Erythema nodosum (EN) is an inflammatory condition characterized by inflammation of subcutaneous fat tissue, resulting in painful red/blue lumps or nodules that are usually seen symmetrically on both shins, on the thighs, arms, and elsewhere. It can be caused by a variety of conditions but 20 to 50% of cases are

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...

. It typically resolves spontaneously within 30 days. It is common in young people aged 12–20 years.

Signs and symptoms

Pre-eruptive phase

The first signs of erythema nodosum are often flu-like symptoms such as a fever, cough,

malaise In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...

, and aching joints. Some people also experience stiffness or swelling in the joints and weight loss.

Eruptive phase

Erythema nodosum is characterised by nodules (rounded lumps) below the skin surface, usually on the shins. These subcutaneous nodules can appear anywhere on the body, but the most common sites are the shins, arms, thighs, and torso. Each nodule typically disappears after around two weeks, though new ones may continue to form for up to six or eight weeks. A new nodule usually appears red and is hot and firm to the touch. The redness starts to fade and it gradually becomes softer and smaller until it disappears. Each nodule usually heals completely without scarring over the course of about two weeks. Joint pain and inflammation sometimes continue for several weeks or months after the nodules appear. Less common variants of erythema nodosum include: * Ulcerating forms, seen in

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

* Erythema contusiforme, when a subcutaneous

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

(bleeding under the skin) occurs with an erythema nodosum lesion, causing the lesion to look like a

contusion A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur clo ...

(bruise) * Erythema nodosum migrans (also known as subacute nodular migratory panniculitis), a rare form of chronic erythema nodosum characterized by asymmetrical nodules that are mildly tender and migrate over time. File:EN-TBC.PNG, Erythema nodosum lesion in a person with light skin and tuberculosis File:A single EN.JPG, A single lesion of erythema nodosum File:Erythema Nodosum.jpg, Several lesions of erythema nodosum in an individual with dark skin

Causes

EN is associated with a wide variety of conditions.

Idiopathic

About 30–50% of EN cases are

(of an unknown cause).

Infection

Infections associated with EN include: * Streptococcal infection which, in children, is by far the most common precipitant * Several granulomatous mycobacterial infections including

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respir ...

, and M. avium complex * '' Mycoplasma pneumoniae'' * ''

Histoplasma capsulatum ''Histoplasma capsulatum'' is a species of dimorphic fungus. Its sexual form is called ''Ajellomyces capsulatus''. It can cause pulmonary and disseminated histoplasmosis. ''Histoplasma capsulatum'' is "distributed worldwide, except in Antarc ...

'' * ''

Yersinia ''Yersinia'' is a genus of bacteria in the family Yersiniaceae. ''Yersinia'' species are Gram-negative, coccobacilli bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of '' ...

'' * '' Lymphogranuloma venereum'' (LGV), caused by the bacteria ''

Chlamydia trachomatis ''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...

'' * Epstein-Barr virus * ''

Coccidioides immitis ''Coccidioides immitis'' is a pathogenic fungus that resides in the soil in certain parts of the southwestern United States, northern Mexico, and a few other areas in the Western Hemisphere. Epidemiology ''C. immitis'', along with its relativ ...

'' ( Valley fever) * Cat scratch disease

Autoimmune

Autoimmune disorders An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...

associated with EN include: * Behçet's disease

Immune-mediated/Idiopathic granulomatous diseases

Sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...

Pregnancy

Pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

may be associated with EN.

Medications

Medications associated with EN include: * Omeprazole *

Sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

* Oral contraceptives * Penicillins * Bromides * Hepatitis B vaccination

Cancer

Cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s associated with EN include: *

Non-Hodgkin's lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tire ...

(NHL) * Carcinoid tumours *

Pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

EN may also be due to excessive antibody production in lepromatous leprosy leading to deposition of immune complexes. There is an association with the HLA-B27 histocompatibility antigen, which is present in 65% of patients with erythema nodosum. A useful

mnemonic A mnemonic device ( ), memory trick or memory device is any learning technique that aids information retention or retrieval in the human memory, often by associating the information with something that is easier to remember. It makes use of e ...

for causes is SORE SHINS (Streptococci, OCP, Rickettsia, Eponymous (Behçet), Sulfonamides, Hansen's Disease (Leprosy), IBD, NHL, Sarcoidosis.

Pathophysiology

Erythema nodosum is probably a delayed hypersensitivity reaction to a variety of antigens. Although circulating immune complexes have been demonstrated in patients with inflammatory bowel disease, they have not been found in idiopathic or uncomplicated cases.

Diagnosis

Erythema nodosum is diagnosed clinically. A

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, an interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves the extraction of sampling (medicine), sample ...

can be taken and examined microscopically to confirm an uncertain diagnosis. Microscopic examination usually reveals a neutrophilic infiltrate surrounding capillaries that results in septal thickening, with fibrotic changes in the fat around blood vessels. A characteristic microscopic finding is radial granulomas, well-defined nodular aggregates of histiocytes surrounding a stellate cleft. Additional evaluation should be performed to determine the underlying cause of erythema nodosum. This may include a full blood count (FBC),

erythrocyte sedimentation rate The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of in ...

(ESR), antistreptolysin-O (ASO) titer and throat culture,

urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a Test panel, panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and #Microscopic examination, m ...

, intradermal tuberculin test, and a

chest x-ray A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...

. The ESR is typically high, the

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...

elevated, and the blood showing an increase in white blood cells. The ESR is initially very high and falls as the nodules of erythema nodosum. The ASO titer is high in cases associated with a streptococcal throat infection. A

chest X-ray A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...

should be performed to rule out

pulmonary The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...

diseases, in particular

sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...

and

Löfgren syndrome Löfgren syndrome is a type of acute sarcoidosis, an inflammatory disorder characterized by swollen lymph nodes in the chest, tender red nodules on the shins, fever and arthritis. It is more common in women than men, and is more frequent in those o ...

Treatment

Erythema nodosum is self-limiting and usually resolves itself within 3–6 weeks. A recurring form does exist, and in children, it is attributed to repeated infections with

streptococcus ''Streptococcus'' is a genus of gram-positive spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs along a sing ...

. Treatment should focus on the underlying cause. Symptoms can be treated with bed rest, leg elevation, compressive bandages, wet dressings, and nonsteroidal anti-inflammatory agents (NSAIDs). NSAIDs are usually more effective at the onset of EN versus with chronic disease.

Potassium iodide Potassium iodide is a chemical compound, medication, and dietary supplement. It is a medication used for treating hyperthyroidism, in radiation emergencies, and for protecting the thyroid gland when certain types of radiopharmaceuticals are u ...

can be used for persistent lesions whose cause remains unknown.

Corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s and

colchicine Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...

can be used in severe refractory cases.

Thalidomide Thalidomide, sold under the brand names Contergan and Thalomid among others, is an oral administered medication used to treat a number of cancers (e.g., multiple myeloma), graft-versus-host disease, and many skin disorders (e.g., complication ...

has been used successfully in the treatment of Erythema nodosum leprosum, and it was approved by the U.S. FDA for this use in July 1998. According to a 2009 meta-analysis, there is some evidence of benefit for both thalidomide and clofazimine in the treatment of erythema nodosum leprosum.

Epidemiology

Erythema nodosum is the most common form of panniculitis. It is most common in the ages of 20–30, and affects women 3–6 times more than men.

Eponym

The term, Subacute Migratory Panniculitis of Vilanova and Piñol, was named after the two Catalan dermatologists who provided a brief description and explanation of the disease, Xavier Montiu Vilanova (1902–1965) and Joaquin Aguade Piñol (1918–1977), in 1954, and was named in 1956.

References

External links

{{DEFAULTSORT:Erythema Nodosum Autoimmune diseases Erythemas Reactive neutrophilic cutaneous conditions Conditions of the subcutaneous fat Medical mnemonics