Digital clubbing is one of the oldest, yet poorly
understood, signs in clinical medicine.
Hypertrophic osteoarthropathy is a clinical
syndrome characterised by clubbing of digits,
periosteal bone formation and arthritis. Clubbing
is an invariable feature of HOA but can also occur
as an isolated manifestation. It is now believed
that isolated clubbing represents either an early
stage or one element in the spectrum of HOA4.
The clinical significance of isolated clubbing is the
same as that of HOA.
The bulbous deformity of the digits results from
oedema and excessive collagen deposition. The
small blood vessels in the digits are dilated and
have thickened walls. The number of arteriovenous
anastomoses is also increased. The
pathogenesis of HOA is not known. Two theories
traditionally put forward to explain HOA are:
(a) Neurogenic theory
(b) Humoral theory
The neurogenic theory proposes that a neural
reflex initiated by vagal stimulation from the site
of disease leads to vasodilatation and other
features of HOA. This is supported by the fact that
the disorders associated with HOA involve sites
innervated by the vagus nerve. Also, vagotomy
may result in resolution of symptoms5. The
humoral theory6 postulates that mediators
responsible for HOA are humoral and normally
present in the venous circulation. These are
ordinarily inactivated by the lung. In conditions
like cyanotic congenital heart disease these
mediators escape filtration/inactivation by the
lungs. A strong argument in favour of the humoral
theory is afforded by causes of congenital cyanotic
heart disease in which bone abnormalities are
limited to cyanotic limbs. Even in conditions like
lung cancer, intestinal polyposis, and
hepatopulmonary syndrome of liver cirrhosis,
lesser degrees of right to left shunt are evident.
However, recent studies suggest that platelets play
an important role in the development of HOA.
The circulating megakaryocytes and large platelet
particles present in the venous circulation normally
break up in the pulmonary vascular bed. In
patients with right to left shunt, macrothrombocytes
reach distal extremity sites where they interact with
endothelial cells resulting in release of platelet
derived growth factor (PDGF) and fibroblast
growth factor(s) thus inducing acropachy7.
Stimulation of fibroblasts by PDGF and
transforming growth factor beta results in cell
growth and collagen synthesis. The finding of
elevated levels of von Willebrand factor antigen
in patients with cardiogenic hypertrophic
osteoarthopathy as well as those with primary
HOA lends further support to this hypothesis8.
Other putative mediators include prostaglandins,
estrogen, growth hormone, etc. In idiopathic cases
a genetically determined overproduction of bone
remodelling substance may be culprit6.
The clinical features of HOA include asymptomatic
deformity of digits. The digital clubbing may
precede the clinical features of underlying illness.
HOA occurs in 5-10% of patients with intrathoracic
Journal, Indian Academy of Clinical Medicine Vol. 2, No. 1 and 2 January-June 2001 37
malignancy. Some patients complain of burning
sensation in finger tips and and deep seated bone
pains in distal extremities. These may be more in
the lower extremities due to limb dependency.
Bone thickening may be evident in some patients.
Joint effusions without synovial hypertrophy may
also be seen. Wrists, matacarpophalangeal, ankle,
knee, and the metatarsophalangeal joints may be
affected. Arthrocentesis yields non-inflammatory
fluid (cells typically less than 1000/mm3). It is
believed that the joint effusion is not due to synovial
disease but more of a sympathetic reaction to the
adjacent periostitis9. Plain X-rays of the extremities
may reveal new perisosteal bone. Radionuclide
bone scan is a sensitive method for demonstrating
this phenomenon. It reveals pericortical linear
uptake along the cortical margins of long bones.
Periostosis is symmetrical in distribution and
evolves in a centripetal fashion. Bone changes
occur in toes first. Radiographic evidence of
periostitis coupled with preservation of joint space
and absence of erosions/periarticular osteopenia
help one to exclude inflammatory arthritis.
Primary hypertrophic osteoarthropathy is less
common than secondary HOA. It is also known
as pachydermoperiostitis or Touraine-Solente-
Gole syndrome. This has a high male to female
ratio (9:1). It is inherited as an autosomal
dominant trait with variable expression. Skin
changes may be very prominent in primary
HOA9,10. This takes the form of cutaneous
hypertrophy and glandular dysfunction. The skin
hypertrophy roughens facial features. The
furrowed forehead, deep nasolabial folds and
corrugated scalp give rise to a leonine
appearance. The extreme skin hyprtrophy is
termed ‘cutis verticis gyrata’9. Glandular
dysfunction of skin results in hyperhidrosis,
seborrhoea, or acne. Acrolysis of terminal
phalanges has been reported. In contrast,
excessive sweating, oily skin, and thickening of
facial features are uncommon in secondary HOA.
Some of the variants of HOA include thyroid
acropachy seen in Graves’ disease. Here clubbing
and periostititis commonly co-exist with
exophthalmos and pretibial myxoedema.
Unilateral clubbing has been reported in
association with aneurysms of the aorta,
subclavian or innominate artery and with
arteriovenous fistlula of brachial vessels4. Clubbing
of toes without finger involvement is seen in
infected abdominal aortic aneurysm. Trauma,
sarcoidosis, and tophaceous gout may give rise
to single digit clubbing4.
Hypertrophic osteoarthropathy is usually
asymptomatic and does not require any treatment.
Joint and bone pains, if present, are treated with
NSAIDs or analgesics. Elevation of the affected
limb may afford pain relief. The treatment of
secondary HOA is to treat the underlying cause.
Removal of lung cancer, correction of cardiac
malformation, and successful treatment of
bacterial endocarditis may lead to a reversal of
the clinical features.
In conclusion, HOA is a syndrome characterised
by abnormal proliferation of skin and osseous
tissue at the distal extremities. The presence of
bone pains with joint pains in a patient with
clubbing should alert a clinician to the possibility
of HOA. Treatment is directed towards removal
of underlying cause, if any, and symptom relief.
