Basics
Description
Delayed, cell-mediated hypersensitivity panniculitis characterized by red, tender, nodular lesions most often seen on the pretibial surface of the legs
Epidemiology
- Girls are affected more often than boys.
- Incidence peaks in adolescence and is rare under 2 years of age.
Incidence
Greatest seasonal incidence in spring and fall
Pathophysiology
- Most likely a host hypersensitivity immune response to circulating immune complexes secondary to infectious and/or inflammatory stimuli
- The response results in chronic injury to the blood vessels of the reticular dermis and subcutaneous fat.
Etiology
- Most cases are idiopathic (~50% of cases).
- Infectious associations
- Bacterial: β-hemolytic streptococcal infection is the most common cause in children.
- Other bacteria: Mycoplasma, Yersinia, Shigella, Brucella, Neisseria meningococcus and gonococcus, chlamydia, cat-scratch disease, rickettsial diseases including syphilis
- Viral: Epstein-Barr virus (EBV), HIV, hepatitis B virus (HBV)
- Mycobacterial: tuberculosis and atypical mycobacteria, leprosy
- Fungal: histoplasmosis, coccidioidomycosis
- Systemic associations
- Sarcoidosis
- Inflammatory bowel disease
- Beh §et disease
- Malignancy (lymphoma, leukemia)
- Pregnancy
- Medications
- Oral contraceptives
- Sulfonamides
- Phenytoin
- Halides
Diagnosis
History
- Arthralgia is commonly noted 2-8 weeks prior.
- Prodromal symptoms of fatigue/malaise or upper respiratory infection often occur by 1-3 weeks.
- Pain and tenderness of the extremities is common, sometimes causing difficulty in ambulation.
- Important questions to ask:
- Recent streptococcal infection
- Medication history (oral contraceptives, sulfonamides, iodides/bromides)
- Last menses (erythema nodosum is seen in pregnancy)
- History of diarrhea (inflammatory bowel disease or infectious diarrhea)
- Tuberculosis exposure
Physical Exam
- Red, often tender nodules on anterior lower legs, 2-6 cm in diameter
- Lesions can also be present in other areas with subcutaneous fat such as the thighs, arms, trunk, and face.
- Overlying skin is normal except for erythema.
- Initially, lesions are slightly elevated, bright to deep red nodules with palpable warmth.
- Later, lesions develop a brownish red or violaceous, bruise-like appearance.
- Exam pearls
- Symmetric distribution
- Erythema nodosum never ulcerates or suppurates.
- Usually, there are no more than 6 lesions at a time.
Diagnostic Tests & Interpretation
Lab
- Throat culture
- Antistreptolysin-O titer
- Tuberculin skin test
- CBC
- Erythrocyte sedimentation rate (ESR)
- Stool culture, if history of diarrhea
- Serologic testing, if yersiniosis, rickettsial disease, histoplasmosis, or coccidioidomycosis suspected
Imaging
Chest radiograph can help screen for possible underlying tuberculosis or sarcoidosis.
Diagnostic Procedures/Other
- Erythema nodosum is a clinical diagnosis.
- Biopsy for histopathology and culture (bacterial, fungal, mycobacterial) is used if diagnosis is in doubt.
Pathologic Findings
- Septal panniculitis: lymphocytic perivascular infiltrate in the dermis; lymphocytes and neutrophils in the fibrous septa in the subcutaneous fat
- Older lesions: Histiocytes, giant cells, and occasionally plasma cells can be seen.
- No fat cell destruction or vasculitis is present.
Differential Diagnosis
- Infection
- Erysipelas/cellulitis
- Erythema induratum (nodular vasculitis)
- Deep fungal infection or Majocchi granuloma
- Superficial or deep thrombophlebitis
- Trauma: accidental or from child abuse
- Palmoplantar hidradenitis
- Metabolic
- Panniculitis secondary to pancreatic disease
- Pretibial myxedema
- Major insect bite reaction
- Psychosocial (self-injection with foreign material)
- Cutaneous sarcoidosis
- Polyarteritis nodosa
- Granuloma annulare
Treatment
First Line
- Bed rest
- Leg elevation
- Salicylates or other NSAIDs, such as ibuprofen, naproxen, or indomethacin
Additional Therapies
- Potassium iodide 300 mg PO t.i.d. for 3-4 weeks, especially for cases diagnosed early in course
- Colchicine
- Corticosteroids (rarely used) for severe cases; courses generally last 2-4 weeks
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Can expect improvement within 1 week
- If lesions recur after cessation of treatment, an underlying infection/inflammatory trigger may still be present.
- If atypical locations or exuberant or suppurative nodules are present, a biopsy is warranted to rule out a disseminated infection.
Prognosis
- Most individual lesions will completely resolve in 10-14 days.
- In general, erythema nodosum resolves in 3-6 weeks with or without treatment unless the underlying cause is a chronic infection or systemic disorder.
- Aching of legs and swelling of ankles may persist for weeks; rarely, symptoms may persist for up to 2 years.
- In children, the recurrence rate is 4-10% and is often associated with repeated streptococcal infection.
Additional Reading
- Chachkin S, Cheng JW, Yan AC. Erythema nodosum. In: Burg FD, Ingelfinger JR, Polin RA, et al, eds. Current Pediatric Therapy. 18th ed. Philadelphia, PA: WB Saunders; 2006.
- Garty BZ, Poznanski O. Erythema nodosum in Israeli children. Isr Med Assoc J. 2000;2(2):145-146. [View Abstract]
- Gonzalez-Gay MA, Garcia-Porrua C, Pujol RM, et al. Erythema nodosum: a clinical approach. Clin Exp Rheumatol. 2001;19(4):365-368. [View Abstract]
- Kakourou T, Drosatou P, Psychou F, et al. Erythema nodosum in children: a prospective study. J Am Acad Dermatol. 2001;44(1):17-21. [View Abstract]
- Paller A, Mancini A. The hypersensitivity syndromes. In: Paller AS, Mancini AJ, eds. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. Philadelphia, PA: Elsevier Health Sciences; 2011.
- Pettersson T. Sarcoid and erythema nodosum arthropathies. Best Pract Res Clin Rheumatol. 2000;14(3):461-476. [View Abstract]
Codes
ICD09
- 695.2 Erythema nodosum
- 17.1 Erythema nodosum with hypersensitivity reaction in tuberculosis, unspecified
ICD10
- L52 Erythema nodosum
- A18.4 Tuberculosis of skin and subcutaneous tissue
SNOMED
- 32861005 Erythema nodosum (disorder)
- 402969008 Erythema nodosum due to streptococcal infection (disorder)
- 74610006 Tuberculous erythema nodosum (disorder)
- 240411003 Erythema nodosum leprosum (disorder)
- 240360007 Yersinia erythema nodosum (disorder)
- 297940005 Drug-induced erythema nodosum (disorder)
FAQ
- Q: Will the lesions leave a scar?
- A: In the vast majority of cases, erythema nodosum heals without scarring.