Erythema Nodosum

Erythema Nodosum With Elevated Antistreptolysin O Titer

Christiaan R. de Vries, PhD

Rutgers Robert Wood Johnson Medical School,
New Brunswick, New Jersey

Srividya Naganathan, MD

K. Hovnanian Children’s Hospital at Jersey Shore
University Medical Center, Neptune, New Jersey 

A 5-year-old boy with no significant past medical history presented to the emergency department (ED) with a chief concern for bilateral lower extremity swelling and erythema of 2 days’ duration. The boy’s parents reported a history of sore throat in the boy that had resolved before the onset of the lower extremity swelling. The swelling had started on one leg and had spread to the other within 24 hours. 

The patient also had experienced fever of 38.3°C prior to arrival in the ED. His parents noted that he had been limping secondary to pain, which had resolved partially with ibuprofen. There was no history of any other medication use. 

On presentation, the patient had a temperature of 36.9°C, respiratory rate of 22 breaths/min, heart rate of 100 beats/min, blood pressure of 101/62 mm Hg, and oxygen saturation of 100% on room air. He appeared well and was in no acute distress.

Physical examination findings were significant for the presence of erythematous, indurated, nodular lesions on both shins that were tender to palpation. The remainder of physical examination findings were normal.

Pertinent laboratory test results included an elevated white blood cell count of 18,100/µL with a left shift. Rapid streptococcal antigen test results were negative, and throat culture showed scant growth of normal oropharyngeal flora. However, the antistreptolysin O (ASO) titer was elevated at 309.0 IU/mL (> 200 IU/mL is considered a positive result). Interferon-γ tuberculosis test results were negative.

(Diagnosis and discussion on next page)

The patient received a diagnosis of erythema nodosum (EN), which most likely was secondary to streptococcal pharyngitis. He was discharged home with instructions for rest, ibuprofen for symptomatic relief, and scheduled follow-up with his primary care provider.


EN is an acute panniculitis of the subcutaneous fat that presents as erythematous, tender nodules, most commonly in the pretibial region of the lower legs.1 Approximately 50% of EN cases are idiopathic.2-5 The most common identifiable cause of secondary EN in pediatric patients is streptococcal infection, which accounts for approximately 20% of cases. Infection with other pathogens, such as Mycobacterium tuberculosis, Mycoplasma pneumoniae, Francisella tularensis, Yersinia pestis and cytomegalovirus have been implicated.2-4 Connective tissue disorders, inflammatory bowel disease, malignancy, and certain drugs have been associated with this condition.2,4,6 Most cases are self-limited and can be treated symptomatically, although identification and treatment of underlying causes of secondary EN is warranted.

The case described here raises the question of whether EN with an elevated ASO titer, in the absence of confirmable streptococcal infection by rapid strep testing and throat culture, warrants treatment with antibiotics. In one study,acute rheumatic fever (ARF) was found in 3 of 29 patients with EN who presented to a pediatric rheumatology clinic in Brazil; secondary prophylaxis was initiated with penicillin G.7 However, all of these patients met the Jones criteria for the diagnosis of ARF, which was not the case in our patient.

Similarly, a case report of a 9-year-old boy reported EN as a presenting symptom of rheumatic heart disease, but the boy had signs, symptoms, and echocardiography results supporting the ARF diagnosis and, thus, the need for secondary prophylaxis with antibiotics.8 Of note, case reports have been published of adults presenting with EN and elevated ASO titers whose EN resolved rapidly after they were treated with antibiotics.9,10

In our literature review, we were unable to find definitive information on whether pediatric patients with EN and elevated ASO titers need to be treated in the setting of negative results of rapid strep tests and throat cultures for group A streptococcus. Does withholding treatment for these cases lead to sequelae of group A streptococcus-like rheumatic fever or glomerulonephritis? Further investigation of the utility of ASO titers in clinical decision-making for patients presenting with EN may be warranted.


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