What are the key points for diagnosing and managing Sarcoidosis (a systemic granulomatous disease)?

From the Guidelines

Sarcoidosis should be diagnosed and managed based on organ involvement and symptom severity, with corticosteroids being first-line therapy for symptomatic disease, as recommended by the European Respiratory Journal in 2021 1.

Key Points for Diagnosing Sarcoidosis

• Sarcoidosis typically presents in young adults (20-40 years old) with bilateral hilar lymphadenopathy on chest X-ray, pulmonary infiltrates, and systemic symptoms like fatigue, weight loss, and fever.
• The pathognomonic finding is non-caseating granulomas on biopsy.
• Laboratory findings include hypercalcemia, elevated angiotensin-converting enzyme (ACE) levels, and elevated inflammatory markers.

Key Points for Managing Sarcoidosis

• Treatment depends on organ involvement and symptom severity.
• Corticosteroids are first-line therapy for symptomatic disease.
• Methotrexate, hydroxychloroquine, or TNF-alpha inhibitors may be used for refractory cases.
• The disease has a variable course, with spontaneous remission occurring in about two-thirds of patients, while others develop chronic, progressive disease with potential pulmonary fibrosis.

Treatment Algorithm

• The treatment algorithm should be based on disease progression and response to treatment, with escalation of care based on disease severity and lack of response to initial therapy, as recommended by the European Respiratory Review in 2020 1.
• The algorithm should include the use of corticosteroids, methotrexate, and biologics, such as infliximab, as well as other treatments like repository corticotrophin injection or concomitant levofloxacin, ethambutol, azithromycin, rifampin (CLEAR) therapy.

Quality of Life and Treatment

• Treatment should aim to improve quality of life (QoL) and reduce the risk of death and permanent disability, as recommended by the European Respiratory Journal in 2021 1.
• The impact of treatment on QoL should be assessed using sarcoidosis-specific QoL instruments.

From the FDA Drug Label

Symptomatic sarcoidosis The key point for managing Sarcoidosis is that prednisone can be used for symptomatic sarcoidosis 2.

• The FDA label does not provide information on diagnosing Sarcoidosis.
• The FDA label does not provide detailed information on managing Sarcoidosis beyond symptomatic treatment.

From the Research

Diagnosis of Sarcoidosis

• A diagnosis of sarcoidosis should be suspected in any young or middle-aged adult presenting with unexplained cough, shortness of breath, or constitutional symptoms, especially among blacks or Scandinavians 3
• Diagnosis relies on three criteria:
  • a compatible clinical and radiologic presentation
  • pathologic evidence of noncaseating granulomas
  • exclusion of other diseases with similar findings, such as infections or malignancy 3
• Early and accurate diagnosis of sarcoidosis remains challenging because initial presentations may vary, many patients are asymptomatic, and there is no single reliable diagnostic test 4, 3

Management of Sarcoidosis

• Treatment is aimed at recovering organ function, reducing symptom burden, and improving quality of life 5
• Corticosteroids are the cornerstone of treatment and allow disease remission, but only with a suspensive effect 6
• Immunosuppressive drugs, hydroxychloroquine, and infliximab may be useful in some patients 6, 7
• Half of the patients recover spontaneously without any treatment, while the remaining patients require treatment either at presentation or during follow-up in the presence of a disease flare 6
• The main indications of systemic treatment include ophthalmologic, neurologic, cardiovascular, renal, laryngeal involvements, severe pulmonary manifestations, lupus pernio, and marked hypercalcaemia 6

Treatment Approaches

• Initially, patients should receive prednisone or prednisolone at 0.5 to 1 mg/kg daily for 6 to 12 weeks to obtain complete remission, followed by a gradual dose reduction every 6 to 12 weeks 6
• Low-dose methotrexate and azathioprine are the most useful immunosuppressive drugs and are indicated in patients with failure or contraindication of corticosteroids or in those who need a long-term prednisone dose higher than 10 mg daily to control sarcoidosis 6, 7
• Cyclophosphamide is used in severe neurologic or heart involvement that is resistant to corticosteroids and other immunosuppressive drugs 6
• Hydroxychloroquine and chloroquine are indicated in extensive skin lesions or as corticosteroid-sparing agents 6, 7
• Infliximab can be useful in some severe sarcoidosis patients refractory to classical treatment, except for cardiac involvement 6, 7