Nail clubbing
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Nail clubbing, also known as digital clubbing or clubbing, is a deformity of the finger or toe nails associated with a number of diseases, anomalies and defects, some congenital, mostly of the
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
and
lungs The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...
.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . When it occurs together with
joint effusion A joint effusion is the presence of increased intra-articular fluid. It may affect any joint. Commonly it involves the knee (see knee effusion). Diagnostic approach The approach to diagnosis depends on the joint involved. While aspiration ...
s, joint pains, and abnormal skin and bone growth it is known as
hypertrophic osteoarthropathy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component Cell (biology), cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Al ...
. Clubbing is associated with
lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
, lung infections,
interstitial lung disease Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium (the tissue) and space around the alveoli (air sacs) of the lungs. It concerns alveolar epithelium, pulm ...
,
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
, or
cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
. Clubbing may also run in families, and occur unassociated with other medical problems. Clubbing has been recognized as a sign of disease since the time of
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
.


Causes

Clubbing is associated with * Lung disease: **
Lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
**
Interstitial lung disease Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium (the tissue) and space around the alveoli (air sacs) of the lungs. It concerns alveolar epithelium, pulm ...
most commonly
idiopathic pulmonary fibrosis Idiopathic pulmonary fibrosis (IPF) synonymous with cryptogenic fibrosing alveolitis is a rare, progressive illness of the respiratory system, characterized by the thickening and stiffening of lung tissue, associated with the formation of scar ...
** Complicated
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
** Suppurative lung disease:
lung abscess Lung abscess is a type of liquefactive necrosis of the lung tissue and formation of cavities (more than 2 cm) containing necrotic debris or fluid caused by microbial infection. This pus-filled cavity is often caused by aspiration, which m ...
, empyema,
bronchiectasis Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...
,
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
**
Mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The area most commonly affected is the lining of the lungs and chest wall. Less commonly the lini ...
of the pleura **
Sarcoidosis Sarcoidosis (; also known as Besnier–Boeck–Schaumann disease) is a disease involving abnormal collections of White blood cell, inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph n ...
* Heart disease: ** Any disease featuring chronic hypoxia **
Cyanotic heart defect Cyanosis is the change of tissue color to a bluish-purple hue, as a result of decrease in the amount of oxygen bound to the hemoglobin in the red blood cells of the capillary bed. Cyanosis is apparent usually in the body tissues covered wit ...
(most common cardiac cause) **
Infective endocarditis Infective endocarditis is an infection of the inner surface of the heart (endocardium), usually the heart valve, valves. Signs and symptoms may include fever, petechia, small areas of bleeding into the skin, heart murmur, feeling tired, and anem ...
**
Atrial myxoma A myxoma is a rare benign tumor of the heart. Myxomata are the most common primary cardiac tumor in adults, and are most commonly found within the left atrium near the valve of the fossa ovalis. Myxoma may also develop in the other heart chambers. ...
(benign tumor) ** Arteriovenous fistula or malformation * Gastrointestinal and hepatobiliary: **
Malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...
**
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
and
ulcerative colitis Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD), with the other type being Crohn's disease. It is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary sympto ...
**
Cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
, especially in
primary biliary cholangitis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to buil ...
** Hepatopulmonary syndrome, a complication of cirrhosis * Others: **
Graves' disease Graves' disease, also known as toxic diffuse goiter or Basedow's disease, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyro ...
(autoimmune hyperthyroidism) – in this case it is known as ''thyroid acropachy'' ** Familial and hereditary clubbing and "pseudoclubbing" (people of African descent often have what appears to be clubbing) ** Vascular anomalies of the affected arm such as an axillary artery aneurysm (in unilateral clubbing) ** Primary hypertrophic osteoarthropathy Nail clubbing is not specific to
chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...
(COPD). Therefore, in patients with COPD and significant degrees of clubbing, a search for signs of bronchogenic carcinoma (or other causes of clubbing) might still be indicated. A congenital form has also been recognized.


Hypertrophic pulmonary osteoarthropathy

A special form of clubbing is hypertrophic pulmonary osteoarthropathy (HPOA), known in continental Europe as Pierre Marie-Bamberger syndrome. This is the combination of clubbing and thickening of
periosteum The periosteum is a membrane that covers the outer surface of all bones, except at the articular surfaces (i.e. the parts within a joint space) of long bones. (At the joints of long bones the bone's outer surface is lined with "articular cartila ...
(connective tissue lining of the bones) and synovium (lining of joints), and is often initially diagnosed as
arthritis Arthritis is a general medical term used to describe a disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, Joint effusion, swelling, and decreased range of motion of ...
. It is commonly associated with lung cancer.


Primary hypertrophic osteoarthropathy

Primary hypertrophic osteoarthropathy is HPOA without signs of pulmonary disease. This form has a hereditary component, although subtle cardiac abnormalities can occasionally be found. It is known eponymously as the Touraine–Solente–Golé syndrome. This condition has been linked to mutations in the gene on the fourth chromosome (4q33-q34) coding for the enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD); this leads to decreased breakdown of
prostaglandin E2 Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnanc ...
and elevated levels of this substance.


Pathogenesis

The exact cause for sporadic clubbing is unknown. Theories as to its cause include: *
Vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...
(i.e., distended blood vessels). * Secretion of
growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...
s (e.g.,
platelet-derived growth factor Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing bloo ...
and
hepatocyte growth factor Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts ...
) from the lungs. * Overproduction of prostaglandin E2 by other tissues. * Increased entry of
megakaryocyte A megakaryocyte () is a large bone marrow cell with a lobation, lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal blood coagulation, clotting. In humans, megakaryocytes usually account for 1 out of 10,00 ...
s into the systemic circulation. Under normal circumstances in healthy individuals, megakaryocytes that arise from the bone marrow are trapped in the pulmonary capillary bed and broken down before they enter the systemic circulation. It is thought that in disorders where there is right-to-left shunting or lung malignancy, the megakaryocytes can bypass the breakdown within the pulmonary circulation and enter the systemic circulation. They are then trapped within the capillary beds within the extremities, such as the digits, and release
platelet-derived growth factor Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing bloo ...
(PDGF) and
vascular endothelial growth factor Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...
(VEGF). PDGF and VEGF have growth promoting properties and cause connective tissue hypertrophy and capillary permeability.


Diagnosis

When clubbing is observed, pseudoclubbing should be excluded before making the diagnosis. Associated conditions may be identified by taking a detailed
medical history The medical history, case history, or anamnesis (from Greek: ἀνά, ''aná'', "open", and μνήσις, ''mnesis'', "memory") of a patient is a set of information the physicians collect over medical interviews. It involves the patient, and ev ...
—particular attention is paid to lung, heart, and gastrointestinal conditions—and conducting a thorough
clinical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition A disease is a particular abnormal co ...
, which may disclose associated features relevant to the underlying diagnosis. Additional studies such as a
chest X-ray A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...
and a chest CT-scan may reveal otherwise asymptomatic cardiopulmonary disease.


Stages

Clubbing is present in one of five stages: * No visible clubbing – Fluctuation (increased ballotability) and softening of the nail bed only. No visible changes of nails. * Mild clubbing – Loss of the normal <165° angle (Lovibond angle) between the nailbed and the fold (cuticula). Schamroth's window (see image) is obliterated. Clubbing is not obvious at a glance. * Moderate clubbing – Increased convexity of the nail fold. Clubbing is apparent at a glance. * Gross clubbing – Thickening of the whole
distal Standard anatomical terms of location are used to describe unambiguously the anatomy of humans and other animals. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position provi ...
(end part of the) finger (resembling a drumstick) *
Hypertrophic osteoarthropathy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component Cell (biology), cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Al ...
– Shiny aspect and
striation Striations means a series of ridges, furrows or linear marks, and is used in several ways: * Glacial striation * Striation (fatigue), in material * Striation (geology), a ''striation'' as a result of a geological fault * Striation Valley, in A ...
of the nail and skin Schamroth's sign or Schamroth's window test (originally demonstrated by South African cardiologist Leo Schamroth on himself) is a popular test for clubbing. When the distal
phalanges The phalanges (: phalanx ) are digit (anatomy), digital bones in the hands and foot, feet of most vertebrates. In primates, the Thumb, thumbs and Hallux, big toes have two phalanges while the other Digit (anatomy), digits have three phalanges. ...
(bones nearest the fingertips) of corresponding fingers of opposite hands are directly opposed (place fingernails of same finger on opposite hands against each other, nail to nail), a small diamond-shaped "window" is normally apparent between the nailbeds. If this window is obliterated, the test is positive and clubbing is present. File:Clubbing of fingers.jpg, Severe clubbing Clubbing2.JPG, Front view Clubbing1.JPG, Side views CongenitalHeartCase-133.jpg, Cyanotic nail beds


Epidemiology

The exact frequency of clubbing in the population is not known. A 2008 study found clubbing in 1%, or 15 patients, of 1511 patients admitted to a department of
internal medicine Internal medicine, also known as general medicine in Commonwealth nations, is a medical specialty for medical doctors focused on the prevention, diagnosis, and treatment of diseases in adults. Its namesake stems from "treatment of diseases of ...
in
Belgium Belgium, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...
. Of these, 40%, or 6 patients, turned out to have significant underlying disease of various causes, while 60%, or 9 patients, had no medical problems on further investigations and remained well over the subsequent year.


History

At least since the time of
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
, clubbing has been recognized as a sign of disease. The phenomenon has been called "Hippocratic fingers". The Dutch painter
Dick Ket Dick Ket (October 10, 1902 – September 15, 1940) was a Dutch painter noted for his still lifes and self-portraits in a style he referred to as New Realism. Biography Born in Den Helder, Ket spent his childhood in Hoorn and then Ede, Nether ...
had nail clubbing as is seen from his paintings. He had an underlying disease, probably dextrocardia.(in Dutch
Dick Ket, een schilder en zijn ziekte
W.H.D. de Haas, Nederlands Tijdschrift voor Geneeskunde, 1984


See also

* Clubbed thumb (unrelated congenital deformity)


References

{{Respiratory system symptoms and signs Conditions of the skin appendages Symptoms and signs: musculoskeletal system