Löfgren's Syndrome

Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Löfgren's syndrome is a subtype of acute sarcoidosis involving:[1]

  • Hilar lymphadenopathy
  • Erythema nodosum
  • Joint symptoms
  • Fever

It is named after Swedish researcher, Sven Löfgren (1910-1978), who worked on sarcoidosis in the 1940s and 1950s.

Patients with Löfgren's syndrome generally have a good prognosis, are unlikely to develop chronic disease (sarcoidosis is considered chronic when symptoms last for more than three years) and most patients with Löfgren's can expect a self-limiting illness and spontaneous remission.[2]As with other forms of sarcoidosis, aetiology is unknown - the interaction of an unidentified environmental trigger and a genetically susceptible host is likely. 'A case-control etiologic study of sarcoidosis' (ACCESS) - a large US-based case-control study - failed to find any single environmental or occupational causative factor.[3, 4]

What differentiates individuals who develop Löfgren's syndrome from other forms of sarcoidosis is also unclear: the effects of different polymorphisms in the the CR2 gene on chromosome 3 are being investigated, one particular haplotype of which appears to be associated with an increased risk of Löfgren's syndrome.[5, 6]

  • Incidence varies widely around the world, with some populations (notably the Irish and Nordic people) more prone to developing Löfgren's syndrome.
  • In Europe and the USA, sarcoidosis initially presents with Löfgren's syndrome in 10% of patients.[7]
  • A study in Catalonia suggested an incidence of 0.65 per 100,000 per annum. It is much rarer in other areas of the world, such as Japan.[8]

Risk factors

  • Strong female predominance.
  • Young to middle-age (mean age of onset - 35 years).
  • There is a strong association with human leukocyte antigen (HLA)-DRB1 alleles. The association with HLA-DRB1*03 is particularly striking and is a very strong marker for a good prognosis.[9, 10]
  • Seasonality - presentation is more common in spring months (northern hemisphere).[11]

Symptoms

  • Arthralgia.
  • Cough or dyspnoea.
  • Fever or malaise.

Signs

  • Erythema nodosum.
  • Periarticular ankle inflammation/bilateral ankle arthritis.
  • Bilateral Achilles tendonitis (rare).[12]
  • Uveitis.

Presentation appears to differ between men and women, with a predominance of erythema nodosum amongst women and bilateral ankle arthritis in men.[13]

Löfgren's syndrome needs to be distinguished from other causes of:

Investigations indicating active sarcoidosis include:[1]

  • CXR (abnormalities include mediastinal lymphadenopathy or pulmonary infiltration).
  • Gallium-67 scan may be used when CXR is normal; shows increased hilar or paratracheal uptake).
  • Lung function tests (decreased forced vital capacity).
  • Serum calcium level (may be elevated).
  • Serum angiotensin-converting enzyme (may be increased).
  • Lymph node biopsy.
Always remember to perform CXR in those presenting with periarticular ankle signs.

The ankle arthritis may best be demonstrated by MRI scan.[15]

  • Once Löfgren's syndrome can be confidently diagnosed, the patient can be reassured that the condition is benign and normally self-limiting.
  • Routine biopsy is not required to confirm the diagnosis unless there are atypical features.
  • Management is supportive - eg, non-steroidal anti-inflammatory drugs for arthralgia.
  • Prednisolone may be required for more severe cases.
  • Follow-up should continue until any hilar lymphadenopathy has resolved.

Prognosis is usually very good, typically resolving within one year. In a minority, disease remains active (8%) or relapses (6%), sometimes after a long period.[1]Good prognostic markers include:

  • Normal serum angiotensin-converting enzyme levels at diagnosis.
  • Particular HLA types - being HLA-DRB1*03 negative increases the risk of non-resolving disease.[16]

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Original Author:
Dr Chloe
Current Version:
Dr Colin Tidy
Peer Reviewer:
Prof Cathy Jackson
Document ID:
2396 (v22)
Last Checked:
24 November 2014
Next Review:
23 November 2019

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. Patient Platform Limited has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.