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ULY CLINIC

ULY CLINIC

25 Mei 2025, 18:03:26

Clubbing

Clubbing
Clubbing
Clubbing

Clubbing is a painless, bilateral hypertrophy of the soft tissues of the distal digits (fingers and toes) characterized by increased curvature and swelling of the nail bed and terminal phalanges without bony deformity. The hallmark is loss of the normal angle (~160°) between the nail plate and proximal nail fold, which increases toward 180° or more.


Pathophysiology

  • Clubbing results from chronic tissue hypoxia and altered vascular dynamics in the distal digits.

  • Proposed mechanisms:

    • Increased blood flow to the distal phalanges mediated by vasodilatory prostaglandins (particularly PGE2).

    • Platelet-derived growth factors released into systemic circulation due to pulmonary shunting or vascular abnormalities → stimulate connective tissue proliferation.

    • Hypoxia induces vascular endothelial growth factor (VEGF) release → neovascularization and fibroblast proliferation.

  • Genetic mutations (e.g., in SLCO2A1 or HPGD genes) can cause isolated or primary hypertrophic osteoarthropathy with clubbing.


Clinical presentation

  • Early: Soft tissue swelling at nail base, nail bed feels spongy ("floating nail" sign).

  • Progression: Nail bed thickens, angle increases >180°, nails become convex both longitudinally and transversely ("drumstick" appearance).

  • Late: Increased bulbous enlargement of distal digits ("watch-glass nails").


Diagnostic Approach

History
  • Review symptoms of underlying cardiopulmonary disease (e.g., chronic cough, dyspnea, cyanosis, fever, weight loss).

  • Duration and progression of clubbing.

  • Family history for congenital or inherited forms.

  • Medication, occupational, or environmental exposures.


Physical Examination
  • Measure nail angle with a goniometer if available.

  • Look for associated signs: cyanosis, peripheral edema, chest deformities.

  • Examine all digits including toes.

  • Evaluate for signs of infective endocarditis (Osler nodes, Janeway lesions), heart failure (JVD, edema), or pulmonary disease (crackles, wheezing).


Diagnostic Tests
  • Pulse oximetry and arterial blood gases: To assess oxygenation status.

  • Chest X-ray / CT scan: To identify pulmonary causes (bronchiectasis, interstitial fibrosis, lung abscess, neoplasms).

  • Echocardiography: To evaluate for cyanotic congenital heart disease, infective endocarditis, or heart failure.

  • Laboratory tests: CBC (anemia, infection), inflammatory markers, blood cultures (endocarditis), sputum analysis.

  • Genetic testing: If primary hypertrophic osteoarthropathy or congenital clubbing suspected.


Differential diagnosis

Condition

Distinguishing Features

Primary hypertrophic osteoarthropathy

Familial, isolated clubbing with periostosis and arthritis, normal cardiopulmonary function.

Curved nails (normal variant)

Nail angle remains ~160°, no soft tissue swelling.

Thyroid acropachy

Clubbing with pretibial myxedema, usually in Graves' disease.

Psoriatic arthritis

Clubbing-like changes, but with skin and joint symptoms.

Acromegaly

Enlarged hands/feet but different morphology.


Common medical causes of clubbing

The table below shows common medical causes of clubbing

Condition

Typical Features & Associated Signs

Bronchiectasis

Late-stage clubbing, cough with copious foul-smelling mucopurulent sputum, hemoptysis, coarse inspiratory crackles, weight loss, fatigue, dyspnea, rhonchi, fever, halitosis.

Chronic Bronchitis

Late sign, chronic productive cough, barrel chest, dyspnea, wheezing, accessory muscle use, cyanosis, tachypnea, crackles, rhonchi, prolonged expiration.

Emphysema

Late stage, anorexia, malaise, dyspnea, tachypnea, diminished breath sounds, peripheral cyanosis, pursed-lip breathing, barrel chest.

Infective Endocarditis

Subacute form, fever, anorexia, weakness, night sweats, fatigue, tachycardia, weight loss, arthralgia, petechiae, Osler’s nodes, splinter hemorrhages, Janeway lesions, splenomegaly, Roth’s spots, cardiac murmurs.

Heart Failure

Late sign, wheezing, dyspnea, fatigue, jugular vein distension, hepatomegaly, tachypnea, palpitations, dependent edema, weight gain, nausea, hypotension, diaphoresis, narrow pulse pressure, gallop rhythm, inspiratory crackles.

Interstitial Fibrosis

Advanced disease, intermittent chest pain, dyspnea, crackles, fatigue, weight loss, possible cyanosis.

Lung Abscess

Clubbing reversible with treatment, pleuritic chest pain, dyspnea, crackles, productive foul-smelling bloody sputum, halitosis, weakness, fever, chills, weight loss, decreased breath sounds.

Lung & Pleural Cancer

Commonly causes clubbing, hemoptysis, dyspnea, wheezing, chest pain, weight loss, anorexia, fatigue, fever.


Clinical implications

  • Clubbing indicates chronic hypoxia or chronic systemic disease and warrants thorough investigation.

  • May precede other clinical signs of underlying disease or indicate disease progression.

  • Persistent clubbing despite therapy may suggest irreversible tissue changes or undiagnosed disease.


Management

  • Treat the underlying cause aggressively (e.g., antibiotics for infection, surgery for congenital heart defects or lung abscess, chemotherapy for lung cancer).

  • Monitor progression or regression of clubbing as an indicator of disease control.

  • Patient education: Clubbing is not harmful by itself but is a marker for significant systemic disease.

  • Referral to specialists (pulmonologists, cardiologists, oncologists) as indicated.


Pediatric and geriatric considerations


Pediatrics
  • Common in cyanotic congenital heart disease and cystic fibrosis.

  • Surgical correction may reverse clubbing.


Geriatrics
  • Arthritic changes or deformities may mask or confuse diagnosis.

  • Careful clinical evaluation is needed.


Recent research and genetic insights

  • Mutations in SLCO2A1 (prostaglandin transporter) and HPGD (prostaglandin degradation enzyme) genes are linked to hereditary primary hypertrophic osteoarthropathy with clubbing.

  • These findings help differentiate primary (genetic) from secondary (acquired) clubbing and open pathways for targeted therapies.


Summary table: Key features of clubbing in major diseases

Disease

Clubbing Onset

Associated Clinical Signs

Reversibility

Bronchiectasis

Late

Copious sputum, hemoptysis, crackles

Possible with treatment

Chronic Bronchitis

Late

Barrel chest, chronic productive cough, cyanosis

Usually irreversible

Emphysema

Late

Dyspnea, pursed-lip breathing, barrel chest

Usually irreversible

Infective Endocarditis

Variable

Fever, murmurs, petechiae, Osler nodes, splenomegaly

Reversible with antibiotics

Heart Failure

Late

JVD, edema, tachypnea, gallop rhythm

Depends on cardiac function

Interstitial Fibrosis

Advanced

Dyspnea, crackles, weight loss

Usually irreversible

Lung Abscess

Initial

Foul sputum, fever, chest pain

Usually reversible

Lung/Pleural Cancer

Variable

Weight loss, hemoptysis, chest pain

Usually irreversible

References
  1. Seifert et al. (2012). Mutations in SLCO2A1 gene cause primary hypertrophic osteoarthropathy and digital clubbing. Human Mutations, 33, 660–664.

  2. Tariq et al. (2009). Mutation in HPGD gene causing isolated congenital nail clubbing. Journal of Medical Genetics, 46(1), 14–20.

  3. Seifert W, Kühnisch J, Tüysüz B, Specker C, Brouwers A, Horn D. Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated digital clubbing. Hum Mutat. 2012;33(4):660–4.

  4. Tariq M, Azeem Z, Ali G, Chishti MS, Ahmad W. Mutation in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase underlies isolated congenital nail clubbing (ICNC). J Med Genet. 2009;46(1):14–20.

  5. Braunwald E, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 20th ed. New York: McGraw-Hill; 2018.

  6. Fishman AP, Elias JA, Fishman JA, Grippi MA, Senior RM, Pack AI, editors. Fishman’s Pulmonary Diseases and Disorders. 5th ed. New York: McGraw-Hill; 2015.

  7. Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Diseases. 9th ed. Philadelphia: Elsevier; 2020.

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