a compact and concise summary on clubbing. Includes, mechanism, causes, and clinical approach to clubbing.

1. Clubbing
- Definition: A characteristic bulging of the distal finger and nail bed
- Stages of clubbing:
 Softening of the nail bed, causing a spongy feeling when the nail is pressed
 Loss of the normal <165° angle between nail bed and fold
 Convex nail growth
 Thickening of the distal part of the finger
 Shine and striation of the nail and skin
- Clubbing has a large number of differential diagnoses.
 The vast majority of clubbing is bilateral.
 Unilateral clubbing is very rare and has been seen in patients with:
 Hemiplegia
 Dialysis AV fistulas
 Ulnar artery AV malformations
 Pulmonary and neoplastic causes are by far the most common causes
- Mechanism/s of clubbing
 Vasodilatation and proliferation of the distal nail beds is thought to be key
and has been demonstrated in small MRI studies.
 This theory is supported by observation that patients with untreated patent
ductus arteriosus (PDA) demonstrate clubbing that is confined to the feet.
 The case report of a 24-year-old woman with reversed shunting through a
PDA and SaO2 >90% in her arms and 63% in her femoral artery with clubbing
and cyanosis only of her toes (and HOA of her lower extremities) suggests that
hypoxia plays a role.
 The most currently accepted explanation involves platelets and platelet-
derived growth factor (PDGF).
 It is hypothesised that in healthy individuals, megakaryocytes are broken down
into fragments in the lungs and these fragments become platelets. If this
fragmentation does not occur, whole megakaryocytes can become wedged in the
small vessels of distal extremities. Once trapped, they release PDGFs, which recruit
cells and promote proliferation of muscle cells and fibroblasts. This cell
proliferation causes the characteristic appearance of clubbing. Therefore, any
pathology that affects normal pulmonary circulation (such as cardiac shunts or lung
disease) may allow whole megakaryocytes to enter the peripheral circulation
unfragmented.
 In bowel disease, it is suggested that the polycythaemia and arteriovenous
malformations of the lung seen in some instances contribute to this process.
 In addition, vascular endothelial growth factor (VEGF) has been isolated in some
patients with lung cancer and hypertrophic pulmonary osteoarthropathy (HPOA)
and is likely to contribute to hyperplasia of the distal digits.

2. - Patients with acquired clubbing have a distinctive, abnormal capillary growth
pattern, with plexus formation at right angles to the normally vertically oriented
capillary loops, arborized loops with branches budding from the tips, and splayed
afferent and efferent limbs of the capillary loop.
- Platelet clusters aggregating in the distal vasculature of the digits may mediate the
morphological changes of clubbing. Furthermore, human megakaryocytes within
bone marrow produce and secrete VEGF in an inducible manner. VEGF delivered to
sites of vascular injury by activated platelets may initiate angiogenesis.
 In normal neonates, plasma VEGF levels are elevated but within 3 months fall rapidly. In
cyanotic children, VEGF levels remain elevated and are inversely related to oxygen
saturation, and the functional capacities of circulating endothelial progenitor cells
(proliferation, migration, and adhesion) are augmented.
- In active inflammatory bowel disease, especially when macroscopic disease is
confined to the area of the gut innervated by the vagus nerve (ie, the small and
large intestine as far as the midtransverse colon).
 Mucosa with active disease shows higher spontaneous VEGF production than normal
mucosa, and the expression of VEGF-A and its receptor, VEGFR-2, are increased in
inflamed bowel. Thus, VEGF appears to be a promoter of angiogenesis and inflammation
in bowel disease and, when overexpressed in a mouse colitis model, worsens the
condition.
- In patients with bronchogenic carcinoma and unequivocal clubbing, both VEGF and
platelet-derived growth factor, which are released with platelet aggregation and
are hypoxically regulated, are increased in the digits that contain platelet clusters
compared with control subjects.
 In patients with lung cancer, plasma levels of VEGF are significantly higher than in control
subjects, and VEGF is known to be a predominant angiogenic tumor growth factor.
 Removal of a pulmonary large-cell adenocarcinoma in a female patient with digital
clubbing and primary HOA dramatically reduced abnormally high plasma and serum VEGF
levels. Her bone pain and clubbing deformities regressed and were absent a year after
surgery.
 The resected lung tumor showed 45% greater VEGF mRNA expression than normal lung.

3. - Differential diagnosis
- Examination sequence:
 Inspection
 Look across the nail bed from the side of each finger. Observe the distal
phalanges, nail and nail bed:
 Estimate the interphalangeal depth at the level of the distal interphalangeal
joint (this is the AP thickness of the digit rather than the width). Repeat at
the level of the nail bed.
 Assess the nail-bed (hyponychial) angle
 Ask the patient to place the nails of corresponding (ring) fingers back to
back and look for the normal ‘diamond-shaped’ gap between the nail
beds (Schamroth’s window sign)
 Palpation
 Place your thumbs under the pulp of the distal phalanx and use your index
fingers alternately to see if there is fluctuant movement of the nail on the
nail bed
- Finger clubbing is likely if:
 the interphalangeal depth ratio is > 1 (that is, the digit is thicker at the level of the nail bed
than the level of the distal interphalangeal joint)
 The nail fold angle is > 190 degrees
 Schamroth’s window sign is absent
- Increased nail-bed fluctuation may be present and may support the finding of
clubbing, but its presence is subjective and less discriminatory than the above
features.

6. REFERENCES
 Macleod's Clinical Examination 14th
Edition
 Mechanisms Of Clinical Signs by Dennis, Bowen and Cho 2nd Edition
 https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.112.000163
 https://pdfs.semanticscholar.org/2787/cceec17dba6758c81865e00994bac32f58
2d.pdf
 http://www.cjhr.org/temp/CHRISMEDJHealthRes6172-5592316_153203.pdf
 https://www.racgp.org.au/afp/2015/march/evaluation-of-digital-clubbing/
Done by: Aly Barakat
Senior medical student at OMC (Oman Medical College- NUST)