CLUBBING

Nail clubbing, or digital clubbing, refers to soft tissue swelling of the bilateral fingertips, resulting in flattening of the angle between the nail bed and the nail. Nail clubbing is most often associated with underlying pulmonary or cardiovascular diseases and occasionally disease of the gastrointestinal tract. The mechanism of nail clubbing is thought to be secondary to clumped platelets and megakaryocytes (i.e., large bone marrow cells that produce platelets) in the peripheral vasculature that are otherwise sequestered in the lungs. These peripheral megakaryocytes produce platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), proteins that are involved in increasing vascularity (i.e., increased number of blood vessels), permeability of blood vessels, and inducing connective tissue changes. The release of PDGF and VEGF are thought to be enhanced by hypoxic conditions, such as those seen commonly in pulmonary or cardiovascular disease. 

The diagnosis of nail clubbing can be made based on medical history and physical examination, specifically through assessment of the Lovibond angle, the angle between the proximal nail fold (i.e., the base of the nail) and the nail itself. Normally, this angle is around 160 degrees; however, with nail clubbing, the angle is greater than 180 degrees. Once nail clubbing is found on physical examination, chest radiography images or a computed tomography (CT) scan can be ordered to look for underlying causes. Treatment and management of nail clubbing is focused on addressing the underlying etiologies.  

The “C” in CLUBBING represents cyanotic heart disease and cystic fibrosis. Cyanotic heart disease refers to a group of congenital heart defects that result in decreased oxygenation in the blood. Some examples of cyanotic heart disease include tetralogy of Fallot, transposition of the great arteries, truncus arteriosus, total anomalous pulmonary venous return, and hypoplastic left heart syndrome. Each of these conditions results in inadequate oxygenation of blood prior to being delivered to systemic circulation, and the baby is often cyanotic (i.e., appearing blue) and tachypneic (i.e., breathing rapidly) within the first few days of life.  

Cystic fibrosis is a genetic condition caused by a defect in the CFTR gene, resulting in abnormally thick mucus that causes damage to the respiratory and digestive systems. The mucus can obstruct the passageways of the lungs, resulting in frequent lung infections. It can also affect the pancreatic ducts, resulting in pancreatic insufficiency and fat malabsorption. In individuals with either cyanotic heart disease or cystic fibrosis, clubbing can be common and occurs due to chronically low oxygen saturation.  

The “L” in CLUBBING represents lung cancer and lung abscess. Lung cancer is one of the most common causes, contributing to nearly 90% of cases of nail clubbing; and it occurs in 5-15% of those with lung cancer. Since chronic cigarette smoking can lead to lung cancer and cause yellow pigmentation of the nail plate, a clubbed yellow nail may indicate lung cancer. Nail clubbing is more common in a specific type of lung cancer known as non-small cell lung carcinoma (NSCLC) and is also present in cases of lung adenocarcinoma. Clubbing is partly due to vascular endothelial growth factor released by the malignant tumor, which contributes to the increased capillary density and soft tissue changes.  

Lung abscess refers to a microbial infection, resulting in pus or necrotic tissue within the lung parenchyma that leads to a cavity (i.e., air-filled space) in the lungs. While most causes of clubbing are chronic and the process takes several years to develop, lung abscess is a condition where clubbing may develop sub-acutely (i.e., over months to years).  

The “I” in CLUBBING represents infective endocarditis and idiopathic pulmonary fibrosis. Infective endocarditis refers to inflammation of the endocardium and heart valves, commonly due to bacterial infection (e.g., gram-positive streptococci, staphylococci, and enterococci). Infective endocarditis usually causes a milder form of clubbing compared to the clubbing caused by cyanotic heart disease.  

Idiopathic pulmonary fibrosis is a type of interstitial lung disease and is the most common pulmonary cause of digital clubbing in developed countries. Clubbing has been reported in up to 67% of individuals with idiopathic pulmonary fibrosis, and correlation has been found between clubbing and the extent of smooth muscle proliferation in pulmonary fibrotic changes. Finger clubbing is more commonly noted among genetic males with idiopathic pulmonary fibrosis.