Sex-specific manifestations of Löfgren's syndrome.
BACKGROUND
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.
Grunewald
Johan
J
Department of Medicine, Division of Respiratory Medicine, Karolinska Institutet Lung Research Laboratory L4:01, Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. johan.grunewald@ki.se
Eklund
Anders
A
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016516:CD4-CD8 Ratio; D004893:Erythema Nodosum / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008206:Lymphatic Diseases / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D013902:Radiography, Thoracic; D012129:Respiratory Function Tests; D017565:Sarcoidosis, Pulmonary / Q000175:diagnosis* / Q000235:genetics; D012737:Sex Factors; D013577:Syndrome
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen