Sarcoidosis can have multiple clinical presentations, including arthritis, bilateral hilar adenopathy, and erythema nodosum. The initial publications of Lofgren included a series of 113 patients with erythema nodosum and bilateral hilar adenopathy (Table 1
). One hundred four of these patients had fever. One hundred one patients had joint involvement. Considerable periarthritic edema was noted around the ankles. Other authors have described series of patients with acute sarcoid arthritis. Therefore, the clinical information and the authors’ perspective vary from series to series. Lofgren syndrome typically involves large joints, especially the knees and ankles, in a symmetrical and additive pattern. The ankle swelling in these patients may reflect acute arthritis, tenosynovitis, or tendonitis. Periarticular inflammation with soft tissue swelling with no direct joint involvement is considered a variant of Lofgren syndrome. Ultrasound and MRI can provide an exact anatomic location of the inflammatory process. The joint fluid, if present, is usually mildly inflammatory with a WBC in the range of 4,000 to 15,000/μL and a predominance of lymphocytes. Synovial biopsy specimens typically reveal nonspecific proliferative inflammatory changes. Noncaseating granulomas are uncommon in the acute arthritic presentation. The association between articular involvement and erythema nodosum in patients with Lofgren syndrome is not constant. Patients often have ankle involvement as an initial presentation, and then erythema nodosum appears 1 to 2 weeks later. However, Caplan et al described 19 patients in whom periarticular ankle inflammation was associated with bilateral hilar adenopathy without erythema nodosum. Pennec et al analyzed 16 patients and concluded that there was no difference between patients with and without erythema nodosum. The skin lesion in erythema nodosum is a panniculitis that presents with poorly defined very tender erythematous plaques and nodules. Biopsy specimens reveal widening of connective tissue septa secondary to edema and neutrophilic infiltration. Biopsy specimens from older plaques reveal lymphocytes, histocytes, multinucleated giant cells, and occasional eosinophils usually associated with septal fibrosis. These plaques do not contain noncaseating granulomas or areas of necrosis. Erythema nodosum is associated with the infections (including tuberculosis and fungal infections), drugs (eg, sulfonamides and oral contraceptives), inflammatory bowel disease, some malignant neoplasms, and sarcoidosis. Skin biopsy specimens obtained near inflamed joints in patients with Lofgren syndrome may reveal panniculitis, noncaseating granulomas, and/or nonspecific inflammation. The arthritis and skin lesions in this syndrome often precede hilar adenopathy by several weeks. In the series by Lofgren, hilar adenopathy developed in 104 patients after their presentation with erythema nodosum. Thirty-eight patients had paratracheal adenopathy. The chest radiographs usually do not reveal parenchymal infiltrates. Visser and coworkers identified 55 patients with acute sarcoid arthritis and compared them to 524 patients with other forms of acute arthritis. They identified four clinical criteria that helped make the diagnosis of acute sarcoid arthritis. These included symmetrical ankle arthritis, symptoms for < 2 months, age < 40 years, and erythema nodosum. The presence of at least three of these criteria had a sensitivity of 93% and a specificity of 99% (Table 2
). However, some authors have published case reports describing unusual difficulty with this diagnosis. Patients with sarcoidosis may have positive rheumatoid factor, and/or positive antinuclear antibody assays, and/or elevated uric acid levels, and these laboratory results can lead to confusion. Most patients with sarcoidosis (> 90%) have intrathoracic lymphadenopathy. Biopsies reveal noncaseating granulomas. However, similar results occur in patients with granulomatous infection and malignancy. Most patients with Lofgren syndrome have complete resolution of their symptoms, and this syndrome represents a benign acute presentation of sarcoidosis with a good prognosis. In the series of Lofgren, 102 patients (91.9%) had complete resolution of hilar adenopathy and infiltrates, if present, by 2 years. In the series of Visser et al, all patients with acute sarcoid arthritis went into clinical remission within 3 months. Treatment with nonsteroidal antiinflammatory drugs or short courses of steroids is usually satisfactory. However, some patients can have a full recurrence of the syndrome. Patients with chronic sarcoidal arthritis usually have noncaseating granulomas on synovial biopsy, often have chronic skin disease, and usually acquire this complication during the course of chronic pulmonary sarcoidosis.