Nail clubbing is one of the first things we look for when examining patients, but just like C-reactive protein in a blood test, it is a non specific sign of disease that often won’t help narrow your differential. To name just a few, it is associated with forms of heart, lung, gastrointestinal, and thyroid disease. But what causes clubbing? The most widely accepted theory is the ‘Platelet Theory’.
Megakaryocytes are large bone marrow derived cells released into the circulation that give rise to platelets but also a series of growth factors. A significant proportion of megakaryocytes reside in the lungs but during inflammation, megakaryocytes migrate from the lungs to the peripheries and become trapped in nail bed capillaries where they deposit their growth factors such as PDGF and VEGF. This leads to connective tissue proliferation and the characteristic thickening of the distal phalanx, increased nail curvature, and reduction of the angle between the nail and the cuticle.
What about non inflammatory disease? In congenital heart disease, a right to left shunt will cause megakaryocytes to bypass the pulmonary circulation into the systemic circulation where they will also be trapped in capillaries in the nail beds.