What diseases are associated with clubbing?

Diseases Associated with Digital Clubbing

Digital clubbing is a clinical sign associated with numerous pulmonary, cardiovascular, gastrointestinal, and other systemic diseases, and its presence should prompt a thorough investigation for underlying pathology.

Pulmonary Causes

• Lung Cancer: Clubbing is the fourth most common presenting feature of lung cancer 1
• Interstitial Lung Diseases (ILDs):
  • Idiopathic pulmonary fibrosis (IPF) - present in 7-52% of cases 2
  • Other fibrotic ILDs 2
• Bronchiectasis: Especially in cases with chronic infection 1
• Lung Abscess/Empyema: Associated with chronic suppurative lung conditions 3
• Cystic Fibrosis: Clubbing is a negative prognostic factor in this condition 4
• Pulmonary Arterial Hypertension: Though rare in idiopathic PAH 1

Cardiovascular Causes

• Infective Endocarditis: Can cause rapid development of clubbing that may regress after treatment 5
• Cyanotic Congenital Heart Disease:
  • Tetralogy of Fallot 1
  • Other cyanotic heart defects with right-to-left shunting 1
• Arteriovenous Malformations: Including pulmonary AVMs 4

Gastrointestinal Causes

• Inflammatory Bowel Disease: Particularly Crohn's disease and ulcerative colitis 5, 3
• Gastrointestinal Malignancies:
  • Esophageal adenocarcinoma 6
  • Other digestive tract cancers 5, 3
• Liver Disease: Particularly cirrhosis with portal hypertension 1

Other Causes

• Thyroid Disease: Particularly thyroid acropachy in Graves' disease
• Familial/Idiopathic: Primary hypertrophic osteoarthropathy (rare)

Clinical Significance and Assessment

Digital clubbing can be assessed using several methods, though agreement between different assessment techniques is poor 2:

• Phalangeal depth ratio: Comparing the distal phalangeal depth to interphalangeal depth
• Lovibond's profile sign: Loss of the normal angle between the nail and nail bed
• Schamroth's sign: Disappearance of the diamond-shaped window normally seen when dorsal surfaces of terminal phalanges are opposed

Pathophysiology

Three main mechanisms have been proposed 4:

1. Hypoxia: Chronic tissue hypoxia leading to vasodilation
2. Chronic inflammation: Release of growth factors and cytokines
3. Aberrant vascularization: Vascular endothelial growth factor (VEGF) plays a prominent role

Clinical Approach to Patients with Clubbing

When clubbing is identified:

1. Perform targeted history:

   • Respiratory symptoms (cough, dyspnea, hemoptysis)
   • Cardiac symptoms (palpitations, chest pain, exercise intolerance)
   • Gastrointestinal symptoms (abdominal pain, change in bowel habits, weight loss)
   • Family history (hereditary causes)

2. Physical examination:

   • Assess for cyanosis, which may suggest congenital heart disease 1
   • Check for hepatomegaly, spider nevi suggesting liver disease 1
   • Evaluate for joint pain/swelling suggesting hypertrophic osteoarthropathy 3
   • Look for skin changes of connective tissue disorders 1

3. Initial investigations:

   • Chest radiograph (mandatory in all patients with clubbing) 1
   • Spirometry 1
   • Complete blood count and inflammatory markers
   • Oxygen saturation

4. Further investigations based on clinical suspicion:

   • CT chest for suspected lung cancer or interstitial lung disease
   • Echocardiography for suspected cardiac causes
   • Endoscopy for suspected gastrointestinal causes
   • Specialized testing as indicated by initial findings

Important Considerations

• Digital clubbing in a smoker with weight loss should raise high suspicion for lung cancer 1
• The presence of clubbing in pulmonary fibrosis may indicate more severe disease with lower diffusion capacity 2
• Clubbing can regress rapidly after treatment of the underlying condition, as seen in cases of infective endocarditis 5
• The absence of clubbing does not rule out serious underlying pathology

Remember that while clubbing itself is benign, its presence often signals significant underlying disease that requires prompt evaluation and treatment.