[Inflammation and structural organ damage: chicken or egg?]

It is not inflammation but functional and/or anatomical loss of integrity of target organs that is the major determinant of morbidity in many immune-mediated inflammatory diseases (IMIDs). This structural and often irreversible tissue damage is generally considered to be a direct or indirect consequence of inflammation (through failed repair mechanisms). However, recent clinical observations in rheumatic diseases, demonstrate clearly that the postulated causal relationship between inflammation and structural damage does certainly not hold true in all IMIDs. On the contrary, potent anti-inflammatory treatments suggest an uncoupling of inflammation and damage in diseases such as ankylosing spondylitis. The author proposes a third and intriguing alternative hypothesis: inflammation and stromal remodelling are causally linked but it is the latter that drives the former. If this hypothesis is correct, we should focus our therapeutic efforts on pathways of tissue remodelling rather than on inflammation in IMIDs such as ankylosing spondylitis, but potentially also scleroderma or asthma.