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Erythema nodosum Causes, Symptoms and Treatment

The subcutaneous adipose tissue located between the dermis at the top and the superficial aponeurosis of the muscles in depth is called hypodermis in medical terms.

Erythema nodosum is a hypodermatitis, therefore an inflammation of the subcutaneous fatty tissue.

It is a skin disease of ancient description (1798), characterized by the presence of knots (kind of balls under the skin poorly defined) painful, touching the extension of the legs, more rarely the thighs and thighs. forearm, evolving over 3 to 6 weeks leaving no dermatological sequelae.

It affects 2 to 3 per 10,000 inhabitants per year. The women are 3 times more often affected than men. The age of onset is between 20 and 45 years with a peak between 20 and 30 years. There is a seasonal incidence with a higher incidence of erythema nodosum in the first half of the year .


Causes of erythema nodosum

1 / Beta hemolytic streptococcal infection

It is most often angina occurred 3 weeks ago, sometimes a high respiratory infection, or even a dental infection .

2 / Sarcoidosis

Sarcoidosis is a granulomatous inflammatory disease . It is a common cause of erythema nodosum in young women, particularly in the context of Löfgren’s syndrome (ganglions in the mediastinum, fever, joint pain, erythema nodosum and inflammation in the blood).

3 / Yersiniose

This is a common cause in Europe, especially in France. Yersiniosis gives digestive pains often resembling appendicitis, followed by diarrhea . The bacilli in question are Yersinia enterocolitica in adults and Yersinia pseudotuberculosis in children and adolescents.

4 / Tuberculosis

It is a cause whose frequency tends to increase because tuberculosis becomes again an endemic disease

5 / Drugs and vaccines

The drug origin is difficult to prove. Antibiotics (sulfonamides, minocycline, and cefixime) and proton pump inhibitors ( gastric protectors such as omeprazole) are often implicated . Cases have been described during a vaccination against hepatitis B and under the influence of estrogen (estrogen-progestin contraception, pregnancy, hormone replacement therapy of menopause …).

6 / Chronic Inflammatory Bowel Disease (IBD) and other enteropathies

Erythema nodosum can occur during ulcerative colitis or even Crohn’s disease . It can also be seen during celiac disease, diverticulitis, and primary biliary cirrhosis .

7 / Cancers

The leukemia, visceral cancers and malignant lymphomas Hodgkin and non-Hodgkin’s are rare causes of erythema nodosum

These are just the most common causes, here is a chart with most of the known causes of erythema nodosum:

Causes of erythema nodosum.

Bacterial and viral infections:




Q fever


Diseases of cat’s claws

Infectious mononucleosis






Hepatitis B and C

Nodule of milkers

Epstein-Barr Virus

HIV: human immunodeficiency virus


Mycotic and parasitic infections:






Ascaridiosis and taeniasis


Malignant diseases:

Hodgkin’s disease




General diseases:

Maldaie de Behçet


Celiac disease


Sweet’s Syndrome

Horton’s disease

IgA nephropathy

Lupus erythematosus

Still’s disease


Drugs and vaccines:





Hepatitis B vaccine

Non-exhaustive list

Symptoms of erythema nodosum

Erythema nodosum is always stereotyped evolution and has three successive phases

1 / Prodromic phase

Erythema nodosum is sometimes preceded by an ENT or upper respiratory infection 1 to 3 weeks before the rash, suggestive of streptococcal origin . Most often, we find only fever, joint pain, sometimes abdominal pain …

2 / State phase

The knots (kind of balls under the skin, poorly limited) are installed in 1-2 days on the extension of the legs and knees , more rarely thighs and forearms. They are of variable size ( 1 to 4 cm ), few ( 3 to 12 lesions ), bilateral but not symmetrical . They are painful (pain accentuated by standing), warm, firm. There is often an edema of the ankles and persistent joint pain .

3 / Regression phase

It is even earlier when the treatment is well followed. Each knot evolves in about ten days by taking blue-green and yellowish aspects , like the evolution of a hematoma. The knots disappear without sequelae . The erythema nodosum may include several outbreaks over 1 to 2 months, favored by the standing position.

Should I make examinations in case of erythema nodosum?

The doctor is looking for a cause for erythema nodosum to treat it. He has examinations most often led by the clinical signs (stool analysis in case of diarrhea only for example):

Blood test with blood cell count (red blood cells, white blood cells …), liver test, inflammation test, search for antistreptolysin O (ASLO) and antistreptodornases (ASD), tuberculin tests, enzyme test of angiotensin conversion  , serodiagnosis of yersiniosis, thorax adiography. 

Medical treatments for erythema nodosum

1 / Treat the cause

Example: antibiotic treatment of Streptococcal infection , treatment of sarcoidosis by corticosteroid therapy …

2 / Symptomatic treatment of erythema nodosum

2.1 / Rest in bed

The bed rest for two weeks is a critical measure because the standing position favors the occurrence of new outbreaks.

2.2 / Combating pain

The doctor prescribes analgesics:

– paracetamol , 1 to 3 g / 24 h, spacing the catch by a minimum of four hours;

Acetylsalicylic acid, 2 to 4 g / 24 h for 7 to 15 days.

2.3 / In case of joint pain or in the absence of improvement under analgesic:

The doctor then prescribes non-steroidal anti-inflammatory drugs for 10 days:

– indomethacin (Indocid, 50 to 150 mg / 24 h in divided doses);

– naproxen (Naprosyne, 250 mg twice daily during meals).

2.4 / Other treatments

The iodide potassium , at a dose of 300 mg / day for 7 to 15 days, is an efficient and rapid processing but which is less and less used. Prolonged use exposes to hyperthyroidism.

The oral corticosteroid therapy is justified only in severe cases after eliminating active infection or cancer

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