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CLUBBING
LEARNING OBJECTIVES:

At the end of this tutorial you should be able to:

1. Define and grade clubbing
2. Form a differential diagnosis for clubbing
3. Take a history from a patient with clubbing, focussing on features which aid in determining
the aetiology.
4. Examine patients with clubbing to elicit features suggestive of underlying aetiology.
5. Choosing and justifying appropriate investigations of the patient with clubbing.

DEFINITION: Digital clubbing is defined by structural changes at the base of the nails that results in a
convex distal phalanx.

Digital clubbing, alternatively called Hippocratic fingers, watch-glass nails or drumstick fingers can
be an isolated finding or may occur as part of the syndrome of hypertrophic osteoarthropathy (HOA).
HOA is characterised by:

1. Periostosis of long bones

2. Joint pain
3. Clubbing

HOA may be:

1. Primary: Also known as pachydermoperiostosis

2. Secondary: Secondary to a variety of disease processes.

Primary HOA: Primary HOA is an autosomal dominant disorder the presents in otherwise healthy
children as clubbing, periostosis and skin manifestations including thickening of the skin of the face
and scalp, coarse facial features, hyperhidrosis and seborrhoea.

Secondary HOA: Secondary HOA may also present as the full spectrum of HOA or as isolated finger
clubbing. Clubbing in secondary HOA may be:

1. Unilateral
2. Bilateral

Clubbing has been described as occurring in stages:

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Stages of Clubbing:

Stage I Periungal erythema and a softening of the nail

bed giving a spongy sensation on palpation
(increased fluctuance)
Stage II Loss of angle between the nail and the nail bed

Stage III Increased curvature of the nail (increased AP

diameter)

Stage IV Expansion of the terminal phalanx resulting in a

drumstick appearance

Stage V Full spectrum of HOA (periostosis of long bones

indicated by the arrows, joint pain and clubbing)

PATHOPHYSIOLOGY

Clubbing in patients with hypertrophic osteoarthropathy is believed to be stimulated by PDGF leading

to proliferation of connective tissue and periosteum. Several mechanisms have been proposed by
which platelet clumps accumulate in the finger tips and release PDGF.

Secondary clubbing is caused by a pathological condition which seems to cause changes in cytokine
levels in the blood. This is suggested by diseases that cause clubbing, i.e., either tumours or
conditions characterised by chronic hypoxia, chronic inflammation or chronic mechanical stress.
Examinations of the latter conditions include cyanotic heart disease and inflammatory bowel disease.
All these diseases result in release of cytokines.
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DIFFERENTIAL DIAGNOSIS

Unilateral Clubbing:

1. Hemiplegia
2. AV fistula (dialysis)
3. Takayasu's arteritis
4. Ulnar artery aneurysm

Causes of Bilateral Clubbing

MNEMONIC: CLUBBING + OTHER

C Cardiac 1. Cyanotic heart disease

2. Atrial myxoma
L Lung 3. Cystic fibrosis
4. Lung abscess
5. Emypema
6. Asbestosis
7. Hypersensitivity pneumonitis
8. Idiopathic pulmonary fibrosis (IPF)
9. Pulmonary AVM
10. Hepatopulmonary syndrome (HPS)
11. Sarcoidosis
U UC/CD 12. Ulcerative Colitis/Crohn's Disease
B Birth 13. Primary HOA
B Biliary 14. Primary biliary cirrhosis
15. Chronic Active hepatitis
I Infectious 16. TB
17. Infective endocarditis
18. Chronic parasitic infection (Trichuris trichiura,
schistosomal colonic polyposis)
N Neoplastic 19. Bronchogenic carcinoma
20. Lymphoma
21. Nasopharyngeal carcinoma
22. Mesothelioma
G Gastrointestinal 23. Coeliac disease
(Other) 24. Juvenile Polyposis Coli
One Other Endocrine 25. Thyroid acropathy
26. POEMS Syndrome: Pulmonary disease,
organomegaly, oedema, endocrinopathy,
monoclonal paraprotein, skin changes.
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HISTORY:

Unilateral Clubbing:

1. Hemiplegia: The most common cause of hemiplegia is a cerebrovascular accident, also

known as a stroke. Strokes can cause a variety of movement disorders, depending on the
location and severity of the lesion. Hemiplegia is common when the stroke affects the
corticospinal tract. Other causes of hemiplegia include spinal cord injury, specifically Brown-
Séquard syndrome, traumatic brain injury, or disease affecting the brain. As a lesion that
results in hemiplegia occurs in the brain or spinal cord, hemiplegic muscles display features
of the Upper Motor Neuron Syndrome.
2. AV Fistula: A history of renal failure and dialysis requirement.
3. Takayasu's Arteritis: A systemic disease with generalised symptoms including malaise,
fever, weight loss, night sweats arthralgias and anorexia. These symptoms may merge into
those related to vascular compromise and organ ischemia.
4. Ulnar Artery Aneurysm: A history of penetrating trauma in 70% of cases, blunt trauma in
20% and no trauma in 10%

Bilateral Clubbing:

Cardiac:

1. Cyanotic Heart Disease: Causes of cyanotic heart disease include 5 T's:

(a) Tetralogy of Fallot

(b) Truncus arteriosus
(c) Transposition of the great vessels
(d) Tricuspid atresia
(e) Total anomalous pulmonary venous return

2. Atrial Myxoma: Myxomas commonly present with obstructive, embolic or constitutional

symptoms.

Lung:

3. Cystic Fibrosis: Cough productive of copious amount of purulent sputum is usually the main
complaint in bronchiectasis.
4. Lung Abscess: There may be a preceding history of pneumonia or aspiration in addition to
pyrexia, malaise, weight loss and productive cough.
5. Empyema: There may be a preceding history of pneumonia or aspiration in addition to
pyrexia, malaise, weight loss and productive cough.
6. Asbestosis: Exposure to asbestos, usually occupational.
7. Hypersensitivity Pneumonitis: The clinical picture is that of an interstitial pneumonitis and
may present in the following ways:

(a) Acute: Symptoms such as cough, fever, chills, malaise and dyspnoea may occur 6-8 hours
after exposure to the antigen (Farmer's lung - thermophilic actinomycetes for example).
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(b) Sub-acute: Insidious presentation over a course of a few weeks marked by cough and
dyspnoea.
(c) Chronic: Clinically indistinguishable from pulmonary fibrosis due to a variety of causes.

8. Idiopathic Pulmonary Fibrosis: Usually presents with exertional dyspnoea, non-productive

dry cough and clubbing.
9. Pulmonary AVM: Over 50% of patients with AVM are asymptomatic. Symptomatic
patients are usually adults between the fourth and sixth decades of life. Symptoms include
fatigue and exertional dyspnoea (which may relate to high-output cardiac failure). Affected
patients may develop MI and mesenteric, renal or limb ischemia. Stroke occurs in up to 40%
of patients PAVM.
10. Hepatopulmonary Syndrome: HPS is characterised by the triad hypoxemia, orthodeoxia (a
fall in arterial oxygen tension on assuming the upright position) and platypnoea (difficulty in
breathing when erect and relieved by lying down).

UC/CD:

11. Ulcerative Colitis/Crohn's Disease: Malaise, diarrhoea, abdominal pain and weight loss
experienced by most patients with inflammatory bowel disease. The presence of aphthous
ulceration, fistulae and perianal sepsis is suggestive Crohn's disease.

Birth:

12. Primary HOA: May complain of skin changes and hyperhidrosis.

Biliary

13. Primary Biliary Cirrhosis: The majority of patients are asymptomatic and the disease is
initially detected on the basis of elevated serum alkaline phosphatase. Among patients with
symptomatic disease, 90% are women aged 35-60 years of age. Often the earliest symptom is
pruritus, which may be generalised or limited initially to the palms and soles.
14. Chronic Active Hepatitis: A thorough history for risk factors for viral hepatitis should be
sought (hepatitis B and C).

Infectious:

15. TB: Symptoms of tuberculosis include productive cough, haemoptysis, fever, weight loss and
night sweats. Assess for risk factors for HIV disease, chronic alcohol abuse or foreign travel
to an endemic region.
16. Infective Endocarditis: Fever and weight loss. Assess for risk factors for infective
endocarditis: dental extraction, IVDU, prosthetic heart valve etc.
17. Chronic Parasitic Infection: Travel to endemic region (Trichuris trichiura, schistosoma).
18. Bronchogenic Carcinoma: Cough, haemoptysis, weight loss, dyspnoea a history of chronic
smoking. Symptoms of metastasis (bone pain and jaundice) and paraneoplastic involvement
(neuropathy, thirst and polyuria from hypercalcemia) should be ascertained.
19. Lymphoma: Fever, weight loss, night sweats, shortness of breath from anaemia etc.
20. Nasopharyngeal Carcinoma: Cervical lymphadenopathy is the initial presentation in many
patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to
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the primary tumour include trismus, pain, otitis media, nasal regurgitation due to paresis of
the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal
obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or
organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy may occur with
widespread disease.
21. Mesothelioma: Relatively short term asbestos exposure of 1-2 years or less occurring some
20-25 years in the past have been associated with the development of mesotheliomas. The
risk of the tumour peaks 30-35 years after initial exposure. Most patients present with
effusions.

Gastrointestinal (Excluding IBD/Hepatobiliary):

22. Coeliac Disease: Diarrhoea, abdominal cramps, weight loss, intolerance to gluten containing
foodstuffs.
23. Juvenile Polyposis Coli

Other

24. Thyroid Acropachy: Symptoms suggestive of hyperthyroidism including anorexia, weight

loss, diarrhoea, insomnia, fatigue, intolerance of heat, menorrhagia etc.
25. POEMS

EXAMINATION:

1. General Inspection:

(a) Cachexia: The presence of wasting may be accounted for by cachexia of malignancy, chronic
lung or gastrointestinal disease.
(b) Cyanosis: The mucous membranes should be inspected for central cyanosis which may be a
feature of or a consequence of congenital heart disease or severe lung disease.
(c) Aphthous Ulceration: Crohn's and coeliac disease.
(d) Goitre, Exophthalmos, Ophthalmoplegia and Tremor: Grave's disease.

2. Hands:

(a) Fistula: AV fistula for dialysis.

(b) Ulnar Artery Aneurysm: Expansile pulsatile mass.
(c) Features of Infective Endocarditis: Splinter haemorrhages, Osler's nodes, Janeway lesions
(d) Palmar Erythema: Thyrotoxicosis

3. Vitals: Pyrexia is notable in several important causes of clubbing, namely suppurative lung
disease, infective endocarditis and active inflammatory bowel disease.
4. Chest: Findings on chest examination include:

1. Widespread Coarse Crepitations: Retained secretions of bronchiectasis.

2. Fine End Inspiratory Crepitations: Idiopathic pulmonary fibrosis
3. Lung Abscess: More localised coarse crepitations and dullness to percussion.
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4. Pleural Effusion: Findings suggestive a pleural effusion include unilateral decreased

expansion, dullness to percussion and absent breath sounds may be due to malignancy. The
presence of fever may suggest an empyema.

5. Abdomen:

(a) Ascites: May indicated chronic liver disease.

(b) RIF Tenderness: RIF tenderness or a mass may be found in Crohn's disease.
(c) Splenomegaly: May indicated portal hypertension with liver disease, or enlargement
accompanying infective endocarditis.

INVESTIGATIONS:

General Investigations:

Bloods

1. FBC: Anaemia in carcinomatosis, inflammatory bowel disease, infective endocarditis.

Raised white cell count in lung abscess, empyema and inflammatory bowel disease.
2. U&E: Deranged in patients getting haemodialysis (may have AV fistula).
3. LFTs: Liver cirrhosis/active liver disease.
4. ESR/CRP: May be raised non-specifically in infection, inflammatory bowel disease and
infective endocarditis.
5. CPM/Albumin: Hypercalcemia of malignancy.
6. TFTs: Suppressed TSH and raised T4 in thyrotoxicosis.
7. TTG Ab: Coeliac disease.

Imaging:

CXR: This should be performed if respiratory symptoms are present. Bronchial carcinoma may
manifest as a hilar or perihilar opacity, cavitating mass, collapse of a segment of lung due to luminal
obstruction, pleural effusion, elevated hemi-diaphragm due to phrenic nerve palsy or destruction of an
adjacent rib due to invasion. Lung abscesses present as a spherical shadow with a central lucency or
air fluid level. Bronchiectatic lungs have visibly dilated bronchi and multiple areas of consolidation.
With IPD - hazy shadowing at the lung bases may be present.

Specific Investigations:

1. Urinalysis: Haematuria from micro-emboli in infective endocarditis.

2. Blood Cultures: Three sets for infective endocarditis.
3. TOE: Valvular vegetations in infective endocarditis.
4. OGD: D2 biopsy for coeliac disease.
5. Sigmoidoscopy/Colonoscopy: Suspected inflammatory bowel disease.
6. CT Thorax: If bronchogenic carcinoma or thoracic empyema suspected. Also useful in the
diagnosis of bronchiectasis/pulmonary fibrosis.
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Diagnostic Algorithms in a Patient Presenting with Clubbing

Unilateral Clubbing:

Unilateral
Clubbing

Unilateral clubbing
Hemiplegia Yes
secondary to hemiplegia
No

Dialysis fistula, AV
Yes Unilateral clubbing secondary
anastomosis or aneurysm
to vascular lesion
detected on H + P

No

Refer to vascular surgery for

angiography of aorta and
vascular supply of affected
extremity
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Bilateral
Clubbing
Secondary HOA.
Arthralgia, Family Hx of
Aggressive evaluation of
Bone pain ? HOA?
underlying malignancy
Familial
HOA
Isolated clubbing.
Screening Refer to pulmonology
Findings on
CXR for further evaluation
complete H & P?
Idiopathic
Clubbing

Abdominal
HIV Risk Exophthalmos, Family Hx of Fever, chills,
RUQ tenderness, pain and Cough, SOB, Weakness,
Factors Pre-tibial clubbing night sweats,
Jaundice, diarrhoea Smoking Hx, paraesthesias, oedema,
myxoedema weight loss
Hepatitis Risk TB exposure, skin findings,
Factors Asbestos hepatosplenomegaly
exposure

TSH, Free T4, Haematology

Check AST, Gastro referral CXR, PPD, HIV Testing Incomplete FBC, CXR, PPD,
Endocrine referral for
ALT, Bilirubin, for further Consider CT familial HOA Consider CT TAP,
Referral evaluation for
Hepatitis evaluation for Thorax, (i.e., familial Blood Cultures, POEMS
serologies, GI IBD or Coeliac Pulmonology clubbing) HIV Test,
referral for PBC Disease referral Haem/Onc referral
if suspected
lymphoma, ID
referral for
IE/parasite work-
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