Erythema nodosum (EN) symptoms can include painful bumps under the skin on the legs, fever, fatigue, and joint swelling. Treatment may include rest, ice, and anti-inflammatory medications.

The condition is one of the most common forms of a rare inflammatory problem called panniculitis that affects subcutaneous fat under the skin.

A majority of erythema nodosum (EN) cases occur in people between the ages of 20 and 45 years old. Women are five times more likely than men to develop EN.

The condition is usually relatively harmless, but it can be a sign of an underlying infection, other inflammatory conditions, or an abnormal response to an allergen or medication.

Erythema nodosum on the shins Share on Pinterest
Erythema nodosum may be caused by an infection or medication.
Image credit: James Heilman, MD, 2010

Up to 55 percent of EN cases are idiopathic, meaning they have no known cause.

In some cases, EN is the result of an abnormal immune response, most often triggered by infection, medications, or conditions that cause chronic inflammation.

Researchers are not entirely sure how EN develops. One theory is that it may be caused by the buildup of immune complexes in tiny blood vessels and connections in the subcutaneous fat. These buildups lead to inflammation.

Around 1.2 percent of people with Hansen’s disease (leprosy) develop a type of EN called erythema nodosum leprosum or type 2 lepra reaction.

Possible causes of EN include:

  • infections, such as Streptococcal pharyngitis or strep throat
  • bacterial infections, such as Mycoplasma pneumonia or tuberculosis
  • viral infections
  • deep fungal infections
  • sarcoidosis
  • cancer
  • antibiotics
  • oral contraceptives
  • pregnancy
  • conditions that cause chronic inflammation, such as inflammatory bowel disease (IBS), ulcerative colitis (UC), and Crohn’s disease
  • sulphonamides, salicylates, and other nonsteroidal anti-inflammatory drugs (NSAIDs)
  • bromides and iodides
  • genetics

EN can develop suddenly without any warning signs. Some people experience non-specific symptoms before EN lesions develop.

Many of the early signs of EN, especially joint pain, continue once the sores develop and may last for weeks to months after they have gone.

Common early signs and symptoms of EN include:

  • fever
  • unexplained exhaustion
  • lung, throat, or nose infections
  • joint and muscle pain and weakness
  • swollen joints, often the ankles and knees
  • conjunctivitis
  • cough
  • weight loss

The symptoms vary between individuals, but once EN lesions have developed, they normally have a few common characteristics.

Most EN sores are usually:

  • very painful
  • hot to touch
  • bright red for a week to 10 days then fade to purple or blue
  • on both sides of the body equally
  • on the front of the shins, but also sometimes the ankles, knees, thighs, and forearms
  • slightly raised
  • rounded in shape
  • non-ulcerating, or not causing breaks or tears in the surface of the skin
  • varying in size from a grape to a grapefruit, but mostly between 1 centimeter (cm) and 5 cm
  • varying in number, from 2 to more than 50
  • shiny in appearance

Rarely, the spots may bond together to form a crescent-shaped ring that spreads for a few days before fading.

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Common treatment for EN may include changing medication, elevating the affected area, and bed rest.
Image credit: ErikH, 2005

With proper rest, most cases of EN resolve on their own within 1 to 2 months, with new sores continuing to develop or spread throughout the first few weeks.

However, some people experience EN symptoms for 6 months or more. This is more likely if it is caused by an underlying medical condition or untreated infection. Chronic or long-term EN will also cause joint pain.

Doctors will usually diagnose EN by taking a biopsy, or small tissue sample, from the sores.

The treatment recommended for each case of EN depends on the cause. Underlying infections or medical conditions will also require treatment.

Common forms of treatment for EN include:

  • bed rest, especially if swelling and pain is severe
  • changing any medications that cause EN, but only at a doctor’s discretion
  • applying ice wrapped in a towel to the affected area for 15 to 20 minutes at a time, several times daily
  • elevating the affected area using a prop, such as a pillow
  • over-the-counter pain and anti-inflammatory medications
  • light compression stockings or supportive bandages and wraps
  • oral tetracycline
  • potassium iodide, often 400 to 900 micrograms (mcg) per day for 1 month when symptoms begin
  • systemic corticosteroids, often prednisone
  • steroid creams

Hormonal changes are also known to cause EN. About 2 to 5 percent of cases are linked to pregnancy.

EN that develops during pregnancy usually clears after childbirth but may return if the woman becomes pregnant again.

Some people who take oral contraceptives, or hormone control medications develop EN, usually within the first few months on the medication.

Despite its uncomfortable symptoms, EN is usually harmless. Sometimes it can be a sign of infection or medical condition that requires treatment, so should always be seen by a doctor.

Cases of EN usually resolve with proper rest and basic care within a few months. But for some people, EN can become chronic and cause joint pain and sores for 6 months to 2 years.

If signs or symptoms of EN occur, a person should seek medical attention to rule out the risk of more serious underlying conditions. People should also talk with a doctor if their EN does not clear up with rest and home care.