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Symptoms: Joint Aches, Painful BumpsDiagnosisErythema Nodosum

Wiler, Jennifer L. MD, MBA

doi: 10.1097/
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Dr. Wiler is the assistant chief of clinical operations in the department of emergency medicine at Washington University in St. Louis.



A 49-year-old man presents to the emergency department complaining of joint aches and painful bumps on his legs for the past week. He has had subjective fevers, but denies any past medical conditions, intravenous drug use, foreign travel, trauma, cough, or shortness of breath.



What is the diagnosis, and how would you confirm it? What causes this condition? See p. 27.

Erythema nodosum is an acute inflammation of fat cells under the skin resulting in tender erythematous or violet subcutaneous nodules that usually develop in the pretibial location. Erythema nodosum was originally described in 1798 by the English dermatologist Robert Willan, MD, in his monograph on erythemas. (On Cutaneous Diseases, [1798, Vol 1.] London: J. Johnson, St. Paul's Church-Yard.)

Erythema nodosum is thought to be a delayed hypersensitivity reaction in the subcutaneous tissue (panniculitis) to antigens, which are idiopathic or associated with a variety of systemic diseases or drug therapies. The exact pathophysiological mechanism is still unclear, but erythema nodosum typically develops three to six weeks after an inciting event or illness.

The peak incidence of erythema nodosum occurs in patients between 20 and 30, affecting women three to six times more than men. (Cutis 1978;21:806.) The exact national and worldwide prevalence is not known, but one English study found the prevalence of erythema nodosum to be 2.4 per 1000 population per year. (Br J Dermatol 1959;71:139.)

The most common cause of erythema nodosum in children is streptococcal infection and in adults streptococcal infection and sarcoidosis. Many other etiologies have been implicated including but not limited to tuberculosis, Yersinia enterocolitica, Mycoplasma pneumoniae, lymphogranuloma venereum, Salmonella, Campylobacter, coccidioidomycosis, histoplasmosis, blastomycosis, Epstein-Barr virus, psittacosis, cancer, medications (sulfonamides, gold, sulfonylureas, oral contraceptive pills, omeprazole, hepatitis B vaccine, isotretinoin, leukotriene receptor antagonists, Levaquin), leprosy, HIV, dental infection, syphilis, cat scratch disease, ulcerative colitis, Crohn's disease, Hodgkin's disease, lymphoma, acute myelogenous leukemia, Behçet disease, pancreatitis, Whipple's disease, lupus and other connective tissue diseases, and pregnancy. (Semin Cutan Med Surg 2007;26[2]:114.) In about 30 percent to 50 percent of cases, the cause of erythema nodosum is unknown. (Scand J Infect Dis 2004;36[6–7]:424.)

Patients with erythema nodosum may present with flu-like symptoms including arthralgias, fever, abdominal pain, headache, cough, and malaise. Arthralgia occurs in more than 50 percent of patients, and begins during the eruptive phase or can precede the eruption by two to four weeks. In the majority of cases, patients present with sudden onset of symmetric, tender, warm, shiny, erythematous nodules with ill-defined borders 1 cm to 5 cm in diameter on the shins, but lesions have been known to appear on the thighs, arms, trunk, face, and neck. Nodules are usually palpable deep below the skin surface.

As the nodules resolve, they become violaceous, then brownish/yellow and green much like a resolving bruise. The lesions eventually self-resolve within one to eight weeks without ulceration or scarring. New lesions can appear for three to six weeks. Recurrences are rare. In children, the duration of symptoms is much briefer. (Dermatology Online Journal;

Erythema nodosum is a clinical diagnosis confirmed by biopsy for atypical presentations. The classic features of erythema nodosum on histopathology include a septal panniculitis with slight superficial and deep perivascular inflammatory lymphocytic infiltration. The reason the anterior aspects of the legs are so susceptible to the development of erythema nodosum lesions is unknown. Some authors deduce that there is no other skin surface where the combination of a relatively sparse arterial supply, a vascular system subject to routine gravitational effects and cooling, and poor lymphatic drainage in a relatively muscle-poor environment exists, which may favor erythema nodosum development on the shins. (Semin Cutan Med Surg 2007;26[2):114.)

There is no serum test diagnostic for erythema nodosum, but the serum erythrocyte sedimentation rate may be significantly elevated. In children, the elevation of that rate correlates significantly with the number of cutaneous lesions. (J Am Acad Dermatol 2001;44:17.) Emergency department studies should be directed at identifying the underlying etiology, if one exists. Studies to consider include but are not limited to complete blood count and differential, liver function tests, serum urea nitrogen and creatinine, Antistreptolysin-O titer (ASO), chest radiograph (to identify hilar adenopathy/pulmonary sarcoidosis, tuberculosis, or fungal infection), urinalysis, throat culture (for group A beta-hemolytic streptococcal infection), stool studies (if patient has gastrointestinal complaints), blood cultures, and tuberculin skin test. In patients with erythema nodosum secondary to streptococcal infection, at the time of cutaneous eruption, routine throat cultures will be negative but ASO titers will be elevated. (Semin Cutan Med Surg 2007;26[2]:114.)



The differential diagnosis in erythema nodosum includes erysipelas, erythema induratum (nodular vasculitis/Bazin disease), Weber-Christian panniculitis (relapsing febrile nodular panniculitis), insect bite, urticaria, superficial migratory thrombophlebitis, subcutaneous infections, and cutaneous vasculitides. Treatment should be directed at treating the underlying etiology. In general, complete resolution of nodules typically occurs by four to six weeks. Symptoms can be treated with bed rest, leg elevation, compressive bandages, cool dressings, and nonsteroidal anti-inflammatory agents. (Wolff K, et al. [2005.] Section 7: Miscellaneous Inflammatory Disorders, Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology, 5th ed., New York, NY: McGraw-Hill Professional.)

Oral potassium iodide is an option for persistent lesions (400 mg to 900 mg daily or a saturated solution of potassium iodide, two to 10 drops in water or orange juice three times per day) has been reported to be useful. (Arch Dermatol 1981;117:29.) The mechanism of action of potassium iodide in erythema nodosum is unknown, but a theoretical mechanism involves the stimulation of heparin release from mast cells. These solutions have been reported to cause hypothyroidism and are contraindicated in pregnancy because iodine can cause a congenital goiter. It is best to let the dermatologist decide which patients are appropriate candidates for this therapy.

Glucocorticoids are rarely indicated for idiopathic erythema nodosum. An underlying infection should be ruled out before steroids are prescribed. Reports of successful treatment of erythema nodosum lesions with colchicine, 0.6 to 1.2 mg twice a day and hydroxychloroquine 200 mg twice a day have been reported (Semin Cutan Med Surg 2007;26[2]:114), but should be given in consultation with a dermatologist.

Complications of erythema nodosum are uncommon. Disposition depends on the underlying etiology and the patient's condition. Consultations with dermatology and internal medicine should be considered. The patient presented here was found to have pulmonary sarcoidosis during his inpatient evaluation.

© 2007 Lippincott Williams & Wilkins, Inc.