there is a chance that it will return at some point. Therefore, in frequent encounter attacks, antiviral medication is helpful to stop them.


Does Erythema Multiforme Cause Pain?

Although some patients may feel burning, most erythema multiforme lesions are not painful. However, mucous membrane lesions, such as those on the mouth, throat, genitalia, or eyes, can be uncomfortable.


Who Is at Risk for Acquiring Erythema Multiforme?

A rare, severe type can also have fatal effects on the eyes, mouth, and genitalia. Erythema multiforme major is the medical term used for this. Although it can occur at any age, erythema multiforme primarily affects adults under 40.


Does Erythema Multiforme Show Malignant Changes?

Rarely erythema multiforme (EM) shows a cutaneous sign of underlying cancer. However, it does not usually show a malignant transformation. The most toxic form is toxic epidermal necrolysis.


Does Erythema Multiforme Lead to Swelling?

Swelling of the hands and feet is frequently present with large hives, although this is not the case with erythema multiforme. Antihistamines will help large hives go away, but they will not help with erythema multiforme.


Can Erythema Multiforme Occur Twice?

In erythema multiforme minor, the lesions develop over two weeks, and the patient will be scar-free in three weeks. However, erythema multiforme minor recurrence is frequent (up to one-third of cases), and it is typically brought on by subclinical or apparent herpes simplex virus (HSV) infection.


Is Erythema Multiforme Minor Infectious?

Although the origin of erythema multiforme is unknown, some cases are brought on by an infection or medication reaction. No one can transmit the ailment to another.


Do Steroids Help in the Treatment of Erythema Multiforme?

Mild erythema multiforme typically goes away on its own within four weeks. However, severe illness like Stevens-Johnson syndrome affects the mucous membranes, lasting up to six weeks. Therefore, steroid use is not recommended for the mild version.


Why Is Erythema Multiforme Lethal?

Erythema multiforme major, a severe type of condition, has the potential to be lethal. Instead of an illness, a drug reaction is frequently to blame. Stevens-Johnson syndrome is another name for erythema multiforme major. Much bigger patches of skin blister and peel are seen in major form, which is considered fatal.
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Dr. Filza Hafeez



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