• Ivan Bristow

Clubbing of the nails





Figure 1 : Toenail clubbing in a patient with lung carcinoma


As a student I remember being struck by a patient with a lung tumour demonstrating overly curved nails and bulbous digits which I later learned were clubbed nails. The condition was first recognised and documented by Hippocrates around 430 BC (hence it is also known as Hippocratic nails). It is most often observed in patients with lung disease, but other conditions can also lead to the nail abnormality. In this blog I have undertaken a review of the condition, its aetiology and its associations.




Figure 2 : Fingernail clubbing in a patient with lung carcinoma



Clinical Features / Diagnosis


The diagnosis of clubbing is defined by changes in both the nail plate and nail bed (Figure 1 & 2):


· Increased nail curvature (proximal to distal, and laterally, side to side).

· Hypertrophy of the pulp of the digit

· Localised cyanosis (in just over half of cases)

· Pain in the digit (not a consistent finding)


The diagnosis of club nails by visual assessment can be challenging, particularly with low grade disease. Various diagnostic angles have been used to assess the abnormal curvature – such as the angles of Curth and Lovibond (figure 3) and, the disappearance of Schamroth’s window (see figure 4). Images taken from (1).



Figure 3 : Angles of Curth & Lovibond in normal and clubbed nails (1).




Figure 4: Schamroth’s window. In normal nails a”Window” of light is seen in profile (left image), but this is lost with clubbed nails (right image) (1).


Associated Conditions

The literature demonstrates a wide range of causes of clubbing, but primarily they tend occur in patients with lung, liver, alimentary or cardiovascular disease. For many conditions, clubbing has been seen to be reversible when the underlying disease has been effectively treated or resolved.





What causes the nail unit changes?


The exact mechanism of clubbing has not fully elucidated but a review of early studies conducted in the 1940’s and 1950’s demonstrated digital vasodilation as a consistent feature (2). Hall suggested that a vasodilatory substance, normally detoxified by the lungs, remained in the bloodstream causing the vasodilation within the digits (3). Many suspected chemicals have been studied including ferritin, prostaglandins, bradykinin, tumour necrosis factor and growth hormone. Latterly, Dickinson proposed a hypothesis of platelet clumping to explain the observed nail changes. In his 1993 paper (4), he suggested that cells called megakaryocytes (the precursor cells of platelets) impact and clump in the distal vascular bed of the fingers and toes. These clumps release platelet derived growth factors (PDGFs) in these areas causing soft tissue hyperplasia and the typical observed nail changes seen in clubbing.


So why does this not occur in everyone? This is probably physiological. In normal circulation, megakaryocytes produced in the bone marrow are particularly abundant in mixed venous blood and are conveyed by the venous system through the right side of the heart and into the lungs. The microvasculature of the lungs is able to trap these large precursor cells and prevent them from entering the arterial blood supply. However, they may defragment into smaller platelet cells which can return to the arterial circulation by virtue of their smaller diameter, without causing any problems.


Dickinson proposes that any physiological disturbance that leads to a shunt or bypass of venous blood into the arterial system, avoiding the lung microvasculature, means that the large megakaryocytes can escape into the arterial system. By the nature of the axial blood flow in arteries, the cells preferentially tend to end up impacted into the digital pulp areas of the fingers and toes. For example, in congenital heart disease a right to left cardiac hole exists, meaning venous blood can flow directly through into the systemic arterial circulation, avoiding entrapment in the lungs. This is confirmed when examining the blood of children with congenital heart disease where platelet clumps and megakaryocytes can be observed in arterial blood and in the distal pulp of the digits.


When lodged in the distal pulps of the digits the clumps locally release PGDFs which are known to stimulate cell growth and mitogenesis causing increased vascularity, swelling of the distal digit causing pulp enlargement. This swelling also leads to nail matrix distortion causing the characteristic change in digit and nail plate shape.



How do various diseases lead to clubbing?


Any condition affecting the lungs which leads to clubbing perhaps can be easily explained due to the arteriovenous shunting of clumps described above. Indeed, studies comparing the digits and nails of lung disease patients with and without clubbing at post-mortem has demonstrated evidence of platelet clumping in clubbed nail specimens whilst those without the nail deformity showed no evidence of this phenomenon (5).


In severe liver disease, it has been recognised that this impacts on lung function – for example patients with hepatic disease may show cyanosis. Small arteriovenous shunts have been identified in the lungs of patients with liver disease. Curiously, transplantation with a healthy liver leads to reversal of any nail changes. In Inflammatory bowel disease, no direct venous to arterial shunts have been reported however, increased PDGF activation has been detected in the digits of patients with Crohns disease (6). For other conditions with observed clubbing there has been little research regarding platelet function and activity, as Dickinson points out, although their cause maybe as yet unknown, platelet clumping has not been ruled out as a potential cause. Other theories have been suggested and debated (7) that may lead to clubbing but nothing appears to be as solid as Dickinson’s theory. So, for the moment, it remains the most plausible explanation.



Assessment of the patient with clubbing of the nails


Any patient presenting with club nails should undergo an assessment to elucidate the cause particularly where the nail change is a recent or acquired event. It should be borne in mind that not all patients with clubbed nails will have an underlying disease as hereditary and idiopathic causes exist. In addition, the extent of clubbing in nails can show a wide degree of variation and diagnosis consequently can be somewhat subjective. Assessment of the angles of Curth and Lovibond can be helpful, but like all measurements are subject to error. Where there is any doubt, patients should be referred for a full assessment of their condition (8).


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References


1. de Berker D, Bristow I, Baran R, Dawber RPR. Nails: Appearance and therapy. London: Dunitz; 2003.

2. Stanley NN, Woodgate DJ. The circulation, the lung, and finger clubbing in hepatic cirrhosis. Br Heart J. 1971;33(4):469-72.

3. Hall GH. Cause of clubbing. The Lancet. 1959;273(7083):1151.

4. Dickinson CJ. The aetiology of clubbing and hypertrophic osteoarthropathy. Eur J Clin Invest. 1993;23(6):330-8.

5. Fox SB, Day CA, Gatter KC. Association between platelet microthrombi and finger clubbing. Lancet. 1991;338(8762):313-4.

6. Collins CE, Cahill MR, Rampton DS. Clubbing in Crohn's disease. BMJ. 1993;307(6902):508-.

7. Spicknall KE, Zirwas MJ, English JC, 3rd. Clubbing: an update on diagnosis, differential diagnosis, pathophysiology, and clinical relevance. J Am Acad Dermatol. 2005;52(6):1020-8.

8. Burcovschii S, Aboeed A. Nail Clubbing. Florida, USA: Statpearls; 2021 [Available from: https://www.ncbi.nlm.nih.gov/books/NBK539713/.

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