Erythema multiforme

Erythema multiforme (EM) is a common skin disease that gives rise to red ring-shaped lesions on various regions of the body. Get detailed information about the disorder, including its causes, symptoms, diagnosis, and treatment options.

What is Erythema multiforme?

It is a condition affecting the skin that is regarded as an allergic reaction occurring in response to some ailments, infections or medications.

Erythema multiforme Synonyms

This skin disorder is also known by various other names, such as:

  • Lyell’s syndrome
  • Stevens-Johnson syndrome
  • Erythema multiforme minor
  • Erythema multiforme major

Erythema multiforme ICD9 Code

The ICD9 Code for this disease is 695.1.

Erythema multiforme History

The disease was first described by Ferdinand von Hebra in 1860. Ferdinand described it a severe, self-limiting disorder that is characterized by red skin lesions that appear as papules. However, it was not much later in 1922 that a more severe variant of EM was described by Johnson and Stevens who reported it as:

  • Disseminated cutaneous eruption
  • Severe conjunctivitis
  • Febrile erosive stomatitis

In 1950, the terms “Erythema Multiforme Major” and “Erythema Multiforme Minor” were coined by Thomas to describe this skin ailment.

Erythema multiforme Incidence

The exact prevalence of this disorder is not known. However, the disease is supposed to account for at least 1% of all dermatological outpatient visits. Approximately 0.8 to 6% of all cases of EM occur each in the United States alone in every 1 million people. The disease is 2-3 times more common in men than in women. In cases of EM major arising due to drug usage the condition is found to affect men and women equally.

Although people of all ages are equally susceptible to this disease, people between 20 and 40 years of age are at greater risk of suffering from EM. The condition rarely arises in people aged over 50 years of age.

Erythema multiforme Types

The condition is classified into three types:

Major EM

The condition is also referred to as Stevens Johnson Syndrome (SJS). It is a rare, but fatal form of EM that usually results in target lesions having painful blisters in the middle. The rashes are red in appearance and tend to develop on various regions of the body, such as the eyes, inside the mouth, on the trunk and over the genitals. The rashes are common on the moist areas of the body, such as the eyes and the lips. In some cases, the internal organs are also affected. The disease often arises after the symptoms of cough, fever, sore throat and malaise for anytime between 1 – 2 weeks.

In 5-15% cases of EM, the condition may result in death of affected individuals. However, modern treatment procedures have brought down the number of deaths associated with the condition.

Minor EM

It is less severe in nature and accounts for 80% of all cases of EM. In this form, rashes arise over a course of a few days. In some patients, however, a number of rashes may develop during a single outbreak. Sufferers may experience mild itching and/or burning sensations in the affected regions. The rashes developing in this form are usually most severe over the back side of the hands and feet. The nodules are usually round-shaped and look like “bull’s eye” rings over palms.

In acute cases, a few of these blisters may occur on the skin as well as over the lips of affected individuals. The rashes persist for 1-2 weeks and then resolve, leaving behind only a brown patch in their place.

Toxic Epidermal Necrolysis

It is also known as TENS and is a potentially fatal disorder characterized by necrosis, widespread erythema, bullous detachment

Erythema multiforme Symptoms

The symptoms of this skin condition can range from moderate to severe in intensity. The disorder is mainly characterized by the development of more than one skin lesions, which may appear fast and may also recur sometime after being resolved. The lesions may look like macules, papules, nodules or hives.

The lesions are generally circular in shape and have a red middle with a pale ring as the border. This is further encircled by an outer ring that is dark red in appearance. In the early stages, these look like small red patches and arise on the skin of the hands and feet. In the later stages, they spread to the face, arms and legs and may even develop into blisters. The rashes arise equally on both sides of the body and take anywhere from 1-6 weeks to go away.

The papules usually occur along with joint aches, itchiness of the skin, malaise and fever.

Some other symptoms associated with the condition include:

  • Mouth sores
  • Eye pain
  • Vision problems
  • Bloodshot eyes
  • Dry eyes
  • Eye burning, itching, and discharge

Erythema multiforme Causes

As aforesaid, EM usually arises as a response to an infection or as an allergenic reaction to a few medicines. EM minor commonly develops due to an infection by the Herpes Simplex virus which is the causative agent for cold sores. EM major is triggered by drugs like:

  • Ampicillin
  • Amoxicillin
  • Anticonvulsants
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Sulfonamides
  • Tetracyclines

People with a history of radiotherapy or cocaine use are also likely to suffer from EM major. The condition can also affect individuals who are suffering from Mycoplasma infection (bacterial lung infection).

However, the actual cause of the disease is often unknown.

Erythema multiforme Diagnosis

Physicians diagnose the disease by asking patients about their medical history and symptoms. Patients may be referred to a dermatologist, who specializes in the remedy of skin disorders.  A skin examination and analysis of medical history is usually enough to resolve most cases of EM.

The diagnosis of the disorder is usually straightforward if target lesions are present. If the skin lesions are uncommon in nature, a biopsy of the skin may be done and the skin sample observed and analyzed under a microscope.

The medical tests used for detecting this condition may involve:

  • Nikolsky’s sign
  • Complete Blood Count (CBC)
  • Skin lesion biopsy, with immunofluorescent examination
  • Skin culture (rapid test)
  • Microscopic examination of the tissue

Erythema multiforme Treatment

The condition is usually self-limiting and does not need any treatment. Medical cure is generally necessary when the condition is severe or gives rise to extremely discomforting symptoms in sufferers. In such cases, the treatment of EM involves managing the symptoms and curing the underlying cause. In patients with EM major, cure also involves preventing the lesions from getting infected.

People with secondary infections, occurring due to EM, may be successfully treated with antibiotic medications. The administration of systemic corticosteroids is controversial. However, use of topical corticosteroids may yield some benefit.

If the rashes develop due to reactions occurring as a result of using some medicines, the drugs should be discontinued and their substitutes should be prescribed. Patients with oozing lesions may find relief by application of wet compresses over the affected area. In severe cases, use of sedatives and pain-relieving (analgesic) medicines may be helpful.

Management of the symptoms involves moist compresses over the affected regions and application of:

  • Steroid creams or Topical antihistamines, to manage itching and discomfort
  • Acetaminophen, to reduce fever and pain
  • Oral antihistamines, to help control itchiness

There is no specific treatment for this disease. If the outbreak occurs due to herpes simplex virus infection, antiviral medicines might be required. Such medicines may be administered to avoid a recurrence as these are not found to be effective enough in curing lesions that are already present. Antiviral drugs are generally helpful for those suffering from frequent episodes of EM.

Acute cases of EM major may require treatment with oral steroids. In case of widespread lesions, that are fatal in nature, hospitalization is needed.

In severe cases of the disease, patients may require leave for treatment. Once patients recover, they do not need any special accommodations or work restrictions.

Erythema multiforme Prevention

Prevention of EM involves understanding its actual cause or trigger factor. Avoiding an infection or a drug, that can cause this skin ailment, would help prevent the recurrence of this disorder. If Herpes Simplex Virus acts as the trigger factor, physicians may prescribe a daily oral antiviral drug to prevent the recurrence of EM.

Erythema multiforme Risk Factors

The term “risk factor” refers to any infection, medication or an object or environmental condition that increases the risk of getting a disorder. An exposure to any of the known causative factors of EM elevates the risk of getting it. The condition is more common in:

  • People with a history of genital herpes or cold sores
  • Males
  • HIV positive individuals
  • Children and young adults
  • Individuals with a history of the disease

The risk of having the disease is also elevated due to the use of Penicillins, Phenytoin, Barbiturates and Sulfonamides also increases the susceptibility to this condition.

Erythema multiforme and Medications

The medications that elevate the risk of having EM include:


These include sulphonamides, including cephalosporins, fluoroquinolones, co-trimoxazole, penicillin and vancomycin.

Non-steroidal anti-inflammatory drugs (NSAIDs)

These involve medications such as piroxicam, ketoprofen, naproxen, fenbufen, ibuprofen, sulindac, tenoxicam and diclofenac.

Anti-TB drugs

Thesse include isoniazid, rifampicin, ethambutol and pyrazinamide.


These consist of medications like barbiturates, phenytoin, valproate, carbamazepine and lamotrigine.


These comprise of nystatin, fluconazole and griseofulvin.


These include sertraline and lamotrigine.

Other drugs that are most commonly associated with the condition involve:

  • Allopurinol
  • Acarbose
  • Corticosteroids
  • Cimetidine
  • Clofibrate
  • Hydralazine
  • Lamotrigine
  • Methotrexate
  • Minoxidil
  • Mefloquine
  • Nifedipine
  • Nevirapine
  • Oestrogen
  • Progesterone
  • Pantoprazole
  • Sertraline
  • Tramadol
  • Thiouracil
  • Verapamil

Erythema multiforme Complications

The possible complications of this disease include:

  • Shock
  • Loss of body fluids
  • Skin infection
  • Cellulitis
  • Sepsis
  • Widespread infection of the body
  • Permanent damage and scarring of the skin
  • Occasional development of lesions on internal organs, causing inflammation of heart, long, liver and kidney

The condition may also result in destruction and other changes in affected body tissues. Although rarely life-threatening, the condition may worsen to:

  • Meningitis
  • Blindness
  • Necrotizing tracheobronchitis
  • Kidney damage (renal tubular necrosis)

Lesions that develop on internal organs may give rise to Myocarditis, Nephritis, Hepatitis or Pneumonitis. Affected individuals may find t difficult to eat due to eat due to swelling of the mouth (Stomatitis) and swelling and cracking of the lips (Cheilitis). There may be problems in urination due to inflammation of the vulva (Vulvitis) or the glans penis (Balanitis). Some patients may also suffer from severe problems of the eye such as swelling of the conjunctiva (Conjunctivitis) which may result in ulceration and inflammation of the cornea (Keratitis).

Erythema multiforme Prognosis

Moderate forms of this disorder, such as minor EM, usually gets better within 2-6 weeks. However, they may recur at a later date. The treatment of more acute forms may be difficult. The death rate is quite high in cases of Toxic epidermal necrolysis and Stevens-Johnson Syndrome.

Erythema multiforme Pictures

Take a peek at these images to know about the physical appearance of individuals affected with this disease.

Picture of Erythema multiforme

Picture 1 – Erythema multiforme

Image of Erythema multiforme

Picture 2 – Erythema multiforme Image


If you are suffering from the symptoms of EM, call 911 or get in touch with a local healthcare professional. Medical attention may be needed on an urgent basis if a large part of the body is involved. This is to be viewed as an emergency situation and treated immediately. Timely medical cure would help you recover from the potentially life-threatening symptoms of EM and get back to health in the least possible time.


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