Erythema Multiforme - Causes, Diagnosis, and Treatment

What Is Erythema Multiforme?

Erythema multiforme (EM) is a self-contained immune-driven mucocutaneous illness with distinctive target lesions. Erythema multiforme major can be differentiated from erythema multiforme minor by significant mucosal involvement. It can occur once, come back repeatedly, or persist for a long time.

Herpes simplex virus (HSV) infection is the most common cause of erythema multiforme; other triggers include other infections, drugs, and immunizations. The fingers and toes seem to show these lesions more clearly. Traditional target lesions may or may not involve mucosal membranes.

They manifest as symmetrically developing concentric rings of color variation. The skin condition may recur and usually lasts 2 to 4 weeks. Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are not the same as erythema multiforme. Both toxic epidermal necrolysis and Stevens-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 is 20 to 30 years, while 20% of cases involve youngsters. It is more prevalent in men. Although the prevalence is unknown, it appears to be far lower than 1%. 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 infections with herpes simplex virus (HSV) types 1 and 2.

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 fewer 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 severely affected, with involvement of at least two distinct mucosal sites.

What Are the Related Disorders of Erythema Multiforme?

Some skin conditions can look similar to erythema multiforme:

• Stevens-Johnson syndrome (SJS) affects up to 10 percent of the body surface area and is usually more severe than erythema multiforme. The target-like spots are often irregularly shaped and have only two rings. Mouth and mucosal sores may be similar, but the typical “classic” target lesions seen in erythema multiforme are usually absent.

• Urticaria (hives) may look similar, but the difference is in how long the spots last. In erythema multiforme, the lesions usually stay for about seven days. In urticaria, they often disappear within 24 hours.

• Erythema nodosum is an inflammatory condition that causes painful red lumps, mainly on the shins and sometimes on the arms or other parts of the body.

• Bullous pemphigoid is a blistering skin disorder that mostly affects older adults.

• Dermatitis herpetiformis (Duhring disease) causes groups of itchy blisters, small raised bumps, and hive-like rashes.

• Pemphigus is a rare but serious skin disease that causes blisters in the upper layer of the skin and on the mucous membranes.

What Are the Diagnostic Methods for Erythema Multiforme?

• Erythema multiforme is usually diagnosed by taking a proper medical history and doing a physical examination. Asking about recent infections is important. In most cases, no additional tests are needed.

• A skin biopsy and some lab tests may be done to rule out other conditions. A special test called direct immunofluorescence helps doctors distinguish erythema multiforme from autoimmune blistering diseases.

• Testing for herpes simplex virus is advised in people who have repeated episodes of erythema multiforme. This may include swab tests from skin or mouth lesions. If there is no clear cause in recurrent or long-lasting cases, further tests may be needed to check for internal organ or blood-related cancers.

How to Treat Erythema Multiforme?

Treatment of Acute Erythema Multiforme:

◦ Local treatment includes antiseptics for blistered lesions, antiseptic mouthwashes, and pain-relieving agents. Applying petroleum jelly to the lips and vitamin A eye ointment helps support healing.

◦ If a person cannot control the pain, eat properly, or maintain hydration, hospital admission is necessary. Large or widespread lesions need daily monitoring.

◦ If a definite or suspected cause is identified, treatment for that cause should be started. For example, azithromycin for 3 days is recommended for Mycoplasma pneumoniae infection, even before bacteriological results are available.

Treatment for Recurrent Infection:

◦ Herpes is the most common cause. Long-term treatment with acyclovir or valacyclovir should be considered, even if laboratory samples do not confirm the infection.

◦ Valacyclovir helps prevent outbreaks of erythema multiforme triggered by herpes simplex virus.

◦ If no cause is found, other long-term treatment options such as hydroxychloroquine, dapsone, or early use of systemic corticosteroids during flare-ups may be considered.

Treatment for Severe Cases:

◦ Severe erythema multiforme requires hospital care to manage complications, dehydration, and secondary infection.

◦ Any suspected triggering medications must be stopped immediately. Proper nutritional support is essential.

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 include uveitis (inflammation of the uvea), conjunctivitis (inflammation of the conjunctiva), scarring, panophthalmitis (a complete purulent inflammation and dissolution 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 observed in fewer than 5% of 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 disease, and herpes simplex virus infection can all cause this.

Conclusion

Erythema multiforme is a skin disorder that can be 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 electrolyte replacement. Recurrent herpes simplex virus cases should be treated with prophylactic antiviral therapy. If you or your loved ones have similar skin reactions, consult our skin doctor at iCliniq.

Key Takeaways

• Erythema multiforme is a skin disease that causes reddish, target-shaped rashes on the skin and sometimes sores in the mouth.

• It is uncommon and affects less than 1% of the population.

• The most common cause is infection, especially herpes simplex virus.

• The rash usually lasts about 1 week and often settles on its own in mild cases.

• Severe cases are rare, but a medical check-up is important to rule out serious conditions.