Summary
An important nail sign of systemic disease linked with underlying pulmonary, cardiovascular, neoplastic, infectious, hepatobiliary, mediastinal, endocrine, and gastrointestinal disorders.
Digital clubbing may also occur in isolation (e.g., familial clubbing, as an autosomal-dominant trait).
Definition
Clubbing is a bulbous uniform swelling of the soft tissue of the terminal phalanx of a digit with subsequent loss of the normal angle between the nail and nail bed.
The first stage of clubbing is a periungual erythema and a softening of the nail bed; this is followed by an increase in the Lovibond angle (the angle between the proximal nail fold and the nail plate). Eventually the depth of the distal phalanx increases and the distal interphalangeal joint may become hyperextensible.[1][2]
The Schamroth window test can be used to identify or confirm clubbing. If 2 opposing fingers are held back to back against each other, a diamond-shaped space should normally appear between the nail beds and the nails of the 2 fingers. In clubbing, this space (or window) is missing. [Figure caption and citation for the preceding image starts]: Schamroth window test demonstrating a diamond-shaped window when fingers are not clubbedCreated by BMJ Knowledge Centre [Citation ends].
[Figure caption and citation for the preceding image starts]: Schamroth window test demonstrating lack of window with clubbed fingersCreated by BMJ Knowledge Centre [Citation ends].
Clubbing is usually bilateral, although unilateral clubbing does exist (e.g., axillary artery aneurysm and brachial arteriovenous malformations). It is painless unless associated with underlying conditions such as pulmonary hypertrophic osteoarthropathy. The vast majority of patients are unaware of its presence. However, an understanding of the causation and diseases associated with clubbing alerts the physician to the seriousness of this sign and the need to investigate the patient appropriately.[Figure caption and citation for the preceding image starts]: Finger clubbingFrom the collection of Dr Murlidhar Rajagopalan [Citation ends].
[Figure caption and citation for the preceding image starts]: Pachydermoperiostosis: toe clubbingFrom the collection of Dr Murlidhar Rajagopalan [Citation ends].
[Figure caption and citation for the preceding image starts]: Clubbing of nails showing loss of the classic Lovibond angle (normally ≤160° in a normal distal digit, but >180° with definitive clubbing)From the collection of Dr Murlidhar Rajagopalan [Citation ends].
Pathophysiology
Vascular endothelial growth factor (VEGF) is key.[3] This platelet-derived factor is stimulated by hypoxia and produced in diverse malignancies and conditions that affect circulation. VEGF induces vascular hyperplasia, edema, and fibroblast or osteoblast proliferation at a peripheral level in the nails. In primary pulmonary conditions such as lung cancer, this is the operative mechanism. When there is extrapulmonary shunting of blood - for example, in cyanotic heart disease - large megakaryocytic fragments gain access to the systemic circulation and affect distal sites such as the nails. Here, these fragments release growth factors, including VEGF.[1][4]
Unilateral clubbing secondary to local disorders (e.g., axillary artery aneurysm) is not due to a pulmonary circulation defect.[5] In cases of bronchogenic carcinoma, growth hormone has been implicated as a cause of clubbing. In hypertrophic osteoarthropathy, an additional unknown factor is considered necessary to produce this syndrome; cyanosis may also be required.[6][7]
Platelet derived growth factor (PDGF) may have a role.[2] Platelets release PDGF in the vasculature of the fingertips. PDGF stimulates growth, vascular permeability, and monocyte and neutrophil chemotaxis, and leads to proliferation of vascular smooth muscle cells and fibroblasts, as is seen in clubbing.[6] In addition, clubbing may be stimulated by local arteriovenous anastomoses provoked by neurocirculatory stimuli. Conditions that have chronic platelet excess (e.g., inflammatory bowel disease) result in peripheral platelet trapping and release of PDGF.[6]
Differentials
Common
- Lung cancer
- Bronchiectasis
- Lung abscess
- Empyema
- Congenital heart disease
- Infective endocarditis
- Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
Uncommon
- Cystic fibrosis
- Interstitial pulmonary fibrosis
- Sarcoidosis
- Asbestosis
- Pleural mesothelioma
- Cavitating pulmonary tuberculosis (TB)
- Pulmonary metastases
- Atrial myxoma
- Axillary artery aneurysm
- Brachial arteriovenous malformations
- Thyroid acropachy
- Acromegaly
- Severe secondary hyperparathyroidism
- Hodgkin lymphoma
- Disseminated chronic myelogenous leukemia
- Ulcerative colitis
- Crohn disease
- Primary biliary cholangitis
- Cirrhosis
- Thyroid cancer
- Thymus cancer
- Lipoid pneumonia
- Pulmonary artery sarcoma
- Ulcerative esophagitis
- Achalasia
- Celiac disease
- Tropical sprue
- Leiomyoma of the esophagus
- Familial clubbing
- Pachydermoperiostosis (primary hypertrophic osteoarthropathy)
- Secondary hypertrophic osteoarthropathy
- Palmoplantar keratoderma
- Pregnancy
- Pseudoclubbing
- Myelofibrosis
Contributors
Authors
Murlidhar Rajagopalan, MD
Senior Consultant Dermatologist and Coordinator
Apollo Hospitals
Chennai
India
Disclosures
MR declares that he has no competing interests.
Robert A. Schwartz, MD, MPH, DSc (Hon), FRCP Edin, FAAD
Professor & Head
Dermatology
Rutgers New Jersey Medical School
Newark
NJ
Disclosures
RAS declares that he has no competing interests.
Peer reviewers
Krishna Sundar, MD, FCCP
Associate Professor (Clinical)
Department of Medicine
University of Utah
Director
Pulmonary and Critical Care Research
IHC Urban South
Utah Valley Pulmonary Clinic
UT
Disclosures
KS declares that he has no competing interests.
Santhanam Lakshminarayanan, MD
Assistant Professor of Medicine
Director
Rheumatology Fellowship
University of Connecticut Health Center
Farmington
CT
Disclosures
SL declares that he has no competing interests.
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