Epidemiology and Etiology
Sarcoidosis is the most common idiopathic interstitial lung disease. It occurs worldwide, though it demonstrates marked geographic and racial variations. For example, in North America, the incidence among Black populations is 15 times higher than among white populations. In Europe, the disease disproportionately affects women in Ireland and Scandinavian countries.
The exact etiology of the disease remains unknown. Infectious hypotheses have been proposed, implicating L-forms of Mycobacterium tuberculosis, Chlamydia, Borrelia burgdorferi, Mycoplasma, and viruses. The mycobacterial theory is supported by the detection of mycobacterial DNA fragments in granulomas via PCR and the accumulation of $\gamma$-$\delta$ T cells, though research findings remain controversial.
Pathogenesis
The development of sarcoidosis is driven by a type IV hypersensitivity immune reaction (delayed-type hypersensitivity). The key pathogenic driver is a sharp increase in the number and proliferation of CD4+ T lymphocytes, resulting in an altered CD4/CD8 ratio (reaching up to 10:1 with a predominance of CD4+ cells).
The mechanism of granuloma formation is as follows:
- Activated CD4+ T lymphocytes produce cytokines, predominantly IFN-$\gamma$.
- Under the influence of IFN-$\gamma$, macrophages transform into epithelioid cells.
- Epithelioid cells fuse to form multinucleated giant cells.
- A typical non-caseating granuloma is established.
Concurrently, a paradoxical pattern is observed in the peripheral blood: circulating T lymphocyte counts decrease, while nonspecific stimulation of B lymphocytes leads to hypergammaglobulinemia.
Morphology of Sarcoid Granulomas
Sarcoid granulomas are classified as immune-type granulomas. Their most critical feature is the absence of caseous necrosis. The granulomas have distinct borders due to a peripheral rim of fibroblasts and collagen, giving them a characteristic 'punched-out' appearance. Furthermore, all granulomas within a given lesion are typically at the same stage of development.
Cellular components include macrophages, epithelioid cells, CD4+ T lymphocytes, fibroblasts, and Langhans-type multinucleated giant cells. Specific inclusions are frequently found in the cytoplasm of giant cells:
- Asteroid bodies (in 60% of cases) — stellate, star-shaped crystals.
- Schaumann bodies — laminated, calcified structures containing calcium and iron salts.
- Hamazaki-Wesenberg bodies — yellow-brown inclusions with lipofuscin-like properties that stain fuchsinophilic.
Respiratory System Involvement
Pulmonary changes progress through two stages: initially, a lymphocytic alveolitis develops (minimal inflammation), which subsequently transitions into granulomatous inflammation. The process frequently involves the bronchi, causing endobronchitis with a risk of luminal obstruction by granulomatous tissue.
In 2/3 of patients, vasculitis is identified, affecting branches of the pulmonary arteries and veins. These are typically granulomatous vasculitides that can eventually lead to pulmonary hypertension, cor pulmonale, and pulmonary veno-occlusive disease.
Clinical Variants and Outcomes
The disease may be asymptomatic (discovered incidentally on imaging) or present with an acute or chronic course. A distinct acute presentation is Löfgren syndrome, which occurs in 20–50% of patients and is characterized by a classic clinical triad:
- Erythema nodosum.
- Bilateral hilar lymphadenopathy.
- Polyarthralgia.
The prognosis for Löfgren syndrome is favorable, frequently resulting in spontaneous remission. Overall outcome statistics show that 65–70% of patients retain only minimal changes (mild pulmonary fibrosis), 20% develop a chronic relapsing course, and only 10% progress to severe, advanced fibrosis resulting in a 'honeycomb lung'. A rare but dangerous complication is the development of secondary aspergillosis within cavities, leading to hemoptysis.