What Conditions is Erythema Nodosum Associated With?

Patient Presentation
A 12-year-old male came to clinic with a history of 3-4 days of painful bruising on his shin and lower arms. He had Streptocococcal pharyngitis diagnosed by rapid strep testing approximately 4 weeks previously and had taken all of his amoxicillin antibiotic per his parents. He had recovered without any problems until 3-4 days ago when his legs and arms started to have painful bruises along the shins and lower arms. They were raised, red/purple and painful mainly in the center of the lesions. He denied pain elsewhere nor any fever (Tmax was 99.5F), chills, sweats, weight loss, joint stiffness, abdominal pain, vision or eye changes, or mucous membrane changes. He had normal bowel and bladder habits without hematuria. The family had traveled to visit relatives in Central America 3 months previously but denied any tuberculosis risks. The past medical history was non-contributory. The family history was positive for heart disease and osteoarthritis in an older grandmother. The review of systems was otherwise negative.

The pertinent physical exam had normal vital signs including weight that was 75% and consistent with previous weights. HEENT, heart, lung and abdomen examination were negative. He had some shotty nodes in the anterior cervical, posterior cervical and groin. He had 1-2 cm nodular purple/red lesions over the extensor surfaces of the bilateral anterior tibia and ulnar areas. They were painful to the touch but the bones were not painful otherwise. No pain could be elicited in the adjacent muscle groups. His extremities had full range of motion without pain and had no swelling or erythema.

The diagnosis of of erythema nodosum probably due Streptocococcus was made. The evaluation included a complete blood count, complete metabolic panel, urinalysis, chest radiograph, throat culture, and QuantiFERON-TB GOLD® were negative. His Anti-streptolysin O titre was positive, as were his erythrocyte sedimentation rate (= 42 mm/hr, normal 1-25 mm/hr) and C-reactive protein were 8 mg/L (normal < 3 mg/dL). The patient was started on ibuprofen and rest, along with clindamycin to make sure that his streptococcal infection was treated. It was felt that this was not a drug reaction but a penicillin was avoided. The patient’s clinical course over the next week was that he had no new lesions and his other lesions were slightly less painful. Over the next 3 weeks he had almost complete resolution of the lesions and they were completely gone by 6 weeks. Repeated labs were negative.

Erythema nodosum (EN) is a common dermatological eruption characterized by inflammatory nodules of the subcutaneous fat (panniculitis) on the extensor surfaces of the extremities especially the shins, thighs, and forearms. They are usually painful, nodular, bilateral and multiple. They can be found on other areas and be unilateral. They can be red, purple or blackish. They usually resolve without problems in 3-6 weeks.

Diagnosis is usually clinical but biopsy may be needed if there is atypical presentation or history, physical examination or laboratory testing reveals potential underlying diseases. Treatment is usually conservative with rest and non-steroidal anti-inflammatory drugs. Identified underlying causes of the EN should be treated but in some studies more than 50% of the causes remain unidentified. Other treatments include steroid medication and even potassium iodide has been used.

Learning Point
A study of 39 Turkish children in 2014 found the following causes of EN (some had two infections):

  • Idiopathic = 43.5%
  • Streptococcal infection = 23%
  • Mycoplasma pneumonia = 7.7%
  • Tularemia = 10.2%
  • Tuberculosis, latent = 5%, pulmonary = 2.5%
  • Behçet disease = 2.5%
  • Cytomegalovirus = 2.5%
  • Giardia lamblia infection 2.5%
  • Sarcoidosis = 2.5%

EN has been associated with a variety of other causes including:

  • Drugs – Bromides and iodides, Oral contraceptives, Penicillin, Sulfonamides
  • Infections
    • Bacteria – Brucellosis, Campylobacter, Chlamydia trachomatis, Leprosy(*), Leptospirosis, Salmonella, Yersinia
    • Fungus – Blastomycosis, Coccidioidomycosis, Histoplasmosis
    • Viral – Bartonella henselae, Epstein Barr virus, Hepatitis B, Lymphogranuloma venereum, Paravaccinia, Psittacosis
    • Gastrointestinal – Crohn’s disease, Ulcerative colitis
  • Malignancy – Carcinosis, Leukemia, Lymphoma,
  • Other – Pregnancy, Sweet Syndrome, Whipple disease

*EN should not be confused with erythema nodosum leprosum (ENL) which is a rare immune-mediated systemic disease associated with Leprosy.

Questions for Further Discussion
1. How do you diagnosis inflammatory diseases such as Behçet disease, Crohn’s disease, or Ulcerative colitis?
2. What is the role of a consultants in the evaluation and treatment of EN?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Skin Conditions and Skin Infections.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Aydın-Teke T, Tanır G, Bayhan GI, Metin O, Oz N. Erythema nodosum in children: evaluation of 39 patients. Turk J Pediatr. 2014 Mar-Apr;56(2):144-9.

Jones M, de Keyser P. Rash on the arms and legs. BMJ. 2015 Aug 3;351:h4131.

Walker SL, Balagon M, Darlong J, et.al.
ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum. PLoS Negl Trop Dis. 2015 Sep 9;9(9):e0004065.

Kroshinsky D. Erythema nodosum. UpToDate. (rev. 11/30/2016, cited 5/16/17).

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa