Erythema Nodosum

A Teenaged Girl With Painful Brownish Leg Lesions

Alexander K. C. Leung, MD—Series Editor, and Benjamin Barankin, MD

A 15-year-old girl presented with painful lesions on both legs of 7 days’ duration. The lesions initially had been erythematous but had turned brownish in the past 2 days. 

Two weeks earlier, she had had a fever, a sore throat, enlarged tonsils with tonsillar exudates, a strawberry tongue, and enlarged, tender anterior cervical lymph nodes. A throat culture at that time grew group A β-hemolytic streptococcus. She had been treated with oral penicillin V for 10 days. Her past health was otherwise unremarkable.

Physical examination showed numerous round, tender, brownish, subcutaneous nodules on the extensor surfaces of her legs. The nodules measured 1 to 3 cm in diameter with indistinct borders. The rest of the physical examination findings were unremarkable.

What’s your diagnosis?

(Answer and discussion on next page)

Answer: Erythema nodosum

Erythema nodosum is the most common form of panniculitis, or inflammation of subcutaneous fat, in children and adults alike.1,2 The disorder is characterized by the acute onset of painful, subcutaneous nodules bilaterally on the pretibial legs. The condition was first described by Robert Willan in 1798.3


The estimated annual incidence 1 to 5 cases per 100,000 persons.1,4-6 In adults, the male to female ratio is approximately 1 to 6.4,6 In children, the sex ratio is approximately equal.2,7 Peak incidence is between 18 and 30 years of age,4,8 with a smaller peak in adolescence.2 The greatest incidence is in the spring and fall.2

ETIOLOGY and Pathogenesis

The potential causes of erythema nodosum are shown in the accompanying Table.2,4,5,8-14 Approximately 50% to 55% of cases are idiopathic.1 Worldwide, β-hemolytic streptococcal infection (especially pharyngitis) is the most frequent identifiable cause of erythema nodosum, followed by gastrointestinal infections, particularly Yersinia enterocolitica.2,4,5 Tuberculosis is an important cause of erythema nodosum in countries where tuberculosis is endemic.4 In North America and Europe, sarcoidosis is an important cause.4,5 In general, infections account for more than one third of pediatric cases.2

Erythema nodosum is thought to result from an exaggerated type IV delayed hypersensitivity response to various triggering antigens, which leads to immune complex deposition and complement activation within the subcutaneous fat.5,7,14 Reactive oxygen intermediates produced by activated neutrophils in early lesions may lead to inflammation and tissue damage.2,4,7 The predilection for the pretibial areas suggests that physical factors may play a role in disease development.7


The classic histologic picture is that of septal panniculitis without associated vasculitis.14 Histologic findings of early lesions include septal edema and thickening with a predominately neutrophilic infiltrate.1 Older lesions show enlargement of the septa with fibrosis, lymphocytic and histiocytic infiltration, and multinucleated giant cells.1,8 Miescher radial granuloma refers to a collection of histiocytes around a small cleft-like space within the septa or at the septa/lobule interface and is a histologic marker of erythema nodosum.1,2,7,8


Erythema nodosum is often preceded by a nonspecific prodrome lasting 1 to 3 weeks, which can include fever, fatigue, malaise, cough, and arthralgias.1,2,11 Cutaneous lesions then follow, which typically present with an acute onset of slightly warm, erythematous, raised, tender, rounded or oval, subcutaneous nodules on the extensor surfaces of the legs, most commonly on the pretibial areas.11 Less commonly, lesions can occur elsewhere on the body, including the ankles, knees, anterior thighs, trunk, upper limbs, neck, and face.1,2,13 In children, lesions rarely may occur on the palms and soles.2 The nodules are poorly demarcated because of their subcutaneous anatomic location and often are more easily palpated than visualized.1 Typically, the lesions are bilateral and symmetric, ranging from 1 cm to a few centimeters in diameter.1,2 Occasionally, nodules may become confluent, resulting in erythematous plaques.9

Within a few days, the color changes from red to purple and brown. The nodules then slowly involute and subsequently evolve into yellow-brown or yellow-green, bruise-like macules (which are often referred to as erythema contusiformis) in approximately 2 to 8 weeks.7,8,11 Crops of new lesions may appear for 3 to 6 weeks.8 As such, older lesions may coexist with new nodules as they occur.


The diagnosis is mainly clinical. A skin biopsy or referral to a dermatologist should be considered if the diagnosis is in doubt.

Erythema nodosum should be differentiated from nodular vasculitis (erythema induratum). The latter more commonly involves the posterior aspects of the legs and is more prone to ulceration and recurrence.5 Other differential diagnoses include bruises, cellulitis, erysipelas, insect bites, cold-induced panniculitis, pancreatic panniculitis, Henoch-Schönlein purpura, nodular fat necrosis, polyarteritis nodosa, erythema elevatum diutinum, lupus erythematosus profundus, subcutaneous granuloma annulare, thrombophlebitis, subcutaneous panniculitic T-cell lymphoma, α1-antitrypsin deficiency, Wegener granulomatosis, and Churg-Strauss syndrome.2,5,6


Laboratory tests should be ordered when indicated based on the history and physical findings to identify the underlying cause of erythema nodosum. These can include, among others, complete blood count with differential, erythrocyte sedimentation rate, C-reactive protein test, throat swab culture, antistreptolysin O titer, anti-deoxyribonuclease B titers, urinalysis, pregnancy test, chest radiography, tuberculin skin test, sputum acid-fast bacilli test, stool culture for bacteria, stool ova and parasite analysis, antinuclear antibody test, appropriate serologic testing, hepatic function tests, and renal function tests.1,5,6


The nodules are self-limiting and resolve without ulceration, scarring, or atrophy, usually in 2 to 8 weeks.1 In about 15% to 30% of cases, the disease may recur.4 Complications are those that would be expected as a result of the underlying disease.2


The underlying cause should be identified and treated or removed if possible. Otherwise, treatment is mainly symptomatic. Bed rest, leg elevation, and restriction of physical activity until resolution of lesions may be beneficial and can help prevent exacerbations.2,7 Compression stockings also can be beneficial. Pain relief can be achieved with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen and indomethacin.6,7 NSAIDs, however, should be avoided in the treatment of erythema nodosum associated with inflammatory bowel disease.2 Oral potassium iodide is another treatment option.6 Intralesional or oral corticosteroids can be considered if rapid involution of the nodules is desired.2

Alexander K. C. Leung, MD, is a clinical professor of pediatrics at the University of Calgary and a pediatric consultant at the Alberta Children’s Hospital in Calgary.

Benjamin Barankin, MD, is a dermatologist and the medical director and founder of the Toronto Dermatology Centre.


1. Blake T, Manahan M, Rodins K. Erythema nodosum – a review of an uncommon panniculitis. Dermatol Online J. 2014;20(4):3.

2. Dadlani C. Erythema nodosum. Clinical Decision Support: Pediatrics. Published 2012. Accessed June 16, 2015.

3. Willan R. On Cutaneous Diseases. Vol 1. London, England: J. Johnson; 1808.

4. Papagrigoraki A, Gisondi P, Rosina P, Cannone M, Girolomoni G. Erythema nodosum: etiological factors and relapses in a retrospective cohort study. Eur J Dermatol. 2010;20(6):773-777.

5. Shojania KG. Erythema nodosum. UpToDate. Updated November 27, 2013. Accessed June 16, 2015.

6. Vigilante JA, Scribmer J. Erythema nodosum. J Spec Oper Med. 2014; 14(4):122-123.

7. Rosenbach M. Erythema nodosum. Clinical Decision Support: Dermatology. Published 2012. Accessed June 16, 2015.

8. Passarini B, Infusino SD. Erythema nodosum. G Ital Dermatol Venereol. 2013;148(4):413-417.

9. Requena L, Yus ES. Erythema nodosum. Dermatol Clin. 2008;26(4):425-438.

10. Acosta KA, Haver MC, Kelly B. Etiology and therapeutic management of erythema nodosum during pregnancy: an update. Am J Clin Dermatol. 2013;14(3):215-222.

11. Cohen PR. Combined reduced-antigen content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine-related erythema nodosum: case report and review of vaccine-associated erythema nodosum. Dermatol Ther (Heidelb). 2013;3(2):191-197.

12. Ampuero J, Rojas-Feria M, Castro-Fernández M, Romero-Gómez M. Predictive factors for erythema nodosum and pyoderma gangrenosum in inflammatory bowel disease. J Gastroenterol Hepatol. 2014;29(2):291-295.

13. Faulkes RE. Upper limb erythema nodosum: the first presentation of Crohn’s disease. Clin Case Rep. 2014;2(5):183-185.

14. Milman PJ, Goldenberg SP, Scheinfeld N, Pereira FA. Erythema nodosum and pernicious anemia. Dermatol Online J. 2013;19(7):9.