- Hilar lymphadenopathy
- Erythema nodosum
- Joint symptoms
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.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.
- 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.
- 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).
- Cough or dyspnoea.
- Fever or malaise.
- Erythema nodosum.
- Periarticular ankle inflammation/bilateral ankle arthritis.
- Bilateral Achilles tendonitis (rare).
Presentation appears to differ between men and women, with a predominance of erythema nodosum amongst women and bilateral ankle arthritis in men.
Löfgren's syndrome needs to be distinguished from other causes of:
- Erythema nodosum - eg, infection (Streptococcus spp., tuberculosis (TB), mycoplasma); drugs, inflammatory bowel disease, non-Hodgkin's lymphoma, Behçet's disease.
- Hilar lymphadenopathy - lymphoma, TB and lung cancer need to be excluded, particularly where lymphadenopathy is not symmetrical.
- Pyrexia of unknown origin.
Investigations indicating active sarcoidosis include:
- 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.
The ankle arthritis may best be demonstrated by MRI scan.
- 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.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.
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- Sven Halvar Löfgren; whonamedit.com
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- Darlington P, Gabrielsen A, Sorensson P, et al; HLA-alleles associated with increased risk for extra-pulmonary involvement in sarcoidosis. Tissue Antigens. 2014 Apr 83(4):267-72. doi: 10.1111/tan.12326.
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