Sex-specific manifestations of Löfgren's syndrome

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.

Figure 1.

Sex difference. Relative numbers of women and men in acute sarcoidosis patients with EN (EN pos) and in patients without EN (EN neg). Light-gray hatched bars, males; dark-gray hatched bars, females.

Figure 2.

Seasonal distribution. Relative numbers of patients (EN pos and EN neg are shown separately) in relation to the month of disease onset. Squares on solid line, EN pos; triangles on dashed line, EN neg.