Lofgren's Syndrome: Human Leukocyte Antigen Strongly Influences the Disease Course

• Published in: American journal of respiratory and critical care medicine 2009-02, Vol.179 (4), p.307-312
• Main Authors: Grunewald, Johan, Eklund, Anders
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Ankle; Antigens; Arthritis; Biomarkers - blood; Biopsy; Bronchoscopy; Disease Progression; Female; Fever; Flow Cytometry; Follow-Up Studies; Genetic Predisposition to Disease - genetics; HLA-DR Antigens - blood; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Inflammation; Leukocytes; Male; Middle Aged; Patients; Ratios; Sarcoidosis; Sarcoidosis - genetics; Sarcoidosis - immunology; Syndrome; Women; Young Adult
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200807-1082OC

Sarcoidosis may consist of a number of distinct disease entities, one of which could be Löfgren's syndrome. Patients with Löfgren's syndrome have an acute onset of erythema nodosum (EN) and/or periarticular inflammation or arthritis of the ankles, with bilateral hilar lymphadenopathy (and in some cases parenchymal infiltrates) and usually fever. There is a known association between HLA-DRB1*03 and Löfgren's syndrome. To investigate whether human leukocyte antigen type influences clinical manifestations, including the disease course in Löfgren's syndrome. We clinically characterized and HLA-DRB1 typed 301 patients with Löfgren's syndrome. A total of 275 of the patients were followed for more than 2 years and classified as having a nonresolving or a resolving disease. Almost every DRB1*03-positive patient had a resolving disease within 2 years, and 49% of the DRB1*03-negative patients developed a nonresolving disease. Mucosal granulomas were identified significantly more often in DRB1*03-negative patients. Among DRB1*03-negative patients who were treated with oral steroids at disease onset, 80% developed a nonresolving disease. Patients with Löfgren's syndrome have a different disease course depending on whether they are DRB1*03 positive or not. This observation has clinical implications, and by comparing DRB1*03-positive and DRB1*03-negative patients with Löfgren's syndrome, we can search for additional markers of importance for developing a resolving or a nonresolving disease, respectively.