Erythema nodosum
Encyclopedia
Erythema nodosum (red nodules) is an inflammation
of the fat cells under the skin (panniculitis
) characterized by tender red nodules or lumps that are usually seen on both shins. EN is an immunologic response to a variety of different causes.
Erythema nodosum usually resolves itself 3–6 weeks after an event, either internal or external to the body, that initiates a hypersensitivity
reaction in subcutaneous fat. EN is frequently associated with fever, malaise, and joint pain and inflammation. It presents as tender red nodules on the shins that are smooth and shiny. The nodules may occur anywhere there is fat under the skin, including the thighs, arms, trunk, face, and neck. The nodules are 1–10 cm in diameter, and individual nodules may coalesce to form large areas of hardened skin.
As the nodules age, they become bluish purple, brownish, yellowish, and finally green, similar to the color changes that occur in a resolving bruise. The nodules usually subside over a period of 2–6 weeks without ulceration or scarring.
Dermatophytids
are similar skin lesions that result from a fungus infection such as ringworm in another area of the body.
, streptococcal
, Mycoplasma pneumoniae
, Yersinia
, and Epstein-Barr virus
), Coccidioides immitis
, sarcoidosis
, autoimmune disorders (e.g., Inflammatory bowel disease
or Behçet's disease
), pregnancy, medications (sulfonamides, oral contraceptives, bromides), and cancer. 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 erythma nodosum.
Once EN is diagnosed, additional evaluation needs to be performed to determine the underlying cause. A complete blood count, erythrocyte sedimentation rate
(ESR), antistreptolysin-O (ASO) titer, urinalysis
, throat culture, intradermal tuberculin test, and chest x-ray are part of the initial examination.
The ESR is initially very high, and falls as the nodules fade. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray
should be performed to rule out pulmonary diseases. Hilar lymphadenopathy may be due to tuberculosis, sarcoidosis
, or Löfgren syndrome
(a form of acute sarcoidosis with erythema nodosum, bilateral hilar adenopathy, fever and often accompanied by joint symptoms).
. Treatment should focus on the underlying cause. Symptoms can be treated with bedrest, 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
can be used for persistent lesions whose cause remains unknown. Corticosteroid
s and colchicine
can be used in severe refractory cases. Thalidomide
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.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
of the fat cells under the skin (panniculitis
Panniculitis
Panniculitis is a group of diseases whose hallmark is inflammation of subcutaneous adipose tissue...
) characterized by tender red nodules or lumps that are usually seen on both shins. EN is an immunologic response to a variety of different causes.
Classification
Erythema nodosum may be divided into the following types:- Acute erythema nodosumAcute erythema nodosumAcute erythema nodosum is a skin condition, a reactive process commonly associated with a streptococcal infection which, in children, is by far the most common precipitant.- See also :* Chronic erythema nodosum* Erythema nodosum...
- Chronic erythema nodosumChronic erythema nodosumChronic erythema nodosum is a form of septal panniculitis that is much less common than acute erythema nodosum....
Signs and symptoms
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
reaction in subcutaneous fat. EN is frequently associated with fever, malaise, and joint pain and inflammation. It presents as tender red nodules on the shins that are smooth and shiny. The nodules may occur anywhere there is fat under the skin, including the thighs, arms, trunk, face, and neck. The nodules are 1–10 cm in diameter, and individual nodules may coalesce to form large areas of hardened skin.
As the nodules age, they become bluish purple, brownish, yellowish, and finally green, similar to the color changes that occur in a resolving bruise. The nodules usually subside over a period of 2–6 weeks without ulceration or scarring.
Dermatophytids
Dermatophytids
Dermatophytids are fungus-free disseminated skin lesions resulting from induced sensitization in patients with ringworm infections.The most common dermatophytid is an inflammation in the hands resulting from a fungus infection of the feet. Dermatophytids normally disappear when the primary ringworm...
are similar skin lesions that result from a fungus infection such as ringworm in another area of the body.
Causes
In about 30-50% of cases, the cause of EN is unknown. EN may be associated with a wide variety of diseases, including infections (e.g., hepatitis C, tuberculosisTuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, streptococcal
Streptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
, Mycoplasma pneumoniae
Mycoplasma pneumoniae
Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease.-Cell wall/Treatment:...
, Yersinia
Yersinia
Yersinia is a genus of bacteria in the family Enterobacteriaceae. Yersinia are Gram-negative rod shaped bacteria, a few micrometers long and fractions of a micrometer in diameter, and are facultative anaerobes. Some members of Yersinia are pathogenic in humans; in particular, Y. pestis is the...
, and Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
), Coccidioides immitis
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....
, sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, autoimmune disorders (e.g., Inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
or Behçet's disease
Behçet's disease
Behçet's disease is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular involvements...
), pregnancy, medications (sulfonamides, oral contraceptives, bromides), and cancer. EN may also be due to excessive antibody production in lepromatous
Lepromatous leprosy
Lepromatous leprosy is a skin condition consisting of pale macules.It results from the failure of Th1 cell activation which is necessary to eradicate the parasite....
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 erythma nodosum.
Diagnosis
Diagnosis is clinical. A deep punch biopsy or an incisional biopsy may be performed in cases where the diagnosis is unclear. Microscopic examination will reveal a septal panniculitis with acute and chronic inflammation in the fat and around blood vessels.Once EN is diagnosed, additional evaluation needs to be performed to determine the underlying cause. A complete blood count, erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
(ESR), antistreptolysin-O (ASO) titer, urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
, throat culture, intradermal tuberculin test, and chest x-ray are part of the initial examination.
The ESR is initially very high, and falls as the nodules fade. The ASO titer is high in cases associated with a streptococcal throat infection. A chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
should be performed to rule out pulmonary diseases. Hilar lymphadenopathy may be due to tuberculosis, sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
, or Löfgren syndrome
Löfgren syndrome
Löfgren syndrome is a type of acute sarcoidosis that is frequent in Scandinavian, Irish, African and Puerto Rican women.It was characterized in 1953.Some have considered the condition to be imprecisely defined.-Presentation:...
(a form of acute sarcoidosis with erythema nodosum, bilateral hilar adenopathy, fever and often accompanied by joint symptoms).
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 streptococcusStreptococcus
Streptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
. Treatment should focus on the underlying cause. Symptoms can be treated with bedrest, 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
Potassium iodide is an inorganic compound with the chemical formula KI. This white salt is the most commercially significant iodide compound, with approximately 37,000 tons produced in 1985. It is less hygroscopic than sodium iodide, making it easier to work with...
can be used for persistent lesions whose cause remains unknown. Corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s and colchicine
Colchicine
Colchicine is a medication used for gout. It is a toxic natural product and secondary metabolite, originally extracted from plants of the genus Colchicum...
can be used in severe refractory cases. Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
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.