Patient Presentation
A healthy 33-year-old man with a long history of fingernail changes was referred by his primary care physician to the nail clinic for a cosmetic consultation and, if indicated, a nail biopsy. The patient denied any active chest pain, diaphoresis, pulmonary or musculoskeletal complaints. The patient denied a history of smoking. He also stated that his uncle had similar fingernail changes, also without any associated lung pathologies. Aside from the fingernail changes, the rest of the physical examination was essentially normal. No lymphadenopathy was noted, and the CBC, chemistry panel and fasting glucose levels were normal.
What’s Your Diagnosis?
Diagnosis: Primary Clubbing
First described by Hippocrates more than 2,400 years ago, the term “clubbing” was used to depict an enlargement of the distal segments of the upper and lower extremities. In 1911, Von Eiselsberg reported the first clinical case of congenital familial clubbing, expressing his conviction that clubbing was not merely a patho-gnomonic sign of an underlying visceral disease, but also a hereditary trait.1
Clubbing is classified as either primary or secondary. Primary processes are hereditary or idiopathic in nature, whereas secondary processes are associated with a variety of pulmonary and non-pulmonary diseases.
Hypertrophic osteoarthropathy, pachydermoperiostosis, familial clubbing, and idiopathic clubbing constitute the major primary forms of digital clubbing.
Hypertrophic osteoarthropathy (HOA) is characterized by periostosis of long bones, joint pain, clubbing, and occurs in approximately 5% of patients with bronchogenic carcinoma and 50% of patients with pleural mesothelioma.2
Pachydermoperiostosis (PDP), also known as primary HOA, is a rare autosomal dominant disorder with incomplete penetrance and variable expression that presents in otherwise healthy children as clubbing, periostosis, and skin manifestations, including thickening of the skin of the face and scalp, coarsening of facial features, hyperhidrosis, and seborrhea with an unknown incidence.
Incomplete forms of primary HOA may present as isolated finger clubbing, periostosis, or pachydermia.3 What was once called familial clubbing in the literature was most likely an incomplete form of primary HOA.4
Pulmonary causes of secondary clubbing include lung cancers, such as non-small cell carcinoma in particular, benign mesothelioma, such as solitary fibrous tumors of the pleura, lung abscesses, bronchiectasis, and cystic fibrosis, while non-pulmonary causes involve neoplastic, cardiac, gastrointestinal, infectious, endocrine, and multisystem diseases.5 In particular, pulmonary neoplasms, such as non-small cell carcinoma, demonstrate strong correlations with this syndrome.6
Clinical Features
Finger clubbing is often difficult to establish solely upon a subjective examination, as the profile angle or distal phalangeal-to-interphalangeal depth ratio are needed to confirm this finding.
The profile angle, hyponychial angle, and phalangeal depth ratio can be quantitatively utilized: Individuals who do not have clubbing do not exceed 176 degrees, 192 degrees, and 1.0, respectively.7 Furthermore, microscopic imaging studies may reveal hypervascularization of the distal digits. As a result, both a detailed history and physical examination should be followed with appropriate laboratory studies.8 According to Sridhar, clubbing can be viewed in five basic stages.6 (See Table.)
Pathogenesis
Although clubbing is common, the exact mechanism remains unclear. Circulating vasodilators in association with cyanotic congenital heart disease, hypoxia, genetic predisposition, or platelet-derived growth factor release can all be attributed to this condition.9 Physiologically, it appears that the vasodilatation within the fingertip vessels increases the hydrostatic pressure in the capillaries, promoting the movement of fluid into the interstitial tissue and resulting in soft-tissue enlargement.
Differential Diagnosis
Clubbing is often an indication of an underlying disease, particularly that of a cardiovascular or pulmonary origin.
Idiopathic pulmonary fibrosis is one of the most common causes of digital clubbing, along with chronic lung infections and persistent interstitial lung diseases.10
However, clubbing is considered atypical in chronic obstructive pulmonary disease (COPD) or asthma, and if it is indeed found in a patient with COPD, an underlying malignancy should be suspected. It is also important to recognize that clubbing is usually accompanied by cyanosis in patients with pulmonary disease.
Hepatocyte growth factor (HGF) is considered a potential stimulator of clubbing.11 Furthermore, higher HGF levels were found in patients with lung cancer who exhibited enlargement of their distal segments. A separate study conducted by Hojo et al found much higher levels of HGF in patients with idiopathic pulmonary fibrosis, suggesting that this growth factor may play a duel role in both the progression of clubbing and the pathogenesis of pulmonary fibrosis.12
Pain is prominent in clubbing associated with HOA. Hypertrophic osteoarthropathy develops as result of subperiosteal formation in the distal long bones, and the proliferation of connective tissue and periosteum. It is attributed to stimulation by platelet derived growth factor (PDGF). The aggregation of platelets in the fingers, which releases PDGF, is the result of a variety of mechanisms.
Clubbing may also be seen specifically in patients with cyanotic congenital heart disease, infective endocarditis, cirrhosis of the liver, and inflammatory bowel disease, such as Crohn’s or ulcerative colitis, and presents without cyanosis. In a study conducted by Dutta, clubbing was found to be most common in patients with chronic liver disease.13
Management
There is no specific treatment for clubbing, but treatment of the underlying malignancy may decrease its incidence and reverse its effects if corrected in time. If significant changes have occurred within the tissues, such as increased collagen deposition, reversal is unlikely. Palliative measures may also be taken into consideration when treating symptoms such as pain.
In a patient with non-small cell bronchial carcinoma, an upper right lobectomy resulted in the regression of the finger clubbing.14
However, this surgical approach is not as effective when treating clubbing itself. Studies have shown that such a procedure produces an inadequate reduction of finger clubbing, and also showed a re-enlarging of the finger, with the nail matrix producing new tissue.15
Summary
Clubbing is associated with a wide array of pathological entities, and may be either primary (hereditary or idiopathic) or secondary in nature. Clubbing is usually visually identifiable and confirmed by the profile angle or distal phalangeal-to-interphalangeal depth ratio. Since clubbing usually presents with an underlying disease, it is important to perform a comprehensive workup and to treat the underlying pathology before taking any further steps. The case above was a primary form of clubbing, and the patient was simply given reassurance.
Patient Presentation
A healthy 33-year-old man with a long history of fingernail changes was referred by his primary care physician to the nail clinic for a cosmetic consultation and, if indicated, a nail biopsy. The patient denied any active chest pain, diaphoresis, pulmonary or musculoskeletal complaints. The patient denied a history of smoking. He also stated that his uncle had similar fingernail changes, also without any associated lung pathologies. Aside from the fingernail changes, the rest of the physical examination was essentially normal. No lymphadenopathy was noted, and the CBC, chemistry panel and fasting glucose levels were normal.
What’s Your Diagnosis?
Diagnosis: Primary Clubbing
First described by Hippocrates more than 2,400 years ago, the term “clubbing” was used to depict an enlargement of the distal segments of the upper and lower extremities. In 1911, Von Eiselsberg reported the first clinical case of congenital familial clubbing, expressing his conviction that clubbing was not merely a patho-gnomonic sign of an underlying visceral disease, but also a hereditary trait.1
Clubbing is classified as either primary or secondary. Primary processes are hereditary or idiopathic in nature, whereas secondary processes are associated with a variety of pulmonary and non-pulmonary diseases.
Hypertrophic osteoarthropathy, pachydermoperiostosis, familial clubbing, and idiopathic clubbing constitute the major primary forms of digital clubbing.
Hypertrophic osteoarthropathy (HOA) is characterized by periostosis of long bones, joint pain, clubbing, and occurs in approximately 5% of patients with bronchogenic carcinoma and 50% of patients with pleural mesothelioma.2
Pachydermoperiostosis (PDP), also known as primary HOA, is a rare autosomal dominant disorder with incomplete penetrance and variable expression that presents in otherwise healthy children as clubbing, periostosis, and skin manifestations, including thickening of the skin of the face and scalp, coarsening of facial features, hyperhidrosis, and seborrhea with an unknown incidence.
Incomplete forms of primary HOA may present as isolated finger clubbing, periostosis, or pachydermia.3 What was once called familial clubbing in the literature was most likely an incomplete form of primary HOA.4
Pulmonary causes of secondary clubbing include lung cancers, such as non-small cell carcinoma in particular, benign mesothelioma, such as solitary fibrous tumors of the pleura, lung abscesses, bronchiectasis, and cystic fibrosis, while non-pulmonary causes involve neoplastic, cardiac, gastrointestinal, infectious, endocrine, and multisystem diseases.5 In particular, pulmonary neoplasms, such as non-small cell carcinoma, demonstrate strong correlations with this syndrome.6
Clinical Features
Finger clubbing is often difficult to establish solely upon a subjective examination, as the profile angle or distal phalangeal-to-interphalangeal depth ratio are needed to confirm this finding.
The profile angle, hyponychial angle, and phalangeal depth ratio can be quantitatively utilized: Individuals who do not have clubbing do not exceed 176 degrees, 192 degrees, and 1.0, respectively.7 Furthermore, microscopic imaging studies may reveal hypervascularization of the distal digits. As a result, both a detailed history and physical examination should be followed with appropriate laboratory studies.8 According to Sridhar, clubbing can be viewed in five basic stages.6 (See Table.)
Pathogenesis
Although clubbing is common, the exact mechanism remains unclear. Circulating vasodilators in association with cyanotic congenital heart disease, hypoxia, genetic predisposition, or platelet-derived growth factor release can all be attributed to this condition.9 Physiologically, it appears that the vasodilatation within the fingertip vessels increases the hydrostatic pressure in the capillaries, promoting the movement of fluid into the interstitial tissue and resulting in soft-tissue enlargement.
Differential Diagnosis
Clubbing is often an indication of an underlying disease, particularly that of a cardiovascular or pulmonary origin.
Idiopathic pulmonary fibrosis is one of the most common causes of digital clubbing, along with chronic lung infections and persistent interstitial lung diseases.10
However, clubbing is considered atypical in chronic obstructive pulmonary disease (COPD) or asthma, and if it is indeed found in a patient with COPD, an underlying malignancy should be suspected. It is also important to recognize that clubbing is usually accompanied by cyanosis in patients with pulmonary disease.
Hepatocyte growth factor (HGF) is considered a potential stimulator of clubbing.11 Furthermore, higher HGF levels were found in patients with lung cancer who exhibited enlargement of their distal segments. A separate study conducted by Hojo et al found much higher levels of HGF in patients with idiopathic pulmonary fibrosis, suggesting that this growth factor may play a duel role in both the progression of clubbing and the pathogenesis of pulmonary fibrosis.12
Pain is prominent in clubbing associated with HOA. Hypertrophic osteoarthropathy develops as result of subperiosteal formation in the distal long bones, and the proliferation of connective tissue and periosteum. It is attributed to stimulation by platelet derived growth factor (PDGF). The aggregation of platelets in the fingers, which releases PDGF, is the result of a variety of mechanisms.
Clubbing may also be seen specifically in patients with cyanotic congenital heart disease, infective endocarditis, cirrhosis of the liver, and inflammatory bowel disease, such as Crohn’s or ulcerative colitis, and presents without cyanosis. In a study conducted by Dutta, clubbing was found to be most common in patients with chronic liver disease.13
Management
There is no specific treatment for clubbing, but treatment of the underlying malignancy may decrease its incidence and reverse its effects if corrected in time. If significant changes have occurred within the tissues, such as increased collagen deposition, reversal is unlikely. Palliative measures may also be taken into consideration when treating symptoms such as pain.
In a patient with non-small cell bronchial carcinoma, an upper right lobectomy resulted in the regression of the finger clubbing.14
However, this surgical approach is not as effective when treating clubbing itself. Studies have shown that such a procedure produces an inadequate reduction of finger clubbing, and also showed a re-enlarging of the finger, with the nail matrix producing new tissue.15
Summary
Clubbing is associated with a wide array of pathological entities, and may be either primary (hereditary or idiopathic) or secondary in nature. Clubbing is usually visually identifiable and confirmed by the profile angle or distal phalangeal-to-interphalangeal depth ratio. Since clubbing usually presents with an underlying disease, it is important to perform a comprehensive workup and to treat the underlying pathology before taking any further steps. The case above was a primary form of clubbing, and the patient was simply given reassurance.
Patient Presentation
A healthy 33-year-old man with a long history of fingernail changes was referred by his primary care physician to the nail clinic for a cosmetic consultation and, if indicated, a nail biopsy. The patient denied any active chest pain, diaphoresis, pulmonary or musculoskeletal complaints. The patient denied a history of smoking. He also stated that his uncle had similar fingernail changes, also without any associated lung pathologies. Aside from the fingernail changes, the rest of the physical examination was essentially normal. No lymphadenopathy was noted, and the CBC, chemistry panel and fasting glucose levels were normal.
What’s Your Diagnosis?
Diagnosis: Primary Clubbing
First described by Hippocrates more than 2,400 years ago, the term “clubbing” was used to depict an enlargement of the distal segments of the upper and lower extremities. In 1911, Von Eiselsberg reported the first clinical case of congenital familial clubbing, expressing his conviction that clubbing was not merely a patho-gnomonic sign of an underlying visceral disease, but also a hereditary trait.1
Clubbing is classified as either primary or secondary. Primary processes are hereditary or idiopathic in nature, whereas secondary processes are associated with a variety of pulmonary and non-pulmonary diseases.
Hypertrophic osteoarthropathy, pachydermoperiostosis, familial clubbing, and idiopathic clubbing constitute the major primary forms of digital clubbing.
Hypertrophic osteoarthropathy (HOA) is characterized by periostosis of long bones, joint pain, clubbing, and occurs in approximately 5% of patients with bronchogenic carcinoma and 50% of patients with pleural mesothelioma.2
Pachydermoperiostosis (PDP), also known as primary HOA, is a rare autosomal dominant disorder with incomplete penetrance and variable expression that presents in otherwise healthy children as clubbing, periostosis, and skin manifestations, including thickening of the skin of the face and scalp, coarsening of facial features, hyperhidrosis, and seborrhea with an unknown incidence.
Incomplete forms of primary HOA may present as isolated finger clubbing, periostosis, or pachydermia.3 What was once called familial clubbing in the literature was most likely an incomplete form of primary HOA.4
Pulmonary causes of secondary clubbing include lung cancers, such as non-small cell carcinoma in particular, benign mesothelioma, such as solitary fibrous tumors of the pleura, lung abscesses, bronchiectasis, and cystic fibrosis, while non-pulmonary causes involve neoplastic, cardiac, gastrointestinal, infectious, endocrine, and multisystem diseases.5 In particular, pulmonary neoplasms, such as non-small cell carcinoma, demonstrate strong correlations with this syndrome.6
Clinical Features
Finger clubbing is often difficult to establish solely upon a subjective examination, as the profile angle or distal phalangeal-to-interphalangeal depth ratio are needed to confirm this finding.
The profile angle, hyponychial angle, and phalangeal depth ratio can be quantitatively utilized: Individuals who do not have clubbing do not exceed 176 degrees, 192 degrees, and 1.0, respectively.7 Furthermore, microscopic imaging studies may reveal hypervascularization of the distal digits. As a result, both a detailed history and physical examination should be followed with appropriate laboratory studies.8 According to Sridhar, clubbing can be viewed in five basic stages.6 (See Table.)
Pathogenesis
Although clubbing is common, the exact mechanism remains unclear. Circulating vasodilators in association with cyanotic congenital heart disease, hypoxia, genetic predisposition, or platelet-derived growth factor release can all be attributed to this condition.9 Physiologically, it appears that the vasodilatation within the fingertip vessels increases the hydrostatic pressure in the capillaries, promoting the movement of fluid into the interstitial tissue and resulting in soft-tissue enlargement.
Differential Diagnosis
Clubbing is often an indication of an underlying disease, particularly that of a cardiovascular or pulmonary origin.
Idiopathic pulmonary fibrosis is one of the most common causes of digital clubbing, along with chronic lung infections and persistent interstitial lung diseases.10
However, clubbing is considered atypical in chronic obstructive pulmonary disease (COPD) or asthma, and if it is indeed found in a patient with COPD, an underlying malignancy should be suspected. It is also important to recognize that clubbing is usually accompanied by cyanosis in patients with pulmonary disease.
Hepatocyte growth factor (HGF) is considered a potential stimulator of clubbing.11 Furthermore, higher HGF levels were found in patients with lung cancer who exhibited enlargement of their distal segments. A separate study conducted by Hojo et al found much higher levels of HGF in patients with idiopathic pulmonary fibrosis, suggesting that this growth factor may play a duel role in both the progression of clubbing and the pathogenesis of pulmonary fibrosis.12
Pain is prominent in clubbing associated with HOA. Hypertrophic osteoarthropathy develops as result of subperiosteal formation in the distal long bones, and the proliferation of connective tissue and periosteum. It is attributed to stimulation by platelet derived growth factor (PDGF). The aggregation of platelets in the fingers, which releases PDGF, is the result of a variety of mechanisms.
Clubbing may also be seen specifically in patients with cyanotic congenital heart disease, infective endocarditis, cirrhosis of the liver, and inflammatory bowel disease, such as Crohn’s or ulcerative colitis, and presents without cyanosis. In a study conducted by Dutta, clubbing was found to be most common in patients with chronic liver disease.13
Management
There is no specific treatment for clubbing, but treatment of the underlying malignancy may decrease its incidence and reverse its effects if corrected in time. If significant changes have occurred within the tissues, such as increased collagen deposition, reversal is unlikely. Palliative measures may also be taken into consideration when treating symptoms such as pain.
In a patient with non-small cell bronchial carcinoma, an upper right lobectomy resulted in the regression of the finger clubbing.14
However, this surgical approach is not as effective when treating clubbing itself. Studies have shown that such a procedure produces an inadequate reduction of finger clubbing, and also showed a re-enlarging of the finger, with the nail matrix producing new tissue.15
Summary
Clubbing is associated with a wide array of pathological entities, and may be either primary (hereditary or idiopathic) or secondary in nature. Clubbing is usually visually identifiable and confirmed by the profile angle or distal phalangeal-to-interphalangeal depth ratio. Since clubbing usually presents with an underlying disease, it is important to perform a comprehensive workup and to treat the underlying pathology before taking any further steps. The case above was a primary form of clubbing, and the patient was simply given reassurance.
