Erythema nodosum: Skin infection with painful nodules

Erythema nodosum is a skin infection in part of the fatty layer of the skin. This causes painful and red lumps to develop, especially below the knees, but possibly also in other places. This is a hypersensitivity reaction that may or may not be associated with a medical condition or appears after taking certain medications. As a result, in some cases the patient not only experiences skin-related symptoms, but also other signs resulting from the underlying disease. The treatment of the skin condition itself consists of medications, although other measures are also useful. Most patients recover spontaneously from the disease after a few weeks, although some patients develop a chronic form, causing the symptoms to persist for a longer period of time.

  • Epidemiology and risk factors erythema nodosum
  • Causes of skin infection
  • Symptoms: Painful lumps in the skin on knees
  • Diagnosis and examinations
  • Treatment via medication
  • Prognosis of skin disease is excellent

Epidemiology and risk factors erythema nodosum

The exact incidence of erythema nodosum is not known, but in England it is 2.4 cases per 10,000 per year. Most patients are diagnosed with erythema nodosum between the ages of 20 and 45, with a peak incidence between 20 and 30 years, although the disease can occur at any age. The skin disease is less common in the elderly and children. Erythema nodosum also presents 3-6 times more often in adult women than in adult men. The gender incidence for the onset of puberty is approximately equal. Most patients with erythema nodosum are otherwise in good health, but sometimes they have recently had an infection or illness.

Causes of skin infection

Erythema nodosum is a hypersensitivity reaction with a number of different causes. Erythema nodosum presents with or without another medical condition. Medication use may also contribute to the development of this skin infection.

Erythema nodosum sometimes occurs in pregnant ladies / Source: PublicDomainPictures, Pixabay

Some conditions associated with erythema nodosum are:

  • other bacterial infections such as Mycoplasma pneumonia
  • cat scratch disease (skin lesions and swollen lymph nodes)
  • Behçet’s disease (condition including ulcers and uveitis)
  • a bacterial or viral throat infection
  • a lymphoma (very rare)
  • a normal pregnancy: The skin condition occurs in some women during pregnancy (usually during the second trimester), or returns with subsequent pregnancies.
  • inflammatory bowel diseases such as Crohn’s disease (condition with abdominal pain, diarrhea and weight loss) and ulcerative colitis (chronic intestinal disease with diarrhea, abdominal pain and painful bowel movements)
  • glandular fever (viral infection with sore throat, swollen lymph nodes, fatigue and low-grade fever that occurs mainly in adolescents and young adults)
  • sarcoidosis (disease of the eyes, lungs, nervous system and skin): In adults, sarcoidosis is the most common cutaneous manifestation of erythema nodosum. A characteristic form of acute sarcoidosis is known as Löfgren’s syndrome. This is the combination of erythema nodosum, hilar lymphadenopathy (swollen lymph nodes), fever, arthritis (joint inflammation) and uveitis (eye inflammation).
  • fungal diseases
  • Tuberculosis: Erythema nodosum occurs in this bacterial infection with lung related problems.

Furthermore, erythema nodosum leprosum is also a form of the skin disease. This mainly occurs in patients receiving treatment for leprosy.


Certain drugs sometimes lead to erythema nodosum: birth control pills, estrogens, antibiotics (e.g. sulfonamides, amoxicillin), salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), bromides, iodides, and gold salts.

Symptoms: Painful lumps in the skin on knees

Skin lumps

Erythema nodosum is further characterized by several to dozens of blue-red, painful, sensitive and symmetrical nodules in the skin (skin nodules), which are often located in the lower legs (front of the legs below the knees and also the sides of the knees). Occasionally skin lesions occur on the shins and less often on the thighs, forearms, face and neck, but usually these skin lesions are smaller and more superficial. The tender nodules of erythema nodosum range in size from one to ten centimeters. The inflamed nodules are warm to the touch, bright red when they first appear, but later turn a more purple color. They then fade and undergo the color changes of a bruise. After about two weeks, these lumps shrink and flatten, creating a bruised appearance.

Red eyes in conjunctivitis, an occasional symptom / Source: Marco Mayer, Wikimedia Commons (CC BY-SA-4.0)

Other symptoms
When a patient suffers from an underlying disease, the symptoms are obvious, such as a sore throat with a strep throat infection. (Mild) fever, weight loss, coughing, general pain and a general feeling of illness (malaise) are other symptoms that usually occur one to three weeks before the appearance of the lumps. Joint pain occurs in more than half of patients with erythema nodosum, regardless of the cause. Conjunctivitis (inflammation of the eye) is a less common symptom.

Diagnosis and examinations

Diagnostic research

The doctor first inspects the rash. However, a skin biopsy is necessary to confirm the diagnosis of erythema nodosum. The doctor removes a small part of the damaged skin and then has this small piece of tissue examined microscopically.

Differential diagnosis

Doctors sometimes confuse the nodules of erythema nodosum with insect bites. Sometimes the inflammation of erythema nodosum is more widespread and mimics the skin infection cellulitis (skin infection with painful, red and swollen skin). These are other differential diagnoses:

  • acute hives (skin disease with itchy bumps on the skin surface)
  • complications of leukemia
  • erythema induratum (nodular vasculitis)
  • familial Mediterranean fever (repeated episodes of inflammation with fever)
  • lipodystrophies
  • lupus erythematosus profundus (lupus panniculitis)
  • necrobiosis lipoidica (skin disease with lesions and ulceration)
  • necrobiotic xanthogranuloma
  • nodular fat necrosis (area of fatty tissue after trauma, often on chest)
  • subcutaneous fat necrosis (of the newborn)
  • rose
  • scleroderma (build-up of scar tissue in skin and organs)
  • subcutaneous granulomas
  • thrombophlebitis (local superficial phlebitis with pain)
  • α1-antitrypsin deficiency (liver and lung disease)

Treatment via medication

The doctor first identifies the underlying condition of erythema nodosum and applies treatment for it. He also treats skin lesions. Patients are given anti-inflammatories (anti-inflammatory drugs) and corticosteroids (powerful anti-inflammatory medications) that they take by mouth or are injected. If pain or swelling is severe, bed rest is recommended. Light compression stockings or other support bandages are also possible to relieve the pain.

Prognosis of skin disease is excellent

Erythema nodosum usually resolves spontaneously within three to six weeks. After the skin infection has healed, the patient may still have a temporary bruised appearance or a chronic indentation in the skin where the lesion in the fat layer was present. The skin infection is often annoying and painful, but does not cause damage to the internal organs. The prognosis of patients with erythema nodosum is therefore very good. Occasionally the skin condition develops into a chronic form that lasts for months or even years.

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