History and exam

Key diagnostic factors

common

nodules on shins

Abrupt-onset, red, tender subcutaneous swellings on the legs.[Figure caption and citation for the preceding image starts]: Erythema nodosum on the shin of a patient.From the personal collection of Dr Om P. Sharma, MD, FRCP, DTM&H; used with permission [Citation ends].com.bmj.content.model.Caption@5eaba8e6[Figure caption and citation for the preceding image starts]: Erythema nodosum on a patient's legFrom the collection of Henry W. Lim, MD, Dept of Dermatology, Henry Ford Health System, Detroit, MI; used with permission [Citation ends].com.bmj.content.model.Caption@522cf39

uveitis, red eyes, retinal nodules, or candle-wax drippings

Seen with sarcoidosis. Candle-wax drippings are waxy deposits on the sides of retinal veins.

nodules on other skin areas

Lesions can occur less commonly in areas other than the shins.[Figure caption and citation for the preceding image starts]: Erythema nodosum on a patient's arms and handsCDC Public Health Image Library [Citation ends].com.bmj.content.model.Caption@52a94a6e[Figure caption and citation for the preceding image starts]: Erythema nodosum lesions on skin of back due to hypersensitivity to antigens of Coccidioides immitisCDC Public Health Image Library [Citation ends].com.bmj.content.model.Caption@740641b2

uncommon

anesthetic skin lesions

Raised skin lesions that are typically pale or slightly red, dry, hairless, and numb to touch. May indicate leprosy.

Other diagnostic factors

common

joint pains

Generalized joint pain with erythema and swelling can occur with erythema nodosum; can also suggest underlying rheumatologic disease.

fever

Fever and cough are common in bacterial and viral pneumonia.

uncommon

diarrhea, constipation, abdominal pain, hematochezia

Gastrointestinal symptoms may suggest possible underlying inflammatory bowel disease, Behcet disease, or Yersinia colitis infection.

enlarged spleen

May indicate histoplasmosis, brucellosis, bacterial endocarditis, or sarcoidosis as underlying cause.

miliary nodules on the retina

Seen in brucellosis and tuberculosis.

Risk factors

strong

streptococcal infection

Currently the most common identifiable cause.[3][4][5]

Increased incidence of EN in the first half of the calendar year is believed to be associated with more frequent streptococcal infection etiology at this time.

sarcoidosis

EN may be a presenting feature in patients with sarcoidosis.[18]

Seen with bilateral hilar lymphadenopathy, most commonly in northern Europe.

tuberculosis

Various risk factors, including exposure, institutionalization (in the US), concurrent HIV infection.

Tuberculosis is the most common etiology in developing countries.

coccidioidomycosis

Coccidioidomycosis predominates in the western and southwestern regions of the US.[11][12]

Common in the San Joaquin Valley region of California, and in patients with a history of desert camping or digging.[Figure caption and citation for the preceding image starts]: Erythema nodosum lesions on skin of back due to hypersensitivity to antigens of Coccidioides immitisCDC Public Health Image Library [Citation ends].com.bmj.content.model.Caption@297ec7ca

histoplasmosis

EN is one of the most common skin manifestations of histoplasmosis, which is seen mainly in the southern and midwestern US, the Mississippi valley, Central America, and parts of South America.[10]

blastomycosis

Endemic areas include the Mississippi and Ohio River basins, the midwestern US, and areas of Canada along the St Lawrence River and the Great Lakes. Also reported in Africa.

EN is rarely described in blastomycosis, but may be the cause in these regions.[13]

Behcet disease

In Behcet disease, cutaneous manifestation, including EN, is seen in 40% to 90% of patients.[8] Behcet disease is an important consideration in the Middle East, the Mediterranean region, and East Asia.[9]

oral contraceptives

Less common cause now that hormone concentrations are lower.

leprosy

More common in tropical countries and India.

weak

brucellosis

More common in the Middle East, tropical countries, and in dairy workers and farmers.

EN-like lesions are the most frequently encountered cutaneous lesions in brucellosis.[17]

sulfonamides

Uncommon cause.

Drugs such as sulfonamides, bromides, and oral contraceptives have been identified as the cause of EN in 3% to 5% of patients.[3]

iodides and antiepileptic drugs

Can also be associated with lesions.

psittacosis

Usually associated with exposure to birds.

inflammatory bowel disease

EN is the most common cutaneous manifestation of inflammatory bowel disease.[19][20][Figure caption and citation for the preceding image starts]: Singular erythema nodosum mimicking cellulitis, the most common lesion associated with inflammatory bowel disease, ulcerative colitis, and Crohn disease (4-6% of patients, most often women ages 10-30 years)From the collection of Dr Daniela Kroshinsky, MD, MPH; used with permission [Citation ends].com.bmj.content.model.Caption@5737868b

pregnancy

The cause in 2% to 6% of patients.[3]

malignancy

Hematologic malignancies such as leukemia and lymphoma are the most common malignancies associated with EN lesions.[15][16][3]

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