U01.04.018 Granulomatous inflammation

Granulomatous inflammation is a pattern of chronic inflammation characterized by the formation of granulomas. It is typically induced by a persistent T-cell response to infections, immune-mediated diseases, and foreign bodies. Granulomas function to “wall off” resistant stimuli without fully eradicating or degrading them, leading to persistent inflammation, fibrosis, and potential organ damage.

Histology

Granuloma Structure:

Epithelioid Cells: Activated macrophages with abundant pink cytoplasm.
Lymphocytes: Surrounding the central area.
Multinucleated Giant Cells: Formed by the fusion of several activated macrophages.

Types of Granulomas:

Caseating Granulomas:
- Central Necrosis: Associated with infections such as tuberculosis (TB) and certain fungal infections.
Noncaseating Granulomas:
- No Central Necrosis: Associated with autoimmune diseases such as sarcoidosis and Crohn’s disease.

Mechanism of Formation:

Antigen-presenting cells (APCs) present antigens to CD4+ Th cells and secrete IL-12.
CD4+ Th cells differentiate into Th1 cells.
Th1 cells secrete IFN-γ, activating macrophages.
Activated macrophages secrete cytokines (e.g., TNF), leading to the formation of epithelioid macrophages and giant cells.

Points to Remember:

Anti-TNF Therapy: This can cause sequestering granulomas to break down, leading to disseminated disease. Always test for latent TB before starting anti-TNF therapy.
Hypercalcemia: Associated with granulomatous inflammation due to increased 1α-hydroxylase activity in activated macrophages, leading to enhanced vitamin D activity.

Etiologies

Infectious:

Bacterial:
- Mycobacteria: Tuberculosis, leprosy.
- Bartonella henselae: Cat scratch disease (stellate necrotizing granulomas).
- Listeria monocytogenes: Granulomatosis infantiseptica.
- Treponema pallidum: Secondary syphilis.
Fungal:
- Endemic Mycoses: Histoplasmosis.
Parasitic:
- Schistosomiasis.

Noninfectious:

Immune-Mediated:
- Sarcoidosis.
- Crohn Disease.
- Primary Biliary Cholangitis.
- Subacute (de Quervain/Granulomatous) Thyroiditis.
Vasculitis:
- Granulomatosis with Polyangiitis (Wegener).
- Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss).
- Giant Cell (Temporal) Arteritis.
- Takayasu Arteritis.
Foreign Bodies:
- Berylliosis.
- Talcosis.
- Hypersensitivity Pneumonitis.
Chronic Granulomatous Disease: A genetic disorder affecting the ability of phagocytes to kill certain bacteria and fungi.

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U01.04.018 Granulomatous inflammation

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