Lofgren's syndrome

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

• Hilar lymphadenopathy
• Erythema nodosum
• Joint symptoms
• Fever

It is named after Swedish researcher, Sven Löfgren (1910-1978), who worked on sarcoidosis in the 1940 and 50s.¹

Patients with Löfgren's 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. ACCESS (a large US-based case-control study) failed to find any single environmental or occupational causative factor.^2,3 What differentiates individuals who develop Löfgren's 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.^4,5

Incidence varies widely around the world, with some populations (notably the Irish and Nordic people) more prone to developing Löfgren's syndrome. A study in Catalonia suggested an incidence of 0.65 per 100,000 per annum.⁶ It is much rarer in other areas of the world, such as Japan.⁷

Risk factors⁸

• Strong female predominance (85%)
• Young to middle-age (mean age of onset - 35 years)
• Seasonality⁹ - presentation is more common in spring months (northern hemisphere)

Symptoms

• Arthralgia
• Cough or dyspnoea
• Fever or malaise

Signs

• Erythema nodosum
• Periarticular ankle inflammation/bilateral ankle arthritis¹⁰
• Bilateral Achilles tendonitis (rare)¹¹
• Uveitis

Presentation appears to differ between men and women with a predominance of erythema nodosum amongst women and bilateral ankle arthritis in men.¹²

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

• Erythema nodosum e.g. infection (Streptococcus, TB, mycoplasma), drugs, inflammatory bowel disease, Non Hodgkin lymphoma, Behcets disease
• Hilar lymphadenopathy - lymphoma, tuberculosis and lung cancer need to be excluded, particularly where lymphadenopathy is not symmetrical
• Arthritis
• Pyrexia of unknown origin

Investigations indicating active sarcoidosis include:⁸

• 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 or ACE (may be increased)
• Lymph node biopsy

• 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 e.g. NSAID for arthralgia.
• Follow-up should continue until any hilar lymphadenopathy has resolved.

Prognosis is usually very good, typically resolving within 6 months to 2 years. In a minority, disease remains active (8%) or relapses (6%), sometimes after a long period. Good prognostic markers include:

• Normal serum ACE levels at diagnosis
• Particular HLA types (e.g. HLA-DRB1*0301)¹³