Lofgren Syndrome: Symptoms and Treatment

Introduction

An acute clinical manifestation of systemic sarcoidosis known as Lofgren syndrome includes the classic triad of fever, erythema nodosum (red bumps present under the skin usually found near the shin area), and bilateral hilar adenopathy (enlargement of the lymph nodes of pulmonary hila). However, the condition is also characterized by acute polyarthritis, but it is not always seen. Sarcoidosis is a condition involving multiple systems and is characterized by granulomas. In addition, the exact cause of sarcoidosis is unknown, and it most frequently affects the lungs and skin. Sven Lofgren, a Swedish pulmonologist, originally identified Lofgren syndrome as a distinct clinical type of sarcoidosis in 1946.

What Causes Lofgren Syndrome?

• It is unclear what causes sarcoidosis and, consequently, Lofgren syndrome.

• Genetic and environmental factors are thought to contribute to the development of Lofgren syndrome.

• It is understood that sarcoidosis is a cell-mediated immunological response to an unidentified antigen in which activated macrophages and CD4 T (helper T) cells produce cytokines that cause granulomas to develop.

• Although acute sarcoidosis is not contagious, some experts believe that certain cases may be caused by an abnormal host response to exposure to one or more infectious agents, such as Propionibacterium or Mycobacterium tuberculosis. Moreover, exposure to certain agents, like beryllium and dust, can also lead to this atypical response.

What Are the Risk Factors for Lofgren Syndrome?

• The condition is more likely to affect females than males.

• It is more common in the northern hemisphere (spring season).

• It occurs at the age of 35 or above or in middle age.

• The condition has a strong association with HLA or human leukocyte antigen-DRB1 alleles.

What Are the Clinical Features of Lofgren Syndrome?

The symptoms of Lofgren syndrome include:

• Erythema nodosum often appears symmetrical, painful, bright red subcutaneous nodules on the anterior shins.

• Bilateral hilar lymphadenopathy - bilateral enlargement of pulmonary Hila’s lymph nodes.

• Fever.

• In Lofgren syndrome, acute polyarthritis usually affects two to four joints at first and is normally symmetrical. Most frequently, it affects both ankles bilaterally before spreading to other joints in the lower limbs.

• Men are more likely to have arthritis associated with Lofgren syndrome, typically characterized by periarticular inflammation involving soft tissue and tenosynovitis and not actual arthritis. It may also be reported, although it frequently concerns ankle, elbow, wrist, and knee involvement.

• Acute uveitis (inflammation of the pigmented part of the eye).

• Iridocyclitis (inflammation of the eyes).

• The lesions of Lofgren syndrome, along with the fever, usually subside within six weeks.

• Lymphadenopathy associated with the syndrome may take about a year to resolve, but it has been reported to resolve in almost 90 percent of the cases.

Who Is Affected by Lofgren Syndrome?

• Sarcoidosis and Lofgren syndrome have a prevalence of ten to 20 per 100,000 persons. However, there are some tendencies and patterns for increased disease activity.

• Lofgren syndrome is more prevalent in women as compared to men.

• European Caucasians, particularly those of Scandinavian ancestry, are most affected by Lofgren syndrome.

• Lofgren syndrome is prevalent among young adults, and the average age of occurrence is around 37 years.

• Symptoms of Lofgren syndrome vary amongst men and women. Erythema nodosum is commonly reported in women, and arthritis is more commonly reported in men.

What Is the Histopathology of Lofgren Syndrome?

Typically, Lofgren syndrome can be diagnosed without a histologic evaluation. Pathologically, it resembles other types of sarcoidosis. It typically appears as non-caseating epithelioid granulomas, commonly known as naked granulomas (visible on biopsy), with a few surrounding lymphocytic inflammation.

How Is Lofgren Syndrome Diagnosed?

Lofgren syndrome is diagnosed in the following ways:

• History and Physical Examination: There are no definitive diagnostic criteria and tests for Lofgren syndrome. Although the typical trio of hilar lymphadenopathy, erythema nodosum, and acute polyarthritis is highly specific, not all components are always present in patients with Lofgren syndrome. A thorough patient history and detailed physical and clinical examination are necessary to evaluate and diagnose the condition.

• Chest Radiograph: All patients suspected of having Lofgren syndrome should undergo chest radiography at least once since it is crucial to determine whether they have hilar lymphadenopathy. High-resolution computed tomography (HRCT) scans can be done in cases where chest radiography is inconclusive. These scans offer more comprehensive imaging and can pinpoint lymphadenopathy's exact site and degree.

• Biopsies: Biopsies are often only performed in cases where Lofgren syndrome cannot be detected by HRCT and other imaging tests when the disease is resistant to treatment or the course of the disease deviates from the normal course. Bronchoalveolar lavage (BAL) is typically carried out with endobronchial or transbronchial biopsies.

What Is the Differential Diagnosis of Lofgren Syndrome?

Erythema nodosum, polyarthritis, and the resulting fever are symptoms of numerous diseases. Therefore, differential diagnosis of Lofgren syndrome includes

• Infections: Erythema nodosum and arthritis, which might appear as reactive arthritis or infectious arthritis, can be caused by various diseases. Streptococcus, Chlamydia, Yersinia, Salmonella, Campylobacter, and tuberculosis are a few examples of these infections.

• Drug Reactions: Erythema nodosum can occur due to drug reactions to oral contraceptives, Penicillin, sulfonamides, bromides, and iodides.

• Malignancies: Erythema nodosum can occur due to lymphoma (cancer of the lymphatic system), leukemia (blood cell cancer), and carcinomas (epithelial tissue cancer). These cancers can also induce fever but rarely cause arthritis (joint pain and inflammation).

• Inflammatory Bowel Disease: Both enteropathic arthritis, erythema nodosum, and accompanying fever are possible symptoms of ulcerative colitis and Crohn's disease (chronic inflammation of the gastrointestinal tract).

How Is Lofgren Syndrome Treated?

• Erythema nodosum, acute polyarthritis, and hilar lymphadenopathy often heal within a few weeks to months, with the majority of cases doing so within a year, making Lofgren syndrome essentially a self-limited condition.

• Usually, supportive care is used to treat Lofgren syndrome, and the condition typically resolves independently for one to two years.

• Non-steroidal anti-inflammatory drugs (NSAIDs) or Colchicine can be used to treat constitutional symptoms and arthralgias (joint pain).

• Some rare cases may require the administration of corticosteroids, which are typically quickly reduced over a few weeks to months.

• Swelling and discomfort associated with erythema nodosum can be decreased by compression stockings.

Conclusion:

Lofgren syndrome is an extremely rare condition affecting young adults. The condition is often misdiagnosed because of its common symptoms or underdiagnosed because of a lack of definitive diagnostic tests. Lofgren syndrome has an excellent prognosis. Moreover, there is about a 90 percent chance of the condition subsiding on its own within two years. However, it is best to consult a medical professional if any of the symptoms of Lofgren syndrome are experienced.