Abstract
MOTIVATION: It has been debated whether patients need to have erythema nodosum to be classified as having Löfgren's syndrome. In this study, we have therefore in detail evaluated and compared a large number of patients with an acute onset of sarcoidosis and bilateral hilar lymphadenopathy (BHL), with or without erythema nodosum (EN). This study is important because it may lead to a more accurate definition of Löfgren's syndrome, and an exact phenotype of patients is crucial in modern medical research. BACKGROUND: Löfgren's syndrome is commonly regarded as a distinct clinical entity. METHODS: We have in detail evaluated a large group of patients (n = 150) with an acute onset of sarcoidosis with BHL, in most cases with fever, EN, and/or bilateral ankle arthritis or periarticular inflammation. Within this group, 87 patients had EN (EN positive), whereas 63 were without EN (EN negative), though with distinct symmetric ankle inflammation. RESULTS: EN-positive and EN-negative patients were identical in every aspect except that there were significantly more women in the EN-positive group: 58 women (67%) in the EN-positive group compared with only 17 (27%) women in the EN-negative group (p < 0.0001). In all other aspects, such as age, smoking habits, seasonal clustering of disease onset, rate of positive biopsies, chest radiography, pulmonary function, bronchoalveolar lavage cell distributions including the typically increased CD4/CD8 ratio, and clinical development of the disease, the EN-positive and EN-negative groups were close to identical. The two groups were also identically strongly associated with HLA-DRB1*0301/DQB1*0201, with 60 (69.0%) and 44 (69.8%) patients having this particular HLA type in the EN-positive and EN-negative groups, respectively. Such patients recovered to the same degree-that is, at almost 100%. CONCLUSIONS: We conclude that manifestations of Löfgren's syndrome differ between men and women, with EN found predominantly in women, whereas a marked periarticular inflammation of the ankles or ankle arthritis without EN is seen preferentially in men.