Pulmonary sarcoidosis

Epidemiology and etiology

Sarcoidosis is the most common disease among interstitial lung diseases of unknown etiology. It occurs universally, but has pronounced geographical and racial features. For example, in North America, the incidence among the Black population is 15 times higher than among the white population. In Europe, the disease affects women extremely frequently in Ireland and Scandinavian countries.

The exact etiology of the disease is unknown. There are hypotheses regarding an infectious nature: the proposed role of 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 by PCR and the accumulation of $\gamma$-$\delta$ T cells, but study results remain contradictory.

Pathogenesis

The development of sarcoidosis is based on a type IV hypersensitivity immune reaction (delayed-type hypersensitivity). The key link in the pathogenesis is a sharp increase in the number and proliferation of CD4+ T lymphocytes. At the same time, the CD4/CD8 ratio changes (reaching 1:10 against the background of CD4+ growth).

The mechanism of granuloma formation is as follows:

1. Activated CD4+ T lymphocytes produce cytokines, primarily IFN-$\gamma$.
2. Under the action of IFN-$\gamma$, macrophages transform into epithelioid cells.
3. Epithelioid cells fuse to form multinucleated giant cells.
4. A typical non-caseating granuloma is formed.

In parallel, a paradoxical picture is observed in the blood: the level of circulating T lymphocytes decreases, and nonspecific stimulation of B lymphocytes leads to hypergammaglobulinemia.

Morphology of sarcoid granulomas

Sarcoid granulomas belong to granulomas of the immune type. Their most important feature is the absence of caseous necrosis. The granulomas have clear borders due to the peripheral arrangement of fibroblasts and collagen, which gives them a characteristic "punched-out" appearance. In addition, all granulomas in the lesion are usually at the same stage of development.

The cellular composition includes macrophages, epithelioid cells, CD4+ T lymphocytes, fibroblasts, and Langhans-type multinucleated giant cells. Specific inclusions are often found in the cytoplasm of giant cells:

• Asteroid bodies (in 60% of cases) — star-shaped crystals.
• Schaumann bodies — laminated calcified structures with calcium and iron salts.
• Hamazaki-Wesenberg bodies — yellow-brown inclusions possessing lipofuscin properties and staining fuchsinophilically.

Respiratory system involvement

Changes in the lungs go through two stages: lymphocytic alveolitis develops first (minimal inflammation), which then transitions into granulomatous inflammation. The process often affects the bronchi, causing endobronchitis with the risk of lumen obstruction by granulomatous tissue.

In 2/3 of patients, vasculitis is detected with involvement of branches of the pulmonary artery and veins. Usually, these are granulomatous vasculitides, which in the future can lead to pulmonary hypertension, the formation of cor pulmonale, and veno-occlusive disease.

Clinical variants and outcomes

The disease can be asymptomatic (detected incidentally during imaging studies) or have an acute/chronic course. A special variant of the acute course is Löfgren syndrome (Löfgren syndrome), which occurs in 20–50% of patients. It is characterized by a clinical triad:

1. Erythema nodosum.
2. Bilateral hilar lymphadenopathy.
3. Polyarthralgia.

The prognosis for Löfgren syndrome is good, and spontaneous remission often occurs. In general, according to outcome statistics: in 65–70% of patients, only minimal changes remain (insignificant pneumosclerosis), and in 20%, the disease acquires a chronic recurrent course. Only in 10% of cases does severe progressive fibrosis develop with the formation of a "honeycomb lung". A rare but dangerous complication is the addition of aspergillosis with the formation of cavities and hemoptysis.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Necrotizing sarcoid granulomatosis: detailed morphology and differences from classical sarcoidosis.
• Mechanisms of development of pulmonary hypertension and chronic cor pulmonale against the background of sarcoid vasculitis.
• The role of CD4+ T lymphocytes and the cytokine profile (IL-1, IL-12, TNF-α) in granuloma formation.
• Extrapulmonary manifestations of sarcoidosis: involvement of the skin, liver, spleen, heart, and eyes.
• Differential diagnosis of sarcoidosis with other interstitial lung diseases.

Other topics in the "Lung Diseases" section

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