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Erythema Multiforme - Causes and Treatment

Published on Oct 11, 2022 and last reviewed on Oct 18, 2022   -  4 min read


Erythema multiforme is a skin disorder triggered by medicine or an infection. Read the article below to know more about its causes, symptoms, and treatment.

What Is Erythema Multiforme?

Erythema multiforme is an acute, self-limiting skin condition with lesions that can be isolated, recurrent, or persistent. It often affects children and younger adults and is characterized by symmetric red, patchy lesions on the arms and legs.

How Common Is Erythema Multiforme?

The prevalence of erythema multiforme is estimated below less than 1 %. It may begin at any age, but the average age is between 20 and 30. There is no apparent association with race. People with HIV, weakened immune system, on corticosteroids, having undergone a bone marrow transplant and lupus are predisposed to developing erythema multiforme.

The skin condition may happen repeatedly and usually lasts two to four weeks.

How Do You Get Erythema Multiforme?

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:

What Are the Stages of Erythema Multiforme?

The two stages are:

  • Erythema Multiforme Minor: It only affects the skin, the mucosal involvement is rare, and when it is present, it involves a single mucosa, often the mouth.

  • Erythema Multiforme Major: The skin lesions are more extensive but do not exceed 10 % of the body surface area. The mucosal involvement is severe, and the oral mucosa is typically involved.

Related Disorders of Erythema Multiforme

Some disorders may have symptoms similar to erythema multiforme:

  • For example, Stevens-Johnson Syndrome (SJS) affects up to 10 % 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 seen mainly in the elderly.

  • 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.

How to Test 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.

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 vaseline on the lips and vitamin A ointment on the eyes.

  • General treatment includes hospitalization to treat the pain, hydrate, or re-enter the patient.

  • Etiological treatment must be provided when a cause is identified. For example, for Mycoplasma pneumoniae infection, Azithromycin for three days.

Treatment for Recurrent Infection:

  • Recurrent herpes simplex virus (HSV) erythema multiforme is treated with long-term antiviral therapy.

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

  • If the germ is not identified, other therapeutics may be proposed long-term, such as Hydroxychloroquine, Dapsone, or early treatment of sprouts by systemic corticosteroids.

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, conjunctivitis, scarring, panophthalmitis, 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 5 % of the cases, mainly in those caused due to 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.

  • Ocular sequelae can be severe, leading to blindness.

  • At the genital level, synechiae (adhesions formed between adjacent structures within the eye usually due to inflammation) can produce functional sequels.

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

  • Some patients may develop continuous erythema multiforme, which is unresponsive to treatment. For example, people with herpes simplex virus infection, Epstein-Barr Virus (EBV) reactivation, inflammatory bowel disease, and occult renal cell cancer.


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.

Last reviewed at:
18 Oct 2022  -  4 min read




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