Hypotheses explaining the pathogenesis of clubbing and osteoarthropathy implicate autonomic influences, arteriovenous shunting, and bloodborne substances. The precise pathophysiology is uncertain, but it is known that intrathoracic vagotomy can abolish clubbing and osteoarthropathy, as can correction of an arteriovenous shunt or removal of a pulmonary tumor. A leading hypothesis holds that disruption of normal pulmonary circulation prevents megakaryocytes from being fragmented into platelets. The intact megakaryocytes then lodge in the fingertip circulation, where fragments are activated to release platelet-derived growth factor, which promotes growth and vascular permeability.

The pathologic examination of clubbed fingers reveals increased vascularity consistent with the megakaryocyte hypothesis. In hypertrophic osteoarthropathy, the periosteum is found to be edematous, hyperemic, and infiltrated by mononuclear cells. Periosteal elevation, new bone formation, and endosteal resorption in the distal ends of long bones, metacarpals, and metatarsals are all present. Soft tissue swelling in the distal ends of the fingers and toes may lead to clubbing.

Clubbing is usually asymptomatic. Patients with hypertrophic osteoarthropathy may have pain in the wrists, ankles, hands, and feet; erythema and effusions are sometimes noted. Hypertrophic osteoarthropathy may precede clubbing or occur without it, but generally, the two appear together. Clubbing often takes place in the absence of osteoarthropathy. Either finding may develop before the clinical presentation of one of the conditions associated with it.

Idiopathic hypertrophic osteoarthropathy, sometimes referred to as pachydermoperiostosis, is a benign condition that must be distinguished from hypertrophic osteoarthropathy secondary to systemic disease. These patients show periosteal new bone formation, swelling of the joints, and thickened and furred skin in addition to clubbing. The benign syndrome can be differentiated from secondary hypertrophic osteoarthropathy by its development in adolescence, slow growth, a paucity of joint symptoms, and the absence of concurrent hepatic, bowel, or pulmonary disease.

Clubbing and hypertrophic osteoarthropathy occur in 2% to 12% of patients with lung cancer, developing with equal frequency in patients with large cell cancer, squamous cell cancer, or adenocarcinoma but rarely in the setting of small cell cancer. Clubbing alone may be more frequent, and the prevalence depends on the sensitivity of the diagnostic criteria used to designate digits as “clubbed.” A recently proposed sensitive, standardized measure identified clubbing in 37% of those with lung cancer and found no difference in prevalence among patients with squamous cell cancer, adenocarcinoma, or small cell cancer. Metastatic lung tumors are rarely responsible for such changes. In one series, 14% of patients with pleural tumors exhibited clubbing. With the decline in the incidence of chronic pulmonary infectious diseases (such as tuberculosis, lung abscess, and bronchiectasis), carcinoma of the lung has emerged as the leading cause of hypertrophic osteoarthropathy. Clubbing and osteoarthropathy are seen in patients with cyanotic congenital heart disease with right-to-left shunts, subacute bacterial endocarditis, and cystic fibrosis. Clubbing is a classic sign of chronic hypoxemia in patients with chronic obstructive lung disease. In addition, there are hereditary or idiopathic forms of clubbing and hypertrophic osteoarthropathy that have no clinical significance. Unilateral clubbing is associated with impairment of the vascular supply to the arm that occurs with aortic, subclavian, or innominate artery lesions. Clubbing may develop in jackhammer operators.