Crystallopathy

Lore & Background

Crystallopathies can be associated with three main kinds of crystalline structures: amorphous nano-scale solid particles, crystalline micro-scale solid particles, and polycrystalline larger solid structures. They can be composed of various minerals, metabolites, proteins, and microparticles. Crystal formation can happen anywhere in the body, with well-known places being excretory organs like the biliary and urinary tracts, as well as intracellular and extracellular spaces of tissues, such as within the arterial wall in atherosclerosis. Mechanical obstruction by mineral stones causes conditions like nephrolithiasis, urolithiasis, cholecystolithiasis, and sialolithiasis, while acute inflammation caused by crystals in joints causes gout and pseudogout.

Reader's Guide

Crystallopathy is significant as a unifying concept for a range of diseases linked by the common mechanism of crystal formation and aggregation. Local supersaturation is a common trigger, and crystals can self-perpetuate. The main pathological mechanisms are acute necroinflammation, chronic tissue remodelling, and mechanical obstruction. Necroinflammation involves cytotoxicity and cell death via necroptosis, ferroptosis, and apoptosis, followed by release of alarmins and activation of inflammatory pathways. Macrophages attempt to remove crystals via phagocytosis, but if digestion fails, they undergo autophagy, form foam cells and giant cells, or perform frustrated phagocytosis. Chronic tissue remodelling can occur when crystals are shielded by compartmentalization or molecular coating, or when inflammatory responses are suppressed. Potential interventions include dissolving crystals, modifying inflammatory pathways with IL-1a and IL-1b antagonists or NLRP3-antagonists, and for protein-based crystallopathy, using pharmacologic chaperones or protein stabilizing small molecules.

Did You Know?

• Crystals can cause acute necroinflammation via cytotoxicity, including actin depolymerization, free radical synthesis, and activation of NLRP3 inflammasomes.
• Potential treatments include crystal dissolvents like cyclodextrin, IL-1a and IL-1b antagonists, NLRP3-antagonists, and blockers of ferroptosis and necroptosis.