Löfgren's syndrome: human leukocyte antigen strongly influences the disease course

Am J Respir Crit Care Med. 2009 Feb 15;179(4):307-12. doi: 10.1164/rccm.200807-1082OC. Epub 2008 Nov 7.


Rationale: 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.

Objectives: To investigate whether human leukocyte antigen type influences clinical manifestations, including the disease course in Löfgren's syndrome.

Methods: 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.

Measurements and main results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Genetic Predisposition to Disease / genetics
  • HLA-DR Antigens / blood*
  • HLA-DR Antigens / genetics*
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Middle Aged
  • Sarcoidosis / genetics
  • Sarcoidosis / immunology*
  • Syndrome
  • Young Adult


  • Biomarkers
  • HLA-DR Antigens
  • HLA-DRB1 Chains