A 35-year-old man presents with bilateral ankle pain and swelling. He has had fevers over the past 5 days. Physical examination: temperature, 38° C; pulse, 90; blood pressure, 140/70 mm Hg. Ext: Edema bilateral ankles, ankle joints tender. No other joints are involved. Lab: WBC, 6,000; polys, 4.8; mono, 0.5; lymph, 0.7.

What is the most useful diagnostic test?



C. Uric acid.

D. Chest x-ray.

E. Rheumatoid factor.

This patient has acute onset of fevers and bilateral ankle pain and swelling. The acute onset and presence of a fever makes rheumatoid arthritis unlikely. Bilateral ankle arthritis is a very unusual presentation for gout, and would be very unlikely in such a young patient unless there were other risk factors for gout. Inflammatory markers (C-reactive protein and erythrocyte sedimentation rate) will not help make a specific diagnosis.

This patient has Lofgren’s syndrome (acute presentation of sarcoidosis). A chest x-ray would be diagnostic, as the presence of bilateral hilar adenopathy along with the other symptoms would be diagnostic of Lofgren’s syndrome. The patient also has a low peripheral lymphocyte count, which is common with active sarcoidosis.

The combination of bilateral ankle swelling and inflammation is a clue to think about sarcoidosis. Juan Mañá, MD, and his colleagues reviewed the charts of 330 sarcoid patients who presented over a 20-year period.1 A total of 33 patients presented with periarticular ankle inflammation. Interestingly, the majority of these patients presented in the spring (54%). The average age of the patients was 33 years, and about 80% had stage 1 sarcoid on chest radiography (bilateral hilar adenopathy). All 24 patients who were followed up were in remission a year later.

In another study, the same investigators reported on the clinical features and course of Lofgren’s syndrome in 186 patients. Almost all the patients (93%) had erythema nodosum or periarticular ankle inflammation at presentation.2 Half of the patients presented in the spring, and the vast majority (87%) had no respiratory symptoms at the time of presentation. Most of the 133 patients (86%) who were available for follow-up (mean follow-up, 5 years) were in complete remission from sarcoid.

Johan Grunewald, MD, and Anders Eklund, MD, reported on 150 patients with Lofgren’s syndrome.3 In that study, 87 patients had erythema nodosum, and 63 had no erythema nodosum but did have symmetric ankle inflammation. There was an increase in patients presenting in the spring, about 80% had stage 1 sarcoid on chest x-ray, and the majority of the patients who presented with bilateral ankle inflammation and no erythema nodosum were men. They also found that there was a strong association with the presence of HLA-DRB1*0301/DQB1*0201 in patients who developed Lofgren’s syndrome. Resolution of disease was very common (85%) without recurrences.

There are several pearls to emphasize. Think of Lofgren’s syndrome in patients with symmetrical ankle inflammation or erythema nodosum. Order a chest x-ray to make the diagnosis; these patients usually will have no pulmonary symptoms to lead you in that direction. The prognosis is very good for these patients, with the great majority of them having full clinical resolution without recurrences.

Key pearl: Think of Lofgren’s syndrome in patients presenting with bilateral ankle inflammation.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu .


1. J Rheumatol. 1996 May;23(5):874-7 .

2. Am J Med. 1999 Sep;107(3):240-5 .

3. Am J Respir Crit Care Med. 2007 Jan 1;175(1):40-4 .