Löfgren syndrome

Overview

Löfgren syndrome is an acute form of sarcoidosis, a multisystem inflammatory disease characterized by the formation of noncaseating granulomas, clusters of immune cells in various organs, most commonly the lungs and lymph nodes. Löfgren syndrome is distinguished by a triad of features: erythema nodosum (painful red nodules on the skin), bilateral hilar lymphadenopathy (enlarged lymph nodes in the chest), and arthritis, usually in the ankles. It typically has a sudden onset and, unlike other forms of sarcoidosis, often resolves spontaneously within a few months to two years.

Causes

The exact cause of Löfgren syndrome is unknown, but it is believed to result from an exaggerated immune response to an unidentified environmental or infectious trigger in genetically predisposed individuals. Sarcoidosis, including Löfgren syndrome, is thought to involve:

• Genetic susceptibility – particularly associated with the HLA-DRB1*03 allele

• Environmental triggers – such as microbial agents or occupational exposures (e.g., inorganic dusts)

• Autoimmune dysregulation – abnormal immune response leads to granuloma formation

Löfgren syndrome is more common in young adults, particularly females, and shows a higher prevalence in Scandinavian and Northern European populations.

Symptoms

The hallmark symptoms of Löfgren syndrome usually appear suddenly and include:

• Erythema nodosum – tender, red bumps typically located on the shins

• Bilateral hilar lymphadenopathy – visible on chest X-ray, often asymptomatic but may be associated with chest discomfort or dry cough

• Arthritis or arthralgia – especially in the ankles, knees, or wrists; may cause swelling, pain, and stiffness

Other associated symptoms may include:

• Fever

• Fatigue

• Loss of appetite

• Weight loss

Not all patients will present with the complete triad, but its presence is strongly suggestive of Löfgren syndrome.

Diagnosis

Löfgren syndrome is typically diagnosed based on clinical presentation and imaging. Diagnostic steps include:

• Physical examination – confirming the presence of erythema nodosum and joint inflammation

• Chest X-ray or CT scan – showing bilateral hilar lymphadenopathy

• Blood tests – may show elevated inflammatory markers (e.g., ESR, CRP), hypercalcemia, and elevated angiotensin-converting enzyme (ACE) levels

• HLA typing – identification of HLA-DRB1*03 supports the diagnosis and suggests a favorable prognosis

• Exclusion of other causes – such as infections, lymphoma, or other granulomatous diseases

In most cases, invasive diagnostic procedures like biopsy are not necessary due to the characteristic presentation.

Treatment

Löfgren syndrome often resolves on its own without the need for aggressive treatment. However, symptomatic relief may be needed. Treatment options include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) – for joint pain and inflammation

• Corticosteroids – such as prednisone, used in cases with severe or persistent symptoms

• Rest and supportive care – during acute episodes

• Monitoring – regular follow-up to assess resolution or progression of symptoms

Immunosuppressive drugs are rarely required due to the usually self-limiting nature of the condition.

Prognosis

The prognosis of Löfgren syndrome is generally excellent. In over 80% of cases, symptoms resolve spontaneously within 6 months to 2 years without long-term complications. The presence of HLA-DRB1*03 is associated with a particularly good outcome. Chronic or progressive sarcoidosis is uncommon in patients with Löfgren syndrome. Recurrences may happen but are typically mild and manageable. Early recognition and supportive care help ensure a favorable prognosis.