Pellagra--increased viscosity of extracellular matrix.

Pellagra is the result of increased viscosity of extracellular matrix (ECM). The skin changes in pellagra localize at sites of sun exposure or trauma because the mediators which are released cannot diffuse from the area. Edema is reported as the first clinical and microscopic change. Changes in the ECM are not directly visible. Increased viscosity of ECM in the gastrointestinal tract would decrease absorption of fluid and nutrients from the bowel resulting in diarrhea. In the tongue the excess ECM viscosity holds water producing swelling. The effect of climate and seasons relates to the increased demand for ECM repair on sunlight exposed areas. Infections increase the severity of pellagra by requiring increased tissue repair. Local infections are often unusually severe. Infections have a greater inflammatory component at sites of high ECM viscosity. Nicotinic acid reverses the neurologic and gastrointestinal changes of pellagra in 24 h. This suggests a simple rapid mode of action. Nicotinic acid plays a major role in tissue respiration which is essential for tissue repair and degradation of glycosaminoglycans. Altering ECM viscosity is a method of modulating inflammation, immunity, and normal tissue physiology.