Erythema Nodosum

What is Erythema Nodosum?

Erythema nodosum (nodular erythema) is an immune skin disease with polyetiological genesis, which occurs in various acute or chronic diseases and intoxications. It is characterized by a spring-autumn seasonal succession of exacerbations and remissions.

Erythema Nodosum
Erythema nodosum is considered the most frequent reactive cutaneous manifestation,appearing one to three weeks after the initial respiratory symptoms. It is a self-limited, inflammatory disorder of the skin andsubcutaneous tissues characterized by multiple erythematous, painful nodules usuallylimited to the extremities
Source: https://openi.nlm.nih.gov

Most often the condition affects children and adolescents and the female organism is more prone to erythema nodosum. The higher prevalence of erythema nodosum among young people is considered to be due to the higher incidence of sarcoidosis in this age group.

The typical rash associated with this condition is represented by the erythema-nodular lesions on the lower limbs.

According to, “The prevalence varies from country to country. It is most prevalent in women in their 20s to 30s. It has a prevalence of 2.4 per 10,000[1]

This is the immune response of the skin to factors such as viruses, bacteria, pharmaceuticals and the like. There has been a reaction to the skin under different conditions.

Treatment primarily involves the identification and elimination of the agent causing erythema nodosum symptoms. The condition can become chronic or recurrent.

Rheumatology, as part of medicine, most often occurs with erythema nodosum: “Histopathology of the nodular lesions was consistent with erythema nodosum (EN). With a diagnosis of rheumatic heart disease and active carditis, benzathine penicillin prophylaxis and aspirin were started. On follow-up after 3 weeks, the nodules had disappeared”[2]


Nodular erythema is an immunological reaction of the skin to various factors:

    • Viruses

    • Bacteria

    • Drugs (antibiotics, triazole, analgesics, contraceptives, etc.)

    • Malignancies (Hodgkin’s disease, leukemia)

    • Sarcoidosis

    • Leprosy

    • Ulcerative colitis

    • Terminal ileitis

    • Pregnancy

    • Sometimes the agent remains undiscovered

The above factors are related to the formation in the body of foreign matter against which we produce immune complexes to deal with foreign bodies. These developments, however, are not eliminated from the body and remain to circulate in the vessels.

Because of various reasons, they enter into the walls of the cutaneous vessels, where occurs the immunological reaction. The walls of these vessels are damaged by the inflammatory response in their walls and disturbance of blood perfusion of the skin and bleeding start occurring.


Erythema nodosum is provoked by:

Certain drugs

  •  salicylates
  • antipyretics
  • sulfonamides

According to the American Family Physician, “Hypersensitivity reactions to medications have been recognized as a cause of 3 to 10 percent of erythema nodosum cases. Oral contraceptives and numerous antibiotics, including amoxicillin and especially sulfonamides, have been associated with erythema nodosum” [3]


  •  Streptococcal infections
  • Yersiniosis
  • Tuberculosis
  • Ornithosis

Other diseases

  • Crohn’s disease
  • sarcoidosis
  • neoplastic processes
  • aphthous stomatitis
  • neoplastic processes
  • aphthous stomatitis.


Before the onset of erythema nodosum, there is a prodromal stage, which is manifested by fever, malaise, sore throat, joint pain, gastrointestinal disorders.

A few hours later are formed painful, red, raised, rigid plates, symmetrically on both legs, around the knees and the upper surface of the feet.

Later they spread in depth and in a few days form nodular changes with the size of 2-3 cm. Sometimes they blend in very large infiltrates. The skin on them is red, hot, taut and shiny. During pressures, skin fades and remains recess because of pronounced edema of the plate.

Gradually 10 days color changes are observed, varying from red to blue-violet, green-yellowish to brown. This discoloration is the same as for injuries, indicating hemorrhage origin of erythema nodosum.

At the end of the 3rd or 4th-week of swelling, the redness significantly declines and disappears, and the skin surface starts scaling.

Sometimes the disease lasts for months or even years without remission (lasting for 6 months and occasionally for years). Usually, patients are in good general condition, without common complaints.


The main pathogenic units in erythema nodosum are the immune complexes, deposited in the blood vessels deep in the dermis, which activate the monocyte-macrophage system and are phagocytosed. Inflammation passes rapidly and blood vessels are back to their normal condition.

The clinical picture is characterized by the occurrence of painful inflammatory nodules that are raised compared to the surrounding skin and firm to the touch, with a hemispherical shape and purplish-red color.

Such nodules usually appear on the extensor surfaces of the knees, shins and dorsal surface of the feet. The appearance of the rash is often preceded by several days prodromal period (the symptoms may not be very specific or severe.

The affected person can still perform usual functions although distress or discomfort may be felt) with low-grade fever and general weakness. The rash completely passes over 3 to 6 weeks.

When the condition affects children, the disease is usually acute. Besides the lower limbs, rashes may be located in the upper limbs and the facial area.

Particular clinical forms of nodular erythema are migratory erythema nodosum (affecting only one tight and frequently occurs in pregnant women) and syndrome Löfgren (manifestation of sarcoidosis).


Diagnosis is based on the typical clinical picture. Histological studies indicate inflammatory infiltrates around the blood vessels of the skin and subcutis (mainly around the veins).

In infectious etiology there are clinical and laboratory signs of inflammation (accelerated ESR, leukocytosis), in streptococcal infection – increased antistreptolysin O antibodies (specific antibodies; the increased levels of ASO titre in the blood could cause damage to the heart and joints. In most cases, penicillin is used to treat patients with increased levels of ASO titre.).

Differential diagnosis of cutaneous forms of tuberculosis disease (nodosa periarteritis [4], nodular vasculitis [5], thrombophlebitis [6]), inflammation of the subcutis is usually made.

Sometimes a nodule is removed and analyzed under a microscope (biopsy) to confirm the diagnosis.
Other testing is done to look for possible causes and can include a chest x-ray, blood tests, and skin testing for tuberculosis.


The basic principle in the treatment of the disease is the identification and removal of the causative agent of the disease.

Usually, nodules of erythema nodosum regress spontaneously within a few weeks, and bed rest is often sufficient treatment.It is highly recommended for the exacerbation periods of the disease to ensure bed rest and pain Nonsteroidal anti-inflammatory drugs [7] like aspirin, ibuprofen etc.

Particularly useful in chronic cases is potassium iodate taken orally. Topically applied anti-inflammatory and dermatological antiseptics are also recommended. General treatment is carried out with antihistamines, aspirin, NSAIDs, vitamin C.

When an infection is available, a therapy with broad-spectrum antibiotics is carried out. In idiopathic forms are administered iodine preparations. Avoid the use of glucocorticosteroids, as there is an established aggravation of subsequent recurrence of the disease after application.

Erythema nodosum responds well to physical therapy – light treatment with ultraviolet rays.

Erythema Nodosum Treatment
) Symmetric, tender, erythematous plaques on the anterior aspects of both knees. (B) Two days after discontinuing intramuscular progesterone injection, the color of the lesions became darker and then started to resolve.

What is the prognosis?

In most cases the disease goes for 4-6 weeks, there is only a temporary change in skin color. Pain and stiffness in the joints, however, may persist for several years. Recurrences usually do not appear except in cases where there is an unresolved infection.


    Erythema Nodosum – Epidemiology
    Erythema Nodosum as the Presenting Feature of Rheumatic Heart Disease
    Erythema Nodosum: A Sign of Systemic Disease
    Polyarteritis nodosa
    Erythema Induratum (Nodular Vasculitis) Clinical Presentation
    Management of Superficial Thrombophlebitis
    Erythema Nodosum Medication

About the author

Monika Hristova

Monika is the Editor-in-Chief at SkinPractice. She is a skin care addict and researcher, who feels strongly about helping people with different dermatology conditions from alopecia to warts.

You can read her recommendations and advice both here at SkinPractice or at Quora where she answers skincare-related questions frequently and is the most viewed author in the Skincare category with more than 3 million views or follow her on LinkedIn.

She is also a certified skin care specialist with certification from the Medical College in Sofia.

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