Erythema Multiforme
Erythema multiforme is a skin condition that causes a distinctive rash that looks like a target or bulls-eye. It is usually triggered by an infection or, less commonly, by certain medications, and typically resolves on its own within a few weeks.
Table of contents
- What is Erythema Multiforme?
- Medical Classification Codes
- Other Names
- Types of Erythema Multiforme
- Who Gets Erythema Multiforme?
- What Causes Erythema Multiforme?
- Signs and Symptoms
- How is it Diagnosed?
- Treatment and Management
- Outlook and Recovery
- Is it Contagious?
What is Erythema Multiforme?
Erythema multiforme is a skin reaction that usually occurs in response to an infection or medication. The name comes from the fact that it takes different forms on the skin, such as a rash, raised bumps, or blisters[1]. It is an immune-mediated condition, meaning the body’s own defense system causes the reaction[2].
The condition gets its name because it can appear in multiple different forms. The most recognizable feature is round marks on the skin that look like targets or bulls-eyes, with a dark center surrounded by a pale ring and an outer red ring[1][3]. These are called target lesions and are the hallmark of this condition.
Erythema multiforme is now understood to be a separate and distinct condition from more serious disorders like Stevens-Johnson syndrome and toxic epidermal necrolysis, even though they were previously thought to be related[5][7].
L51; L51.0; L51.9
L51; L51.0; L51.9
Medical Classification Codes
Healthcare providers use standardized codes to classify erythema multiforme in medical records and research. The condition is identified using several coding systems[3].
Other Names
EM, Erythema multiforme minor, Erythema multiforme major
Types of Erythema Multiforme
There are two main types of erythema multiforme, which differ in severity and which parts of the body they affect[1].
Erythema multiforme minor is the mild form of the condition. It only affects the skin and causes a rash. This form is unlikely to involve the mucous membranes (the moist tissues inside the mouth, eyes, or genitals), and people with this type usually do not have symptoms like fever or chills[1].
Erythema multiforme major is the more severe form. It can be life-threatening because it causes large areas of skin to blister and peel. This type affects the mucous membranes in the mouth, eyes, and genitals. People with this form usually have body-wide symptoms such as fever or joint pain[1][3].
Who Gets Erythema Multiforme?
Erythema multiforme is a rare condition that affects less than 1% of the population[3][5]. Anyone can develop it, but it is most common in young adults between the ages of 20 and 40[3]. The condition is also seen in children, particularly when triggered by certain infections[2].
Men are slightly more likely to develop erythema multiforme than women[3]. There is no apparent association with race[5][7].
Some people appear to have a genetic predisposition to developing erythema multiforme, particularly those who carry certain genes. People with a specific gene variant called HLA-DQB1*0301 may be more likely to develop the condition, especially when it is related to herpes virus infections[3].
What Causes Erythema Multiforme?
The exact cause of erythema multiforme is not fully understood, but it appears to be triggered by specific events that prompt the immune system to overreact[1]. The reaction is caused by a cell-mediated immune response, where certain immune cells attack the skin and mucous membranes[5].
Infections are responsible for about 90% of erythema multiforme cases[3][5]. The most common trigger is the herpes simplex virus, which is the same virus that causes cold sores. Both type 1 and type 2 herpes simplex virus can trigger erythema multiforme[1][5].
Another important infectious trigger, especially in children, is Mycoplasma pneumoniae, a type of bacteria that causes lung infections[2][5]. Other infections that can trigger the condition include Epstein-Barr virus, cytomegalovirus, influenza virus, and hepatitis C virus[3][5].
Medications cause fewer than 10% of erythema multiforme cases[5]. Drugs that can trigger the condition include antibiotics (such as penicillins, sulfonamides, erythromycin, nitrofurantoin, and tetracyclines), anti-seizure medications, nonsteroidal anti-inflammatory drugs (NSAIDs like ibuprofen), barbiturates, and statins[1][3][5].
Vaccines have occasionally been associated with erythema multiforme, though this is rare. Vaccines that have been linked to the condition include those for measles, mumps, and rubella, hepatitis B, meningococcal disease, pneumococcal disease, varicella, influenza, and Haemophilus influenzae[5]. The condition has also been reported in rare cases following COVID-19 vaccination and infection[16].
Less commonly, erythema multiforme has been associated with other conditions including inflammatory bowel disease, certain cancers (leukemia, lymphoma, and solid organ cancers), hepatitis C, and even menstruation[3][5]. In many cases, however, the trigger remains unknown[3].
Signs and Symptoms
Many people with erythema multiforme report early symptoms such as tiredness, general discomfort, muscle aches, or fever before the rash appears. These symptoms likely reflect the underlying infection rather than the erythema multiforme itself[3].
The main symptom of erythema multiforme is a distinctive rash on the skin. The rash usually starts as small, round, slightly raised red areas. Over a few days, these develop into the characteristic target or bulls-eye lesions[3][4].
Target lesions have three concentric rings of different colors: a dark center (which may be dusky red or have a blister or scab), surrounded by a lighter or paler ring, with a red ring around the edge[3][5]. The rash may be itchy or cause a burning sensation, or it may not cause any discomfort at all[1][4].
The rash typically appears first on the hands and feet, then spreads upward toward the trunk of the body. The arms, legs, and face are commonly affected[1][3][5]. The rash is usually symmetrical, appearing on both sides of the body[3]. Most lesions appear within 48 to 72 hours and then remain in one location for at least 7 days before beginning to heal[2][5].
In more severe cases (erythema multiforme major), the condition affects mucous membranes. This can cause painful sores inside the mouth, making it difficult to eat or drink. The lips may become covered with crusts. Eyes can become red, swollen, and sensitive to light, with blurred vision. Involvement of the genital area can cause pain when urinating[1][3].
Additional symptoms that may occur include headache, feeling very tired, fever, and joint pain and soreness[1]. Depending on the skin color, the rash may appear red, pink, or purple, or it may look darker than the surrounding skin[4].
Symptoms affecting the skin usually go away after two to four weeks[1][4]. As the rash heals, the skin where the spots were may look dark for a few months, but it typically does not leave permanent scars[8].
How is it Diagnosed?
Doctors usually diagnose erythema multiforme by looking at the rash. The distinctive target or bulls-eye appearance of the lesions makes it recognizable[8]. In most cases, the characteristic appearance of the rash is enough for diagnosis[3].
To help identify what triggered the condition, the doctor will ask about recent illnesses, any medications being taken, and any history of cold sores or other infections[1][8]. This information can help guide treatment decisions, especially if a medication needs to be stopped or if an underlying infection needs to be treated.
In some cases, additional tests may be performed. Blood tests can check for signs of infection or antibodies to certain viruses. A small sample of skin (biopsy) may be taken and examined under a microscope to confirm the diagnosis or rule out other conditions[1].
It is important to distinguish erythema multiforme from other conditions with similar appearances. Erythema multiforme can be differentiated from urticaria (hives) by how long the lesions last. Erythema multiforme lesions remain fixed in one place for at least seven days, while hives typically resolve within one day[5]. The condition must also be distinguished from more serious conditions like Stevens-Johnson syndrome, which usually features widespread flat red or purple spots with blisters rather than raised target lesions[5].
Treatment and Management
In most cases, erythema multiforme gets better on its own without specific treatment and resolves within two to four weeks[4][14]. The main goals of treatment are to relieve symptoms, treat any underlying cause, and prevent complications.
If the cause of erythema multiforme is identified, treating that cause is the first step. If an infection is present, it should be treated appropriately. For example, antiviral medications may be given for viral infections[4][14]. If a medication is suspected as the trigger, that medication must be stopped as soon as possible. However, people should never stop taking medications without first talking to their doctor[4][14].
For mild cases (erythema multiforme minor), treatment focuses on relieving symptoms. Options include moisturizers or steroid creams applied to the skin to reduce itching and speed recovery[4][14]. Antihistamine medications can help with itching[5]. Cool compresses with saline or special solutions can soothe the skin[13].
Pain relievers such as acetaminophen or ibuprofen may be used for discomfort or fever[8]. Taking cool baths or showers can also provide relief[8].
For mouth involvement, rinsing with antiseptic or anesthetic mouthwashes can help reduce pain and prevent infection[5][13]. Viscous lidocaine, a numbing medication, can be helpful for painful mouth sores[13].
If the eyes are affected, it is important to see an eye specialist urgently[5]. Artificial tears and lubricating eye drops may be recommended[13].
Severe cases (erythema multiforme major) may require hospitalization for more intensive care. This may include intravenous fluids to prevent dehydration, especially if mouth sores make eating and drinking difficult[5][13]. Electrolyte imbalances may need to be corrected. Wound care for large blistered areas may be necessary.
The use of systemic corticosteroids (steroid medications taken by mouth or injection) is controversial in erythema multiforme. Some experts believe they may help in severe cases, while others are concerned they could lead to complications. If used, the treatment course should be short, typically limited to 10 days to 2 weeks[13].
For people who experience recurrent erythema multiforme triggered by herpes simplex virus (more than five episodes per year), preventive antiviral therapy is recommended[5][11]. Daily antiviral medications such as acyclovir, valacyclovir, or famciclovir can prevent both herpes outbreaks and erythema multiforme episodes[13]. This preventive treatment may need to be continued for 6 to 12 months or longer[13]. It is important to note that antiviral treatment started after the erythema multiforme rash has already appeared does not affect the course of the current episode[13].
For recurrent cases that do not respond to antiviral therapy, other treatments that have been reported to help in individual cases include immunosuppressive medications, certain antibiotics, antimalarials, and other specialized drugs[11][13].
Outlook and Recovery
Erythema multiforme is usually a self-limiting condition, meaning it goes away on its own without causing lasting problems[2][3]. Most people recover fully within two to four weeks[1][4].
The lesions typically appear over a period of 3 to 4 days, remain in place for about 7 to 21 days, and then begin to heal[2]. As the rash heals, the affected areas may remain darker than the surrounding skin for several months, but permanent scarring is uncommon[8].
Recurrences are common in some people, particularly when herpes simplex virus is the trigger[2][3]. Some individuals may experience several episodes per year. The condition can be isolated (occurring just once), recurrent (coming back multiple times), or persistent (ongoing)[3].
Complications from erythema multiforme are rare. When they do occur, they are mainly related to scarring that can develop after the condition heals, particularly in the mouth or eyes[21]. Severe mucosal involvement can occasionally lead to complications, which is why close monitoring and appropriate treatment are important in more severe cases.
Is it Contagious?
No, erythema multiforme itself is not contagious. The rash cannot spread from person to person[1][8].
However, if a virus or bacteria caused the erythema multiforme, that infection can spread to other people. For example, if someone develops erythema multiforme after a herpes simplex infection, they could potentially spread the herpes virus to others through direct contact. But even if another person catches the infection, they may not develop erythema multiforme[1][8].
