From the Guidelines
Sarcoidosis is primarily a Type IV hypersensitivity reaction, also known as delayed-type hypersensitivity or cell-mediated hypersensitivity. This condition involves the formation of non-caseating granulomas in various organs, most commonly the lungs, lymph nodes, skin, and eyes. The pathophysiology of sarcoidosis centers around an exaggerated immune response to an unknown antigen, characterized by the accumulation of activated T lymphocytes (particularly CD4+ T cells) and macrophages. These cells release inflammatory cytokines like interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, which drive granuloma formation. Unlike Type I, II, or III hypersensitivity reactions which involve antibodies, Type IV reactions are mediated by T cells and develop over 24-72 hours after antigen exposure. The chronic nature of sarcoidosis reflects ongoing stimulation of this cell-mediated immune response, with persistent granuloma formation that can lead to tissue damage and fibrosis if left untreated.
Key Features of Sarcoidosis
- Formation of non-caseating granulomas in various organs
- Exaggerated immune response to an unknown antigen
- Accumulation of activated T lymphocytes and macrophages
- Release of inflammatory cytokines driving granuloma formation
- Mediated by T cells, developing over 24-72 hours after antigen exposure
Diagnosis and Detection
The diagnosis of sarcoidosis is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease 1. Histological features that are typical of a sarcoidosis granuloma include the presence of well-formed, concentrically arranged layers of immune cells, most prominent being the central core of macrophage aggregates and multinucleated giant cells 1.
Treatment and Management
The decision of who and when to treat an individual sarcoidosis patient depends on two major factors: risk for death or organ failure and impairment of quality of life (QoL) 1. Anti-inflammatory therapy for less severe but impaired patients may prevent progression to irreversible disease. Recent studies have identified features associated with increased risk for death from pulmonary disease, including pulmonary hypertension, reduced lung function, and pulmonary fibrosis 1.
Recent Guidelines
The European Respiratory Society (ERS) has developed new guidelines for treating sarcoidosis using a standardized methodology 1. The committee systematically reviewed treatment for pulmonary, cutaneous, cardiac, and neurologic manifestations as well as sarcoidosis-associated fatigue (SAF) and small-fibre neuropathy (SFN). Specific recommendations for each PICO question using GRADE criteria are shown in the guidelines.
From the Research
Sarcoidosis and Hypersensitivity
- Sarcoidosis is a systemic, granulomatous disease that can affect multiple organs and has a variable clinical course 2.
- The exact type of hypersensitivity involved in sarcoidosis is not explicitly stated in the provided studies.
- However, it is known that sarcoidosis is characterized by the development of non-caseating epitheloid granulomas, which are a type of immune response 3.
- Granulomatous diseases like sarcoidosis are often associated with a type of hypersensitivity reaction known as delayed-type hypersensitivity or cell-mediated immunity.
- This type of hypersensitivity involves the activation of T cells and the formation of granulomas in response to an antigen or foreign substance.
Treatment of Sarcoidosis
- The treatment of sarcoidosis typically involves the use of corticosteroids, such as prednisone, as the first-line therapy 2, 4, 5.
- For patients who are intolerant or refractory to corticosteroids, immunosuppressive drugs like methotrexate, azathioprine, and leflunomide may be used as sparing agents 2, 4, 6.
- Biologic therapies, including monoclonal anti-TNF agents like infliximab, have also been shown to be effective in the treatment of sarcoidosis, particularly in patients with severe or refractory disease 4, 6, 3.